This lecture will discuss the advent and development of new concepts in chemical synthesis, ...... Application of transition metal catalysis in organic synthesis is an area of outstanding progress ...... Put forward by one of the authors, the idea about the possible role of mobile nanodefects as ...... of Chemistry, Chennai, India.
RUSSIAN ACADEMY OF SCIENCES (RAS) DIVISION OF CHEMISTRY AND MATERIAL SCIENCES, RAS RUSSIAN FOUNDATION FOR BASIC RESEARCH SCIENTIFIC COUNCIL ON ORGANIC CHEMISTRY, RAS ND ZELINSKY INSTITUTE OF ORGANIC CHEMISTRY, RAS
International Conference
Molecular Complexity in Modern Chemistry MCMC-2014
BOOK OF ABSTRACTS September 13-19, 2014 Moscow, Russia
International Advisory Committee H. Alper, University of Ottawa, Canada D. Astruc, University of Bordeaux, France J. Dupont, Institute of Chemistry, Brazil P. J. Dyson, EPFL, Switzerland R. G. Finke, Colorado State University, USA G. C. Fu, California Institute of Technology, USA A. Furstner, Max Planck Institut fur Kohlenforschung, Germany V. K. Jain, Bhabha Research Centre, India C.W. Jones, Georgia Institute of Technology , USA P.-H. Leung, Nanyang Technological University, Singapore C. Najera, Universidad de Alicante, Spain E.-i. Negishi, Purdue University, USA L. A. Oro, University of Zaragoza-CSIC, Spain R. Poli, Institut National Polytechnique, France V. Snieckus, Queen's University, Canada M. Taillefer, Institut Charles Gerhardt, France A. M. Trzeciak, University of Wroclaw, Poland Y. Yamamoto, Tohoku University, Japan
Local Organizing Committee ND Zelinsky Institute of Organic Chemistry, RAS
M. P. Egorov, Chairman V. P. Ananikov, Vice-chairman A. D. Dilman A. M. Sakharov A. Y. Stakheev A.M. Starosotnikov A. O. Terentev O. V. Turova S. G. Zlotin
National Advisory Committee G. A. Abakumov, N. Novgorod I. P. Beletskaya, Moscow Y. N. Bubnov, Moscow V. N. Charushin, Ekaterinburg O. N. Chupakhin, Ekaterinburg A. I. Konovalov, Kazan V. V. Lunin, Moscow V. I. Minkin, Rostov O. M. Nefedov, Moscow V. N. Parmon, Novosibirsk O. G. Syniashin, Kazan V. A. Tartakovsky, Moscow B. A. Trofimov, Irkutsk M. S. Yunusov, Ufa N. S. Zefirov, Moscow
Index Plenary Lectures ........................................................................................... 7 Invited Lectures .......................................................................................... 22 Oral Communications ................................................................................. 60 Posters ....................................................................................................... 110 Authors Index ........................................................................................... 326
Plenary Lectures
7
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PL1 THE APPLICATION OF PHOTOREDOX CATALYSIS TO NEW TRANSFORMATIONS IN CHEMICAL SYNTHESIS D.W.C. MacMillan Merck Center for Catalysis, Princeton University,Princeton, NJ 08544
This lecture will discuss the advent and development of new concepts in chemical synthesis, specifically the combination of photoredox catalysis with organic catalysis. This new approach to “synergistic catalysis” will demonstrate that multiple yet separate catalytic cycles can be aligned to generate activated intermediates that rapidly combine with each other, thereby allowing new approaches to enantioselective C–C and C-heteroatom bond formation. We will also introduce an approach to the discovery of new chemical reactions that we term accelerated serendipity. Accidental or ‘serendipitous’ discoveries have led to some of the most important breakthroughs in scientific history, many of which have directly affected human life. Given our overarching goal of developing fundamentally new and useful chemical transformations using catalysis and by acknowledging the tremendous impact of serendipity in scientific discovery, we questioned whether this phenomenon could be forced or simulated and therefore employed as a tool for reaction discovery. In this presentation, we will describe several new transformations that have been discovered via “accelerated serendipity” that we expect will find widespread adoption throughout the field of chemical synthesis. Moreover, we will further describe how mechanistic understanding of these processes has led to the design of a valuable, new yet fundamental chemical transformation. Acknowledgements Financial support was provided by NIHGMS (R01 01 GM093213-01) and kind gifts from Merck, Amgen, and Abbott.
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PL2 GOLD CATALYSIS 2.0 A.S.K. Hashmi Organisch-Chemisches Institut, Fakultät für Chemie und Geowissenschaften, Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany Homogeneous catalysis by gold has developed to an important sector of catalysis research.1 Initially, efforts in methodology development clearly dominated, in the last years also an increasing number of applications in synthesis has been reported.2,3 Efforts to understand the basic mechanism of these reactions continuously accompanied the field.4 For twelve years most of the reactions followed simple reaction mechanisms basing on the interaction of one gold centre in a gold complex or organogold compound with the substrate molecule. In most of these reactions vinylgold or alkylgold intermediates are involved, sometimes also gold carbenoids. Now an entirely new family of reactions, basing on the activation of the organic substrates by two gold complexes at the same time (one -coordinated, the other -coordinated), has been discovered. These open up entirely new synthetic possibilities and follow quite complex mechanisms. These mechanisms, which are new to the field of organometallic chemistry, will be discussed in detail. Some of the new reactions even allow positional selective C,H activations of alkyl side chains, as exemplified below.
The presentation will also contain results from computational chemistry. References: 1. A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180-3211. 2. A. S. K. Hashmi, M. Rudolph, Chem. Soc. Rev. 2008, 37, 1766-1775. 3. M. Rudolph, A. S. K. Hashmi, Chem. Soc. Rev. 2012, 41, 2448-2462. 4. A. S. K. Hashmi, Angew. Chem. Int. Ed. 2010, 49, 5232-5241.
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PL3 HOW MUCH CATALYST DO WE NEED? C. Bolm Institute of Organic Chemistry, RWTH Aachen University, 52056 Aachen, Germany
Various C-N-, C-O-, and C-C-bond forming reactions leading to cross coupling-type products can be performed without transition metals. In this presentation we will discuss cyclizations affording benzimidazol-2-ones1 and indazoles2 (eqs. 1 and 2, respectively). Photochemical initiations (eq. 3) led us to other directions.3,4 R2
R2
H N
N R1
X
N
KOH/DMSO
R3
O
40 °C, 24 h
O
R3
X = I, Br (Cl, F) R2
R2
diamine/K2CO3
N
R1 X
HN
R3
R1
N R3
X = I, Br O TMS
hn CH2Cl2, RT
O
(eq. 2)
N
toluene, RT, 2.5 h
O R1
(eq. 1)
N
R1
TMS R2
R1
(eq. 3)
O
R2
Finally we will present mechanochemical activations in ball mills that allow reducing the catalyst loadings in asymmetric organocatalyses.5-7
References: 1. a) Yuan, Y.; Thomé, I.; Kim, S. H.; Chen, D.; Beyer, A.; Bonnamour, J.; Zuidema, E.; Chang, S.; Bolm, C. Adv. Synth. Catal. 2010, 352, 2892. b) Beyer, A.; Reucher, C. M. M.; Bolm, C. Org. Lett. 2011, 13, 2876. c) Thomé, I.; Bolm, C. Org. Lett. 2012, 14, 1892. d) Beyer, A.; Buendia, J.; Bolm, C. Org. Lett. 2012, 14, 3948. e) Baars, H.; Beyer, A.: Kohlhepp, S. V.; Bolm, C. Org. Lett. 2014, 16, 536. 2. Thomé, I.; Besson, C.; Kleine, T.; Bolm, C. Angew. Chem. Int. Ed. 2013, 52, 7509. 3. a) Zhang, H.-J.; Becker, P. Huang, H.; Pirwerdjan, R.; Pan, F.-F.; Bolm, C. Adv. Synth. Catal. 2012, 354, 2157. b) Becker, P.; Priebbenow, D. L.; Zhang, H.-J.; Pirwerdjan, R.; Bolm, C. J. Org. Chem. 2014, 79, 814. c) Becker, P.; Priebbenow, D. L.; Pirwerdjan, R.; Bolm, C. Angew. Chem. Int. Ed. 2014, 53, 269. 4. For a photochemical activation in a metal catalysis, see: Bizet, V.; Buglioni, L.; Bolm, C. Angew. Chem. Int. Ed. DOI: 10.1002/anie.201310790. 5. a) Jörres, M.; Mersmann, S.; Raabe, G.; Bolm, C. Green Chem. 2013, 15, 612. See also in: b) Kleine, T.; Buendia, J.; Bolm, C. Green Chem. 2013, 15, 160. 6. For a video, see: http://www.beilstein.tv/tvpost/asymmetric-organocatalysis-in-a-ball-mill/ 7. For a general overview, see: James, S. L.; Collier, P.; Parkin, I.; Hyett, G.; Braga, D.; Maini, L.; Jones, B.; Friscic, T.; Bolm, C.; Krebs, A.; Mack, J.; Waddell, D. C.; Shearouse, W. C.; Orpen, G.; Adams,C.; Steed, J. W.; Harris, K. D. M. Chem. Soc. Rev. 2012, 41, 413.
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PL4 “MOLECULAR METATHESIS CATALYSTS” AT THE DAWN OF INDUSTRIAL IMPLEMENTATION D.E. Fogg University of Ottawa
Ruthenium-catalyzed olefin metathesis has enormous potential for impact on the chemical enterprise, in sectors ranging from pharma to specialty polymers and “green” feedstocks. Phosphine-free metathesis catalysts, particularly those of the Hoveyda type (HII, see Figure 1), occupy a position of increasing prominence. In one of the most high-profile current applications of metathesis chemistry, transformation of seed oils into functionalized olefins, HII significantly outperforms the benchmark Grubbs catalyst GII, [1,2] despite the fact that the two catalysts generate a common active species (A). Reports from pharma R&D indicate that HII also offers superior performance in some demanding RCM applications (RCM = ring-closing metathesis).[3] As these and closely related molecular metathesis catalysts enter deployment in process chemistry, understanding the mechanistic basis of their performance takes on added importance. We will discuss potential contributors to the improved productivity of HII: the absence of free PCy3, the presence of the styrenyl ether ligand, and operation of HII via interchange-associative pathways. The relevance of each of these factors will be considered in the context of demanding ring-closing and cross-metathesis reactions..
Figure 1. Molecular structure of an organometallic product. References [1] Miao, X.; Fischmeister, C.; Dixneuf, P. H.; Bruneau, C.; Dubois, J. L.; Couturier, J. L. Green Chem. 2012, 14, 2179-2183. [2] Biermann, U.; Bornscheuer, U.; Meier, M. A. R.; Metzger, J. O.; Schafer, H. J. Angew. Chem. Int. Ed. 2011, 50, 3854–3871. [3] van Lierop, B. J.; Lummiss, J. A. M.; Fogg, D. E., Ring-Closing Metathesis: A How-To Guide. In Olefin Metathesis: Theory and Practice, Grela, K., Ed. Wiley: Weinheim, 2014.
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PL5 REDUCTIONS WITH ORGANIC REAGENTS — THE ELECTRON AS A CATALYST! A. Studer WWU Muenster, Chemistry, Germany
In the lecture reduction processes for generation of various radicals using different organic reagents will be presented. Reactions are generally conducted using stoichiometric SET-reagents. However, also some catalytic variants will be presented. In the presentation radical perfluoroalkylations and azidations will be addressed. Moreover, the concept of using the electron as a catalyst will be discussed and some examples provided.
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PL6 NANOELECTRONICS: MOLECULAR METAL WIRES AND RELATED MOLECULAR MATERIALS S.M. Peng Department of Chemistry, National Taiwan University, Taipei, Taiwan
We have designed a series of new ligands such as oligo-α-pyridylamines, and used them to construct an unique class of quadruple helix of metal strings. This achievement leads to a new direction to the application of molecular wires in the nanoelectronics. The outline is as follows: I. Linear Metal String Complexes (1) ◎ Synthesis, Structure, Bonding II. Potential Application as Molecular Metal Wires & Molecular Switches (2) ◎ STM-bj Study on the Conductivity of Metal Strings ◎ Comparative Study on the I-V Characterisics (Theory V.S. Experiment) III. Tuning of the Metal Strings (3-9) ◎ Naphthyridyl Amino Ligands: Low Oxidation Mixed Metal Strings ◎ Asymmetrical Ligands: Toward Molecular Rectifier ◎ Heteronuclear Metal String Complexes ◎ Chiral Quadruple Helixes IV. Conclusion
X
N
N
N
N
M
M
M
M
N M
4 X
M = N i, C o , C r m = 0, 1, 2, 3 X = C l, N C S
m
Fig.1 Metal Strings of Oligo- -pyridylamido Ligands 1. C.-Y. Yeh, C.-C. Wang, Y.-H. Chen and S.-M. Peng, in Redox Systems Under Nano-Space Control, Ed: T, Hirao, Springer, Germany 2006, Ch. 5. 2. I.-W. P. Chen, M.-D. Fu, W.-H. Tseng, J.-Y. Yu, S.-H. Wu, C.-J. Ku, C.-H. Chen, and S.-M. Peng, Angew. Chem. Int. Ed. Engl. 2006, 5414. 3. (a) C.-H. Chien, J.-C. Chang, C.-Y. Yeh, G.-H. Lee, J.-M. Fang and S.-M. Peng, Dalton Trans. 2006, 2106. (b) C.-H. Chien, G.-H. Lee, Y. Song and S.-M. Peng, Dalton Trans. 2006, 3249. 4. M.-M. Rohmer, I. P.-C. Liu, J.-C. Lin, M.-J. Chiu, C.-H. Lee, G.-H. Lee, M. Benard, X. Lopez, S.-M. Peng, Angew. Chem. Int. Ed. Engl. 2007, 46, 3533. 5. I. P.-C. Li, W.-Z. Wang, and S.-M. Peng, Chem. Commun. 2009, 4323-4331. 6. R. H. Ismayilov, W.-Z.Wang, G. H. Lee, C. Y. Yeh, S. A. Hua, Y. Song, M. M. Rohmer, M. Bénard, S.-M. Peng, Angew. Chem. Int. Ed., 2011, 50, 2045-2048. 7. I. P.-C. Liu, C.-H. Chen, S.-M. Peng, Bull. Jpn. Soc. Coord. Chem., 2012, 59, 1-8.
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8. M.-C. Cheng, C.-L. Mai, C.-Y. Yeh, G.-H. Lee, S.-M. Peng, Chem. Commun. 2013, 49, 79387940 9. M.-J. Huang, S.-A Hua, M.-D. Fu, G.-C. Huang, C. Yin, C.-H. Ko, C-K. Kuo, C-H. Hsu, G.-H. Lee, K.-Y. Ho, C.-H. Wang, Y.-W. Yang, I.-C Chen, S.-M. Peng, C.-h. Chen, Chem. Eur. J. 2014, DOI: 10.1002/chem.201400067
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PL7 NEW CYCLOADDITION STRATEGIES BASED ON STRAINED AND UNUSUAL MOLECULES R.L. Danheiser Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Highly substituted carbocyclic and heterocyclic rings are key structural features in many biologically significant and commercially important compounds. Although classical synthetic approaches to such compounds have generally relied on linear substitution strategies, convergent cycloaddition and annulation strategies have emerged as powerful alternative methods for the assembly of highly substituted cyclic compounds. The intrinsic convergent nature of cycloaddition and annulation strategies facilitates the efficient assembly of highly substituted systems that would have required long, multistep routes using alternative methods. This talk will focus on the application of strained and unusual molecules as building blocks in cycloaddition strategies for the construction of complex carbocyclic and heterocyclic compounds. The synthetic utility of highly unsaturated, conjugated molecules such as vinylketenes, conjugated enynes, vinylallenes, allenylimines, and iminoacetonitriles will be described, as well as their application in the total synthesis of natural products.
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PL8 SILICON TETHER MOTIF IN C-H ACTIVATION REACTIONS V. Gevorgyan University of Illinois at Chicago
We have developed a set of new transition metal-catalyzed C-H activation methodologies employing a silicon-tether motif. These methods feature: (a) use of silyl group as a tether between a substrate and a reagent, thus transforming intermolecular reaction into intramolecular reaction;1-2 (b) employment of a silicon-tethered directing group, which is traceless or easily convertable into valuable functionalities;3-8 (c) use of silyl-tethered hydrosilane reagent;9-10 and (d) introduction of new N/Si-chelation concept that allows for a remote activation of aliphatic C-H bonds.11 The scope of these transformations will be demonstrated and the mechanisms will be discussed. References 1. Huang C., Gevorgyan V. J. Am. Chem. Soc. 2009, 131, 10844. 2. Huang, C.; Gevorgyan, V. Org. Lett. 2010, 12, 2442. 3. Chernyak N., Dudnik A. S., Huang C., Gevorgyan V. J. Am. Chem. Soc. 2010, 132, 8270. 4. Dudnik A. S., Chernyak N., Huang C., Gevorgyan V. Angew. Chem., Int. Ed. 2010, 49, 8729. 5. Huang C., Chattopadhyay B., Gevorgyan V. J. Am. Chem. Soc. 2011, 133, 12406. 6. Huang C., Ghavtadze N., Chattopadhyay B., Gevorgyan V. J. Am. Chem. Soc. 2011, 133, 17630. 7. Gulevich, A. V.; Melkonyan, F. S.; Sarkar, D.; Gevorgyan, V. J. Am. Chem. Soc. 2012, 134, 5528. 8. Sarkar, D.; Melkonyan, F. S.; Gulevich, A. V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2013, 52, 10800. 9. Kuznetsov, A.; Gevorgyan, V. Org. Lett. 2012, 14, 914. 10. Kuznetsov, A.; Onishi, Y.; Inamoto, Y.; Gevorgyan, V. Org. Lett. 2013, 15, 2498. 11. Ghavtadze, N; Melkonyan, F. S.; Gulevich, A.; Huang, C.; Gevorgyan, V. Nat. Chem. 2014, 6, 122.
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PL9 WERNER COMPLEXES: A NEW CLASS OF CHIRAL HYDROGEN BOND DONOR CATALYSTS FOR ENANTIOSELECTIVE ORGANIC REACTIONS J.A. Gladysz Department of Chemistry, Texas A&M University, PO Box 30012, College Station, Texas 778423012, USA Salts of the chiral tris(ethylenediamine)-substituted octahedral trication [Co(en)3]3+, and related species, have played important historical roles in the development of inorganic chemistry and stereochemistry.1,2 As Werner described in 1912, the two enantiomers, commonly designated and , can be separated by crystallization of the diastereomeric tartrate salts. 2 However, despite the low cost and ready availability of the building blocks, there have been no applications in enantioselective organic synthesis. L
H 2N
NH 2 H 2 N 3+ Co
H 2N NH 2
N H2
H 2 H 2N N 3+ Co
NH 2
N H2
NH 2
D
H 2N
We have found that [Co(en)3]3+ and related cations can be rendered soluble in organic solvents by using lipophilic anions such as "BArf–".3 Suitably functionalized derivatives act as highly enantioselective catalysts for a variety of carbon-carbon bond forming reactions. The mechanisms involve outer sphere activation of the electrophile by hydrogen bonding to the NH moieties. Other types of metal-containing chiral hydrogen bond donors are also effective, including a chelate of the CpRuL fragment. O NO 2
O
O
MeO
X
10 mol% cat. OMe
1.2 eq.
O
MeO
OMe NO 2
Et 3N, acetone 0 °C X
Ph
Ph Ph H 2N H 2N Ph
NH 2 H 2 3+ N Co N H NH 2 2
Ph 2Cl – BAr f– Ph
H 2N Ph
L
Ph
H 2N
Ph
Ph Ph
NH 2 H 2 3+ N Co N H NH 2 2
H 2N 2BF4– BAr f–
Ph
H 2N
L
Ph
Time Conversion ee (h) (%) (%) O
Ph
NH 2 H 2 3+ N Co N H NH 2 2
Ph
Ph
Time Conversion ee (h) (%) (%)
Ph 2PF6 – BAr f– Ph
L
Time Conversion ee (h) (%) (%)
O
MeO
O
OMe NO 2
15
>99
88
10
94
90
4
>99
86
OMe NO 2
22
98
94
7
98
97
4
>99
94
O
MeO
O Ph
1 2 3 4
Kauffman, G. B. Coord. Chem. Rev. 1974, 12, 105-149. Werner, A. Chem. Ber. 1911, 44, 1887-1898 and 1912, 45, 121-130. Ganzmann, C.; Gladysz, J. A. Chem. Eur. J. 2008, 14, 5397-5400. Ghosh, S. K.; Ojeda, A. S.; Guerrero-Leal, J.; Bhuvanesh, N.; Gladysz, J. A. Inorg. Chem. 2013, 52, 9369-9378. 5 Thomas, C.; Gladysz, J. A. ACS Catalysis 2014, 5, 1134-1138. 18
PL10 COMPLEXITY IN SIMPLICITY: THE PROTOTYPE REACTIONS OF CARBENE ANALOGS M.P. Egorov Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russia
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PL11 SELECTIVELY ALKYLATED AND ARYLATED N-HETEROAROMATICS VIA ACCEPTORLESS DEHYDROGENATIVE CONDENSATION (ADC) REACTIONS R. Kempe Lehrstuhl Anorganische Chemie II (Catalyst Design),University of Bayreuth, Bavaria, Germany
Dwindling reserves of crude oil and the resulting price increase of this and other fossil carbon sources combined with environmental concerns have resulted in a call for the use of alternative, preferably renewable, resources. Aside from fuel, ultimately a wide variety of chemical feedstocks are derived from fossil sources. Renewable lignocellulosic materials are indigestible and therefore not useful as food products and can be processed to give alcohols and polyols. These rather highly oxidized hydrocarbons differ drastically in their chemical nature from the cracking products of crude oil. Thus, there is a high demand for new reactions that utilize alcohols and convert them into key chemicals. Recently, our group developed a sustainable catalytic pyrrole synthesis.[1] Secondary alcohols and amino alcohols are deoxygenated and linked selectively via the formation of C–N and C–C bonds. Two equivalents of hydrogen gas and two equivalents of water are eliminated in the course of the reaction (Acceptorless Dehydrogenative Condensation, ADC). Alcohols based entirely on renewable resources can be used as starting materials. The catalytic synthesis protocol tolerates a large variety of functional groups, which includes olefins, chlorides, bromides, organometallic moieties, amines and hydroxyl groups. Furthermore, we have developed a catalyst that operates efficiently under mild conditions. This methodology could also be used to synthesize selectively functionalized pyridines from alcohols.[2] In the talk, the development of alcohol re-functionalization reactions and the design of catalyst systems that mediate these reactions are discussed. [1] S. Michlik, R. Kempe, Nature Chem. 2013, 5, 140. [2] S. Michlik, R. Kempe, Angew. Chem. Int. Ed., 2013, 52, 6450.
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PL12 THE CATALYST TODAY: BIG BANG AND LIFE AFTER I.P. Beletskaya Lomonosov Moscow State University, Department of Chemistry, Moscow, Russia
Nanocatalysis and catalysis by Lewis and Broensted acids will be considered in the lecture.
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Invited Lectures
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IL1 CYCLIZATIONS OF ALKYNES: FROM STEREOELECTRONICS TO CASCADE TRANSFORMATIONS I.V. Alabugin Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Fl
One of the simplest organic functional groups, the alkyne moiety, is also one a useful starting point for the design of cascade transformations which proceed through the formation of multiple C-C, CH, C-N and C-O bonds. [1] In this talk, I will illustrate how the revised stereoelectronic rules for alkyne cyclizations [2] can be used for the bottom-up preparation of carbon nanostructures for molecular electronics (i.e., graphene nanoribbons). In our approach, alkyne chains of varying sizes, shapes and functionalities, are built in a modular fashion and “zipped” up into graphene substructures via controlled cascades of all-exo or all-endo cyclizations. [3] Even in the presence of multiple functionalities, alkyne cascades can be made chemoselective via kinetic self-sorting of the pool of equilibrating radicals. [4] Further synthetic opportunities are presented by fusion of cyclization cascades with self-terminating fragmentations that allow use of alkenes as synthetic equivalents of alkynes. [5] [1] Alabugin, I. V.; Gold, B. J. Org. Chem., 2013, 78, 7777. [2] Alabugin, I. V.; Gilmore, K.; Manoharan, M. J. Am. Chem. Soc. 2011, 133, 12608. Alabugin, I. V.; Gilmore, K. Chem. Commun., 2013, 49, 11246. [3] Byers, P. M.; Rashid, J. I.; Mohamed, R. K.; Alabugin, I. V. Org. Lett., 2012, 14, 6032. Byers, P.; J. Am. Chem. Soc. 2012, 134, 9609. [4] Mondal, S.; Mohamed, R. K.; Manoharan, M.; Phan, H.; Alabugin, I. V. Org. Lett., 2013, 15, 5650. [5] Mondal, S.; Gold, B.; Mohamed, R. K.; Alabugin, I. V. Chemistry – Eur. Journal, 2014, in print.
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IL2 ARTIFICIAL PHOTOSYNTHESIS USING TRANSITION METAL COMPLEXES O. Ishitani Department of Chemistry, Tokyo Institute of Technology, Japan
Both the problems of the global warming and shortage of the fossil fuels have brought about great interest in photochemical utilization of CO2 with solar energy. Efficient photocatalysts for CO2 reduction must be necessary for development of such an important technology. We have developed novel types of photocatalytic systems using metal complexes and/or semiconductors as a photocatalyst.1 In this presentation, I will focus on the architecture of two types of the photocatalysts using transition metal complexes: (1) A mixed photocatalytic system including a ring-shaped Re(I) multinuclear complex as a photosensitizer2 (2) Ru(II)-Re(I) and Ru(II)-Re(I) supramolecular photocatalysts.3 The efficiency of the former photocatalytic system has been highest in the reported CO2-reduction photocatalysts ( = 82%), and the latter photocatalysts have been most robust (TON > 3000). References 1. (a) Yui, T.; Tamaki, Y.; Sekizawa, K.; Ishitani, O., Photocatalytic reduction of CO2: from molecules to semiconductors. Top. Curr. Chem. 2011, 303, 151-84; (b) Sekizawa, K; Maeda, K.; Domen, K.; Koike, K.; Ishitani, O. J. Am. Chem. Soc. 2013, 135, 4596. 2. Morimoto, T; Nishiura, C.; Tanaka, M.; Rohacova, J.; Nakagawa, Y.; Funada, Y.; Koike, K.; Yamamoto, Y.; Shishido, S.; Kojima, T.; Saeki, T.; Ozeki, T.; Ishitani, O. J. Am. Chem. Soc. 2013, 135, 13266. 3. (a) Gholamkhass, B.; Mametsuka, H.; Koike, K.; Tanabe, T.; Furue, M.; Ishitani, O. Inorg. Chem. 2005, 44, 2326; (b) Sato, S.; Koike, K.; Inoue, H.; Ishitani, O. Photochem. Photobiol. Sci. 2007, 6, 454; (c) Koike, K.; Naito, S.; Sato, S.; Tamaki, Y.; Ishitani, O. J Photochem. Photobiol. A: Chem. 2009, 207, 109; (d) Tamaki, Y.; Watanabe, K.; Koike, K.; Inoue, H.; Morimoto, T.; Ishitani, O. Faraday Discuss. 2012, 155, 115; (e) Tamaki, Y.; Morimoto, T.; Koike, K.; Ishitani, O. Proc. Natl. Acad. Sci. USA 2012, 109, 15673. (f) Tamaki, Y.; Koike, K.; Morimoto, T.; Ishitani, O. J. Cat. 2013, 135, 22; (g) Tamaki, Y.; Koike, K.; Morimoto, T.; Yamazaki, Y.; Ishitani, O. Inorg. Chem. 2013, 52, 11902.
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IL3 A PARADIGM FOR THE PRACTICAL AND ECONOMICAL FORMATION OF CARBON—CARBON AND CARBON—HETEROATOM BONDS. ORGANOCATALYTIC REDOX COUPLED, TRANSITION METAL CATALYZED DEHYDRATIVE BOND CONSTRUCTIONS L.S. Liebeskind, M.G. Lindale Emory University, Department of Chemistry, Atlanta, Georgia USA
The current world-wide focus on C-H functionalization is driven, in part, by the conceptual promise of atom-efficient, sustainable syntheses from readily available feedstocks. Of equal conceptual value is the dehydrative formation of C—C, C—N, and C—O bonds from common bioavailable hydroxylic reactants like carboxylic acids, alcohols, and phenols. Given the sustainable generation of hydroxylic feedstocks, dehydrative bond formations can impact all levels of synthesis (commodities, fine chemicals, biologicals), if they are efficient, economical, practical, and substrate general. And, they are uniquely poised to contribute to the search for the sustainable conversion of biomass to biofuels. This lecture describes a paradigm for the conversion of hydroxylic reactants to value-added C—C, C—N, and C—O products based on a practical, organocatalytic redox-coupled, transition metal catalyzed dehydrative bond forming process.
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IL4 CHEMICAL SYNTHESIS USING AMPHOTERIC MOLECULES A.K. Yudin University of Toronto
Over the past seven years, my lab has been exploring the use of amphoteric molecules in chemical synthesis. What started as a curiosity-driven project, has turned into a sustained exploration of a virtually untouched segment of chemistry characterized by molecules with unusual combinations of functional groups. The multifunctional nature arising from forced orthogonality enables amphoteric molecules to participate in reactions of high atom- and step- economy, thereby enabling efficient syntheses characterized by minimal reliance on protecting groups. In this lecture, I will illuminate several classes of reagents developed in our lab. I will discuss the discovery of bench-stable aldehydes equipped with a C-B bond at the alpha position. These intriguing molecules have enabled the synthesis of a rich palette of other reagents that contain carbon-boron bonds at strategic positions. With the growing repertoire of boron-containing amphoteric molecules, we are in a good position to explore ideas that range from reaction discovery to the synthesis of boron-based biologically active compounds. I will also present the evolution of peptide macrocyclization technology driven by amphoteric aziridine aldehydes. As part of this study, we are attempting to understand the conformational preferences of peptide macrocycles. As a result, we are moving closer to our ultimate goal of rationalizing the behavior of a wide range of substrate classes in our cyclization reactions, as well as understanding cellular activity of macrocycles. I will conclude my talk with a discussion of our integrative macrocyclization approaches and will present recent results of our protein crystallization efforts.
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IL5 EMERGENT FUNCTION FROM COMPLEX ADAPTIVE CATALYSTS V.V. Fokin The Scripps Research Institute, Department of Chemistry, La Jolla, California, USA and Moscow Institute of Physics and Technology, Dolgoprudny, Russia
Exploiting the versatility of catalytic processes requires rigorous interrogation of the constantly changing environment of the catalyst. Detailed understanding of critical events affecting a catalyst, such as activation and deactivation, unproductive off-cycle pathways, and changes in the nature of dominant species are of critical importance. The seemingly formidable challenge of controlling the reactivity of complex catalytic systems that involve dynamic and rapidly equilibrating mixtures of intermediates may, in fact, be their advantage: well-defined (i.e. non-adaptable) catalysts are often inefficient when compatibility with many functional groups and conditions is the goal. Examples of investigation of such catalytic reactions will be illustrated by case studies of transition metal-catalyzed transformations of alkynes. Alkynes are among the most energetic hydrocarbons, and transition metals enable selective and controlled manipulation of the triple bond, revealing their unique reactivity: transformations of alkynes into heterocycles and into a variety of molecules with new carbon–heteroatom bonds. These seemingly simple transformations involve an impressive variety of intermediates yet proceed with high selectivity and efficiency, maintaining their reactivity in most complex environments, such as the biological milieu of living organisms.
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IL6 RAPID PHOTOASSISTED ACCESS TO sp3-RICH POLYHETEROCYCLIC SCAFFOLDS O.A. Mukhina, N.N.B. Kumar, W.C. Cronk, W.J. Umstead, A.G. Kutateladze Department of Chemistry and Biochemistry, University of Denver, USA
Photochemical reactions hold unparalleled promise for building prohibitively strained carbo‐ and heterocyclic scaffolds, which offer expeditious access to difficult synthetic targets not accessible via ground state chemistry. Yet, photochemistry is underutilized by the synthetic community, which is especially true for Diversity Oriented Synthesis (DOS). In this context we have been developing a new photoassisted synthetic methodology which will enhance synthetic chemistry toolbox and will be compatible with DOS.1 This new photoassisted synthetic methodology allows for rapid access to topologically diverse polycyclic scaffolds decorated by various functional groups and carbo/heterocyclic pendants rigidly or semi-rigidly held in a unique spatial configuration by these novel core frameworks. Access to such topologically diverse scaffolds is realized via key photochemical steps and their combination with ground state reactions, most prominently via the recently discovered intramolecular cycloaddition reactions of azaxylylenes and quinomethanes photogenerated via excited state intramolecular proton transfer. Details of an experimental and theoretical mechanistic study to gain deeper understanding of underlying processes in the excited states will also be discussed. A typical example of rapid growth of complexity in a photoassisted synthesis of enantiopure conformationally locked ribofuranosylamines spiro-linked to oxazolidino-diketopiperazines via a straightforward “assembly” of a threonine-based photoprecursor, photochemical transformation, and a simple post-photochemical modification, is shown below.
[1] (a) Mukhina, O.A.; Kumar, N.N.B.; Arisco, T.M.; Valiulin, R.A.; Metzel, G.A.; Kutateladze, A.G. Angew. Chem. Int. Ed., 2011, 50, 9423-9428. (b) Nandurkar, N.S.; Kumar, N.N.B.; Mukhina, O.A.; Kutateladze, A.G. ACS Combinatorial Sci., 2013, 15, 73-76. (c) Kumar, N.N.B.; Mukhina, O.A.; Kutateladze, A.G. J. Am. Chem. Soc., 2013, 135, 9608-9611. (d) Cronk, W.C.; Mukhina, O.A.; Kutateladze, A.G. J. Org. Chem., 2014, 79,1235-1246.
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IL7 TRANSITION METAL CLUSTERS: UNAVOIDABLE CONTAMINANTS OR IMPORTANT PLAYERS IN SOLUTION? V.P. Ananikov Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russia; Department of Chemistry, Saint Petersburg State University, Stary Petergof, 198504, Russia
Application of transition metal catalysis in organic synthesis is an area of outstanding progress with prominent achievements in carbon-carbon cross-coupling, carbon-heteroatom bond formation, and atom-economic construction of organic molecules. Mechanistic studies have revealed two different frameworks for catalytic processes in solution depending on the nature of selected system and on the type of catalyst precursor used: single type metal species catalysis or multiple metal species catalysis [1]. The first type of systems is widely utilized and it is based on well-defined metal complex with strongly bound ligands. The catalyst precursor undergoes only partial or minor chemical modifications prior entering the catalytic cycle. In this model, the formation of other metal derivatives is not facilitated and the active core of the catalyst is preserved throughout the catalytic cycle. The second model can be considered as multiple metal species catalysis (in some cases - “cocktail” of catalysts) and involves a range of simultaneously present and dynamically interchangeable metalcontaining species, such as metal complexes, clusters and nanoparticles [2]. Such mechanistic picture may be expected when in situ generated catalysts are employed or upon usage of nanoparticles as catalysts precursors. It is of much interest to reveal the role of metal clusters in these catalytic systems. Formation of clusters was detected in many cases, although their role remains unclear. In some cases the presence of clusters was related to decomposition of the active form, while in the other cases the formation of dinuclear and polynuclear species is an important stage of catalyst evolution in solution. We have investigated soluble metal complexes and nanoparticles of Pd, Ni, Pt and Au for development of efficient catalytic systems for selective carbon-heteroatom and carbon-carbon bond formation in solution [3-5]. Homogeneous transition-metal-catalyzed reactions and heterogeneous nanoparticle-catalyzed reactions were considered, with a focus on metal species interconversions and nanoparticle contamination of homogeneous catalytic systems. References [1] Kashin A.S., Ananikov V. P., J. Org. Chem., 2013, 78, 11117 (doi: 10.1021/jo402038p). [2] Ananikov V. P., Beletskaya I. P., Organometallics, 2012, 31, 1595 (doi: 10.1021/om201120n). [3] Zalesskiy S. S., Sedykh A. E., Kashin A. S., Ananikov V. P., J. Am. Chem. Soc., 2013, 135, 3550 (doi: 10.1021/ja311258e). [4] Ananikov V. P., Orlov N. V., Zalesskiy S. S., Beletskaya I. P., Khrustalev V. N., Morokuma K., Musaev D. G., J. Am. Chem. Soc., 2012, 134, 6637 (doi: 10.1021/ja210596w). [5] Kashin A. S., Ananikov V. P., Top. Catal., 2013, 56, 1246 (doi: 10.1007/s11244-013-0091-5).
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IL8 SIMPLE COPPER CATALYSTS FOR C-C, C-N AND C-O BONDS FORMATION F. Monnier Institut Charles Gerhardt (UMR 5253) ENSCM, FRANCE
Since its renaissance in 2001, [1] the copper cross-coupling of nucleophiles with aryl halides has been increasingly studied. [2] In this account, we exposed our last contribution for the formation of C-C, [3] C-N [4] and C-O [5] bonds catalyzed by a cheap and simple combination of copper salts and -diketone ligands.
1. a) M. Taillefer, H.-J. Cristau, P. P. Cellier, J.-F.Spindler, Env. SAU2001-1009 and SAU200101044; patents Fr2833947-WO0353225 (Pr. Nb. Fr 2001 16547); M. Taillefer, H.-J. Cristau, P. P. Cellier, J.-F. Spindler, A. Ouali, Fr2840303-WO03101966 (Pr. Nb. Fr 2002 06717); b) S. L. Buchwald, A. Klapars, J. C. Antilla, G. E. Job, M. Wolter, F. Y. Kwong, G. Nordmann, E. J. Hennessy,WO02/085838 (priority number US0286268, 2001) 2. For a review, see: F. Monnier, M. Taillefer Angew. Chem., Int. Ed. 2009, 48, 6954-697 3. a) G. Danoun, A. Tlili, F. Monnier, M. Taillefer Angew. Chem. Int. Ed., 2012, 51, 12815. b) M.Taillefer, F. Monnier, A. Tlili, G. Danoun. PCT Int. Appl. (2013), WO 2013 EP61697 20130606; FR20120055275 20120606. 4. a) A. Tlili, F. Monnier, M. Taillefer Chem. Commun., 2012, 48, 6408-6410. b) E. Racine, F. Monnier, J.-P. Vors, M. Taillefer Chem. Commun., 2013, 49, 7412. c) E. Racine, F. Monnier, J.P. Vors, M. Taillefer Org. Lett. 2011, 13, 2818. 5. a) A. Tlili, N. Xia, F. Monnier, M. Taillefer Angew. Chem., Int. Ed., 2009, 48, 8725-8728.
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IL9 INTERACTIONS IN IONIC LIQUIDS PROBED BY NMR SPECTROSCOPY: DISTANCES, CONFORMATIONS, AND MORE R. Giernoth, A. Broehl, Y. Lingscheid University of Cologne, Department of Chemistry, Koeln, Germany One often-mentioned aspect of ionic liquids (ILs) is that they are “designer solvents“ whose properties can be designed for any particular need [1]. Obviously, it is impossible to choose a different property for a given IL but only a different IL entirely. To be able to sensibly do so, it is necessary to know about the supramolecular structures and the governing interactions in the ionic liquid phase. NMR spectroscopy and the nuclear overhauser effect spectroscopy (NOE) in particular is the method of choice for the investigation of ion pair interactions [2]. The NOE arises due to inter- and intramolecular cross relaxation. To be able to precisely measure interactions in solution, an internal distance standard is needed. We have synthesized a monofluorinated ionic liquid which was subsequently employed in NOE-based NMR investigations for the determination of distances and interactions in the ionic liquid phase. In a different project, we are studying the influence of different ionic liquids on peptide conformations, much in accord with the well-known Hofmeister series of ions [3]. With the help of a model system we are going to demonstrate that the choice of ions has a strong effect on the tertiary structure of different peptides in solution, and how these effects can be used for new non-native peptide chemistry. References [1] for reviews see: J.P. Hallett, T. Welton, Chem. Rev., 2011, 111, 3508-3576; E. J. Maginn, J. Phys. Condens. Matter, 2009, 21, 1–17. [2] P. S. Pregosin, Pure Appl. Chem., 2009, 81(4), 615–633; Y. Lingscheid, S. Arenz, R. Giernoth, ChemPhysChem 2012, 13, 261–266. [3] F. Hofmeister, Arch. Exp. Pathol. Pharmakol., 1888, 64, 247.
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IL10 APPLICATION OF α-CF3-SUBSTITUTED DIAZOCOMPOUNDS IN ORGANIC SYNTHESIS AND CATALYSIS S.N. Osipov, D.V. Vorobyeva, I.E. Tsishchuk A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow
An efficient pathway to multifunctional CF3-containing aromatic, heteroaromatic and heterocyclic compounds, including cyclic amino carboxylic and amino phosphonic acid derivatives have been developed. The method is based on in situ generation of highly electrophilic CF3-carbene species from the corresponding α-diazo carboxylates or phosphonates under Cu- or Rh-catalysis and their reactions with appropriate nucleophilic partners.1-4
The further applications of the reaction products in metal-catalysed transformations of different types, e.g. such as ring closing diene and ene-yne metathesis, intramolecular Pauson-Khand reaction as well as [2+2]-cycloaddition, open an access to new families of fluorinated molecules. References: 1. D.V. Vorobyeva, A.K. Mailyan, A.S. Peregudov, N.M. Karimova, T.P. Vasilyeva, I.S. Bushmarinov, C. Bruneau, P.H. Dixneuf, S.N. Osipov, Tetrahedron, 2011, 67, 3524. 2. A.K. Mailyan, I.M. Krylov, C. Bruneau, P.H. Dixneuf, S.N. Osipov, Synlett, 2011, 2321. 3. A.K. Mailyan, I.M. Krylov, C. Bruneau, P.H. Dixneuf, S.N. Osipov, Eur. J. Org. Chem., 2013, 5353. 4. I.E. Tsishchuk, D.V. Vorobyeva, A.S. Peregudov, S.N. Osipov, Eur. J. Org. Chem. 2014, 2480. 33
IL11 NEW ADVANCES IN ORGANOMETALLIC AND PHOSPHORUS ELECTROCHEMISTRY D.G. Yakhvarov, O.G. Sinyashin A.E.Arbuzov Institute of Organic and Physical Chemistry, Laboratory of Organometallic and Coordination Compounds, Kazan, Russian Federation
The development of modern chemical science and creation of new industrially applicable technologies are focused on application of effective and ecologically safe methods for the preparation of important and useful chemical compounds and materials. The combination of transition-metal catalysis and organic electrosynthesis has attracted increasing attention due to the high selectivity and efficiency of this approach in the synthetic preparation of various compounds bearing carbon-carbon and carbon-element bonds. The mild conditions, single-stage process, cyclic regeneration of the catalyst, and convenient and relatively inexpensive form of the energy used are the main advantages of electrochemical methods. Application of electrochemical processes to largescale production (macroscale synthesis) has led to significant development of the chemical technologies of the 21st century, due to easy access to highly reactive intermediates and tuning of the reactivity of the substrate used during the synthetic process by simple adjustment of the electrode potential. The elaborated in our research group electrochemical methods have been successfully applied for generation of organometallic sigma-complexes,1 which are important intermediates of different carbon-carbon and carbon-element coupling processes, selective preparation of organophosphorus compounds from white phosphorus,2 activation of inert oligophosphorus moieties formed in the coordination sphere of transition metal complexes,3 selective cleavage of the tungsten-phosphorus bond resulting in valuable metal-free phosphorus heterocycles obtained via phosphinidene intermediates.4 Herein, we present recent advances in synthetic application of the electrochemical techniques for preparation and activation of organonickel complexes1 and generation of new, previously known as unstable, phosphorus intermediates,5 which can be applied for preparation of practically useful organophosphorus compounds, transition metal catalysts and magnetically active materials.6 Acknowledgements: Financial support from the Russian Scientific Fund (project 14-13-01122) and Russian Foundation for Basic Research (project 09-03-00933-a) is gratefully acknowledged. References: [1] D.G.Yakhvarov, A.F.Khusnuriyalova, O.G.Sinyashin. Organometallics, 2014, in press. [2] D.G.Yakhvarov, E.V.Gorbachuk, O.G.Sinyashin. Eur. J.Inorg.Chem., 2013, 4709. [3] D.Yakhvarov, P.Barbaro, L.Gonsalvi, S.Mañas, S.Midollini, A.Orlandini, M.Peruzzini, O.Sinyashin, F.Zanobini. Angew. Chem. Int. Ed., 2006, 45, 4182. [4] D.G.Yakhvarov, Yu.H.Budnikova, N.H.Tran Huy, L.Ricard, F.Mathey. Organometallics, 2004, 23, 1961. [5] D.Yakhvarov, M.Caporali, L.Gonsalvi, Sh.Latypov, V.Mirabello, I.Rizvanov, O.Sinyashin, P.Stoppioni, M.Peruzzini. Angew. Chem.Int.Ed., 2011, 50, 5370. [6] D.Yakhvarov, E.Trofimova, O.Sinyashin, O.Kataeva, P.Lönnecke, E.Hey-Hawkins, A.Petr, Yu.Krupskaya, V.Kataev, R.Klingeler, B.Büchner. Inorg. Chem., 2011, 50, 4553.
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IL12 TRIFLUOROMETHYLATION BY SUNLIGHT-PROMOTED PHOTOREDOX CATALYSIS T. Koike, M. Akita Tokyo Institute of Technology, Chemical Resources Laboratory, Yokohama, Japan Photoredox catalysis 1 mediated by photo-sensitizers (e.g. [Ru(bipy)3]2+ and relevant Ir complexes) has attracted increasing attention as practical, green synthetic chemical processes, because they are visible light-promoted, redox-neutral reactions. We have demonstrated that photoredox catalysis is a powerful synthetic tool, in particular, for trifluoromethylation of olefinic substrates, which is the topic of the presentation.2,3 In all cases, electron transfer from the photoexcited metal species to an electrophilic CF3-reagent generates the key CF3 radical intermediate together with the cationic species of the catalyst. Subsequent addition of the CF3 radical to the olefinic substrate followed by oxidation of the resultant carbon radical intermediate by the cationic metal species gives the carbocationic intermediate, which is trapped by nucleophiles or deprotonated to furnish the coupling products. The sequential redox processes make the system redox-neutral. It is remarkable that the reactions are promoted not only by artificial light sources (e.g. Xe lamp and blue LED lamps) but also by sunlight.
References: 1) C. K. Prier, D. A. Rankic, and D. W. C. MacMillan, Chem. Rev., 113, 5322 (2013). 2) T. Koike and M. Akita, (a) Synlett., 24, 2492 (2013); (b) Topics in Cat., 259, in press (2014) (DOI: 10.1007/s11244-014-0259-7). 3) Y. Yasu, T. Koike, M. Akita et al., (a) Angew. Chem., Int. Ed., 51, 9567 (2012); (b) Chem. Commun., 49, 2037 (2013); (c) Org. Lett., 15, 2136 (2013); (d) Org. Lett., 16, in press (2014) (DOI: 10.1021/ol403500y); (e) Beilstein J. Org. Chem., submitted; (f) to be submitted; see also (g) Chem. Commun., 48, 5355 (2012); (h) ibid., 49, 7249 (2013).
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IL13 CYCLIC HYPERVALENT IODINE REAGENTS: A TREASURE OF REACTIVITY FOR CATALYSIS AND SYNTHESIS J. Waser Ecole Polytechnique Federale de Lausanne, ISIC SB LCSO, Lausanne, Switzerland
The non-classical four electrons three centers bonds of hypervalent iodine are weaker than normal classical bonds. This confers an exceptional reactivity to these compounds as oxidants or atomtransfer reagents. Cyclic hypervalent iodine reagents are especially interesting, as they combine enhanced stability with unique opportunities for reactivity modulation. In particular, our group has been interested in the development of alkynylation methods using cyclic EthynylBenziodoXolone (EBX) hypervalent iodine reagents.1 Interesting recent results of our research in the area includes the first example of gold-catalyzed domino cyclization-alkynylation2 and a highly efficient and practical alkynylation method for thiols.3 Herein, we will present our most recent work in the area of electrophilic alkynylation, as well as the extension of the use of cyclic hypervalent iodine reagents to other functionalization reactions.
References: 1. J.P Brand, J. Waser, Chem. Soc. Rev. 2012, 41, 4165-4179. 2. Y. Li, J. P. Brand, J. Waser, Angew. Chem., Int. Ed. 2013, 52, 6743-6747. 3. R. Frei, J. Waser, J. Am. Chem. Soc. 2013, 135, 9620-9623.
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IL14 THEORY AND COMPUTATION PROVIDE INSIGHTS AND DISCOVERY ON CHEMICAL REACTIONS OF COMPLEX MOLECULAR SYSTEMS K. Morokuma1,2 1 - Fukui Institute for Fundamental Chemistry; Kyoto University, Kyoto, Japan 2 - Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory University, Atlanta, GA, USA
The chemical reaction that creates, destroys, reorganizes chemical bonds to produce new compounds is the most important subject of chemistry. Theoretical/computational studies have come a long way and are now playing the central role in providing insights in understanding the mechanism and dynamics of chemical reactions as well as in discovery of new reaction mechanisms and reaction systems. The theory can study not only the reaction of the ground state of molecules in gas phase but also reactions of excited electronic states as well complicated reactions of complex molecular systems. The information theoretical/computational studies can provide is often complementary to the information experimental studies provide, and research on chemical reactions is becoming impossible without strong collaboration between theorists and experimentalists. In the present talk, I will discuss some of our recent studies of chemical reactions. We have developed the Global Reaction Route Mapping (GRRM) strategy for automatic exploration of reaction pathways of complex molecular systems. The ADDF (anharmonic downward distortion following) and the AFIR (artificial force induced reaction) methods in the GRRM strategy have been used for determination of not only energy minima and saddle points on the potential energy hypersurfaces but also minima and saddle points on the conical intersection and crossing seam hypersurfaces. I will discuss the GRRM strategy and applications to several reaction systems, including photodissociation reactions, catalytic reactions and enzymatic reactions.
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IL15 COMPUTATIONAL INSIGHTS INTO C-H FUNCTIONALIZATION JUNGLE D. Musaev Cherry L. Emerson Center for Scientific Computation, Emory University, Atlanta, Georgia, U.S.A
I will present our integrated and C-H FUNCTIONALIZATION SELECTIVE collaborative approaches to the RSH/RSeH + C C Pd(II)- PRECATALYST DIRECT Ar-Ar COUPLING Transition metal catalyzed C-H bond F ZR ZR ZR Cs Cs functionalization. I will elaborate our Pd Pd Pd O H O Ph H O i-Pr efforts on understanding the transition RZ ZR ZR I Active O ZR metal catalyzed C-H bond alkylation N Pd Pd H ZR H N Pd and amination reactions, and analyze Pd Ar Ph PG Inactive PR3 the factors controlling the reactivity of RZ ZR Pd ZR ZR "Cs2-I-F" assisted Ligand accelerated these reactions and make intriguing Pd-cluster effect Base (Cs)-effect Protecting Group effect predictions. I will discuss our latest results [1] on the mono-protected amino acid ligands (MPAA) promoted Pd(II)-catalyzed enantioselective C–H activation reactions. The presented computation allowed us to gain insights into the mechanisms, nature of active species, a ligand coordination mode to the Pd(II) and transition state structure of the C–H activation step. Our findings were supported by experiments. [1] D. G. Musaev, T. M. Figg, and A. L. Kaledin, Chem. Soc. Rev., DOI: 10.1039/C3CS60447K, (2014).
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IL16 A NOVEL TRIFLUOROMETHANESULFONYL HYPERVALENT IODONIUM YLIDE FOR TRIFLUOROMETHYLTHIOLATION N. Shibata Nagoya Institute of Technology, Department of Nanopharmaceutical Sciences, Nagoya, Japan
In the last few decades, numerous methods for the introduction of a trifluoromethylthio group into organic compounds have been developed. The main strategies are indirect methods, including halogen-fluorine exchange and trifluoromethylation of sulfur-containing compounds, such as disulfides, thiols and thiolates. Obviously, the most attractive and ideal route to constitute the CF3S moiety is the direct introduction of this functional group. However, in this approach, some limitations are usually encountered, including the use of gaseous and highly toxic reagents, such as CF3SCl, or unstable reagents, and the modest scope of substrates. Although several transition metal-mediated or catalyzed trifluoromethylthiolation methods have been developed, the substrates are mostly limited to aromatic compounds. Recently, Billard and co-workers reported that trifluoromethanesulfanylamides were effective for trifluoromethylthiolation of alkenes, alkynes, indoles and organometallic species. More recently, Lu and Shen also developed a novel hypervalent iodine reagent for the trifuoromethylthiolation of aryl and vinyl boronic derivatives, alkynes and βketoesters. Even though these direct trifluoromethylthiolation reagents are shelf-stable, a more critical issue is the fact that these CF3S regents should be prepared in advance by trifluoromethylthiolations or related trifluoromethylations! Due to these limitations and negative aspects, it is thus still necessary to develop an efficient and easily available reagent to introduce the CF3S moiety directly. In contrast to the CF3S unit, a trifluoromethanesulfonyl (CF3SO2) unit is stable and often found in commonly used organic reagents such as CF3SO2Cl, CF3SO2Na, CF3SO2H and (CF3SO2)2. In this context, we came up with a novel idea of using ubiquitous CF3SO2 compounds as reagents for introducing the CF3S unit under reductive conditions. As a part of our recent work on the chemistry of trifluoromethanesulfonyl compounds (triflones), we herein disclose a novel trifluoromethanesulfonyl hypervalent iodonium ylide as a shelf-stable reagent for electrophilic-type trifluoromethylthiolation. A wide variety of nucleophiles are nicely converted into the corresponding trifluoromethylsulfanyl products by this reagent.
Reference: Y.-D. Yang, A. Azuma, E. Tokunaga, M. Yamasaki, M. Shiro, N. Shibata, J. Am. Chem. Soc., 135, 8782 (2013)
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IL17 CATALYSIS-ASSISTED SIGNAL ENHANCEMENT IN NUCLEAR MAGNETIC RESONANCE I.V. Koptyug International Tomography Center, SB RAS, Novosibirsk, Russia
When parahydrogen (nuclear spin isomer of H2) is used in catalytic hydrogenations instead of normal H2, the NMR signals of reaction products and intermediates can be enhanced by 3-4 orders of magnitude and more owing to the phenomenon of parahydrogen-induced polarization (PHIP). This possibility has been explored previously in the context of activation of H2 by transition metal complexes and clusters in solution. It has been shown that PHIP can help to detect reaction products and short-lived intermediates not detectable by conventional NMR. As most of the industrial catalytic processes are heterogeneous, it would be desirable to employ PHIP in the NMR studies of heterogeneous catalysts and catalytic reactions. The objective of our research is thus to extend the scope of PHIP applications to the heterogeneously (HET) catalyzed hydrogenation reactions, and to develop a hypersensitive NMR-based technique for the in situ and operando studies of heterogeneous catalytic processes. In addition, HET-PHIP can be employed to produce catalyst-free hyperpolarized liquids and gases for novel MRI applications including the advanced in vivo studies. We demonstrate that, similar to their homogeneous counterparts, heterogenized transition metal complexes are able to produce strong NMR signal enhancements when parahydrogen is used in the hydrogenation reactions [1]. Our recent results show that various immobilized metal complexes are can produce HET-PHIP both in liquid phase and in gas phase hydrogenations. In contrast, for supported metal catalysts (e.g., Pt/Al2O3), dissociative hydrogen chemisorption and rapid migration of H atoms on the metal surface were expected to make the required pairwise hydrogen addition to a substrate molecule impossible. Nevertheless, we have shown that PHIP can be successfully observed both in liquid-solid and in gas-solid heterogeneous hydrogenations catalyzed by supported metal catalysts [1]. The NMR signal enhancement was found to be sensitive to the metal nanoparticle size and shape, the nature of the metal and support, and the type of substrate used in the reaction. Recently, HET-PHIP effects were also demonstrated for several metal oxides and bulk unsupported metals used as hydrogenation catalysts [2]. The implications of these results for the mechanisms of heterogeneous hydrogenation processes are discussed [1,3]. Further potential extensions of the technique will be presented, including the use of metal-free catalysts for activating parahydrogen [4], and the prospects of using nuclear spin isomers of molecules other than H2 to further extend the range of reactions and processes that can be explored in detail using the PHIP technique [5]. In addition to applying HET-PHIP to the mechanistic and kinetic studies of heterogeneous hydrogenations, several MRI applications of HET-PHIP have been already demonstrated, including MR imaging of a catalytic reaction in an operating model microreactor [6]. 1. K.V. Kovtunov, V.V. Zhivonitko, I.V. Skovpin, D.A. Barskiy, I.V. Koptyug, Top. Curr. Chem., 338, 123 (2013). 2. K.V. Kovtunov, D.A. Barskiy, O.G. Salnikov, A.K. Khudorozhkov, V.I. Bukhtiyarov, I.P. Prosvirin, I.V. Koptyug, Chem. Commun., 50, 875 (2014) 3. O.G. Salnikov, K.V. Kovtunov, D.A. Barskiy, A.K. Khudorozhkov, E.A. Inozemtseva, I.P. Prosvirin, V.I. Bukhtiyarov, I.V. Koptyug, ACS Catal., 4, 2022 (2014). 4. V.V. Zhivonitko, V.-V. Telkki, K. Chernichenko, T.J. Repo, M. Leskela, V. Sumerin, I.V. Koptyug, J. Amer. Chem. Soc., 136, 598 (2014). 5. V.V. Zhivonitko, K.V. Kovtunov, P.L. Chapovsky, I.V. Koptyug, Angew. Chem. Int. Ed., 52, 13251 (2013). 6. V.V. Zhivonitko, V.-V. Telkki, I.V. Koptyug, Angew. Chem. Int. Ed., 51, 8054 (2012).
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IL18 -BOND ACTIVATION REACTION BY TRANSITION METAL AND MAINGROUP ELEMENT COMPOUNDS AND CATALYTIC REACTION INCLUDING IT S. Sakaki Fukui Institute for Fundamental Chemistry, Kyoto University, Takano, Sakyo-ku, Kyoto 606-8103, Japan
The -bond activation by transition metal complexes attracts a lot of interests in theoretical and organometallic chemistries, because it is crucial in many catalytic reactions by transition metal complexes. In our understanding, -bond activation is classified to two categories; the concerted oxidative addition to M (metal), the stepwise oxidative addition via nucleophilic attack, the oxidative addition to M-L (L = neutral ligand), and the heterolytic activation by M-X (X = anionic ligand). activation by metal center only and that by the metal-ligand moiety.1,2 MLn + R1-R2 cis-MLn(R1)(R2) (1) 1 1 MLn + R1-X [MLn(R )] --(X) trans-MX(R )Ln (2) MLLn + R1-R2 MLn(R1)(L-R2) (3) 1 2 MXLn + R1-R2 MLn(R ) + R -X (4) We theoretically investigated these reactions and elucidated the characteristic electronic processes and clear understanding.2 We also theoretically investigated catalytic reactions including -bond activation. In this talk, we wish to present our recent theoretical studies of carboxylation of phenylchloride catalysed by a nickel(0) complex, hydrosilylation of carbon dioxide catalyzed by germanium(II)- and zinc(II)-hydride compounds.3 In my talk, I wish to present comprehensive understanding of these -bond activation reactions and the importance of -bond activation reaction in such catalytic reactions as CO2 conversion and cross-coupling reactions. References. 1. S. Sakaki, Y.-y. Ohnishi, H. Sato, Chem. Record., 10, 29 (2010). W. Guan, F. B. Saeed, S. Sakaki, Inorg. Chem., in press. 2. N. Ochi, Y. Nakao, H. Sato, S. Sakaki, J. Am. Chem. Soc., 129, 8615 (2007). N. Ochi, Y. Nakao, H. Sato, S. Sakaki, J. Phys Chem. A, 114, 659 (2010). 3. N. Takagi and S. Sakaki, J. Am. Chem. Soc., 135, 8955 (2013). M. Deschmukh, to be submitted.
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IL19 NONPLANAR HETEROAROMATICS: SYNTHESIS AND SELF-ASSEMBLY M. Stepien Wydziaі Chemii, Uniwersytet Wrocіawski Even though π-electron aromaticity is typically associated with planar structures, several classes of distorted π-aromatics are known, including a variety of twisted, helical, bowl-shaped, or tubular systems. Such distortions are of fundamental interest, because they provide a means of testing different aspects of aromaticity theory, but they also may have practical consequences, as a potential method of fine-tuning the electronic structure and self-assembly properties of aromatic compounds. In this contribution, two synthetic approaches to nonplanar heteroaromatics will be discussed. One is based on oxidative coupling reactions of pyrrole-containing precursors, and is exemplified by our recent syntheses of peripherally fused porphyrin derivatives1 (1 and 2) and bipyrroles.2 Compounds 1–2 are characterized by bathochromically shifted electronic absorptions and very high extinction coefficients. Phenanthroporphyrins 1 and their complexes reveal substitution-dependent aggregation in solution and form columnar mesophases in the condensed phase. The zinc(II) complex of benzochrysenoporphyrin 2 was found to form a unique 3D-ordered mesophase containing discrete multiporphyrin aggregates.
The other approach to nonplanar aromatics explored in our laboratory, which is suitable to the synthesis of bowl- or belt-shaped structures, involves the so-called fold-in synthesis,3 performed on appropriately designed macrocyclic precursors. The fold-in concept can be realized using different reactivity types, including Ullmann-type reductive coupling, as in the recent synthesis of chrysaorole (3),3,4 and Friedel–Crafts alkylation.5 (1) Myśliwiec, D.; Donnio, B.; Chmielewski, P. J.; Heinrich, B.; Stępień, M. J. Am. Chem. Soc. 2012, 134, 4822–4833. (2) Gońka, E.; Myśliwiec, D.; Lis, T.; Chmielewski, P. J.; Stępień, M. J. Org. Chem. 2013, 78, 1260–1265. (3) Stępień, M. Synlett 2013, 24, 1316–1321. (4) Myśliwiec, D.; Stępień, M. Angew. Chem. Int. Ed. 2013, 52, 1713–1717. (5) Kondratowicz, M.; Myśliwiec, D.; Lis, T.; Stępień, M. in preparation.
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IL20 RHODIUM N-HETEROCYCLIC CARBENE COMPLEXES AS EFFICIENT CATALYSTS FOR X-H ADDITIONS TO ALKYNES: THE QUEST FOR SELECTIVITY R. Castarlenas, A. Di Giuseppe, L. Rubio-Perez, L. Palacios, R. Azpiroz, V. Polo, J.J. PerezTorrente, L.A. Oro ISQCH Universidad de Zaraaragoza-CSIC
The development of new catalytic systems for the synthesis of added-value products in a selective manner and with high atom economy is nowadays an important task. In this context, our group has recently prepared new rhodium complexes bearing an N-heterocyclic carbene (NHC) ligand that have been disclosed to be very active and gem-selective for X-H additions across C-C triple bonds.1-4 Experimental and theoretical (DFT) mechanistic studies indicate that the presence of a bulky powerful electron-releasing NHC and the rational choice of the auxiliary ligands is essential in order to control the selectivity towards the formation of Markonikov-type products.
1 A. Di Giuseppe, R. Castarlenas, J.J. Perez-Torrente, M. Crucianelli, V. Polo, R. Sancho, F.J. Lahoz, L.A. Oro, J. Am. Chem. Soc. 2012, 134, 8171. 2 L. Palacios, M.J. Artigas, V. Polo, F.J. Lahoz, R. Castarlenas, J.J. Perez-Torrente, L.A. Oro, ACS Catal. 2013, 3, 2910. 3 L. Rubio-Pérez, R. Azpíroz, A. Di Giuseppe, V. Polo, R. Castarlenas, J.J. Perez-Torrente, L.A. Oro, Chem. Eur. J. 2013, 19, 15304. 4 R. Azpíroz, A. Di Giuseppe, R. Castarlenas, J.J. Perez-Torrente, L.A. Oro, Chem. Eur. J. 2013, 19, 3812.
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IL21 CATALYTIC OLEFINATION REACTION – UNIVERSAL METHOD FOR SYNTHESIS OF ALKENES V.G. Nenajdenko Moscow State University, Department of Chemistry, Leninskie Gory, Moscow 119992
Catalytic olefination reaction represents new approach to the preparation of double C=C bond. Nunsubstituted hydrazones can be converted into alkenes by treatment with polyhalogenated alkanes in presence of a base and catalytic amounts of copper salts. The reaction has a wide synthetic scope allowing to prepare both alkyl and aryl halogenoalkenes, including fluorinated ones and derivatives with functional groups. Simple experimental procedure, which does not require using of organometallic or toxic organophospourous compounds, affordable price and availability of starting materials, high yields and stereoselectivity are distinct advantages of the reaction. R1 1
R
R
R1 2
R
1
R1
CN
R2
Cl
R1 2
R
Br
Cl
Cl 2
R
F
CH2OH R1
H
R2
Cl
R1
Cl R1
COOR
H
2
O
R
Br
R1
H
2
R
R
Cl
R2
CONR2
R
Cl
F 2
R2
1
R
Br
2
R 1
R
CBrF2 1
R
F
Cl
R2 F
R2
I
1
F
2
CBrF2R2
R
1
R
1
1
F
2
Cl
R
Cl
R
F
CF3
R2
CClF2 R
CBrF2 R
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O O
IL22 HOW TO MAKE COMPLEX MOLECULES FROM SIMPLE STARTING MATERIAL: THE PALLADIUM, A POWERFUL TOOL J. Suffert University of Strasbourg/CNRS
In addition to molecular complexity, the challenge of the chemist today is also the quest for efficiency of the synthetic route and maximization of structural complexity. Our laboratory investigations focus for several years on the study of an unprecedented cascade reaction involving a rare 4-exo-dig cyclocarbopalladation followed by a terminated cross-coupling with an organometallic reagent. A 6 - or 8 -electrocyclization can occur leading to new tricyclic structures. The seminar will show that we can offer an easy access to complex polycyclic molecules resulting from readily available simple starting materials. Eventually, it will be possible to propose the elaboration of a large collection of unprecedented structurally novel molecules based on recent promising results. Below are represented several complex structures that has been prepared through the powerful 4-exo-dig cyclocarbopalladation. Many other extension of this method have not been so far explored and can afford a multitude of new and original scaffolds.
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IL23 SYNTHESIS OF TIN AND LEAD ANALOGS OF CYCLOPENTADIENYL ANION AND THEIR APPLICATION TO TRANSITION-METAL COMPLEXES M. Saito Department of Chemistry, Graduate School of Science and Engineering, Saitama University, Shimo-okubo, Sakura-ku, Saitama-city, Saitama, 338-8570, Japan We succeeded in the generation of tetraphenyldilithiostannole 1a,[1] and its considerable aromatic character was established by X-ray diffraction analysis and theoretical calculations.[2] The lead analog, tetraphenyldilithioplumbole 2 was also found to be aromatic, indicating that the concept of aromaticity is expanded to lead-bearing carbon cycles.[3] After the synthesis of heavier congeners of Cp anion, attention was next paid to the preparation of transition-metal complexes with such heavier Cp ligands. The first heavier metallocene was a ruthenocene bearing a germole ligand,[4] and transition-metal complexes with silole and germole ligands have already been synthesized. The straightforward method for the synthesis of such metallocenes is the reactions of metallole anions and dianions with transition-metal reagents. However, the reactions using stannole anions and dianions had never been reported until recently. We examined the reaction of tetraphenyldilithiostannole 1b[5] with [Cp*RuCl]4, and butterfly complex 3 was obtained instead of an expected ruthenocene.[6] The reaction of 1b with Cp2TiCl2 afforded three-membered ring compound 4 with unique electronic states.[7] The synthesis of the first neutral triple-decker complex 5 with group 14 metallole ligands was also achieved using silylsubstituted dilithiostannole 1c. R2
Li
R1 M
R2 Li 1a: 1b: 1c: 2:
M =Sn; M =Sn; M =Sn; M =Pb;
Et
Ru Et
Ru
2
R =R =Ph R 1=R 2=Et R 1 = M e 3 S i, R 2 = P h 1 2 R =R =Ph
Ph Et
Sn
Cp
Sn
Et
R1 1
Et
Et
Sn
Et
Cp* Et
Ti Cp
Sn
Ph RuCp* S iM e 3
C p *R u M e3S i
Sn
Cp* 4
3
5
References [1] Saito, M.; Haga, R.; Yoshioka, M. Chem. Commun. 2002, 1002. [2] Saito, M.; Haga, R.; Yoshioka, M.; Ishimura, K.; Nagase, S. Angew. Chem., Int. Ed. 2005, 44, 6553. [3] Saito, M.; Sakaguchi, M.; Tajima, T.; Ishimura, K.; Nagase, S.; Hada, M. Science 2010, 328, 339. [4] Freeman, W. P.; Tilley, T. D.; Rheingold, A. L.; Ostrander, R. L. Angew. Chem., Int. Ed. Engl. 1993, 32, 1744. [5] Saito, M.; Kuwabara, T.; Kambayashi, C.; Yoshioka, M.; Ishimura, K.; Nagase, S. Chem. Lett. 2010, 39, 700. [6] Kuwabara, T.; Saito, M.; Guo, J. D.; Nagase, S. Inorg. Chem. 2013, 52, 3585. [7] Kuwabara, T.; Guo, J. D.; Nagase, S.; Saito, M. Angew. Chem., Int. Ed. 2014, 53, 434.
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IL24 NEW METHODS FOR PEROXIDE SYNTHESIS A.O. Terentev ZIOCh, Moscow, Russia
In the last decades, organic peroxides have received considerable attention from chemists and drug design experts, which is associated with a need in the search for drugs for the treatment of parasitic diseases, such as malaria and helminth infections. Considerable progress has been made in the design of effective peroxide antimalarial drugs. Some synthetic peroxides exhibit activity equal to or higher than that of artemisinin. Peroxides having antitumor or growth-regulatory activity were also documented. In our work we developed new methods for synthesis of various types of peroxides.
It was found that some peroxides posesses pronounced antischistosomal properties and anticancer activity. This work is supported by the Grant of the Russian Foundation for Basic Research (Grant 14-03-00237) and by the Program for Basic Research of the Presidium of the Russian Academy of Sciences. References [1] Terent'ev, A., Borisov, D., Yaremenko, I., Chernyshev, V., Nikishin, G. J.Org.Chem. 75, 50655071, 2010. [2] Terent'ev, A., Yaremenko, I., Chernyshev, V., Dembitsky, V., Nikishin, G. J.Org.Chem. 77, 1833-1842, 2012. [3] Ingram, K., Yaremenko, I.A., Krylov, I., Hofer, L., Terent'ev, A. O., Keiser, J. J.Med.Chem. 55 (20), 8700–8711, 2012. [4] Terent'ev, A. O., Yaremenko, I, A., Vil', V. A., Dembitsky, V. M., Nikishin, G. I. Synthesis 246-250, 2013. [5] Terent'ev, A. O., Yaremenko, I, A., Vil', V. A., Моisееv, I. K., Kon’kov, S. A., Dembitsky, V. M., Levitsky, D. O., Nikishin, G I. Org. Biomol. Chem. 11, 2613–2623, 2013. [6] I.A. Yaremenko, A.O. Terent’ev, V.A. Vil’, R.A. Novikov, V.V. Chernyshev, V.A. Tafeenko, D.O. Levitsky, F. Fleury, G.I. Nikishin. Chemistry - A European Journal DOI: 10.1002/chem.201402594.
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IL25 SYNERGISM BETWEEN THEORY AND EXPERIMENTS IN ASYMMETRIC CATALYSIS: TRANSITION STATE MODELING FOR RATIONALIZATIONS AND CATALYST DESIGN R.B. Sunoj Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076
Computational quantum chemistry has been increasingly employed toward rationalizing the stereochemical outcome of a diverse range of reactions.1 The approach typically involves the identification of kinetically significant transition states and intermediates. In our laboratory, ab initio as well as DFT methods are employed to gain insights into carbon-carbon and carbonheteroatom bond-forming reactions of immediate practical significance.2 The key objective is in establishing the factors responsible for stereoselectivity in such reactions and to employ those insights toward in silico design of novel catalysts for potential asymmetric applications.3 A number of examples wherein the conventional transition state models required systematic improvements toward accounting the observed product distribution and stereochemical outcome will be presented. In general, the presentation would encompass a few contemporary themes in the domain of organo- and organo-metallic catalysis. Interesting interpretations/rationalizations of experimental observations besides meaningful guidelines for rational improvements in asymmetric catalysis would remain the key focus of the presentation. The contents are designed to cater to a broad and diverse group of audience; hence, the chemical insights would receive more emphasis, rather than intricate technical details. [1] (a) Cheong, P. H. –Y.; Legault, C. Y.; Um, J. M.; Celebi-Olcum, N.; Houk, K. N. Chem. Rev. 2011, 111, 5042. (b) Sunoj, R. B. Wiley Interdisciplinary Reviews: Comput. Mol. Sci. 2011, 1, 920. [2] (a) Shinisha, C. B.; Sunoj, R. B. J. Am. Chem. Soc. 2010, 132, 12135. (b) Sharma, A. K.; Sunoj, R. B. Angew. Chem. Int. Ed. 2010, 49, 9373. (c) Sharma, A. K.; Sunoj, R. B. Chem. Commun. 2011, 47, 5759. (d) Jindal, G.; Sunoj, R. B., Chem. Eur. J. 2012, 18, 7045. (e) Jindal, G.; Sunoj, R. B., Angew. Chem., Int. Ed. 2014, 53, 4432. (f) Anand, M.; Sunoj, R. B.; Schaefer, H. F. J. Am. Chem. Soc. 2014, 136, 5535. [3] (a) Shinisha, C. B.; Sunoj, R. B. Org. Biomol. Chem. 2007, 5, 1287. (b) Shinisha, C. B.; Sunoj, R. B. Org. Lett. 2009, 11, 3242. (c) Jindal, G.; Sunoj, R. B. Org. Bimol. Chem. 2014, 12, 2745.
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IL26 CATALYTIC ASYMMETRIC CROTYLATION: METHOD DEVELOPMENT AND APPLICATION IN TOTAL SYNTHESIS A.V. Malkov, P.S. O’hora, C.A. Incerti-Pradillos, M.A. Kabeshov Loughborough University, Loughborough, LE11 3TU, UK
Secondary metabolites 1-5 isolated from marine soft coral Pseudopterogorgia elisabethae exhibit a wide range of useful biological properties, which include anti-tubercular, anti-inflammatory, antimicrobial and analgesic activities [1]. The analgesic properties are superior to the existing industry standards. As a result, partially purified gorgonian extracts are used in commercial skin care products for topical applications [2]. O
H
O
OH
HO
O
H
O
OH
HO
O
HO H
H
H
O
H H 1
2
3 4 (+)-Elisabethadione (–)-Elisapterosin B (–)-Colombiasin A
(+)-Erogorgiaene
5 Pseudopterosin A-D aglycone
Herein, we present a novel general strategy for a scalable enantioselective total synthesis of serrulatane diterpenes 1 and 2. Synthetically, a major challenge associated with the synthesis of these compounds is the control of the three stereocentres in the absence of directing functional groups. Our principal strategy is based on the asymmetric crotylation of cinnamyl-type aldehyde 10 with Z-crotyltrichlorosilane 9 to produce homoallylic alcohol 8 with a set of stereogenic centers that will be used to control the stereochemistry of oxy-Cope rearrangement (8 → 7) and the subsequent transformations towards the advanced intermediate 6. Development of novel efficient Lewis base catalysts for the asymmetric crotylation and completion of the total synthesis of (–)-elisabethadione and (–)-erogorgiaene will be discussed in detail. cationic cyclisation 1
H H
4
1,2
11
Rn
Wittig olefination
Rn
Anionic oxy-Cope
OH
6
O 7
OH O
Rn 10
SiCl3
9
Rn Cat*
References [1] A. D. Rodriguez, C. Ramirez, J. Nat. Prod. 2001, 64, 100-102. [2] A. Kijjoa , P. Sawanwong, Mar. Drugs 2004, 2, 72-82.
49
8
IL27 SYNTHESES OF METAL COMPLEXES WITH TRANS-CYCLOALKANE1,2-DIYL-[OSSO]-TYPE BIS(PHENOLATE) LIGAND AND ISOSPECIFIC POLYMERIZATION OF ALPHA-OLEFINS A. Ishii Department of Chemistry, Graduate School of Science and Engineering, Saitama University, Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan
Efficiency and stereoselectivity of reactions catalyzed by metal complexes are often greatly affected by auxiliary ligands of the catalysts. We have recently developed tetradentate auxiliary ligands 1 featuring oxygen and sulfur coordination sites and fusion of trans-cycloalkane-1,2-diyl rings.1–3 The [OSSO]-bis(phenolate) ligand 1 (n = 3) was applied to the synthesis of zirconium complex 2 and we found that a combination of 2 and an activator catalyzes the polymerization of 1-hexene with high activity and high isospecificity1 in comparison with previously reported group 4 metal complexes bearing [OSSO]-type ligands.4 We have also synthesized Ti,5 Zr,6 Hf,7 V,8 Nb,8 Ta,8 and Al9 complexes with 1 (n = 3) and investigated catalytic reactions with these complexes. In this paper, we report the syntheses and structures of these metal complexes and their catalytic ability with recent progress. tBu
tBu tBu
OH
S
tBu
O
S
Zr n
S
S
O
OH
1
Bu
CH2Ph
2/(Ph3C)[B(C6F5)4] activity = 2,500 g•mmol–1•h–1
tBu
tBu tBu
CH2Ph
Bu
Bu
Bu
Bu
Bu
isotactic poly(1-hexene) ([mmmm] >95%) Mw = 59,000, PDI = 1.7
tBu
2
References 1. Ishii, A.; Toda, T.; Nakata, N.; Matsuo, T. J. Am. Chem. Soc. 2009, 131, 13566–13567. 2. Ishii, A.; Toda, T.; Nakata, N.; Matsuo, T. Phosphorus, Sulfur, Silicon 2011, 186, 1169–1174. 3. Ishii, A.; Asajima, K.; Toda, T, Nakata, N. Organometallics 2011, 30, 2947–2956. 4. Nakata, N.; Toda, T.; Ishii, A. Polym. Chem. 2011, 2, 1597–1610. 5. Nakata, N.; Toda, T.; Matsuo, T.; Ishii, A. Inorg. Chem. 2012, 51, 274–281. 6. Toda, T.; Nakata, N.; Matsuo, T.; Ishii, A. J. Organomet. Chem. 2011, 696, 1258–1261. 7. Nakata, N.; Toda, T.; Matsuo, T.; Ishii, A. Macromolecules 2013, 46, 6758–6764; Nakata, N.; Saito, Y.; Watanabe, T.; Ishii, A. Top. Catal. 2014, 57, 918–922. 8. Toda, T.; Nakata, N.; Matsuo, M.; Ishii, A. ACS Catal. 2013, 3, 1764−1767. 9. Nakata, N.; Saito, Y.; Ishii, A. Organometallics 2014, 33, 1840–1844.
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IL28 NEW APPROACH FOR THE SYNTHESIS OF COMPOUNDS CONTAINING CF2 FRAGMENT A.D. Dilman, V.V. Levin, A.A. Zemtsov, M.D. Kosobokov N. D. Zelinsky Institute of Organic Chemistry
Existing methods for the synthesis of compounds containing CF2 fragment either employ hazardous reagents or require long synthetic sequence. We propose a new approach towards difluorinated compounds based on the coupling of three components — nucleophile, difluorocarbene and electrophile.
As nucleophiles, organometallic reagents can be employed. The insertion of difluorocarbene into carbon-zinc bond of organozinc reagents leads to new organozinc species, which can be quenched by halogen or proton,1 or coupled with allylic electrophiles.2
The interaction of trimethylsilyl cyanide with difluorocarbene affords difluoro(trimethylsilyl)acetonitrile. This reagent was used in reactions with aldehydes and imines furnishing fluorinated alcohols and amines.3 The addition products can be transformed into a variety of heterocyclic molecules.4
This work was supported by the Ministry of Science (project MD-4750.2013.3) and Russian Foundation for Basic Research (projects 13-03-12074, 14-03-00293, 14-03-31253_mol_a, 14-0331265_mol_a). 1. Levin, V. V.; Zemtsov, A. A.; Struchkova, M. I.; Dilman, A. D. Org. Lett. 2013, 15, 917–919. 2. Zemtsov, A. A.; Kondratyev, N. S.; Levin, V. V.; Struchkova, M. I.; Dilman, A. D. J. Org. Chem. 2014, 79, 818–822. 3. Kosobokov, M. D.; Dilman, A. D.; Levin, V. V.; Struchkova, M. I. J. Org. Chem. 2012, 77, 5850–5855. 4. Kosobokov, M. D.; Struchkova, M. I.; Arkhipov, D. E.; Korlyukov, A. A.; Dilman, A. D. J. Fluorine Chem. 2013, 154, 73–79. 51
IL29 TOWARDS REALISTIC FIRST-PRINCIPLES MODELLING OF COMPLEXITY IN HETEROGENEOUS CATALYSIS K.M. Neyman ICREA and Universitat de Barcelona
Active components present in heterogeneous catalysts as nano-aggregates of thousands atoms remain inaccessible for the first-principles (based on DFT) computations due to their size and complexity. However, such species could be rather realistically represented by computationally tractable smaller model nanoparticles (NPs), whose surface sites only marginally change the reactivity with increasing particle size. We illustrate this for decomposition of methane1 and methanol2-4 on Pt and Pd catalysts as well as building of active sites on Pt/ceria catalysts. 5,6 We show that using common slab models and thus neglecting the nanoscopic effects in these and similar systems could lead to severe misrepresentation of the surface reactivity.7 Methane decomposition on Pt NP is calculated to be more exothermic than on Pt(111) surface and proceed via much lower activation barriers for the rate-limiting steps.1 The reason for Pt activation by nanostructuring is that CHx species are stabilized on NP edges, converting the first two steps of CH4 decomposition from endothermic on Pt(111) to exothermic on Pt79. The higher activity of edge Pt atoms was assigned to their lower coordination and higher flexibility. The flexibility affects not only adsorption properties of sites with low-coordinated atoms but also nearby terrace sites. This effect is most pronounced for strongly bound adsorbates, e.g atomic C. It is a common by-product in decomposition reactions on Pd,2 able to modify catalyst properties upon exothermic migration subsurface.3,4 The most spectacular effect of flexibility of Pd NPs is on the subsurface migration barriers of surface C. Near NPs edges these barriers essentially vanish. Presence of subsurface C makes Pd NPs more transparent for subsurface diffusion of adsorbed hydrogen,3 which in turn enables sustainable hydrogenation of olefins on Pd catalysts. Strong metal-support interactions can radically modify surface chemistry. Due to catalysts complexity the microscopic origin of such effects is usually unresolved. However, our study on models of Pt-ceria catalysts succeeded to uncover atomic details of interactions in this system. 5 Calculations identified two types of oxidative Pt-ceria interactions: electron transfer from a Pt particle to the support and O transport from ceria to Pt. The former is favorable on ceria supports regardless their morphology. But the O transfer requires the presence of Pt in close contact with nanostructured ceria, being inherently a nano-effect. Both effects were detected by monitoring the Ce3+/Ce4+ ratio using resonant photoelectron spectroscopy on Pt-CeO2 model catalysts. These case studies reveal very significant differences in the surface reactivity derived from customary slab-model calculations and those employing dedicated NP models. The latter expose a variety of active sites, whose structure and geometric flexibility notably better match those of the sites present under experimental conditions. Thus, we advocate much broader usage of suitable NP models in “catalysis from first principles”. 1. F. Viñes, Y. Lykhach, T. Staudt, M. P. A. Lorenz, C. Papp, H.-P. Steinrück, J. Libuda, K. M. Neyman, A. Görling Chem. Eur. J. 2010, 16, 6530. 2. I. V. Yudanov, A. V. Matveev, K. M. Neyman, N. Rösch - J. Am. Chem. Soc. 2008, 130, 9342. 3. K. M. Neyman, S. Schauermann - Angew. Chemie Int. Ed. 2010, 49, 4743. 4. H. A. Aleksandrov, F. Viñes, W. Ludwig, S. Schauermann, K. M. Neyman - Chem. - Eur. J. 2013, 19, 1335. 5. G. N. Vayssilov, Y. Lykhach, A. Migani, T. Staudt, G. P. Petrova, N. Tsud, T. Skála, A. Bruix, F. Illas, K. C. Prince, V. Matolín, K. M. Neyman, J. Libuda - Nature Mater. 2011, 10, 310. 6. A. Bruix, Y. Lykhach, I. Matolínová, A. Neitzel, K. C. Prince, V. Potin, F. Illas, V. Matolín, J. Libuda, K. M. Neyman, et al. - Angew. Chemie Int. Ed. 2014, 53, doi: 10.1002/anie.201402432. 7. S. M. Kozlov, K. M. Neyman - Top. Catal. 2013, 56, 86.
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IL30 С-С TRIPLE BOND ACTIVATION BY PLATINUM METALS UNDER HOMO- AND HETEROGENEOUS CONDITIONS: DESIGN OF NEW CATALYTIC REACTIONS S.A. Mitchenko L.M. Litvinenko Institute of Physical Organic and Coal Chemistry, National Academy of Sciences of Ukraine, Donetsk, Ukraine
Petroleum and natural gas are the main sources of raw materials for modern bulk and fine chemical industry. Since the middle of the last century this changed the industry redirecting technology previously based on acetylene towards olefinic stuff and synthesis gas. Nevertheless, series of largescale (for example, manufacture of vinyl ethers, pyrrolidone and N-methylpyrrolidone, butanediol, etc.) and fine (drugs and fragrances, crop protecting agents, etc.) chemical production based on acetylene hydrocarbons possesses definite advantages and is still developing. Besides, acetylene hydrocarbons are inevitably formed as by-products in oil processing yielding olefins, and taking into account the modern industrial scales and prices of starting materials these by-products should be efficiently utilized. On the other hand, coal and natural gas supply as against of petroleum allow us to regard them as practically inexhaustible source of acetylene. Increasing interest to the catalytic chemistry of acetylene (see, for example, [1, 2]) can be motivated in particular by these considerations. Results of development of new catalytic transformations of acetylene under homo- and heterogeneous conditions will be presented and discussed. References: 1. Alonso F., Beletskaya I.P., Yus M. Chem. Rev., 2004, 104, 3079. 2. Ananikov V. P., Beletskaya I. P. Organometallics, 2012, 31, 1595.
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IL31 SYNERGISTIC EFFECTS IN DESIGNING COMBINED CATALYTIC SYSTEMS (COMBICAT’S) FOR ABATEMENT OF NITROGEN OXIDES (NOX) A.Yu. Stakheev Zelinsky Institiute of Organic Chemistry, Catalysis division, Moscow, Russia
Anthropogenic emission on nitrogen oxides (NOx = NO, NO2, N2O) becomes an important issue, since the amount of anthropogenic NOx nowadays exceeds biogenic emission (~110 Mt vs. 80 Mt/annual) and their impact on environment is significant. The most effective method for abatement of nitrogen oxides is their selective catalytic reduction (SCR) by urea or NH3: 2NO + 2NH3 + 1/2O2 = 2N2 + 3 H2O However, activity of the traditional NH3-SCR catalysts at the temperatures below 250oC is not sufficient due to the stringent restrictions imposed by environmental legislations on NOx emission from mobile sources. The effective solution can be provided by Cu-containing zeolite catalyst, however high cost often limits their practical application. Our recent study revealed alternative approach and indicated that promising NH3-DeNOx activity at Treact. < 250°C CAN BE ATTAINED OVER combined catalysts (CombiCat) comprising zeolite component (possessing high activity in SCR) and a redox component (having high activity in NO oxidation). For such compositions we found a pronounced synergistic effect and the catalytic activity of the COMBICAT’S significantly exceeds activity of the individual components. A number of compositions have been tested for searching synergistic effects and the most remarkable results have been observed for [Cu/Al2O3 +FeBETA], [Mn/Al2O3 + FeBETA, [CeZr +FeBETA], [Mn/CeZr + FeBETA], Mn/FeBETA. Interestingly that the studied composition exhibits favorable performance in selective oxidation of NH3: 2NH3 + 3/2 O2 = N2 + 3H2O Therefore CombiCat’s are capable to accomplish two functions: SCR catalyst and removal of residual NH3. In addition to that, for the compositions comprising CeO2-ZrO2 component a promising soot oxidation activity has been observed Detailed study of a possible origin of the observed synergistic effects suggests that the improvement of NH3-DeNOx activity can be attributed to a “dual function” reaction mechanism comprising two main stages: (1) NO + O2 ↔ NO2 over redox component (2) NO + NO2 + 2NH3 → N2 + 3H2O over zeolite component However, further research is required for revealing overall reaction network and understanding reaction mechanism responsible for observed synergy.
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IL32 NOVEL COLCHICINOIDS AS POTENTIAL ANTITUMOR AGENTS A. Yu. Fedorov Department of Organic Chemistry, Nizhny Novgorod State University, Gagarina av. 23, Nizhny Novgorod 603950, Russian Federation
A range of indole - and furane-containing allocolchicinoids was synthesized:
Several from synthesized compounds manifested high in vitro and in vivo antitumor activity. Acknowledgment We thank the Russian Foundation for Basic Research (projects 14-03-91342 and 12-03-00214-a), The Ministry of Education and Science of The Russian Federation (project 4.619.2014/K). The research is partly supported by the grant № 02.В.49.21.0003 of The Ministry of Education and Science of the Russian Federation to Lobachevsky State University of Nizhni Novgorod.
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IL33 ENANTIOSELECTIVE CATALYSIS BY CHIRAL BRØNSTED ACIDS AND CHIRAL BRШNSTED BASES M. Terada Tohoku Univsersity, Department of Chemistry, Sendai, Japan
Chiral phosphoric acids 1 have become one of the most versatile types of chiral Brønsted acid catalysts identified to date and have been applied to a broad range of enantioselective transformations.1,2) In my continuing efforts to broaden the scope of enantioselective catalysis by 1, activation of oxygenated functional groups other than imines and related functional groups is our recent research interest. To expand the scope of chiral Brønsted acid catalysis, recently a novel chiral bis-phosphoric acid 2 was developed as a highly active and efficient enantioselective catalyst.3) On the other hand, intense interest has been devoted to the development of chiral uncharged organosuperbase catalysts during the past decade. In an effort to develop efficient chiral organobase catalysts, we designed and synthesized unique axially chiral Brønsted base 3.4) 3 functioned as the efficient enantioselective catalysts for the activation of pro-nucleophile having a relatively acidic proton such as 1,3-dicarbonyl compounds. To expand the scope of chiral Brønsted Base catalysis, development of much stronger organosuperbase is highly demanded. We hence designed a pseudo C2-symmetric bis(guanidino)iminophosphorane 4 as a novel family of chiral organosuperbases.5) In my presentation, I briefly introduce these chiral Brønsted acid catalysts (1 and 2) and base catalysts (3 and 4). In particular, I would like to present a novel chiral Brønsted base catalyst 4 in details.
References 1) (a) Terada, M. Synthesis 2010, 1929-1982. (b) Terada, M. Chem. Commun. 2008, 4097-4112. 2) Uraguchi, D.; Terada, M. J. Am. Chem. Soc. 2004, 126, 5356-5357. 3) Momiyama, N.; Konno, T.; Furiya, T.; Iwamoto, T.; Terada, M. J. Am. Chem. Soc. 2011, 133, 19294-19297. 4) Terada, M.; Ube, H.; Yaguchi, Y. J. Am. Chem. Soc. 2006, 128, 1454-1455. 5) Takeda, T.; Terada, M. Y. J. Am. Chem. Soc. 2013, 135, 15306-15309.
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IL34 IONIC LIQUIDS, WATER AND LIQUID OR SUPERCRITICAL CO2 AS PERSPECTIVE MEDIA FOR ASYMMETRIC ORGANOCATALYSIS S.G. Zlotin N.D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences
Over the last decade amazing results have been associated with the extensive application of asymmetric organocatalysts in organic synthesis. In the presence of small metal-free chiral organic molecules (α-amino acid or cinchona alkaloid derivatives, BINOL phosphoric acids, and other chiral compounds), available prochiral reagents can be easily converted into chiral products of high molecular complexity in high yields and with excellent enantioselectivities. Unlike organometal catalysts, organocatalysts do not contaminate products with toxic heavy metals and this is important in terms of medicinal chemistry. However, in some cases they may be responsible for hardly separable and potentially dangerous organic impurities. To facilitate product purification and recovery of precious chiral catalysts, immobilized forms of organocatalysts tagged to polymers or ionic groups have been designed and organocatalytic reactions have been carried out in so called “neoteric” green solvents, particularly in ionic liquids (IL), water and liquid or supercritical (sc) carbon dioxide. In these systems a catalyst and a product are located in different phases during the catalytic process and/or the working-up step. We developed highly efficient enantioselective cross-aldol reactions between various carbonyl compounds in the presence of proline or prolinamide-derived organocatalysts in the IL and/or aqueous environment. An original method for adapting -amino acid-sourced IL-supported chiral organocatalysts to the aqueous medium via an incorporation of long-chain alkyl groups and hydrophobic anions into their molecules and by performing asymmetric reactions in reagents/water two-phase systems was elaborated. Corresponding aldol products were obtained in high yields and with extremely high anti -diastereo- (dr up to 98 : 2) and enantioselectivities (ee up to 99%) under proposed conditions. After product isolation, the remaining catalyst-water heterogeneous system could be reused up to 15 times without a decrease of product yield and selectivity of the reaction.1 Carbon acids, in particular malonates, malononitrile, and anthranone, appeared to react enantioselectively with nitroalkenes in the presence of tertiary amine/thiourea-derived bifunctional organocatalyst in liquid CO2 as a green substitute of toxic organic solvents to afford the respective Michael adducts in moderate to high yields and with enantioselectivities of up to 92% ee.2 The first “green” asymmetric organocatalytic reaction in sc-CO2, namely, a bifunctional squaramidecatalyzed addition of diphenylphosphite to α-nitroalkenes to afford β-nitrophosphonates in high yields and with ee-values of up to 94% was elaborated.3 In this way, the most active (R)-enantiomer of the therapeutically useful GABAB receptor agonist baclofen, a key precursor of the chiral anticonvulsant, pregabalin, and both enantiomers of pharmacologically important β-amino phosphonic acid derivatives were synthesized. A significant potential of the supercritical extraction for product isolation and catalyst recovery, which completely eliminates the use of organic solvents during the working-up procedure, was demonstrated. The work was financially supported by the Russian Foundation of Basic Research (projects 12-0300420, 14-03-31321 and 14-03-92701). 1. D.E. Siyutkin, A.S. Kucherenko, S.G. Zlotin. In “Comprehensive Enantioselective Organocatalysis: Catalysts, Reactions, and Applications”, ed. by P.I. Dalco, Wiley-VCH, 2013, v. 2, p. 617-650. 2. A.G. Nigmatov, I.V. Kuchurov, D.E. Siyutkin, S.G. Zlotin. Tetrahedron Lett., 2012, 53, 3502. 3. I.V. Kuchurov, A.G. Nigmatov, E.V. Kryuchkova, A.A. Kostenko, A.S. Kucherenko, S.G. Zlotin. Green Chem., 2014, 16, 1521. 57
IL35 MAKING OLEFIN METATHESIS WORK - RECENT RESULTS IN RUTHENIUM CATALYSTS DESIGN K.L. Grela Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw
Ruthenium-catalyzed olefin metathesis reactions represent an attractive and powerful transformation for the formation of new carbon-carbon double bonds [1]. This area is now quite familiar to most chemists as numerous catalysts are available that enable a plethora of olefin metathesis reactions [1]. However, formation of substituted and crowded double bonds, decreasing the amount of metal, using metathesis in green context, etc. still remain a challenge, making industrial applications of this methodology difficult [2]. These limitations can be solved by designing new, more active and stable catalysts and catalysts that can be easier removed / recycled [3]. During the lecture a number of representative examples will be presented.
Artwork © Katarzyna Felchnerowska, www.fb.com/effe.fineart
References [1] Olefin Metathesis: Theory and Practice, Grela, K. (Ed.), John Wiley & Sons, 2014 [2] Thayer, A. Chemical & Engineering News 2007, 85 (07), 37. [3] Clavier, H.; Grela, K.; Kirschning, A.; Mauduit, M.; Nolan, S. P. Angew. Chem. Int. Ed. 2007, 46, 6786-6801
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Oral Communications
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OC1 THE FIRST CYCLOPENTADIENYL NICKEL COMPLEXES BEARING A SILYL GROUP OR HYDROGEN SUBSTITUTED PHOSPHINE CHELATING SIDECHAIN I. Werner, H. Butenschoen Institute of Organic Chemistry, Leibniz Universitaet Hannover, Hannover, Germany
The only known secondary phosphine pendant cyclopentadienyl complexes are those of zirconium and hafnium, reported by Ishiyama et al. in 2002.[1] Since these complexes contain a reactive phosphorus-hydrogen bond, they were converted into the corresponding phosphide-substituted cyclopentadienyl chelate complexes.[2] Both systems were successfully applied in catalytic ethylene and styrene polymerization reactions as well as in ethylene/styrene copolymerization reactions.[3] To our knowledge, no analogous complexes of late transition metals containing a phosphorushydrogen or a phosphorus-silyl bond have so far been reported. We report on the synthesis of the first cyclopentadienyl nickel complexes 1-4 and 5, 7 bearing a silyl group and hydrogen substituted phosphine chelating sidechain, respectively. Treatment of complex 5 with SIMes induced the decomplexation of the secondary phosphane substituted tether, delivering exclusively nickel carbene complex 6. Recrystallization of complex 7 from hexane/ethyl acetate (1:1) at 30 °C afforded crystals suitable for an X-ray crystal structure analysis.
References: [1] T. Ishiyama, H. Nakazawa, K. Miyoshi, J. Organomet. Chem. 2002, 648, 231. [2] T. Ishiyama, T. Mizuta, K. Miyoshi, H. Nakazawa, Organometallics 2003, 22, 1096. [3] T. Ishiyama, K. Miyoshi, H. Nakazawa, J. Mol. Cat. A-Chem. 2004, 221, 41.
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OC2 EXPANDED RING N-HETEROCYCLIC CARBENE TRANSITION METAL COMPLEXES. SYNTHESIS, STRUCTURE, APPLICATIONS IN CATALYSIS M.S. Nechaev1, A.F. Asachenko2, P.B. Dzhevakov2, O.S. Morozov2, G.V. Proskurin1, P.S. Gribanov1 1 - Moscow State University, Department of Chemistry, Moscow, Russia 2 - A. V. Topchiev Institute of Petrochemical Synthesis, RAS, Moscow, Russia
N-heterocyclic carbenes (NHCs) became widely used as organocatalysts and as ligands in transition metal catalysis. Most of NHC-metal complexes known to date are derived from five-membered ring imidazol-2-ylidene and imidazolin-2-ylidene type carbenes. In recent years, our group develops chemistry of 6-, 7- and 8-membered ring carbenes. Expanded ring carbenes (er-NHCs) exhibit superior stereoelectronic properties in comparison with five-membered ring counterparts. Expansion of the ring leads to significant increase in donor strength and sterical hindrance. In this contribution we report our recent results on theoretical calculations of electronic structure and ligand properties of er-NHCs; efficient methods of synthesis of precursors and generation of free carbenes; synthesis of late transition metal (Cu, Ag, Au, Pd) complexes. It was found that erNHC complexes of palladium are highly active in Suzuki-Miyaura coupling in water, and dimerization of terminal alkynes with formation of E-enynes. Cationic gold complexes are active catalysts of addition of nucleophiles to carbon-carbon triple bonds.
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OC3 PALLADIUM-CATALYZED C–H ALKENYLATION OF ARENES USING SULFUR-CONTAINING DIRECTING GROUPS: A COMPARATIVE STUDY K.V. Luzyanin, A.N. Marjanov, V.P. Ananikov Laboratory of Cluster Catalysis, Saint Petersburg State University, Universitetsky pr. 26, Stary Petergof, 198504, Russia
Direct alkenylation of organic substrates via directing-group assisted functionalization of the CH bond has emerged as a valuable tool for creation of new sp2-sp2 bonds. In the contrast to the Mirozoki–Heck reaction that starts from the aryl halides, this procedure works with inactivated arenes and is favorable from both economical and environmental points of view. Several types of directing groups have been evaluated in the direct alkenylation up to date, e.g., ketones and carboxylates, amides, pyridine sulfoxides and ethers, and thioethers. Among them, functionalization of sulfur-containing compounds (Scheme 1), i.e. pyridine thioesters and sulfoxides, as well as structurally related benzylic thioethers (in those, sulfur moiety plays a role of a directing group) attracts rapidly growing attention. On the one hand, functionalization of such compounds leads to interesting derivatives containing both alkene and sulfur functions, while, on the other hand, sulfurbased directing groups in these species can be easily removed after reaction from the resulting products without compromising other functionalities.1–3
Scheme 1. Direct alkenylation of arenes using sulfur-containing directing groups. In the current report, we summarize data accumulated up to date regarding direct CH-alkenylation of sulfur-containing organic compounds. A particular emphasis is given to the evaluation of the assistance provided by different sulfur-containing directing groups in comparison to other common directing moieties known to be employed for this purpose. Acknowledgements: This work has been partially supported by the Saint Petersburg State University (research grant from Laboratory of Cluster Catalysis), and the Russian Fund for Basic Research (grant 14-03-01005). References 1. García-Rubia, A.; Fernández-Ibánez, M. A.; Gómez Arrayás, R.; Carretero, J. C. Chem. Eur. J. 2011, 17, 3567–3570. 2. Yu, M.; Xie, Y.; Xie, C.; Zhang, Y. Org. Lett. 2012, 14, 2164–2167. 3. Zhang, X.-S.; Zhu, Q.-L.; Zhang, Y.-F.; Li, Y.-B.; Shi, Z.-J. Chem. Eur. J. 2013, 19, 11898– 11903.
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OC4 IN PURSUIT OF A NOVEL IMIDATE-BASED SALEN-TYPE LIGAND CLASS J. Van Der Eycken1, P. Janssens1, T. Noel2 1 - Ghent University, Department of Organic Chemistry 2 - Eindhoven University of Technology, Department of Chemistry and Chemical Engineering, Micro Flow Chemistry & Process Technology
An increasing ecological awareness and global competitiveness have challenged the chemical industry towards a higher level of sustainability through innovation and technology. In research, the majority of topics on sustainable process development deals with catalysis.[1] Furthermore, in organic synthesis, transition metal catalysis already plays a vital role in the synthesis of biologically active compounds.[2]
H
H N
O H
N
H O N
OH HO
N
OH
L1
HO L2
Bisimidate ligand L2 shows striking similarities with Salen ligands (L1). We reasoned that this could open new opportunities for our already well-established imidate ligand family. [3-5] Nevertheless, the applicability of this ligand in the MnV-catalyzed asymmetric epoxidation reaction turned out to be more complicated than expected. In this communication, the search towards an effective novel imidate-based Salen-type ligand class will be discussed from a ligand design point of view. References [1] Dichiarante, V.; Ravelli, D.; Albini, A. Green Chem. Lett. Rev. 2010, 3, 105. [2] a) Noyori, R Angew. Chem. Int. Ed. 2002, 41, 2008. b) Busacca, C.A.; Fandrick, D.R.; Song, J.J.; Senanayake, C.H. Adv. Synth. Catal. 2011, 353, 1825. [3] a) Noël, T.; Bert, K.; Van der Eycken, E.; Van der Eycken, J. Eur. J. Org. Chem. 2010, 21, 4056. b) Bert K., Noël T., Van der Eycken J., Org. Biomol. Chem., 2012, 10, 8539. c) Noël, T., Bert, K., Janssens, P. and Van der Eycken, J. (2012) “Chiral Imidate Ligands: Synthesis and Applications in Asymmetric Catalysis”, in: Innovative Catalysis in Organic Synthesis: Oxidation, Hydrogenation, and C-X Bond Forming Reactions (ed P. G. Andersson), WileyVCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527646586.ch14.
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OC5 NITROALKANES IN PPA AS NEW REAGENTS FOR DIRECT METALFREE AMINATION OF ARENES A.V. Aksenov1, N.A. Aksenov1, I.V. Aksenova1, M. Rubin2, D.A. Aksenov1 1 - Department of Chemistry, North Caucasus Federal University, Stavropol, Russian Federation 2 - Department of Chemistry, University of Kansas,Lawrence, USA
Aromatic amines represent an important class of organic compounds. Many of them demonstrate important biological activities. Various multi-step methods for preparation of these compounds have been developed, including electrophilic nitration/reduction sequence, Schmidt and Beckmann rearrangements, etc. The most appealing methods, however, are those that allow for direct introduction of an amino-group to a non-substituted arene over a single step. Direct electrophilic acetamidation of arenes 2 with primary nitroalkanes 1 in polyphosphoric acid (PPA), recently developed in our laboratories can be viewed as an example of such an approach. R R R R N
+
N
O PPA
+
4
OH
3
R
O
R
O
O
O
P
R
O ...
R O
3
N
2
2
OH
4
R
1
R
R
O ...
P
R
O
2
R R
1
4
H N
3
O R
2
1
R
1
6 3 -9 2 %
3
R=Me, Pr, Ph, Bn; R1, R2, R3, R4=H, Me, OH, MeO, CHO. Benzene and arenes with electron-donating substituents can be engaged in this reaction. Electron deficient arenes are inert. The process is highly selective, the electrophilic attack is always directed to para-position with respect to a substituent already present in the ring. Anthracene 4 and indole 5 were successfully involved into the acetamidation reaction. In reaction of dibenzo-18-crown-6 ether monoacetamide was formed along with quite a large amount of bisacetamination isomeric products. The reaction involving secondary nitroalkanes is also interesting. Since the nitroso compound 4, resulting from electrophilic attack to the aromatic ring, is not able to isomerize oxime, it attacks a second molecule of arene. After rearrangement this leads to the formation of diarylamines 5: R
1
+ R
2
N
+
O
R
-H+
1
N
O P O 2 H ...
R
-P P A
OH
O P O 2 H ...
2
R
1
N
-H2O R
R
1
N
OH
1
N
R
R
1
R
2
R
1
H N
R
1
2
R
OH R
R
2
4
PPA
O
2
1
+ R
2
R
2
R 5
2
O
5 5 -6 1 %
R1, R2 =H, Me, MeO, CHO A novel protocol for direct and regioselective metal-free acetamination and amination of arenes in reactions with primary and secondary nitroalkanes in polyphosphoric acid media was developed. A new preparative approach to 5-aminoindoles and diarylamines employing this reaction was demonstrated. This work was carried out with financial support from the Russian Foundation Basic Research (grants 13-03-00304 a and 14-03-31288 mol_a)
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OC6 UROTROPINE ISOMER (1,4,6,10-TETRAAZAADAMANTANE). MOLECULAR SIMPLICITY AND MOLECULAR COMPLEXITY OF HETEROADAMANTANE CAGE A.Yu. Sukhorukov, A.N. Semakin, I.S. Golovanov, S.L. Ioffe, V.A. Tartakovsky N.D. Zelinsky Institute of Organic Chemistry, Moscow, Russia
For more than 100 years, heteroadamantanes have been objects of rapt attention for fundamental and applied chemistry. These cage polycyclic systems represent interest not only due to their unique properties, but also as convenient models for the study of basic problems dealing with structure and reactivity of organic compounds. Among many heteroadamantanes, 1,3,5,7-tetraazaadamantane (urotropine), which was first obtained by A. Butlerow in 1859, plays, probably, the most important role from an applied point of view. Urotropine is widely used in medicine, polymer production, food industry, as well as organic synthesis, coordination chemistry and MOFs design. This simplest Td-symmetrical 1,3,5,7-tetraazaadamantane is the only known representative of the class of tetraazaadamantanes. In this context the possibility of existence of other tetraazaadamantanes isomeric to urotropine represents considerable fundamental interest.
The present report deals with the first synthesis of 1,4,6,10-tetraazaadamantane (“isourotropine”), the C3v-symmetrical structural isomer of urotropine, and a series of its derivatives (see Figure). XRay and quantum-chemical studies demonstrate remarkable distinctions in structures of urotropine and “isourotropine” cages, probably, arising from different types of lp(Neq) *C N interactions in these heterocage systems. Since substitution at bridge and bridgehead nitrogen atoms can be easily installed, 1,4,6,10-tetraazaadamantane can be considered as a new rigid multivalent (3+1) scaffold for the design of complex functional molecules and materials. Acknowledgement The financial support from RFBR (grant 14-03-00933a) and Russian President’s Council for Grants (grant MK-3918.2013.3) is greatly acknowledged.
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OC7 PALLADIUM-CATALYZED CROSS-COUPLING REACTION OF ALCOHOL WITH ARYL CHLORIDE THROUGH C-C BOND ACTIVATION C.-H. Jun, H.-S. Park, D.-S. Kim Yonsei University, Department of Chemistry, Seoul, South Korea The C-C bond activation is one of challenging subjects in organometallic chemistry.1 Especially catalytic version of C-C bond activation has been recently achieved by chelation assisted transition metal catalyst, consisted of Rh(I) and 2-amino-3-picoline.2 During the course of our studies on these types of C-C bond activation, we found decarbonylative esterification of aliphatic alcohol with aryl chloride by palladium metal as shown below. For example, when the reaction of chlorobenzene and 1-naphtylethanol was carried out at 150oC under Pd/C and NaF base, a mixture of three products, 1-naphtylethyl benzoate ester, benzene, and 1-methylnaphthalene, was obtained in reasonable yields.
The reaction mechanism is proposed as follows. The reaction proceeds through several consecutive reactions. Initially, primary alcohol is oxidized by aryl chloride to aldehyde with formation of arylH under palladium catalyst. Aldehyde is decarbonylated by Pd to generate alkane and (CO)Pd. The intermediate (CO)Pd is oxidatively added to aryl chloride to form acyl-PdCl complex, which reacts with alcohol to give ester compounds. In this reaction, reactivity of substrate should be well balanced. The reactivity of chloroarene is suited for this purpose since other aryl halide such as bromobenzene and iodobenzene did not show any reactivity in this reaction. This result is quite interesting since aryl chloride is least reactive for common C-C bond coupling reaction while aryl iodide is very reactive. The reaction works well with aryl chloride. One of merits in this protocol is that carbonylation proceeds without using toxic CO gas, and CO source is non-toxic alcohol. More detailed mechanistic studies using 13C-enriched or deuterated alcohol will be discussed. References 1. Jun, C. -H. Chem. Soc. Rev. 2004, 33, 610-618. 2. Park, Y. J.; Park, J. -W.; Jun, C. -H. Acc. Chem. Res. 2008, 41, 222-234.
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OC8 RADICAL-CATIONS OF ACETYLENE COMPOUNDS IN CARBONCARBON BOND FORMING REACTIONS A.V. Vasilyev Saint Petersburg State Forest Technical University, Institutsky per. 5, Saint Petersburg, 194021, Russia; Saint Petersburg State University, Institute of Chemistry
Radical-cations of acetylene compounds A, generated under oxidation of alkynes I in systems PbO2-strong acid (CF3CO2H, HF, HSO3F), are key reaction intermediates in various new carboncarbon bond forming processes [1-6]. Depending on structure, the species A lead to formation of a variety of products II-VII. When substituents X are moderate electron acceptors CO2R, COAr, COR, PO(OEt)2, trans-ethenes II are stereoselectively formed. In case of stronger acceptors, furan derivatives III (X = COCF3, СОCO2Et), or diketones IV (X = CF3) are formed. In different acidic systems radical-cations of diarylacetylenes (X = Ar) give unsaturated diketones V (in CF3CO2H), butadiene difluiorides VI (in HF) or dichlorides VII (in HSO3F, followed by quenching in HClaqua.,conc.). The last ones are electro-cyclically converted into naphthalenes VIII. O
Cl Ar R
Ar Ar Ar
Ar
X = Ar 1. H+=HSO3F; 2. HCl
C C Cl C C Cl
VII
Ar C C X A X = Ar
F C
Ar C F
Ar Ar VI
X O II
X = COCF3, COCO2Et
X
C Ar C C
Ar C X = CF3
C O III
H+ = CF3CO2H
Ar C C
Ar C
O
X = Ar H+ = HF
Ar Ar
C Ar C C
X = CO2Alk, COAr, COMe, PO(OEt)2
PbO2/H+ -e
VIII
Ar
X
Ar C C X I
Ar C C
Ar C
C Ar O O V
Y Y = CF3, CO2Et
F 3C CF3 H C C H Ar C C Ar O O IV
[1] Vasilyev A.V., Rudenko A.P. Russ. J. Org. Chem. (in Engl.), 1997, V.33, P. 1555-1584. [2] Shchukin A.O., Vasilyev A.V., Fukin G.K., Rudenko A.P. Russ. J. Org. Chem. (in Engl.), 2007, V.43, P.1446-1450. [3] Vasilyev A.V., Aristov S.A., Fukin G.K., Kozhanov K.A., Bubnov M.P., Cherkasov V.K. Russ. J. Org. Chem. (in Engl.), 2008, V.44, P. 791-802. [4] Vasilyev A.V., Shchukin A.O., Walspurger S., Sommer J. Eur. J. Org. Chem., 2008, 4632. [5] Vasilyev A.V., Rudenko A.P. Russ. J. Org. Chem. (in Engl.), 2010, V.46, P.1282-1289. [6] Alkhafaji H.M.H., Vasilyev A.V., Ryabukhin D.S., Rudenko A.P., Muzalevskiy V.M., Nenajdenko V.G. Russ. J. Org. Chem. (in Engl.), 2013, V.49, P. 621-623.
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OC9 ACTIVATION OF Ru-BASED OLEFIN METATHESIS CATALYSTS A. Poater1, L. Cavallo2 1 - Institut de Quimica Computacional i Catаlisi and Departament de Quimica, Universitat de Girona, Campus de Montilivi, E-17071 Girona, Catalonia, Spain 2 - Kaust Catalysis Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
In recent years olefin metathesis catalyzed by N-heterocyclic carbene ruthenium complexes has attracted remarkable attention as a versatile tool to form new C=C bonds.[1] The last developed (pre)catalysts show excellent performances, and this achievement has been possible because of continuous experimental and computational efforts to understand the laws controlling the behavior of these systems. This perspective talk rapidly traces the ideas and discoveries that computational chemistry contributed to the development of these catalysts, with particular emphasis on catalysts presenting a N-heterocyclic carbene ligand. Specifically, one of the most important challenges in ruthenium-catalyzed olefin metathesis is to increase the stability of the catalysts under reaction conditions and this hopefully without loss of activity. Special interest has been addressed to study the activation of the second-generation Grubbs catalysts, which has clarifier either a dissociative or an interchange mechanism is feasible.[2]
Although, in the solid state, most ruthenium-based olefin metathesis catalysts are stable to oxygen and moisture, in solution decomposition usually occurs readily. Understanding the decomposition routes of catalysts is extremely important as any insight gained in this area can guide catalyst design efforts, to participate then in the synthesis of drugs.[3,4] Furthermore, new challenging projects plan to modify the structure of the NHC ligands, or replace this ligand by alkylidene ligands, and even the substitution of the metal is a goal, moving to more environmentally friendly metals. [1] G. C. Vougioukalakis, R. H. Grubbs, Chem. Rev. 110, 1746 (2010). [2] C. A. Urbina-Blanco, A. Poater, T. Lebl, S. Manzini, A. M. Z. Slawin, L. Cavallo, S. P. Nolan, J. Am. Chem. Soc. 135, 7073 (2013). [3] S. Manzini, C. A. Urbina-Blanco, A. Poater, A. M. Z. Slawin, L. Cavallo, S. P. Nolan, Angew. Chem. Int. Ed. 51, 1042 (2012). [4] S. Manzini, A. Poater, D. J. Nelson, L. Cavallo, S. P. Nolan, Chem. Sci. 5, 180 (2014).
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OC10 CHEMICAL REACTIVITY IN PROTEINS AND WATER: QM/MM MD INSIGHTS INTO EFFECTS OF LOCAL STRUCTURAL ENVIRONMENTS ON BOND CLEAVAGE Y. Zhao, B.J. Wang, R.B. Wu, Z.X. Cao Department of Chemistry, Xiamen University, Xiamen 361005, China
Water and proteins play a quite important role in chemical and biological processes. In past few years, we carried out a systematic investigation on the effect of local structural environments on reactivity towards hydrolysis, C-N, C-O, and C-H bond cleavages in proteins and water. Using Born-Oppenheimer ab initio QM/MM MD simulations, a state-of-the-art approach to simulating enzymes, we have investigated the structural features of zinc enzymes, nucleoside hydrolase, and deaminase and plausible enzymatic mechanisms. The molecular complexity of active domain in enzyme and roles of conserved residues and protein environments in enzymatic catalysis have been explored. In particular, the different coordination modes and fast ligand exchanges of zinc coordination has been suggested to be one key catalytic feature of the zinc ion, and the chelation mode of hydroxamate with the zinc ion in HDACs is modulated by water access to the linker binding channel. This new insight into the interplay between the linker binding and the zinc chelation emphasizes its importance for the development of new class-IIa-specific HDAC inhibitors. Our calculations indicate that the reliable theoretical treatment on the water-mediated proton transfer and most hydrolysis reactions of carbonyl compounds, such as aldehydes, ketones, esters, amides, the carboxylic acids, and their derivatives, requires use of the large basis set and suitable cluster-continuum model. The effects of solvent and structural modification on hydration and hydrolysis of carbonyl compounds have been discussed. Acknowledgements. This work was supported by the National Science Foundation of China (21133007 and 21373164) and the Ministry of Science and Technology (2011CB808504). References 1. N Chen, H. Ge, J Xu, Z Cao, and R Wu, Biochim. Biophys. Acta 2013, 1834, 1117. 2. R Wu, W Gong, T Liu, Y Zhang, and Z Cao, J. Phys. Chem. B 2012. 116, 1984. 3. B Wang and Z Cao, Chem. Eur. J. 2011. 17, 11929. 4. B Wang and Z Cao, Angew. Chem. Int. Ed. 2011, 50, 3266. 5. R Wu, Z Lu, Z Cao, and Y Zhang, J. Am. Chem. Soc. 2011, 133, 6110. 6. Y Zhao, N Chen, R Wu, and Z Cao, 2013, submitted.
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OC11 MECHANISM OF INTRAMOLECULAR HECK REACTION BY DENSITY FUNCTIONAL THEORY A. Ayyappan, D. Yogeswara Rao Indian Institute of Technology Kharagpur, Department of Chemistry, West Bengal 721392 India
Heck Reaction, the palladium-catalyzed C-C coupling between aryl halides or vinyl halides and activated alkenes in the presence of a base, is widely used in syntheric chemistry. Intramolecular version of Heck reaction is a route to the generation carbocycles that are scaffolds of many important natural products and biologically active molecules. Although the mechanism of intermoelcular Heck reactions is well established, the intramelecular variant is not analyzed in detail for its mechanistic features. Using Density Functional Theory computations, we have explored the the catalytic cycle of intramolecular Heck reaction, that involves oxidative addition, migratory insertion (cyclization) and β-hydride elimination (See Figure). Two pathways were analyzed, which differ in their initial coordination face (Re or Si) of the terminal alkene with the metal centre. The choice of pathway is not evident from free energy profile, because one of the pathways have higher barrier for oxidative addition, the other requires high activation energy for β-hydride elimination. Detailed analysis of the mechanism will be presented. In addition, our attempts to analyze such complex reaction mechanisms by kinetic simulations will be discussed.
Figure: Catalytic cycle for the intramolecular Heck reaction.
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OC12 CYCLODIMERIZATIONS OF DONOR-ACCEPTOR CYCLOPROPANES: SHORTCUT APPROACH TO COMPLEX RING SYSTEMS E.M. Budynina, O.A. Ivanova, A.O. Chagarovskiy, I.V. Trushkov Moscow State University, Department of Chemistry, Moscow, Russia
Cyclodimerization is among the most challenging and fascinating reactions providing significant increase in structural complexity within one operation step in highly stereoselective manner and occurring both in vivo and in vitro. In organic synthesis, among typical substrates that undergo cyclodimerizations, donor-acceptor (DA) cyclopropanes,1 in which small ring is vicinally activated with donor and acceptor groups, occupy a special place. Currently, at least dozen types of Lewis acid-triggered cyclodimerization of such DA cyclopropanes as 2-(het)aryl-cyclopropane-1,1diesters are known which open rapid approaches to diverse ring compounds, including complex polycyclic and bridged molecular systems.2 Recently, on basis of (3+3)-cyclodimerizations of 2-arylcyclopropane-1,1-diesters we developed straightforward and efficient approaches to 1,4-diarylcyclohexanes, 1-aryltetralins or 9,10dihydroanthracenes.2a (3+2)-Cyclodimerizations of similar cyclopropanes provide an easy access to diarylcyclopentanes2b,c and arylindanes.2d Cyclodimerizations of 3- and 4-indolyl-derived DA cyclopropanes allows for the construction of complex tetra- and heptacyclic cores of bisindoles.2e
1. a) Reissig, H.-U.; Zimmer, R. Chem. Rev. 2003, 103, 1151; b) De Simone, F.; Waser, J. Synthesis 2009, 3353; c) Mel’nikov, M.Ya.; Budynina, E.M.; Ivanova, O.A.; Trushkov, I.V. Mendeleev Commun. 2011, 21, 293; d) Schneider, T.S.; Kaschel, J.; Werz, D.B. Ang. Chem. Int. Ed. 2014, 53, 10.1002/anie.201309886. 2. a) Ivanova, O.A.; Budynina, E.M.; Chagarovskiy, A.O.; Trushkov, I.V.; Melnikov, M.Ya. J. Org. Chem. 2011, 76, 8852; b) Chagarovskiy, A.O.; Ivanova, O.A.; Budynina, E.M.; Trushkov, I.V.; Melnikov, M.Ya. Tetrahedron Lett. 2011, 52, 4421; c) Novikov, R.A.; Korolev, V.A.; Timofeev, V.P.; Tomilov, Yu.V. Tetrahedron Lett. 2011, 39, 4996; d) Ivanova, O.A.; Budynina, E.M.; Skvortsov, D.A.; Limoge, M.; Bakin, A.V.; Chagarovskiy, A.O.; Trushkov, I.V.; Melnikov, M.Ya. Chem. Commun. 2013, 49, 11482; e) Ivanova, O.A.; Budynina, E.M.; Chagarovskiy, A.O.; Rakhmankulov, E.R.; Trushkov, I.V.; Semeykin, A.V.; Shimanovskii, N.L.; Melnikov, M.Ya. Chem. Eur. J. 2011, 17, 11738; f) Novikov, R.A.; Tarasova, A.V.; Korolev, V.A.; Timofeev, V.P.; Tomilov, Yu.V. Ang. Chem. Int. Ed. 2014, 53, 3187; g) Novikov, R.A.; Tomilov, Yu.V. Helv. Chim. Acta 2013, 96, 2068. 73
OC13 USING RING STRAIN RELEASE FOR ALLEVIATION OF TRANSANNULAR STRAIN: SMALL RING-TEMPLATED SYNTHESIS OF MEDIUM HETEROCYCLES M. Rubin, M. Rubina, A. Edwards, P. Ryabchuk University of Kansas, Department of Chemistry
A highly efficient diastereocenvergent reaction of bromocyclopropanes with various nucleophiles have been recently developed in our laboratories.1-7 This reaction involves a base-assisted dehydrohalogenation to produce a highly reactive cyclopropene intermediate, which undergoes subsequent nucleophilic addition across the strained C=C bond. Different intramolecular modes of this reaction will be presented. Possibilities for assembly of heterocyclic scaffolds with various ring sizes, including enantiomerically pure medium heterocycles, will be demonstrated. The mechanistic aspect of this transformation and the means of controlling its diastereoselectivity will be discussed. O
O
Ph
Me HN
O
Me O
N
O Ph
N H
t-BuOK/ DMSO
15-membered
t-BuOK/ THF
5-membered
Nu N
O KOH/THF
R
Br
O
t-BuOK/THF
18-crown-6 (cat) Base/THF
O 8-membered
t-BuOK/ DMSO Ar
Me
H O
R"'
t-BuOK/ THF
Me
O
7-10-membered
R
O
H
R"
HN
O O
N R
R 8-membered
8-9-membered
References [1] Alnasleh, B. K.; Sherrill, W. M.; Rubina, M.; Banning, J.; Rubin, M. J. Am. Chem. Soc. 2009, 131, 6906-6907. [2] Banning, J. E.; Prosser, A. R.; Rubin, M. Org. Lett. 2010, 12, 1488-1491. [3] Prosser, A. R.; Banning, J. E.; Rubina, M. Rubin, M. Org. Lett. 2010, 12, 3968-3971. [4] Banning, J. E.; Prosser, A. R.; Alnasleh, B. K.; Smarker, J.; Rubina, M.; Rubin, M. J. Org. Chem. 2011, 76, 3968-3986. [5] Ryabchuk, P.; Rubina, M.; Xu, J.; Rubin, M. Org. Lett. 2012, 14, 1752-1755. [6] Banning, J. E.; Gentillon, J.; Ryabchuk, P.; Prosser, A. R.; Rogers, A.; Edwards, A.; Holtzen, A.; Babkov, I. A.; Rubina, M.; Rubin, M. J. Org. Chem. 2013, 78, 7601-7616. [7] Ryabchuk, P.; Edwards, A.; Gerasimchuk, N.; Rubina, M.; Rubin, M. Org. Lett. 2013, 15, 6010-6013. 74
OC14 THE STRATEGY FOR ATOM ECONOMICAL REDUCTIVE ADDITION DEOXYGENATION D. Chusov, P.N. Kolesnikov, V.I. Maleev, N.Z. Yagafarov A.N.Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences
Herein we present the concept of using carbon monoxide for atom economical reductive addition deoxygenation without external hydrogen source [1]. We are utilizing this idea by showing that NH and C-H bonds of the reagents could be used as hydrogen source (Fig. 1).
Figure 1 References: D. Chusov, B. List, Angew. Chem. Int. Ed., 2014, 53, DOI: 10.1002/anie.201400059.
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OC15 DINUCLEAR CATALYSIS: ACCELERATED, METAL-DEPENDENT RINGOPENING POLYMERIZATION OF LACTIDE E. Kirillov Universite de Rennes 1, UMR 6226 - CNRS, 35042 Rennes France
Multinuclear olefin polymerization catalysts (incorporating several active metal centers in one and the same molecule) have recently emerged as a distinct and brand new class of molecular catalysts. 1 Implicit cooperative behavior2 of two or more metal centers in active species of these systems can contribute to enhanced performance (with respect to mononuclear analogues) in terms of activity, chain-transfer kinetics and, also, monomers selectivity in copolymerization reactions. Dinuclear complexes of aluminum and indium with a bis(phenoxy-imine) platform have been synthesized and used in the polymerization of lactide.3a Kinetic studies demonstrated that the dialuminum precursor (Scheme 1) provides a more favorable reaction pathway in terms of activation free energy than that of directly related monoaluminum systems. 3b No similar trend was observed with the corresponding diindium / monoindium systems, which was attributed to a dissimilar ROP mechanism. Details of the mechanisms and key factors of the dinuclear catalysis will be discussed.
Scheme 1. A dinuclear aluminum system enables a 5-to-10 fold boost in activity when compared to its monoaluminum analogues.
1. Delferro, M.; Marks, T. J. Chem. Rev. 2011, 111, 2450. 2. Bratko, I.; Gómez, M. Dalton Trans., 2013, 42, 10664. 3. (a) Normand, M.; Roisnel, T.; Carpentier, J.-F.; Kirillov, E. Chem. Commun. 2013, 49, 11692. (b) Normand, M.; Dorcet, V.; Kirillov, E.; Carpentier, J.-F. Organometallics 2013, 32, 1694.
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OC16 RECENT METHODOLOGICAL DEVELOPMENTS FOR THE QUANTUM CHEMICAL STUDY OF COMPLEX SYSTEMS S. Irle Nagoya University, Department of Chemistry, Nagoya, Japan
The structural complexity of molecular clusters increases with size due to the associated, rapidly growing configuration space. Two examples are realized in i) the transition from molecular to bulk systems, and ii) in the simulation of extended biosystems. In such systems, traditional quantum chemical approaches of investigations are hampered by the vastly increasing computational cost, even considering ever-growing supercomputer capabilities. Computationally inexpensive, yet accurate schemes such as the density-functional tight-binding (DFTB) method [1] and there linear scaling versions promise here a significant advantage. We have recently engaged in developing novel methodologies for systems with increasing structural complexity, driven by motivation from experimental studies. In this presentation, we will review a) the Kick-fragment-based “Kick3” conformationally aware approach for studying molecular [2] and ionic liquid clusters with increasing size, and our implementation of the fragment molecular orbital (FMO) method [3] with DFTB, called “FMO-DFTB”, in the popular GAMESSUS quantum chemistry package [4]. The computational effort of the method scales nearly linearly with system size with a negligible pre-factor, and allows the efficient, massively-parallel quantum chemical geometry optimization and direct molecular dynamics (MD) simulations of systems containing several tens of thousands of atoms, in particular when fragments consist of units with less than 50 atoms [5]. The method should be particularly useful to predict structures of new artificial peptides and proteins, predict enzymatic reaction pathways, estimate free energy contributions along pathways where large parts or even the entire protein including surrounding water is treated quantum chemically, and to simulate the effects of highly polarizable and/or charged solvents in explicit-solvent MD simulations. Unlike other linear scaling schemes, such as divide and conquer approaches (DC), FMO-DFTB's very design allows the insightful decomposition of interaction energies between ligands and proteins in terms of electrostatics, exchange-repulsion, charge transfer, dispersion and solvent screening contributions in a straightforward manner. [1] [2] [3] [4]
M. Gaus, Q. Cui, M. Elstner, J. Chem. Theory Comput. 7, 931 (2011). M. A. Addicoat, S. Fukuoka, A. J. Page, S. Irle, J. Comput. Chem. 34, 2591 (2013). D. G. Fedorov, T. Nagata, K. Kitaura, Phys. Chem. Chem. Phys. 14, 7562 (2012). M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S. Gordon, J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. Su, T. L. Windus, M. Dupuis and J. A. Montgomery, Jr., J. Comput. Chem., 1993, 14, 1347; http://www.msg.ameslab.gov/gamess/index.html. [5] Y. Nishimoto, D. G. Fedorov, S. Irle, submitted.
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OC17 QUANTUM CHEMICAL MODELING IN STUDIES OF MOLECULAR MECHANISMS OF ENZYME CATALYSIS A.V. Nemukhin Chemistry Department, M.V. Lomonosov Moscow State University, Moscow, 199991, Russia; N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia
Recent results [1-3] of modeling chemical transformations in enzyme active sites using quantumbased approaches will be discussed. We apply quantum mechanics/molecular mechanics (QM/MM) approaches to compute minimum energy pathways connecting enzyme-substrate and enzymeproduct complexes. Appropriate crystal structures from the Protein Data Bank usually serve as a source of coordinates of heavy atoms to create molecular model systems. After in silico construction of a three-dimensional full-atom model, evolution of the model system along carefully selected reaction coordinates is analyzed. Several examples of such modeling will be presented. The complete cycle of chemical transformations in penicillin acylase, a unique enzyme that belongs to the recently discovered superfamily of N-terminal nucleophile hydrolases, with its most specific substrate, penicillin G, leading to formation of 6-aminopenicillanic and phenylacetic acids [1] will be presented. Ketonketal transformations at the active site of matrix metalloproteinases characterized computationally [2] may be explored to propose specific inhibitors. Chemical reactions in photoreceptor proteins constitute an active field of application of QM/MM modeling; the case of BLUF domains will be discussed [3]. Simulation results of guanosine triphposphate hydrolysis (GTP) by small GTPases, icluding Ras protein, will be in focus. According to newly obtained data, the molecular events of the chemical steps upon GTP hydrolysis include: (i) cleavage of the phosphorus (Pγ) -oxygen bond in GTP upon approach of the properly aligned catalytic water molecule, producing GDP; (ii) formation of a new chemical bond between phosphorus and oxygen of water; (iii) redistribution of protons between reacting species leading to inorganic phosphate Pi. References [1] Grigorenko B.L., Khrenova M.G., Nilov D.K., Nemukhin A.V., Švedas V.K. Catalytic Cycle of Penicillin Acylase from Escherichia coli: QM/MM Modeling of Chemical Transformations in the Enzyme Active Site upon Penicillin G Hydrolysis // ACS Catal. 2014. V. 4. P. 2521–2529. [2] Khrenova M.G., Nemukhin A.V., Savitsky A.P. Computational Characterization of KetoneKetal Transformations at the Active Site of Matrix Metalloproteinases // J. Phys. Chem. B. 2014. V. 118. P. 4345-4350. [3] Khrenova M.G., Nemukhin A.V., Domratcheva T. Photoinduced Electron Transfer Facilitates Tautomerization of the Conserved Signaling Glutamine Side Chain in BLUF Protein Light Sensors // J. Phys. Chem. B. 2013 V. 117. P. 2369-2377.
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OC18 EXCITED STATES AND MOLECULAR INTERACTIONS IN PROTEINS AND SOLUTIONS J.H. Hasegawa Catalysis Research Center, Hokkaido University, Sapporo, Japan
Solvatochromism and fluorescent solvatochromism are well-known phenomena, and there are rich accumulations in experimental publications. Color tuning in proteins, such as human color vision and fluorescent proteins, could be also classified to solvatochromism but with a specific environment where anisotropic molecular interactions play important roles. We have studied biological color tuning with the SAC-CI/MM calculations in which MM description was adopted for the environmental effect. This classical description for the environment works very well for explaining the color tuning mechanisms. In some cases, however, environmental electronic structure effect becomes important. To investigate the origin of the QM effect, we propose a scheme based on the wave function theory with a MO localization scheme. The role of the environmental electronic effect was analyzed in terms of amino acids’ orbital delocalizations, excitonic interactions, excited-state polarization, and dispersion interactions. In the presentation, we would show some results of pilot applications.
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OC19 CATIONIC GOLD-CATALYZED HETEROANNULATIONS E.V. Van Der Eycken University of Leuven (KU Leuven), Department of Chemistry, Leuven, Belgium
Gold catalysis is one of the fast growing research topics of modern organic chemistry. In this context, gold-catalyzed carbocyclization and heteroannulation strategies have recently attracted much attention due to the selective and efficient activation of the C-C triple bond towards a wide range of nucleophiles. Moreover, the combination of multicomponent reactions with gold catalysis, gives access to complex molecular architectures in few steps, as compared to traditional multistep processes. We will comment on our recent findings in this field. A concise route to indoloazocines1 via a sequential Ugi/gold-catalyzed intramolecular hydroarylation2 will be presented. A diversityoriented approach to spiroindoles via a post-Ugi gold-catalyzed diastereoselective domino cyclization3 will be described (Scheme), as well as a regioselective approach for the synthesis of pyrrolopyridinones and pyrroloazepinones employing a gold(I)/platinum(II) switch.4 O
H2N
R1
+ N R2
O
R3
N
R4 NC 5
R
R3
i) Ugi-4CR ii) "cationic gold", rt
COOH
O R
1
N H R2
N R5
(+/-) R
4
13 examples up to 80% yield
References: 1. Synthesis of Azocino[5,4-b]indoles via Au-Catalyzed Intramolecular Alkyne Hydroarylation, V. A. Peshkov, O. P. Pereshivko, E. V. Van der Eycken, Adv. Synth. Cat., 354, 2841-2848, 2012. 2. Concise route to indoloazocines via a sequential Ugi/gold-catalyzed intramolecular hydroarylation, S. G. Modha, D. D. Vachhani, J. Jacobs, L. Van Meervelt, E. V. Van der Eycken, Chem. Commun., 48 (52), 6550–6552, 2012. 3. Diversity-Oriented Approach to Spiroindolines: Post-Ugi Gold-Catalyzed Diastereoselective Domino Cyclization, S. G. Modha, A. Kumar, D. D. Vachhani, J. Jacobs, S. K. Sharma, V. S. Parmar, L. Van Meervelt, E. V. Van der Eycken, Angew. Chem. Int. Ed., 51, 9572-9575, 2012. 4. Gold(I) and Platinum(II) switch: A post-Ugi intramolecular hydroarylation to pyrrolopyridinones and pyrroloazepinones, S. G. Modha, A. Kumar, D. D. Vachhani, S. K. Sharma, V. S. Parmar, E. V. Van der Eycken, Chem. Comm., 48, 10916-10918, 2012.
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OC20 Pd-SUPPORTED BIMETALLIC COMPOSITIONS FOR STEREOSELECTIVE LIQUID PHASE SEMI-HYDROGENATION OF DIPHENYLACETYLENE I.S. Mashkovsky1, A.V. Sergeeva1, O.V. Turova1, M.N. Vargaftik2, N.Yu. Kozitsyna2, A.Yu. Stakheev1 1 - Zelinsky Institute of Organic Chemistry RAS, Moscow, Russia 2 - Kurnakov Institute of General and Inorganic Chemistry RAS, Moscow, Russia
This study was focused on the development of the efficient catalyst for selective semihydrogenation of internal alkene. Diphenylacetylene (DPA) was used as a model compound. The catalytic compositions based on Pd-Zn, Pd-Co, Pd-Ni were investigated. The samples were prepared via two techniques: (1) on the basis of palladium acetate heterobimetallic complexes as precursors and (2) using traditional co-impregnation by individual metal salts. It was found that the systems based on bimetallic acetate complexes exhibited a substantial increase in selectivity to alkene and cis-isomer formation at high conversion of the parent alkyne (DPA), albeit at the expense of some decrease in the activity. The detailed physicochemical study with TEM-EDS, SEM-EDS, EXAFS and IR-spectroscopy reveals that the use of heterobimetallic acetate complex as a precursor allows us to avoid metallic phase segregation during the reduction treatment of the catalyst, which ensures high homogeneity of bimetallic particles and leads to enhanced selectivity. Financial support was provided by RFBR foundation, grants #12-03-31487, 13-03-12176 0.93%Pd-0.53%Co/Al2O3
100
90
0.93%Pd-0.53%Co/Al2O3
90
Selectivity to alkene, %
Selectivity to cis-isomer, %
100
80 70
0.93%Pd-0.53%Ni/Al2O3
60
0.93%Pd-0.52%Zn/Al2O3
50 40 H
30
0.93%Pd/Al2O3
H
80
0.93%Pd-0.53%Ni/Al2O3
70
0.93%Pd-0.52%Zn/Al2O3
60 50
0.93%Pd/Al2O3
40 H
30
20
20
10
10
H
H
+ H
0
0 70
80
90
100
70
80
90
100
DPA conversion, %
DPA conversion, %
Рис. 1 Dependency of selectivity to cis-isomer and alkene on DPA conversion for Pd/Al2O3 catalyst modified with Co, Zn and Ni in liquid phase DPA hydrogenation.
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OC21 DESIGN OF NANOSTRUCTURES ON THE BASIS OF TWO PHARMACOPHORIC FRAGMENTS - FULLERENE AND PIPERIDINE DERIVATIVES G.V. Grishina, I.S. Veselov, I.V. Trushkov M. V. Lomonosov Moscow State University, Department of Chemistry
This communication is described the creation of a new nanobiosystems with high antivirus potential based on the two pharmacophoric fragments - derivatives of fullerene C60 and piperidine ligands. Design of nanoadditive on the basis of two pharmacophoric fragments - functional derivatives of trans-3,4-dihydroxypiperidine and organically modified by fullerene C60 can be a very promising bioactive substances. Such a perspective is related to using, first, as ligands several trans-3,4dihydroxylated piperidines already demonstrated anti-HIV activity, and secondly, the uniqueness of fullerene spheroid significantly reduce the toxicity of biologically active adducts. We believed that binding of two biologically active units in the same system will be very useful and promising. Y
M e N
Y N
X N
O
X
C O O E t
1 : X =H ,Y =O H 2 : X =Y =O H 3 :X = N H R ,Y =O H 4
Monoadducts 1-4 have obtained by the Benguel and Prato reactions, respectively, and have since received 12 new fullerene adducts based on the derivatives of the trans-3,4-dihydroxypyridine and trans-4-amino-3-hydroxypiperidines. Isolation, and identification of these adducts were made using column and preparative chromatography on silica gel, structure and stereochemistry were established with the involvement required in each case, spectral methods, including mass spectrometry and МАLDI, X-ray analysis and 1H, 13C NMR. The main difficulty in undertake researches consisted of significant differences reactivity due to high lipophilicity derivatives of fullerene and high hydrophilicity piperidine ligands. To reduce this difference, we have modified both fragments introduction to piperidine ligands and/or in the molecule organically modified fullerenes functions and/or linkers, which facilitated further obtaining of target adducts. For some samples of adducts managed to get soluble in alcohol salts. A very important factor has been the elucidation of the impact of structural and stereochemical factors on possible synergies in the adduct investigation. Target adducts are a new type of nanostructures for medical chemistry with great pharmacological potential.
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OC22 CHIRASAC STUDY ON CHIRAL SPECTROSCOPY AND PHOTOBIOLOGY H. Nakatsuji, T. Miyahara Quantum Chemistry Research Institute (QCRI), 1-36 Goryo-Oohara, Nishikyo-ku, Kyoto 615-8245, Japan
Weak interactions of molecules with solvents and/or environments are of crucial importance in material science and biology, but rather difficult to investigate quantitatively. Circular dichroism (CD) spectra reflect sensitively the conformational structures of chiral molecules, their (weak) interactions with solvents and/or proteins, etc. The SAC-CI method gives their CD spectra very reliably. From this fact, the SAC-CI method is a useful tool to investigate the conformational geometries of chiral molecules, their interactions with environments, etc by comparing their experimental and SAC-CI theoretical CD spectra. We initiated a systematic molecular technology, called ChiraSac (Chirality + SAC-CI) project (see Figure 1) by using the SAC-CI code and other highly reliable and useful codes on “GAUSSIAN” suit of programs [1]. We have already applied this project successfully to several topics of chiral spectroscopy and photobiology [2-4]. We will present here conformational dependence of α-Hydroxyphenylacetic Acid and similarities and differences between RNA and DNA, etc, as some recent applications of ChiraSac to chiral spectroscopy and photobiology. References: [1] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B Mennucci,. G. A. Petersson, et al., Gaussian 09, Gaussian, Inc., Wallingford, CT, 2009. [2] Circular Dichroism Spectra of Uridine Derivatives: ChiraSac Study, Tomoo Miyahara, Hiroshi Nakatsuji, and Takehiko Wada, J. Phys. Chem. A 118, 2931-2941 (2014). [3] Conformational Dependence of the Circular Dichroism Spectrum of α-Hydroxyphenylacetic Acid: A ChiraSac Study, Tomoo Miyahara and Hiroshi Nakatsuji, J. Phys. Chem. A 117, 14065- 14074 (2013). [4] Helical Structure and Circular Dichroism Spectra of DNA: A Theoretical Study, T. Miyahara, H. Nakatsuji, and H. Sugiyama, J. Phys. Chem. A. 117, 42-55 (2013).
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OC23 A DFT ANALYSIS ON THE ELECTRONIC PROPERTIES OF METHYLAMMONIUM LEAD IODIDE PEROVSKITE K. Yamashita1, G. Giorgi1, J. Fujisawa2, H. Segawa2 1 - Department of Chemical System Engineering, The University of Tokyo, Japan 2 - Research Center for Advanced Science and Technology, The University of Tokyo,Japan
Methylammonium (MA) lead iodide perovskite (CH3NH3PbI3) plays an important role in light absorption and carrier transport in efficient organic−inorganic perovskite solar cells [1]. In my talk, the first theoretical estimation of effective masses of photocarriers and the role of MA cation in CH3NH3PbI3 will be discussed. Spin-polarized DFT calculations have been performed with the generalized gradient approximation. From the charge density of the two-fold degenerate states ((a) and (b)) of CBM and those ((c) and (d)) of VBM, one can see that photogenerated electrons around CBM and holes around VBM exist separately, results related to the ambipolar transport nature of the material. Effective masses of photogenerated electrons and holes are estimated to be me* =0.23m0 and mh* = 0.29m0, respectively, including spin−orbit coupling (SOC) effects. This result is consistent with the longrange ambipolar transport property and with the larger diffusion constant for electrons compared with that for holes in the perovskite, which enable efficient photovoltaic conversion [2]. We also have focused our attention on the MA cation and studied the role it plays in the electronic/optical features of the perovskite, paying attention mainly to the iodide compound [3]. A comparison is performed between the electronic properties of MAPbI3 organic-inorganic perovskite and those of the purely inorganic CsPbI3. References
1. J. Bisquert, J. Phys. Chem. Lett, 4, 2597 (2013). 2. G. Giorgi, J. Fujisawa, H. Segawa, K. Yamashita, J. Phys. Chem. Lett, 4, 4213 (2013). 3. G. Giorgi, J. Fujisawa, H. Segawa, K. Yamashita, J. Phys. Chem. 118, 12176 (2014).
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OC24 A HYBRID MC/MD REACTION METHOD WITH RARE EVENT-DRIVING MECHANISM: ATOMISTIC REALIZATION OF 2-CHLOROBUTANE RACEMIZATION PROCESS IN DMS SOLUTION M. Nagaoka Graduate School of Information Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 4648601, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Honmachi, Kawaguchi 332-0012, Japan; ESICB, Kyoto University, Kyodai Katsura, Nishikyo-ku, Kyoto 615-8520, Japan
We demonstrate a new efficient hybrid MC/MD reaction method with a rare event-driving mechanism as a practical ‘atomistic’ molecular simulation of large-scale chemically reactive systems (Figure 1). Application of the method to (R)-2-chlorobutane molecules in N,Ndimethylformamide (DMF) molecules starting in the optical pure state (100% e.e.) was found to successfully provide such an atomistic state with ~0% e.e., the expected purity of (R)- to (S)enantiomers of the racemic mixture in chemical equilibrium [1]. This hybrid MC/MD reaction method is promising for studies of various properties in chemically reactive systems [2] and their stereochemistry as well.
Figure 1. Schematic representation of the hybrid MC/MD reaction method. The curly curves represent the molecular dynamical (MD) moves in phase space following the equations of motion, while the straight lines with arrows represent the Monte Carlo (MC) moves (or transitions) of the system (right figure), whose dynamical moves would be extremely rare events. In the left figure, the configurational distribution in equilibrium peq is proportional to the exponential factor exp[-βU] where U is the global potential function. The right figure shows regional distributions, e.g., preq exp[-βUr] in region r, etc. The connecting points of the two kinds of moves (open circles) are selected according to the criteria for chemical reaction occurrence. Note that they do not represent real connections since these points correspond to almost identical states in configuration space but not in momentum space and with different configurational gradients. Wr→s and Ws→t are the transition probabilities from state r to s and from s to t, respectively [1]. [1] Masataka Nagaoka, Yuichi Suzuki, Takuya Okamoto, Norio Takenaka, Chem. Phys. Lett. 583, 80 (2013). [2] N. Takenaka, Y. Suzuki, H. Sakai, M. Nagaoka. J. Phys. Chem. C, 118, 10874 (2014).
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OC25 CALIX[4]ARENE-TETRATHIAFULVALENE RECEPTORS FOR RECOGNITION OF ELECTRON DEFICIENT GUESTS V.A. Azov, M.H. Duker, H. Schafer, D. Schluter University of Bremen For more than four decades tetrathiafulvalenes1 (TTFs) have been extensively studied on the account of their outstanding –donating properties. Due to their ability to induce reversible electrochemically-switchable processes,1b TTFs have found their place on the forefront of supramolecular chemistry. Herein, we present synthesis and studies of a family of rationally designed redox-switchable receptors employing monopyrrolo-tetrathiafulvalenes as molecular recognition units. Our group has been long interested in synthesis and studies of tetrathiafulvalene-containing molecular architectures and their application for binding of electron-deficient molecular guests.2 Recently, several upper rim bis-monopyrrolotetrathiafulvalene-calix[4]arene receptors were synthesized using a modular construction approach.3a,b These compounds feature an architecture of molecular tweezers:4 two parallel aligned electron rich TTF arms comprise a molecular recognition center.
Addition of planar electron-deficient guests, such as tetracyanoquinodimethane (TCNQ), to a receptor solution leads to formation of deeply-colored charge-transfer complexes, easily visible by a naked eye. Binding titrations were performed to determine the binding constants, which reached as high as 1 104 M-1. Additionally, tripodal receptors comprising three TTF units attached to the 1,3,5-substituted-2,4,6-triethylbenzene scaffold, showed high affinity to pyridinium derivatives in the gas phase, as it was proven by ESI-MS experiments.3c 1. a) J. L. Segura, N. Martín, Angew. Chem. Int. Ed. 2001, 40, 1372–1409; b) D. Canevet, M. Sallé, G. Zhang, D. Zhang, D. Zhu, Chem. Commun. 2009, 2245–2269. 2. a) V. A. Azov, R. Gómez, J. Stelten, Tetrahedron 2008, 64, 1909–1917; b) M. Skibiński, R. Gómez, E. Lork, V. A. Azov, Tetrahedron 2009, 65, 10348–10354; c) M. H. Düker, R. Gómez, C. M. L. Vande Velde, V. A. Azov, Tetrahedron Lett. 2011, 52, 2881–2884. 3. a) M. H. Düker, H. Schäfer, M. Zeller, V. A. Azov, J. Org. Chem. 2013, 78, 4905–4912; b) V. A. Azov, H. Schäfer, D. Schlüter, manuscript in preparation; c) M.-L. Lieunang Watat, T. Dülcks, D. Kemken, V. A. Azov, Tetrahedron Lett. 2014, 55, 741–744. 4. For a review on topologically similar molecular tweezers, see: F.-G. Klärner, B. Kahlert, Acc. Chem. Res. 2003, 36, 919–932.
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OC26 ENHANCED RATE AND SELECTIVITY BY CARBOXYLATE SALT AS A BASIC COCATALYST IN CHIRAL NHC-CATALYZED ASYMMETRIC ACYLATION OF SECONDARY ALCOHOLS K. Yamada Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 6068501, Japan
Kinetic resolution of racemic secondary alcohols via enantioselective acylation is an important process in synthetic chemistry.1 During a study to extend our previous report,2 we found that the rates and enantioselectivities of chiral NHC-catalyzed asymmetric acylation of alcohols with an adjacent H-bond donor functionality are remarkably enhanced in the presence of a carboxylate cocatalyst. The degree of the enhancement is correlated with the basicity of the utilized carboxylate. Using a cocatalyst and newly developed electron-deficient chiral NHC, kinetic resolution and desymmetrization of cyclic diols and amino alcohols are achieved with extremely high selectivity (up to krel = 218 and 99% ee, respectively) with low catalyst loading (0.5 mol %).3
References 1 Müller, C. E.; Schreiner, P. R. Angew. Chem. Int. Ed. 2011, 50, 6012. 2 Kuwano, S.; Harada, S.; Oriez, R.; Yamada, K. Chem. Commun. 2012, 48, 145. 3 Kuwano, S.; Harada, S.; Kang, B.; Oriez, R.; Yamaoka, Y.; Takasu, K.; Yamada, K. J. Am. Chem. Soc. 2013, 135, 11485.
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OC27 CONFORMATIONAL FLEXIBILITY, INTRA- AND INTERMOLECULAR INTERACTIONS AND CATALYTIC ACTIVITY OF PC(sp3)P PINCER IRIDIUM HYDRIDE COMPLEXES N.V. Belkova1, G.A. Silantyev1, O.A. Filippov1, S. Musa2, D. Gelman2, L.M. Epstein1, E.S. Shubina1 1 - A.N. Nesmeyanov Institute of Organoelement Compounds RAS, Moscow, Russia 2 - The Hebrew University of Jerusalem, Jerusalem, Israel
A variety of recently developed catalysts operate via different ligand-metal cooperating mechanisms and new “non-innocent” ligands and their complexes keep appearing in the literature. Reversible switching between different coordination modes found in these compounds opened new practical reactivity patterns in non-oxidative (i.e. alternative to the conventional oxidative addition/reductive elimination sequence) activation and formation of polar and non-polar bonds. At that, many such systems contain stereochemically rigid pincer ligands and keep their geometry during the catalytic runs.
Bifunctional dibenzobarrelene-based PC(sp3)P pincer iridium complex 1 is known as an efficient catalyst in acceptorless dehydrogenation of alcohols [1] and hydrogenation/hydroformylation of alkenes [2]. In order to shed light on the mechanism of the hydrogen formation/activation, we performed variable temperature IR and NMR (1H, 31P) analysis of intra- and intermolecular interactions involving hydride ligand and hydroxymethyl cooperating group in 1 and its analogues. The results of the spectroscopic measurements in different media (dichloromethane, toluene, DMSO, and mixed solvents) were compared with the quantum chemical (DFT /M06 and B3PW91; AIM) calculations. The data obtained imply flexibility of the dibenzobarrelene-based scaffold unprecedented for conventional pincer ligands. Both the complex 1 and its counterpart 2 prefer facial configuration of the PCP ligand with P-Ir-P angle of ca. 100º. Such geometries are dictated by stabilizing Ir···O interaction and differ by the mutual arrangement of the H and Cl ligands. The complexes show dynamic equilibrium between two most stable fac-isomers, which can be transformed into the meridional ones in the presence of coordinating additives (CH3CN, DMSO or CO, but not Et3N), some of which have been used as auxiliary base in catalytic alcohols dehydrogenation [1]. The mechanism of the H2 activation and C-H bond formation involves intramolecular cooperation between the structurally remote CH2OH functionality and the metal center and proceeds without the change of the oxidation state of the metal. This work was financially supported by the Russian Foundation for Basic Research (projects No. 14-03-00594 and 14-03-31828) and by the German-Russian Interdisciplinary Science Center (GRISC) funded by the German Federal Foreign Office via the German Academic Exchange Service (DAAD) (projects No. C-2011b-4 and C-2012a-4). 1. S. Musa, I. Shaposhnikov, S. Cohen, D. Gelman, Angew. Chem. Int. Ed. 2011, 50, 3533-3537 2. Musa, S.; Filippov, O. A.; Belkova, N. V.; Shubina, E. S.; Silantyev, G. A.; Ackermann, L.; Gelman, D. Chem. Eur. J. 2013, 19, 16906-16909
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OC28 RECENT DEVELOPMENT OF THE FRAGMENT MOLECULOR ORBITAL METHOD K. Kitaura Department of Computational Science, Graduate School of System Informatics, Kobe University , Chuo-ku, Kobe, 650-0047, Japan
The fragment molecular orbital (FMO) method[1] is an approximate ab initio MO computational method for vary large molecules such as proteins. In the method a molecule is divided into fragments and ab initio MO calculations are performed on the fragments, their dimers and optionally trimers to obtain the total enegy and other properties of the whole molecule. The method reproduces regular ab initio properties with good accuracy. Various FMO-based correlation methods have been developed including density functional theory (DFT), 2nd order Møller-Plesset perturbation theory (MP2), coupled cluster theory (CC), and MCSCF. Polarisable continuum model (PCM) was interfaced with FMO, allowing one to treat solvent effects of real size proteins. The FMO codes been incorporated in GAMESS-US[2]. Recently, We have developed the analytical energy gradients [3] and the second derivatives[4] in FMO. In this presentation, I will talk about the applications to geometry optimization, MD simulation, and vibrational frequency calculations of large molecular systems. [1] “The faragment Molecular Orbital Method: Practical Applications to Large Molecular Systems”, Dmitri.G..Fedorov, Kazuo Kitaura, Eds., CRC press, Boca Raton, 2009. [2] GAMESS, http://www.msg.ameslab.gov/gamess/ [3] T. Nagata, et al., J. Chem. Phys. 135, 044110 (2011) [4] H. Nakata, et al., J. Chem. Phys. 138, 164103 (2013)
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OC29 MODELING ADSORPTION IN NANOSCALE DEFECTIVE Pd2-GRAPHENE SYSTEMS M.V. Polynski, V.P. Ananikov ZIOC RAS, Leninsky prospekt, 47, 119991 Moscow, Russia; MSU, Faculty of Chemistry, 1-3 Leninskiye Gory, 119991 Moscow, GSP-1, Russia
Quantum chemical modeling of transition metal particle adsorption on defeted graphene is still challenging due to the fact that periodic systems of tens or even hundreds of atoms have to be considered. We use DFT methods to evaluate Pd2 affinity to defect sites on graphene surface. GPW method [1] implemented in CP2k program [2] (version 2.6, development) was used for all the computations presented. Spin-polarized computations with dispersion-corrected PBE-D3 functional were performed in all cases unless specified explicitly. GTH-type pseudopotentials for PBE functional and DZVP-MOLOPT-SR-GTH basis set were used. The model systems were treated as 2D-periodic unless specified explicitly. The geometry optimizations were performed with the BFGS algorithm. Cell parameters were kept fixed during geometry optimizations. Pd2 molecules were placed near a defect in several spatial configurations and this model systems were subjected to geometry optimization. The affinity of Pd2 species to various point- and 1Ddefects, and steppings was evaluated, and both magnetic and non-magnetic states were found. The PBE-D3 method allowed to model a system with both covalent and non-covalent interactions. Noteworthy, the model systems are truly nanoscale (the cell vectors are longer than ~2 nm) and contain up to ~430 atoms.
Optimized structures of Pd2 binded to double vacancy defect site (left) and Stone-Wales-type defect site (right). The reported study was supported by the Supercomputing Center of Lomonosov Moscow State University [3]. [1] VandeVondele, J.; Krack, M.; Mohamed, F.; Parrinello, M.; Chassaing, T.; Hutter, J. Comp. Phys. Commun. 2005, 167, 103. [2] Hutter, J.; Iannuzzi, M.; Schiffmann, F.; VandeVondele, J. Wiley Interdisciplinary Reviews: Computational Molecular Science 2014, 4, 15. [3] Sadovnichy, V.; Tikhonravov, A.; Voevodin, Vl.; Opanasenko, V. "Lomonosov": Supercomputing at Moscow State University. In Contemporary High Performance Computing: From Petascale toward Exascale; Vetter, J. S., Ed.; Chapman & Hall/CRC Computational Science, CRC Press: Boca Raton, USA, 2013; pp 283-307.
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OC30 CLUSTER EFFECT IN DECHLORINATION OF ORGANOCHLORIDES BY BIMETALLIC Au-Ag SYSTEM: EXPERIMENTAL AND THEORETICAL STUDY L.V. Romashov, L.L. Khemchyan, E.G. Gordeev, V.P. Ananikov N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, Moscow 119991, Russia
Environmental pollution by various chlorinated organic compounds is the problem of great importance nowadays. Various aliphatic and aromatic chlorides have found applications as solvents, dry cleaning fluids, degreasing agents, pesticides, insecticides etc. and have been produced in large quantities during the last decades. Extensive use and chemical stability of chlorinated compounds led to widespread contamination of environment by these pollutants.[1] In recent decades interesting results were achieved using bimetallic systems as promoters of dechlorination process. Interaction between different metal atoms results in superior properties, which significantly exceed a simple combination of individual metals.[2-5] In spite of very promising potential, the origin of bimetallic effect remains unclear and mechanistic picture of bimetallic dechlorination is an open question. Experimental study of dechlorinative activity of Au/Ag bimetallic system has shown formation of a variety of chlorinated bimetallic Au/Ag clusters with well-defined Au:Ag ratio from 1:1 to 4:1 (Figure 1). It is the formation of the Au/Ag cluster species that mediated C-Cl bond breakage, since neither Au nor Ag species alone exhibited a comparable activity (Figure 2). The nature of the products and the mechanism of dechlorination were investigated by ESI-MS, GC-MS, NMR and by quantum chemical calculations at the M06/6-311G(d)&SDD level of theory. It was revealed that formation of bimetallic clusters facilitated dechlorination activity due to thermodynamic factor. An appropriate Au:Ag ratio for efficient hydrodechlorination process was determined in a joint experimental and theoretical study carried out in the present work. High activity of the designed bimetallic system made it possible to carry out dechlorination process under mild conditions at room temperature.
Figure 1. Example of detected bimetallic Figure 2. Bimetallic effect in dechlorination cluster (optimized geometry). reaction. [1] Thornton, J., Pandora's Poison: Chlorine, Health, and a New Environmental Strategy. MIT Press: MA, 2000. [2] Nutt, M. O.; Hughes, J. B.; Wong, M. S. Environ. Sci. Technol. 2005, 39, 1346-1353. [3] De Corte, S.; Sabbe, T.; Hennebel, T.; Vanhaecke, L.; De Gusseme, B.; Verstraete, W.; Boon, N. Water Res. 2012, 46, 2718-2726. [4] De Corte, S.; Hennebel, T.; Fitts, J. P.; Sabbe, T.; Biznuk, V.; Verschuere, S.; van der Lelie, D.; Verstraete, W.; Boon, N. Environ. Sci. Technol. 2011, 45, 8506-8513. [5] Lambert, S.; Ferauche, F.; Brasseur, A.; Pirard, J. P.; Heinrichs, B. Catal. Today 2005, 100, 283289. 91
OC31 PORPHYRIN-FULLERENE DYADS COVALENTLY LINKED VIA PYRROLO[3,4-C]PYRROLE LINKER: ON THE WAY TO MOLECULES FORMING LONG-LIVED CHARGE-SEPARATED STATE A.S. Konev, P.I. Prolubnikov, A.F. Khlebnikov, A.S. Mereshchenko, A.V. Povolotskiy, O.V. Levin St. Petersburg State University, Institute of Chemistry, St. Petersburg, Russian Federation
Porphyrinofullerenes represent promising materials for artificial photosynthesis and for construction of organic photovoltaic devices1 due to their ability to form charge-separated state (CS) upon irradiation with light. The lifetime of the CS thus formed ranges from pico-2 to microsecond3 range, depending on the structure of the dyad and on the conditions of irradiation. The larger the lifetime of the CS, the higher is the probability of worthwhile intermolecular electron transfer from a photochemically generated radical-ion pair, making thus a creation of the systems that are capable to form a long-lived CS an important task. Analysis of the relevant literature shows that a porphyrin-fullerene dyad with rigid linker that enables spatial separation of the chromophors and fixes them in face-to-edge orientation, so that their π-systems are virtually orthogonal one to another, should reduce the rate of back-electron transfer and enhance thus the lifetime of the CS. Keeping in mind this strategy of achieving longlived CS species, we synthesized a series of covalently linked porphyrin-fullerene dyads with a rigid pyrrolo[3,4-c]pyrrolic linker that meets the above requirements and studied them by means of transient absorption spectroscopy and cyclic voltammetry. The lifetime of the charge separated state constituted up to 4 μs, depending on the substituents in the porphyrin core. The effect of the porphyrin substituent on the lifetime of the CS was rationalized on the basis of DFT and TD-DFT B3LYP(6-31G(d)) calculations of ground and excited electronic states of model compounds. Ar CO2Et
O
EtO2C
532 nm
N Ar
N
N
N
NH
HN
N CO2Et
O
EtO2C
F
P
up to 4 μs
Ar CO2Et O
NH2
N
H N N
CO2Et
H2N
Ar-CHO O N
O O
References 1. D. M. Guldi, Chem. Soc. Rev., 2002, 31, 22 2. e.g.: N.V. Tkachenko, H. Lemmetyinen, J. Sonoda, K. Ohkubo, T. Sato, H. Imahori, Sh. Fukuzumi, J. Phys. Chem. A, 2003, 107, 8834 3. e.g.: M.E. El-Khouly, K.-J. Han, K.-Y. Kay, Sh. Fukuzumi, Eur. J. Chem. Phys. Phys. Chem., 2010, 11, 1726. The work was financially supported by the Russian Foundation for Basic Research (Grant No. 1403-00187), St. Petersburg State University (Grants No. 12.38.78.2012, 12.50.1562.2013) and St. Petersburg State University/DAAD joint program (A1178335/12.23.508.2012).
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OC32 PALLADIUM-CATALYZED CASCADE ANNULATION OF ALKYNES WITH UNACTIVATED ALKENES IN IONIC LIQUIDS J.-X. Li, S.-R. Yang, H.-F. Jiang South China University of Technology, School of Chemistry and Chemical Engineering, Guangzhou, P. R. China
Transition metal-catalyzed carbon-carbon or/and carbon-heteroatom bond formations have attracted considerable attention over the past decades, owing to their easy access to highly functionalized molecules in an efficient, atom- and step-economical way.[1] Particularly, palladium-catalyzed cascade reactions have been emerging as a captivating branch of organic chemistry, associating with the mild reaction conditions and excellent functional group tolerance in a fashion of green chemistry.[2] On the other hand, ionic liquids offer an alternative and ecologically sound medium in comparison to conventional organic solvents, as they are nonvolatile, recyclable, highly compatible with transition metal catalysts, limited miscibility with common solvents enables easy product and catalyst separation with the retention of catalyst activity in the ionic phase.[3] Recently, we have investigated various palladium(II)-catalyzed cascade transformations of alkynes and alkenes in ionic liquids (Scheme 1, Path I-III). As part of our research programs in nucleopalladation and Pd-catalyzed cross-coupling reactions in ionic liquids, we herein present the first example of palladium-catalyzed intermolecular cascade annulation of alkynes with unactivated alkenes in ionic liquids to afford a series of functionalized alkene products (Scheme 1, Path IV).
Scheme 1 Reference: [1] Gulevich, A. V.; Dudnik, A. S.; Chernyak, N.; Gevorgyan,V. Chem. Rev. 2013, 113, 3084. [2] Wu, W.; Jiang, H. Acc. Chem. Res. 2012, 45, 1736. [3] Giernoth, R. Angew. Chem., Int. Ed. 2010, 49, 2834.
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OC33 SYNTHESIS OF BENZOTHIADIAZOLE COMPOUNDS FOR OPTICAL MATERIALS Y.L. Li, S.H. Chen Institute of Chemistry, Chinese Academy of Sciences,CAS Key Laboratory of Organic Solids, Beijing, P.R. China
The nature of the substituent groups greatly influences the structural and photophysical properties of D/A molecules. The nature of the linkage between the D and A units also influences the structures and photophysical properties of intramolecular charge transfer (ICT) compounds.1 For example, in the D/A molecules BSC and BEC containing carbazole moieties as their D moieties and a NO2-substituted benzothiadiazole as their A moiety, X-ray crystal data elucidated multiple intermolecular interactions in these systems.2 These interactions were the main driving forces directing the self-organization of the microstructures, with the different linkages exhibiting distinctly different self-assembly behavior. Most D/A-substituted compounds suffer from aggregation-caused emission quenching (ACQ) in the solid phase, greatly limiting their applications.3 We have observed aggregation-induced emission (AIE) effects for several of our ICT compounds, including the carbazole- and benzothiadiazole-based BSE, BEC, BTN-6 and BTN-7. These prepared nanostructures exhibit green, yellow, and especially red emissions. In addition, the distance-dependent photoluminescence image of a single microrod of BTN-7 measured using a near-field scanning optical microscope indicated that these microrods possess outstanding optical waveguide properties, with a waveguide efficiency (a) of 0.018 dB μm–1 and no obvious red-shift.4
References 1. Liu, H.; Xu, J.; Li, Y.; Li, Y. Acc. Chem. Res. 2010, 43(12), 1496–1508. 2. Chen, S.; Qin, Z.; Liu, T.; Wu, X.; Li, Y.; Liu, H.; Song, Y.; Li, Y. Phys. Chem. Chem. Phys., 2013, 15, 12660–12666. 3. Xu, J.; Zheng, H.; Liu, H.; Zhou, C.; Zhao, Y.; Li, Y.; Li, Y. J. Phys. Chem. C 2010, 114, 2925– 2931. 4. Chen, S.; Chen, N.; Yan, Y.; Liu, T.; Yu, Y.; Li, Y.; Liu, H.; Zhao, Y.; Li, Y. Chem. Commun., 2012, 48, 9011–9013.
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OC34 DENDRIMERS AND BIOMASS: SYNTHESIS, CATALYSIS AND ENCAPSULATION S. Bouquillon, B. Menot, J. Stopinski ICMR, Universitй Reims Champagne Ardenne
For several years, our research team is interested in the development of new families of dendrimers using organic by-products from biomass (pentoses, glycerin or corresponding by-products). Some glyco-or glycerodendrimers derived from PPI (polypropylene imines) were already obtained, and valued in the domains of aqueous catalysis and encapsulation of metallic salts or emergent pollutants [1,2]. Glycodendrimers were also previously synthetized and used for the preparation and the stabilization of metallic nanoparticles (Pt, Pd, Au), which could be used in aqueous catalysis [3]. The objective of this presentation is, at first, to describe the synthesis of nitrogenous glycerodendrimers derived of polypropyleneimines (PPis) or of polyAmidoAmines (PAMAMs) and, secondly, to demonstrate their potential in catalyses of hydrogenation and oxidation in the water and in encapsulation of organic pollutants (Figure 1).
Figure 1: Catalysis and encapsulation in biomass derived dendrimers
[1] C. Hadad, J-P Majoral, J. Muzart, A-M Caminade, S. Bouquillon, Tetrahedron Lett. 2009, 50, 1902. [2] S. Balieu, A. El Zein, R. De Sousa, F. Jérôme, A. Tatibouët, S. Gatard, Y. Pouilloux, J. Barrault, P. Rollin, S. Bouquillon, Adv. Synth. & Catal. 2010, 352, 1826. [3] a) S. Gatard, L. Liang, L. Salmon, J. Ruiz, D. Astruc, S. Bouquillon, Tetrahedron Lett. 2011, 52, 1842. b) S. Gatard, L. Salmon, C. Deraedt, J. Ruiz, D. Astruc, S. Bouquillon Eur. J. Inorg. Chem. 2014, 2671.
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OC35 BIOINSPIRED CHIRAL IONIC LIQUIDS AS INNOVATIVE ORGANOCATALYSTS L.C. Branco REQUIMTE, Departamento de Quнmica, Faculdade de Ciкncias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
Chiral Ionic Liquids (CILs) can be useful as chiral solvents or chiral selector in some cases [1]. Recent examples showed the possibility to use chiral ILs as efficient organocatalysts or chiral ligands for Asymmetric Aldol and Michael additions as well as Sharpless dihydroxylation of olefins, among others [2,3]. Asymmetric organocatalysis is an intensively developing area of current organic chemistry in recent years [4]. Aldol and Michael reactions play an important role in carbon-carbon bond forming reaction. The interest of chiral molecules as novel catalysts remains to grow as a wide range of small organic molecules, including L-aminoacids moieties such as Lproline and L-cysteine, which showed to be efficient organocatalysis for asymmetric reactions [5]. In this context, we have been developed novel Bioinspired chiral ionic liquids based on L-cysteine and L-proline derivatives as well as task-specific nucleotides in order to test as chiral organocatalyst of asymmetric organocatalysis and metal catalysis. direct aldol reactions between ketones with nitrobenzaldehydes. For some cases, it was possible to obtain the pure chiral products in good yields and enantiomeric excesses comparable with the conventional systems. Asymmetric direct aldol reactions, Michael additions, Suzuki and Mannich reactions using some bioinspired CILs as chiral catalyst were also tested. Catalytic recycling processes have been performed using efficient sustainable methodologies. Bioinspired Chiral Ionic Liquid
Chiral Recognition
Asymmetric catalysis
Acknowledgements: This work has been supported by FCT/MCTES (PEst-C/EQB/LA0006/2011, PTDC/CTM/103664/2008 and PTDC/CTM-NAN/120658/2010 projects) References: [1] J. Ding, D. W. Armstrong, Chirality 2005, 17, 281. [2] a ) A. Lu, T. Liu, R. Wu, Y. Wang, G. Wu, Z. Zhou, J. Fang, C. Tang, J. Org. Chem. 2011, 76, 3872. b) L. C. Branco, P. M. P. Gois, N. M. T. Lourenco, V. B. Kurteva, C. A. M. Afonso, Chem Comm. 2006, 2371. [3] a) L. C. Branco, A. Serbanovic, M. N. Ponte, C. A. M. Afonso, ACS Catal. 2011, 1, 1408. b) . C. A. M Afonso, L. C. Branco, N. R. Candeias, P.M.P. Gois, N. M. T. Lourenço, N. M. M. Mateus, J. N. Rosa, Chem. Commun. 2007, 2669. [4] K. Bica, P. Gaertner, Eur. J. Org. Chem. 2008, 3235. [5] B. List, R. A. Lerner, C. F. Barbas III, J. Am. Chem. Soc. 2000, 122, 2395. 96
OC36 THE COMPARISON OF COMPUTATIONAL METHODS FOR THE STUDY OF PYRANOSIDE-INTO-FURANOSIDE REARRANGEMENT A.G. Gerbst, V.B. Krylov, D.A. Argunov, N.E. Nifantiev N.D. Zelinsky Institute of Organic Chemistry RAS, Laboratory of Glycoconjugate Chemistry, Moscow, Russia
Furanoside units are often encountered in biologically important complex polysaccharides and smaller oligosaccharides. On the other hand, synthetic methods of furanoside modification are less developed than those for pyranosides. Thus a promising strategy for the introduction of a furanoside moiety into a complex saccharide might be to synthesize first the corresponding pyranoside and then convert it into the pyranoside. Recently, in our laboratory we have discovered a novel rearrangement that allows such transformation of a pyranoside into furanoside (PIF) with good yields. This reaction proceeds under per-sulfation conditions in the acid media. In this communication we present the comparison of different quantum chemical methods for the computational study of the PIF mechanism (Fig. 1). It includes the energy calculations of starting molecules and supposed transition states (TS) and intermediates. Obtained data are correlated with the observed reaction kinetics. TS2
TS1
O3S
-
post-reaction complex
HOH2C -
-
-
HOH2C
OSO3 HO3SO
-
-
Figure 1. Proposed mechanism of the PIF transformation. Ab initio calculations were used in this work with different split-valence basis sets. Taking 6-31G type basis sets we varied number of diffuse and polarization functions in order to find the optimal basis set, which would allow fast calculation with reasonable accuracy. Finally basis set 6-31+G*, having one diffuse and one polarization function was found to give most satisfactory results. Acknowledgement. This work was supported by the grant from Division of Chemistry and Material Sciences of Russian Academy of Sciences, Program 1.
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OC37 GOLD(I) CATALYSED ASYMMETRIC HYDROAMINATION OF ALKENES IN MILD CONDITIONS F. Agbossou-Niedercorn1, M.A. Abadie1, F. Medina1, X. Trivelli2, F. Capet1, C. Michon1 1 - University Lille Nord de France, UCCS UMR 8181 CNRS, ENSCL C7 CS90108, 59652 Villeneuve d Ascq Cedex, France 2 - University Lille Nord de France, LGSF UMR 8576, USTL 59655 Villeneuve d Ascq Cedex, France Gold catalysed hydroamination reactions were recently highlighted on alkenes,1a,b allenes1c and dienes1a,d substrates for both intra- and intermolecular reactions. However, achieving highly selective gold catalysed hydroamination of alkenes, activated or not, remains a challenging endeavor and we would like to report herein our last results.2 First, following our researches on activated alkenes2a,b and allenes,2c the intramolecular gold(I) catalysed asymmetric hydroamination of alkenes was studied screening a wide range of monophosphines. Specially designed phosphoramidite ligands proved to lead to active mononuclear gold(I) catalysts when combined with silver salts. Indeed, chiral amines were obtained in high yields and average enantioselectivities using mild reaction conditions (Scheme 1).2d Second, various binuclear gold(I) catalysts based on selected diphosphine ligands were studied. When combined with a silver salt, a specific gold(I) species proved to perform efficiently the intramolecular hydroamination of alkenes at mild temperatures with high yields and enantioselectivities (Scheme 1).2e The molecular structure of catalyst was determined by X-Ray diffraction analyses and DOSY NMR experiments in order to check the influence of silver salts and water.3 Indeed, water proved to enhance significantly reaction yields and enantioselectivities.
Scheme 1. 1 (a) X. Giner, C. Nájera, G.Kovács, A. Lledós, G. Ujaque, Adv. Synth. Catal. 2011, 353, 3451; (b) M. Kojima, K. Mikami, Synlett 2012, 23, 57; (c) K. L. Butler, M. Tragni, R. A. Widenhoefer, Angew. Chem. Int. Ed. 2012, 51, 5175; (d) O. Kanno, W. Kuriyama, J. Z. Wang, D. F. Toste, Angew. Chem. Int. Ed. 2011, 50, 9919; 2 (a) F. Medina, C. Michon, F. Agbossou-Niedercorn, Eur. J. Org. Chem. 2012, 6218; (b) F. Medina et al., Comptes Rendus Chimie 2013, 16, 311; (c) C. Michon, F. Medina, M.-A. Abadie, F. AgbossouNiedercorn Organometallics 2013, 32, 5589; (d) C. Michon, M.-A. Abadie, F. Medina, F. AgbossouNiedercorn Catalysis Today 2014, doi 10.1016/j.cattod.2014.01.030; (e) M.-A. Abadie, X. Trivelli, F. Medina, F. Capet, F. Agbossou-Niedercorn, C. Michon, submitted. 3 (a) A. Homs, I. Escofet, A. M. Echavarren, Org. Lett. 2013, 15, 5782; (b) Y. Tang, B. Yu, RSC Adv. 2012, 2, 12686; (c) D. Wang, R. Cai, S. Sharma, J. Jirak, S. K. Thummanapelli, N. G. Akhmedov, H. Zhang, X. Liu, J. L. Petersen, X. Shi, J. Am. Chem. Soc. 2012, 134, 9012.
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OC38 SUPRAMOLECULAR GELS FOR CATALYTIC TRANSFORMATIONS AND NANO-MATERIALS SYNTHESIS S. Vatsadze, V. Nuriev, A. Medved’ko Chemistry Department, Lomonosov Moscow State University
Supramolecular gels are gels formed by immobilizations of liquid phase on the 3D network of entangled nano-fibres which themselves are the result of supramolecular polymerization and selforganization [1]. In this report we will focus on the following: 1. supramolecular gels belongs to the family of «smart materials» since they could change their structures in response to the external stimuli; 2. the control over structural and practical properties of gels could be engineered at the stage of molecule design; 3. the possibility of using the organogel as a template for the synthesis of the inorganic replica; 4. post-synthetic transformations, i.e. supercritical fluid drying, expands the scope of materials properties;
5. metal-containing supramolecular gels combine the properties of both heterogeneous and homogeneous catalysts. We thank financial support by RFBR (grant #14-03-91160). 1. V.P.Ananikov, L.L.Khemchyan, Yu.V.Ivanova, V.I.Bukhtiyarov, A.M.Sorokin, I.P.Prosvirin, S.Z.Vatsadze, A.V.Medved'ko, V.N.Nuriev, A.D.Dilman, V.V.Levin, I.V.Koptyug, K.V.Kovtunov, V.V.Zhivonitko, V.A.Likholobov, A.V.Romanenko, P.A.Simonov, V.G.Nenajdenko, O.I.Shmatova, V.M.Muzalevskiy, M.S.Nechaev, A.F.Asachenko, O.S.Morozov, P.B.Dzhevakov, S.N.Osipov, D.V.Vorobyeva, M.A.Topchiy, M.A.Zotova, S.A.Ponomarenko, O.V.Borshchev, Y.N.Luponosov, A.A.Rempel, A.A.Valeeva, A.Yu.Stakheev, O.V.Turova, I.S.Mashkovsky, S.V.Sysolyatin, V.V.Malykhin, G.A.Bukhtiyarova, A.O.Terent'ev, I.B.Krylov. "Development of new methods in modern selective organic synthesis: preparation of functionalized molecules with atomic precision", Russ.Chem.Rev., 2014, 83 (10), in press. DOI: 10.1070/RC2014v083n10ABEH004471 99
OC39 SYNTHESIS AND TRANSFORMATIONS OF STRAINED POLYNITROGEN COMPOUNDS M.A. Kuznetsov, A.S. Pankova Saint Petersburg State University, Institute of Chemistry, Saint Petersburg, Russia The oxidation of many N-aminoheterocycles in the presence of unsaturated compounds is a general way to N-aminoaziridine derivatives containing a strained three-membered ring and combining two heterocyclic moieties in one molecule via a weak N-N bond. This reaction, the so-called oxidative aminoaziridination, is applicable to a wide range of unsaturated substrates and proceeds in a stereospecific manner with a complete retention of a spatial arrangement of substituents at >C=C< bond in the resulted N-aminoaziridines. In this way we have synthesized a set of alkynylaziridines, which possess three endothermic fragments in one molecule, and large series of adducts to styrenes, unsaturated carbonyl compounds, a lot of spiroaziridines etc. With alkenylpyrazoles the expected heterocyclic chains are usually formed in good yields. And it was the same for alkenyl-1,2,4- and 1,3,4-oxadiazoles with one or two double bonds in the side chains. The reaction with alkenylfuranes leads to the unsaturated acyclic compounds exclusively, and can be used for a stereospecific synthesis of 4-oxohexa-2,5-dienal derivatives with (Z)-configuration of 2,3-C=C bond. The oxidative aminoaziridination of the very similar alkenylthiophenes leads to expected adducts onto exocyclic C=C bond, but with thiophene itself and even with selenophene gave the very interesting tricyclic diadducts, though in low yields. Since the classical works of R. Huisgen in 60-ies it is well known that the C-C bond in aziridines can be broken thermally or upon irradiation giving the octet-stabilized 1,3-dipoles, so-called azomethyne ylides, which can be involved in 1,3-dipolar cycloaddition reactions. We have found that for cis- and trans-2,3-disubstituted 1-phthalimidoaziridines this set of transformations proceeds in a stereospecific manner as a concerted process which obeys the rules of orbital symmetry conservation. The intramolecular cycloaddition of 1,3-dipoles should lead to the polycyclic condensed compounds, which are of interest in many aspects. And we have realized it for some Nphthalimidoaziridines with sterically accessible, but inactivated C=C and C≡C bonds. In some cases the regioisomeric imines appeared as the main components of these reaction mixtures. This result caused by 1,2-migration of phthalimidyl rest in the intermediate ylides is often the general one for arylsubstituted aziridines. On another hand, an attempt for intramolecular cycloaddition of aziridines with carbonyl substituents led to quite another products: the 1,5electrocyclization of an intermediate ylide with a participation of C=O bond followed by loss of phthalimide fragment provided aromatic oxazoles in good yields. This transformation of carbonylsubstituted azomethyne ylides into oxazoles competes with an intermolecular cycloaddition too. The yields of oxazoles in all these reactions usually vary from good up to excellent. Taking it into account we have offered the simple and efficient transformation of α,β-unsaturated carbonyl compounds into the corresponding oxazoles via N-phthalimidoaziridines or even via N-arylsulfonylaziridines. This approach is applicable to the synthesis of oxazoles with ethynyl substituent as well. In the case of C-alkenylaziridines, the intermediate ylide contains a conjugated C=C bond, and another kind of 1,5-electrocyclization – into pyrrolines – is conceivable. Combination of the strained three-membered rings and hydrazine moiety makes cyclopropylhydrazines highly energetic compounds. Beside it, the hydrazine fragment occurs in a variety of bioactive compounds. But only two – mono- and 1,2-dicyclopropylhydrazine – out of five possible cyclopropylhydrazines have been known till now. And the last part of our work is devoted to the synthesis of still unknown cyclopropylsubstituted hydrazines. This work was supported by Russian Scientific Fond (research grant no. 14-13-00126).
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OC40 NEW TYPE OF REACTIVITY OF DONOR-ACCEPTOR CYCLOPROPANES: GaCl3-MEDIATED GENERATION OF FORMAL 1,2AND 1,4-DIPOLES R.A. Novikov, A.V. Tarasova, Y.V. Tomilov N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation
A new type of reactivity of donor-acceptor cyclopropanes has been discovered. On treatment with anhydrous GaCl3, they react as sources of even-numbered 1,2- and 1,4-dipoles instead of the classical odd-numbered 1,3-dipoles due to migration of positive charge from the benzyl center. This type of reactivity has been demonstrated for new reactions, viz., cyclodimerizations of donoracceptor cyclopropanes that occur as [2+2]-, [3+2]-, [4+2]-, [5+2]-, [4+3]-, and [5+4]-annulation. The [4+2]-annulation of 2-arylcyclopropane-1,1-dicarboxylates to give polysubstituted 2aryltetralins has been developed in a preparative version that provides exceedingly high regio- and diastereoselectivity and high yields. The strategy for selective cross-combination of donor-acceptor cyclopropanes was also been developed. The mechanisms of the discovered reactions involving the formation of a comparatively stable 1,2-ylide intermediate have been studied. Hitherto unknown complexes of donor-acceptor cyclopropanes with GaCl3 belonging to a new type and having a 1,2dipole (ylide) structure have been obtained and characterized by 1D, 2D and DOSY NMR spectroscopy. Futher transformations of this complex have also been demonstrated. N e w 1 ,2 - a n d 1 ,4 -D ip o la r S y n th e t ic E q u iv a le n ts
G a C l3 C O 2M e Ar
M e O 2C
C O 2M e M e O 2C
C O 2M e
Ar
C O 2M e
M e O 2C
C O 2M e C la s s ic a l 1 , 3 -D ip o le
R
Ar
[2 + 2 ]
[4 + 2 ] R5
C O 2M e
R4
C O 2M e
R3
M e O 2C
C O 2M e
M e O 2C
R1 R2
C O 2M e
Ar Ar
The discovered [4+2]-annulation of DAC is a synthetically valuable process that allows the onestage assembly of polysubstituted tetralins with exceptionally high regio- and diastereoselectivity. The latter may be of interest as synthons in organic synthesis and as compounds possessing biological activity. In fact, the aryltetralin moiety occurs in the structures of a number of compounds that have been isolated from various natural sources and manifest a broad spectrum of biological activity, including antitumor activity. This work was supported by the Russian Federation President Council for Grants (Program for State Support of Leading Scientific Schools of the Russian Federation, grant no. NSh-604.2012.3) Selected Publications: Tetrahedron Lett., 2011, 52, 4996–4999; Organometallics, 2012, 31, 8627–8638; J. Org. Chem., 2012, 77, 5993–6006; Org. Lett., 2013, 15, 350–353; Helv. Chim. Acta., 2013, 96, 2068–2080; Angew. Chem. Int. Ed., 2014, 53, 3187–3191.
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OC41 NEW REACTIONS OF TANTALUM(V) AMIDES M.N. Sokolov, A.L. Gushchin, A.V. Rogachev, P.A. Abramov Nikolaev Institute of Inorganic Chemistry
Transition metal amides are highly reactive compounds which are much employed as reagents, ligand transfer agents, or precursors for more complex molecules. The ready cleavage of the highly polar M-NR2 bond makes the amides particularly important synthons for a wide range of new compounds and materials. The M-NR2 bond can be easily cleaved by protonation using various reagents with acidic E-H bonds (alcohols, thiols, secondary phosphines, pyrazoles etc.). Reactive small molecules such as CS2 or CO2 undergo insertion with the formation of dithiocarbamates and carbamates. In this work we report synthesis of new Ta coordination compounds and clusters by reactions of Ta(NMe2)5 with CS2, Ph2PH and pyrazol; with or without subsequent treatment with sulfur. Ta(NMe2)5 easily react with CS2 with the formation of [Ta(S2CNMe2)3( -CH2-NMe)] (1). The formation of 1 can be explained as triple insertion of CS2 followed by α-elimination of a HNMe2 molecule. Excess of CS2 leads to the formation (in CH2Cl2) of [Ta(S2CNMe2)4]Cl (2). Cyclic voltammetry shows that [Ta(S2CNMe2)4]+ can be reversibly reduced to the neutral [Ta(S2CNMe2)4], the Ta(V)/Ta(IV) couple having E1/2 – 0.74 V vs. Ag/AgCl. Reaction with CS2 in the presence of S8 leads to a complex mixture of Ta(V) dithiocarbamates [TaS(S2CNMe2)3] (3), [Ta(S2)(S2CNMe2)3] (4), and a perthiocarbamate complex [TaS(S3CNMe2)(S2CNMe2)2] (5). HPPh2 rapidly reacts with Ta(NMe2)5 with the formation of an unstable product, which after treatment with S8 yields green crystals of a cuboidal cluster, [Ta4S4(μ-S2PPh2)4(S2PPh2)2] (6), which is, to the best of our knowledge, the first cluster with the {Ta4S4} core. Long Ta-Ta distances (2.973.05 Å) correspond to electron-deficient (only six of the required 12 e) M-M bonding in the cluster core. 3,5-dimethylpyrazol (PzH) is a stronger N-H acid than Me2NH, and reacts with Ta(NMe2)5 with the formation of yellow crystals of the pentakis(pyrazolate), [Ta(pz)5] (7). According to X-ray data, the Ta atom achieves CN 8 by coordinating three pz ligands in the 2, and two pz ligands in the 1 mode. All the compounds have been characterized by single crystal X-ray analysis. Reactivity of complexes 1-7 is being investigated. The work was supported by RFBR grant No. 12-03-33028. [1] M.F. Lappert, A. Protchenko, P. Power, A. Seeber. Metal-Amide chemistry, 2009, John Wiley and Sons, 355 pp.
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OC42 STRUCTURE-REACTIVITY RELATIONSHIPS IN THE REACTIONS OF CAMINO-1H-1,2,4-TRIAZOLES WITH ELECTROPHILES V.M. Chernyshev, D.A. Pyatakov, A.V. Astakhov, A.I. Evdokimova, A.Yu. Chernenko Platov South-Russian State Polytechnic University (NPI), Novocherkassk, Russia
Molecules of C-amino-1,2,4-triazoles (AT) contain several alternative nucleophilic centers, namely NH2 group and any of the ring nitrogen atoms, and therefore can be considered as multifunctional nucleophilic reagents. Such multifunctionality, on the one hand, opens up exciting possibilities for the synthesis of various substituted triazoles and condensed heterocycles [1], however, on the other hand, it causes the problem of selectivity [2, 3]. The present report discusses relationships between the structure of AT and their reactivity towards electrophiles and some novel approaches to the control of selectivity.
On the basis of computational and experimental methods it was established that the position of the endocyclic substituent R has a significant influence on the reactivity of C-amino-1-R-1,2,4triazoles. The global nucleophilicity of the 1-substituted 3-amino-1,2,4-triazoles is higher than the 1-substituted 5-amino-1,2,4-triazoles. Therewith, amino group in the position 3 of triazole ring is substantially more nucleophilic than in the position 5. The atoms N-2 and N-4 of triazole ring as well as the 3-NH2 group are the most favorable sites in the 1-substituted C-amino-1,2,4-triazoles for the attack of electrophiles. Some new approaches to the selective synthesis of substituted triazoles and condensed heterocycles via reactions of AT with electrophilic and bielectrophilic reagents are considered. The structural features and reactions of condensed derivatives of 1,2,4-triazole including some new recyclizations are discussed.
Acknowledgements This work was financially supported by the Russian Foundation for Basic Research (grant no. 13-03-00253) and in part by the Ministry of Education and Science of the Russian Federation, State contract No. 2014/143 (project No. 2945). References [1] Curtis, A.D.M.; Jennings, N. 1,2,4-Triazoles. In Comprehensive Heterocyclic Chemistry III. Elsevier: Oxford, 2008. V. 5. P. 159-209. [2] Chernyshev, V.M.; Astakhov, A.V.; Starikova, Z.A. Tetrahedron 2010, 66, 3301. [3] Chernyshev, V.M.; Pyatakov, D.A.; Sokolov, A.N.; Astakhov, A.V.; Gladkov, E.S.; Shishkina, S.V.; Shishkin, O.V. Tetrahedron. 2014, 70, 684.
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OC43 SILYL NITRONATES IN THE NOVEL [3+3]-CYCLOADDITION REACTION WITH DONOR-ACCEPTOR CYCLOPROPANES A.A. Mikhaylov1, R.A. Novikov1, D.E. Arkhipov2, S.L. Ioffe1 1 - N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation 2 - A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Russian Federation
Cycloaddition reactions are one of the most effective tools for rapid generation of molecular complexity.1 Recently, the formal cycloadditions have evoked special attention due to the intriguing ability of donor-acceptor cyclopropanes, mainly 1,1-cyclopropane diesters 1, to behave as equivalents of 1,3-zwitterions under Lewis acid catalysis.2,3 The formal [3+3]-cycloaddition, discovered by Kerr and co-workers on the nitrones in 2003,4 has already proved itself as a powerful method for six-membered cycles construction.3 In this respect, silyl nitronates 2 can be considered as perspective substrates for formal cycloaddition chemistry due to their 1,3-dipolaric nature. We have shown that different silyl nitronates 2 derived from both primary and secondary nitro compounds can react with 1,1cyclopropane diesters 1 giving rise to polysubstituted six-membered nitroso acetals 3.5 The latters in hand can be easily transformed into isomeric pyrroline-N-oxides 4 and 5 via novel acid-catalyzed ring contraction/silanol elimination reaction. In the presentation the major regularities of the observed [3+3]-cycloaddition reaction will be discussed. The special attention will be focused on the reasons determining stereochemical outcome of nitroso acetals 3. The work was supported by Russian Foundation for Basic Research (Grants #12-03-00278, 14-0331560). References 1. M. Juhl, D. Tanner, Chem. Soc. Rev. 2009, 38, 2983-2992. 2. C. A. Carson, M. A. Kerr, Chem. Soc. Rev. 2009, 38, 3051-3060. 3. T. F. Schneider, J. Kaschel, D. B. Werz, Angew. Chem. Int. Ed. 2014, 53, 5504–5523. 4. I. S. Young, M. A. Kerr, Angew. Chem. Int. Ed. 2003, 42, 3023-3026. 5. A. A. Mikhaylov, R. A. Novikov, Yu. A. Khomutova, D. E. Arkhipov, A. A. Korlyukov, A. A. Tabolin, Yu. V. Tomilov, S. L. Ioffe, Synlett, submitted.
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OC44 SOLID-PHASE SYNTHESIS OF PINCER COMPLEXES: EMERGING ALTERNATIVE TO CONVENTIONAL SYNTHESIS IN SOLUTION D.V. Aleksanyan, V.A. Kozlov A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences
Pincer complexes featuring a tridentate monoanionic framework have become a privileged class of organometallic compounds, finding extensive application in catalysis, materials science, biochemistry and so on.1,2 Several synthetic routes, including direct cyclometalation, oxidative addition, and trans(cyclo)metalation, give access to pincer complexes with almost any type of ligands and metal ions, however, the simplest route seems to be direct cyclometalation. Numerous examples of direct cyclometalation of pincer ligands have been described in solution, but the literature data on the solid-state synthesis of metallacycles are restricted only to several reports dealing with the thermally induced intramolecular cyclometalation of well-defined coordination complexes leading to monometallacyclic species. Recently we have shown that cyclometalation of pincer ligands can be readily carried out in the solid state simply by heating homogeneous mixtures of a ligand and metal precursor obtained by manual grinding in a mortar. 3 This novel solid-phase approach has now been extended to a range of pincer-type ligands which require the activation of the C–H, N–H, and O–H bonds and have different ancillary S-, P-, and N-donor groups (for selected examples see figure). The results obtained show great potential of the solid-phase cyclometalation as an alternative to the conventional synthesis of complex organometallic compounds in solution. Some aspects of the solid-phase cyclometalation will be discussed based on the results of spectral and thermochemical analyses. Ph
Ph P
Ph Ph P S
N
N
S Pd
Cl O
Pd S Cl
S
HN Ph
P h2P
Ph P
S
Pd
N
Cl
Cl
Pd N
S
S
Me
Ph
Ph P
O
S
Cl
Pd N O
S P
Ph Ph
This work was supported by the Russian Foundation for Basic Research (project no. 14-03-31237mol-a) and the Grant of the President of the Russian Federation for young scientists (project no. MK-382.2014.3). 1. The Chemistry of Pincer Compounds, D. Morales-Morales and C. M. Jensen (Eds.), Elsevier, New York, 2007. 2. Organometallic Pincer Chemistry, G. van Koten and D. Milstein (Eds.), Topics Organomet. Chem., 2013, 40. 3. V. A. Kozlov, D. V. Aleksanyan, M. V. Korobov, N. A. Avramenko, R. R. Aysin, O. A. Maloshitskaya, A. S. Korlyukov and I. L. Odinets, Dalton Trans., 2011, 40, 8768. 105
OC45 SYNTHETIC APPROACHES AND ELECTRONIC PROPERTIES OF FUNCTIONALIZED FULLERENES AS NANOSIZED OPTICAL MOLECULAR SWITCHES L.M. Khalilov, A.R. Tuktarov, A.R. Akhmetov, A.A. Khuzin, Z.R. Shakirova, A.R. Tulyabaev, I.I. Kiryanov, V.M. Yanybin, U.M. Dzhemilev Institute of Petrochemistry and Catalysis of RAS
At present, the abilities of the manufacturing technology of traditional materials for modern computers have almost peaked. The main factor that restrains creation of modern supercomputers is a critical size of silicon transistors to be reached which are responsible for a quick response. One possible way to solve the problem is to replace conventional silicon transistors by molecular switches that can be by several orders less than the known smallest devices. Given that the molecular switches must have π-donor groups along with π-acceptor one, we have put forward the idea to use fullerene derivatives, a new allotropic carbon form, that possess high donor-acceptor features. Thus, a new effective methods of synthesis of potential molecular switches and three-dimensional memory elements based on C60 and C70 fullerene derivatives have been suggested. Highly selective methods of cycloaddition of organic azides to fullerenes under metalcomplex catalysts have been developed. This gives the individual aziridine- and azahomofullerenes that able to isomerize into each other under influence of UV irradiation. Algorithms of dichotomous features which are responsible for photochromic properties of molecular switches and generating of the new structures with incorporated fullerenes as doping agents directly into the fullerene core and in the attached moieties to activate the donor-acceptor properties and stability of molecular electronic systems. The results of molecular design of new types of optical molecular switches will be done using calculations of the electronic structure and physicochemical properties of fullerene derivatives with modern high-level quantum chemistry approaches (DFT and ab initio) will be discussed.
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OC46 COORDINATION CHEMISTRY OF BIS(PYRAZOLYL)PYRIDINES WITH 3d-TRANSITION METALS: RECENT DEVELOPMENT AND PROGRESS N.M. Kurnosov Lomonosov Moscow State University, Department of Chemistry, Moscow, Russia
Coordination compounds of transition elements with N-donor ligands are widely used as catalysts, molecular switches (SCO), dye-synthesized solar cell (DSSC). As analogs of terpyridine 2,6-bis(pyrazolyl)pyridines are widely investigated and there are known a lot of results in coordination chemistry of them [1]. Most of results are related to iron complexes and investigation of spin-crossover. The aim of this work is the synthesis and study of complexes of 3d-transition elements with 2,6bis(pyrazolyl)pyridines. A large library of such ligands has been synthesized. There are two major branches of research – copper complexes and iron binuclear complexes with 3,6-bis(pyrazolyl)-1,2,4,5-tetrazine as bridging ligand. It is common fact that such iron complexes can exhibit two-step spin-crossover transition from e.g. HS-HS state to the LS-LS state and also mix-valent species can be stabilized. Also for copper biand polynuclear complexes are much interesting due to the possibility of metal-metal interaction. The resulted complexes were investigated by ESR spectroscopy, electron spectroscopy, mass spectrometry,
Fig. 1. Structures of [Cu(Cl)(bPzPy)]2(ClO4)2 (left) and [Cu(Cl)(bPzPy)(ClO4)] (right).
Fig. 2. The 1D-chains for complex [Cu(bPzPy)(H2O)(NO3)2], hydroden bonds are maked by dotted lines. View along the b axis.
infrared and Raman spectroscopy, their magnetic properties were measured and calculated by quantumchemical qualculations. For some complexes crystals suitable for X-ray structure analysis were obtained. In the case of iron and cobalt complexes of 2,6-bis(pyrazolyl)pyridines have a monomeric structure regardless of counterions and the introduction of additional ligands capable of acting as bridging ligands – halide- and azide- anions. Dimeric complexes with bridging ligands could be obtained for copper and nickel. There is a weak ferromagnetic interaction for dimeric copper complexes with the structure [Cu(Cl)(bPzPy)]2(ClO4)2 (Fig 1.), calculated coupling constant for which is in agreement with the experimental data. For nonsubstituted pyrazole one-dimensional chain with perchlorate-bridging was obtained in the first time (Fig 1.). In some cases 1D-chains or more complicated frameworks are formed by hydrogen bonding (Fig 2.) [2]. Dinuclear iron complexes has been obtain with 3,6-bis(pyrazolyl)-1,2,4,5-tetrazine as bridging ligand and 2,6-bis(pyrazolyl)pyridines the simple ligands. The ground state and possibility of stable mix-valent state depend on the structure of 2,6-bis(pyrazolyl)pyridines. The author thanks Prof. S.I. Troyanov, Prof. Yu.M. Kiselev, Cand.Sc. V.D. Dolzhenko, V.V. Korolev and his students A.A. Vuhovskiy, T.D. Ksenofontova and A.G. Gevondyan. 1. M.A. Halcrow, Coord. Chem. Rev. 2005, 249, 2880–2908. 2. Dolzhenko, V. D., Kurnosov, N. M. and Troyanov, S. I. (2014), Z. anorg. allg. Chem., 640: 347–352.
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OC47 POLYMER-STABILIZED PALLADIUM NANOPARTICLES AS EFFECTIVE CATALYSTS OF SELECTIVE HYDROGENATION OF ALKINOLS L.Zh. Nikoshvili1, V.G. Matveeva1, E.M. Sulman1, B.D. Stein2, L.M. Bronstein3 1 - Tver Technical University, 170026, Tver, Russia 2 - Indiana University, Department of Biology, IN 47405, Bloomington, USA 3 - Indiana University, Department of Chemistry, IN 47405, Bloomington, USA; King Abdulaziz University, Jeddah 21589, Saudi Arabia
Selective hydrogenation of unsaturated carbon-carbon bond using Pd nanoparticles (NPs) is of great importance as widely applicable in synthesis of fine chemicals, vitamins and pharmaceuticals. One of the most complicated problems along with achieving of high activity, selectivity and stability of catalytic system is control over the Pd NP size, size distribution and morphology [1, 2]. To achieve appropriate selectivity, traditional industrial catalysts of alkyne hydrogenation require the addition of modifiers, which are not desirable for environment [3-5]. Though, in the case of terminal alkynes, neither the control of NP morphology [2] nor modification [4] yield the benefits, NP size and stabilizing environment play crucial role and the selectivity problem still exists [5]. Among the organic porous supports for catalyst synthesis, hypercrosslinked polystyrene (HPS) received increased attention due to its high crosslinking degree, which can be higher than 100%. The unique property of HPS is the ability to swell in different solvents, which favors inclusion of various organometallic compounds in the HPS matrix. Besides, HPS based catalysts allow control of the NP formation due to a “cage” effect (by limiting the NP size with the pore size) along with controlling the precursors and reduction conditions. In this work the incorporation of Pd NPs in polymeric matrix of HPS at variation of metal loading, precursor nature and type of polymer (influence of fictionalization) is discussed. Series of Pd/HPS catalysts was tested in the reaction of selective hydrogenation of 2-methyl-3-butyne-2-ol, which is intermediate of synthesis of fragrant substances and vitamins (E and K) and model compound of industrially important acetylene alcohols C10 and C15. Physicochemical characterization was performed via XPS, liquid nitrogen physisorption and TEM. Developed catalysts were found to contain Pd NPs with mean diameter of 3-5 nm (Fig. 1) and provide high selectivity (up to 98.5% at 100% of the substrate conversion). Besides, synthesized HPS-based nanocomposites were highly active in comparison with traditional hydrogenation catalyst (i.e. 2%(wt.)-Pd/CaCO3), and no leaching of catalytically active compound was observed. Financial support was provided by Seventh Framework Programme of the European Community (CP-IP 246095-2 POLYCAT) and Ministry of education and science of Russia (contract P1345). References 1. N. Semagina, L. Kiwi-Minsker. Catal. Lett. 127 (2009) 334. 2. L. Kiwi-Minsker, M. Crespo-Quesada. Top. Catal. 55 (2012) 486. 3. P.W. Albers, K. Möbus, Ch.D. Frost, S.F. Parker. J. Phys. Chem. C. 115 (2011) 24485. 4. J.A. Anderson, J. Mellor, R.P.K. Wells. J. Catal. 261 (2009) 208. 5. P.T. Witte, P.H. Berben, S. Boland, E.H. Boymans, D. Vogt, J.W. Geus, J.G. Donkervoort. Top. Catal. 55 (2012) 505.
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OC48 CATALYTIC CARBONYLATION OF OLEFINS, ALCOHOLS AND BENZYL HALIDES IN MOLTEN SALT MEDIUM O.L. Eliseev, T.N. Bondarenko, A.L. Lapidus N.D.Zelinsky Institute of organic chamistry, Moscow, Russia
Transition metal-catalyzed carbonylation of unsaturated hydrocarbons, alcohols and halides is a direct one-step route to carboxylic acids and esters. In presented work we systematically studied application of some molten salts such as tetrabutylammonium and 1-butyl-3-methylimidazolium derivatives as a media for these reactions. This approach provides a number of unusual possibilities. The most striking result is higher activity of phosphine-free palladium catalyst than that of “traditional” Pd-phosphine complexes. Bromide-containing molten salts stabilize palladium in the form of nano-sized suspension, as demonstrated by TEM. For unsymmetrical olefinic substrates, regioselectivity depends on anion nature in molten salt. In particular, chloride improves selectivity to 2-phenylpropanoic acid in carbonylation of styrene. Due to high solubility of catalyst in molten salt, it can be used repeatedly by simple extraction of products from reaction mixture with diethyl ether. In dodecene-1 carbonylation, ten cycles were carried out without loss of activity and selectivity. Importantly, reloading procedure may be performed in air atmosphere. Reaction scheme for the carbonylation of 1-phenylethanol into phenylpropanoic acids is proposed. Hydroxycarbonylation of benzyl halides in molten salt medium proceeds fast in the absence of base. Therefore, formation of stoichiometric amount of halide salt may be avoided.
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Posters
110
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P1 SYNTHESIS OF FLUORESCENT RECEPTORS VIA Pd-CATALYZED AMINATION OF 6-BROMOQUINOLINE AND 3-BROMOPHENANTHROLINE A.S. Abel1, A.D. Averin1, A.G. Bessmertnykh-Lemeune2, I.P. Beletskaya1 1 - M.V. Lomonosov Moscow State University, Department of Chemistry, Moscow, Russia 2 - Universite de Bourgogne, ICMUB, Dijon, France
Numerous works have been devoted to the design of new fluorescent sensors for various applications such as clinical toxicology, environmental bioorganic chemistry and waste management [1]. To develop optical molecular probes or sensors for toxic metals, ruthenium complexes with ditopic 1,10-phenanthrolines seem to be an appropriate solution. Moreover, aminoquinolines possess good fluorescent properties but have not yet been investigated as a signaling subunit in chemosensors. In this work, Pd-catalyzed amination of 6-bromoquinoline (1) and 3-bromo-1,10-phenanthroline (2) with linear polyamines 3a-d was investigated to prepare fluorescent receptors. The fluorescent derivatives of 6-aminoquinoline 4 were synthesized in good yields (up to 62%) using Pd/BINAP system as catalyst (Scheme). The amination of 3-bromo-1,10-phenanthroline is more complicated and Josiphos ligand should be used to obtain 3-amino-1,10-phenanthrolines 5 in satisfactory yields (32-36%) (Scheme).
Scheme. Pd-catalyzed amination of 6-bromoquinoline (1) and 3-bromo-1,10-phenanthroline (2) This reaction is a key step in the synthesis of fluorescent receptors 6-8 (Figure). The sensing properties of receptors 7 and 8 in the presence of various amounts of environmentally-relevant metal ions were evaluated by UV-vis and fluorescent spectroscopy.
Figure. Fluorescent receptors for metal ions. Acknowledgements: The work was performed in the frames of French-Russian Associated Laboratory “LAMREM” and financially supported by the RFBR (grant N 12-03-93107) and CNRS. [1] A.N. Uglov, A.G. Bessmertnykh-Lemeune, R. Guilard, A.D. Averin, I.P. Beletskaya, Russ. Chem. Rev., 2014, 83, 196.
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P2 MECHANISM OF CARBON MONOXIDE OXIDATION OVER SUPPORTED CuO CATALYSTS Yu.A. Agafonov1, N.A. Gaidai1, N.V. Nekrasov1, L.C. Loc2, N. Tri2, H.T. Cuong2, H.S. Thoang2, A.L. Lapidus1 1 - Institute of Organic Chemistry, RAS, Moscow, Russia 2 - Institute of Chemical Technology, Vietnam Acad. Sci. Techn., Ho Chi Minh City, Vietnam
Supported CuO catalysts with additives of other oxides are effective ones for CO oxidation. Introduction of small amounts of noble metals in these catalysts allows to increase their activity which can exceed the activity of supported platinum catalysts – the most active known ones in CO oxidation. Designing new catalysts for this process requires depth knowledge on the reaction mechanism. This work is devoted to the study of mechanism of CO oxidation over the following supported on -Al2O3 catalysts: 10 (wt.) %CuO (CuAl), 10 %CuO+20% CeO2 (CuCeAl), 10 %CuO+10% Cr2O3 (CuCrAl) without and with addition of Pt. The content of Pt varied in the range of 0.05 – 0.3 wt.%. The following physico-chemical methods were used for catalyst investigation: BET N2-Adsorption, XRD, TPR, SEM, EDS and IR-CO adsorption. There are the surface data of Table. Surface characteristics of the studied catalysts: studied catalysts in Table. specific surface area (SBET), crystal size of Cu (dCu), It is seen that the Cr, Ce and Pt dispersion of Cu (γCu ), maximum reduction enhanced the reducibility of copper temperature (Tmax) and extent of reduction for ions catalysts what expressed in the decrease of the reduction temperature and the Cu2+Catalysts (KRed, %) SBET dCu γCu Tmax KRed increase of the reduction extent (the % % m2/g nm C reducibility of catalysts CuAl and Oxide Catalysts CuCeAl was increased in 2.5 – 3 times). CuAl 177.0 11.9 13.1 375 13.0 It was shown that the optimal Pt content CuCrAl 166.0 15.5 10.0 355 28.4 is 0.1%. With this amount of Pt, catalyst CuCeAl 321 17.6 PtCuCeAl was capable to convert 67.0 completely CO to CO2 at 110oC Pt-containing oxide catalysts o 0.1PtCuAl 95.9 11.6 13.4 274 36.7 (without Pt - at 125 C). The process mechanism was studied by unstationary 0.2PtCuAl 95.1 0.05PtCuCrAl 89.2 18.8 8.3 308 29.9 response method. Relaxation curves, 0.1PtCuCeAl 80.1 35.2 4.4 255 45.8 describing a transition of the system to a new steady state, were obtained by a jump change of the corresponding concentrations. The residence time, defined as the ratio of the reaction system volume to the flow rate, was 2-5 times lower than the turnover time. It is meant that the observed transition phenomena were associated with the intrinsic processes. It was shown that Pt weakened the interaction of active phase which resulted in an increase of the reaction rate. The initial substances participated in the reaction in adsorbed state, the most part of the surface was occupied by oxygen over all the catalysts, Ce was facilitated the mobility of oxygen. Pt was increased the bond strengh of CO, O2 and CO2 with the surface of catalysts. Not only adsorbed oxygen, but lattice oxygen took part in the reaction but the last oxygen in less extent. The change of introduced glass filler in the reactor showed that reaction of CO oxidation proceeds mainly through heterogeneous mechanism, the share of homogeneous mechanism does not exceed 15%. It was shown that CO and O2 adsorption were quick steps, one intermediate compound was formed in slow step of the process. The overall step-scheme of CO oxidation was proposed over studied catalysts. The work is supported by RFBR (№13-03-93001_Viet_a) and NAFOSTED grant № 104.03-2012.60.
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P3 EFFICIENT CATALYTIC HYDRODEOXYGENATION OF UNPROTECTED CYCLIC IMIDES TO CYCLIC AMINES BY HETEROGENEOUS CATALYSIS A.M. Maj, I. Suisse, F. Agbossou-Niedercorn University Lille Nord de France, UCCS UMR 8181 CNRS, ENSCL C7 CS90108, 59652 Villeneuve d Ascq Cedex, France
Cyclic amines comprising fused saturated N-heterocycles are valuable synthetic intermediates. They are found in numerous drug candidates such as bicifadine, cytisine, gliclazide, or telaprevir to name just a few (Figure 1). The catalytic hydrogenation of imides appears to be the most elegant and promising reaction to produce properly and efficiently such amines. Since the reaction might potentially lead to several compounds, it needs to be controlled by an appropriate catalyst, which has to perform selectively two successive reductive cleavages of the C=O functionalities without breaking the cycle. N
O
NH
N NH
H N N pTol
O
Bicifadine
Cytisine
O O O S N N N H H
O
NH
H N
O
O
O
H
N
O
Gliclazide
NH
H
Telaprevir
Figure 1. Bioactive cyclic amines. As part of our ongoing interest for the application of catalytic hydrogenation in the preparation of cyclic amines,[1] we became interested in the synthesis of fused N-heterocycles. Herein, we report on the first efficient total reduction of nitrogen-unsubstituted cyclic imides in the presence of heterogeneous catalysts generated in situ from rhodium and molybdenum carbonyls (Scheme). Various substrates could be reduced with high selectivities and yields (both up to 100%). Platinum catalysts proved also efficient to hydrogenate some cyclic imides. In addition, all catalysts could be recycled at least three times without significant loss of activity. Finally, hydrodeoxygenation of a model cyclic imide was successfully performed on a gram scale.[2] O
O
catalyst ( )n
N H O
solvent
( )n
OH
N H
+
( )n
N H
+
( )n
N H
PH2, T
n = 0 or 1
up to 100% yield
References [1] a) Maj, A. M.; Suisse, I.; Méliet, C.; Agbossou-Niedercorn, F. Tetrahedron: Asymmetry 2010, 21, 2010. b) Maj, A. M.; Suisse, I.; Méliet, C.; Hardouin, C.; Agbossou-Niedercorn, F. Tetrahedron Lett. 2012, 53, 4747. c) Maj, A. M.; Suisse, I.; Hardouin, C.; AgbossouNiedercorn, F. Tetrahedron 2013, 69, 9322. [2] Maj, A. M.; Suisse, I.; Pinault, N.; Robert N.; Agbossou-Niedercorn, F. ChemCatChem accepted.
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P4 REACTIONS OF N-ALKYLHALOGENALDIMINES WITH O,ODIALKYDITHIOPHOSPHORIC ACIDS N.G. Aksenov, R.A. Khairullin, M.B. Gazizov, R.N. Burangulova Kazan National Research Technological University, Department of Organic Chemistry, Kazan, Russian Federation We found that direction of interaction of N-alkyl-2-halogenaldimines (1-2) with О,Оdialkyldithiophosphoric acids (3) mainly depends on the nature of halogen. Reaction between О,Оdialkyldithiophosphoric acids (3) and N-alkyl-2-chloroaldimines (1) was first studied by dynamic 1 Н, 13С and 31Р NMR in the temperature intervals from -60 °C to 25 °С. It was found that reaction proceeds in two steps. At first step, which proceeds at -60 °С, the protonation of imine nitrogen occurs and intermediate iminium salts are formed – О,О-dialkyldithiophosphates Nalkylchloroaldiminium (4). At the second step, which is observable at -5-0 °С, the chlorine atom is substituted by О,О-dialkyldithiophosphate group. The final products of the reaction are chlorides of N-alkyl-2-О,О-dialkyldithiophosphatopropaniminium (5). We propose that salt (4) is transfromed into product (5) through the intermediacy of salt (6) with delocalized azaallyl dication as a result of heterolytic dissociation of the bond tertiary carbon-chlorine.
Synthetic result of the reaction of dithioacid (3) with N-alkyl-2-bromoaldimine (2) is completely different – as major products were obtained phosphorylsulfide (7) and iminium salt of unsubstituted aldimine (8). Thus, we for the first time discovered the reaction of reduction of organic bromine derivative (2) by О,О-dialkyldithiophosphoric acid. At temperatures -80 – -70 °С, 31Р NMR spectroscopy allowed to detect the formation of intermediate salt (9, δ 108 ppm).
The work is supported by RFBR and the Government of Tatarstan, project №13-03-7098_p povolzhe _а/2013 and Ministry of education and Science (task № 2014/56 within the framework of basic part of stat task).
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P5 METAL-FREE TRANSANNULATION REACTION OF INDOLES WITH NITROSTYRENES: SIMPLE PRACTICAL SYNTHESIS OF QUINOLINE DERIVATIVES A.V. Aksenov1, N.A. Aksenov1, I.V. Aksenova1, A.N. Smirnov1, M. Rubin2 1 - Department of Chemistry, North Caucasus Federal University, Stavropol, Russian Federation 2 - Department of Chemistry, University of Kansas,Lawrence, USA
A convenient metal-free method for preparation of a large variety of 3-aryl- and 3-alkylsubstituted 2-quinolones 4, as well as 2,3-disubstituted quinolines, was proposed. This approach involves previously unknown transannulation of 2-substituted indoles 1 in the reaction of β-nitrostyrenes 2 in polyphosphoric acid. The method is based on the ring-expansion of the pyrrole cycle in indoles upon attack of amphyphilic reagents at the enamine double bond. R
+
N 1
R
2
R
R
R
3
N
1
R
O
N O
R
O P ( O )( O H ) 2
3
PPA
+
-H
2
N
N
R
+
R
H2O
O
2
R
+
R + H
R
3 R
2
N
1
+ 3
R
OH
OH
OH
N
O P ( O )( O H ) 2
3
H N
3
1
O P ( O )( O H ) 2
3
O P ( O )( O H ) 2
O P ( O )( O H ) 2
NH
2
N R
1
R
1
2
O
N
N R
1
R
2
NH
O
R
1
R
N
R
O
3
2
O HO
R HN
R2
3
R
3
O
+ N
O P ( O )( O H ) 2 4
R
O
N
1
R
1
N H
O P
O
H
R
+
N R
P
O
O
+
O
3
2
R
N
P
OH
OH N OH NH
O
1
R
O
2
R
R
3
R
2
O
1
R1= H, Me; R2= Ph, Me; R3= Ph, 4-MeOC6H4, 4-iPr-C6H4, 3,4-Me2C6H3, 4-EtOC6H4,2-FC6H4, 3,4Cl2C6H3, 3-BrC6H4, n-Pr Introduction of an alkyl substituent into β-position of β-nitrostyrene 6 renders formation of quinoline 7 as major product. The mechanism of this transformation is identical to the one shown above, but includes elimination of water and aromatization at the last step. 3
3
2
R 1
+
R
+
N
N H
R
O N
O 6
7
2
O
+ 3
2
H2N
R 5
R = Ph, Me; R = Ph, Ph. Convenient and general metal-free approaches to 3-aryl and 3-alkyl-substituted 2-quinolones, as well as to 2,3-disubstituted quinolines were developed, which included the previously unknown process of transannulation of 2-substituted indoles in the reaction with β-nitrostyrenes in polyphosphoric acid. The reaction was also efficiently combined into a cascade with a Fisher indole synthesis. Unlike most other known methods, the described protocol utilizes readily available starting materials. Unique properties of PPA, serving as a mild proton donor, source of efficient leaving group (or temporary protecting group), water scavenger and high boiling solvent makes it an ideal media for the described transformation. This work was carried out with financial support from the RFBR (grant 13-03-003004)
116
P6 MECHANOCHEMICAL SYNTHESIS OF CHROMIUM CARBOXYLATES AND THEIR CATALYTIC PROPERTIES IN ETHYLENE TRIMERIZATION K.A. Alferov1, L.A. Petrova2, V.D. Makhaev2, G.P. Belov1 1 - Institute of Problems of Chemical Physics RAS, Department of Polymers and Composite Materials, Chernogolovka, Russian Federation 2 - Institute of Problems of Chemical Physics RAS, Department of Functional Inorganic Materials, Chernogolovka, Russian Federation
Selective synthesis of individual alpha olefins (1-butene, 1-hexene, 1-octene) is an urgent problem because these compounds are widely used for the production of ethylene copolymers, plasticizers, lubricants, etc. [1, 2]. One of the most efficient systems for ethylene trimerization is a system based on chromium tris(2-ethylhexanoate) (Cr(EH)3), 2,5-dimethylpyrrole and organoaluminum compounds. Methods for the synthesis of Cr(EH)3 based on reactions in solutions are quite laborious and lingering. The products obtained by the methods are sticky and unhandy. The operations for the isolation and purification of the product complicate its production [3, 4, 5]. Nowadays, green chemistry seems as a very promising research area, so the processes of solventfree solid reactant interactions attract much attention. We have developed a method for the synthesis of Cr(EH)3 based on the solvent-free mechanochemical interaction of solid CrCl3 and NaEH with subsequent heating of the reaction mixture [6]. Physicochemical properties of the reaction products and mechanically activated CrCl3-NaEH mixtures at different CrCl3/NaEH ratios were investigated by IR-spectroscopy, XRDA and DCS. The solid phase interaction of CrCl3 and NaEH occurs in two main stages: 1) the reagents mixture mechanical activation resulting in their dispersion and mixing at the molecular or cluster level; and 2) thermally initiated exothermic interaction of the activated reactants to give the final products. The use of the method makes it possible to shorten the process duration appreciably. The obtained reaction mixtures and isolated Cr(EH)3 as well as commercially available Cr(EH)3 (810 % wt. in mineral spirits) were tested as components of the Cr(EH)3/2,5dimethylpyrrole/AlEt3/CCl4 catalytic system for ethylene trimerization. The productivity and selectivity of the catalyst based on Cr(EH)3 synthesized by the mechanochemical method were similar to the results obtained for the commercial Cr(EH)3. Moreover, reaction mixtures produced directly after the synthesis of Cr(EH)3 also form an active catalyst for ethylene trimerization. Syntheses differed in the time of mechanochemical activation (1-4 h) and reagent ratio (NaEH/CrCl3 = 2.3 – 3.9) were also performed. The catalytic systems based on thus obtained reaction mixtures demonstrated close values of productivity (11-13 kg/(gCr·h)) and selectivity (1-С6 = 82-85 % wt., C8+ = 13-15 % wt., PE = 0,1-0,3 % wt.) in ethylene to 1-hexene trimerization. The study was in part financially supported by the Russian Foundation for Basic Research (project no. 12-03-00974-a) and by the Presidium of the Russian Academy of Sciences Basic research Program № 3. [1] Dixon J.T., Green M.J., Hess F.M., Morgan D.H. J. Organomet. Chem. 689(23) 3641-3668 (2004). [2] McGuinness D. S. Chem. Rev. 111(3) 2321-2341 (2011). [3] Briggs J.R. US 466838 (Union Carbide Corporation), March 14, 1986. [4] Knudsen R.D. et al. US 2007/0043181 A1 (Chevron Phillips Chemical Company), August 19, 2005. [5] Sydora O.L. et al. US 2013/0150642 A1 (Chevron Phillips Chemical Company), December 12, 2011. [6] Rus. Patent Application 2013156512/20(088111) (IPCP RAS), December 20, 2013. 117
P7 EFFECT OF CHEMICAL STRUCTURE OF VIOLOGEN-DERIVATIVES AS AN ARTIFICIAL CO-ENZYME ON THE CARBON DIOXIDE REDUCTION ACTIVITY OF FORMATE DEHYDROGENASE Y. Amao1, S. Ikeyama2 1 - Osaka City University,Advanced Research Institute for Natural Science and Technology, Osaka,Japan 2 - Osaka City University,Graduate School of Science, Osaka,Japan
Many studies on electro-catalyzed CO2 reduction have been performed using specific electrode materials. On the other hand, studies on CO2 fixation also have investigated photocatalysis on semiconductors such as titanium dioxide, silicon carbide and strontium titanate. However, these systems use ultraviolet irradiation and the total reaction is low yield, whereas highly efficient CO2 fixation system using visible light is more desirable. We previously reported a system for visible light-induced methanol synthesis from CO2 with the system formate, aldehyde, and alcohol dehydrogenases, and methylviologen (MV2+) photoreduction by the visible light photosensitization of water soluble zinc porphyrin in the presence of an electron donor in aqueous media. On this system, the reduced form of methylviologen (MV.+) is used as an artificial co-enzyme for these dehydrogenases. To improve the yield for methanol production from CO 2, conversion of CO2 to formic acid with formate dehydrogenase (FDH) and reduced formed viologen is most important step. In this work, some artificial co-enzymes with 4,4’- bipyridine skeletons as shown in Figure 1 are synthesized and effect of chemical structures of artificial co-enzymes on the activity of the reduction of CO2 to formic acid with FDH are investigated. The conversion of CO2 to formic acid with FDH and one-electron reduced form of artificial co-enzyme was carried out as following method. The sample solution containing 3.0 µmol of artificial co-enzyme, 5.7 mmol of sodium dithionate, and FDH (10 units) in 3.6 ml of CO2 saturated sodium pyrophosphate Figure 1. Chemical structures of viologen-derivatives as buffer (pH 7.4) at 30.5 ˚C for 1 min. The formic acid artificial co-enzymes for formate dehydrogenase concentration produced is measured by ionic chromatography. By using MV2+ as the reference, the formic acid production increased by using cationic artificial coenzymes (H2NH2CH2C-V-CH2CH2NH2 and CH3-V-CH2CH2NH2). On the other hand, the HCOOH production decreased by using anionic co-enzymes (HOOCH2C-V-CH2COOH and CH3-VCH2COOH). The production of formic acid in this reaction depends on chemical structures of artificial co-enzymes. Among the artificial co-enzymes, H2NH2CH2C-V-CH2CH2NH2 has high affinity for FDH compared with the other compounds.
118
P8 Cu(I)-CATALYZED ARYLATION OF BIOLOGICALLY ACTIVE DI- AND POLYAMINES A.D. Averin, M.V. Anokhin, S.P. Panchenko, I.P. Beletskaya M.V. Lomonosov Moscow State University, Department of Chemistry, Moscow, Russia
Di- and polyamines like putrescine, cadaverine, spermidine and spermine were chosen for the studies of their Cu(I)-catalyzed N,N’-diarylation for the synthesis of new compounds with diverse biological activity. Arylation was carried out using iodobenzene, 4-fluoroiodobenzene, 4(trifluoromethyl)iodobenzene and 4-iodobiphenyl. The reactions of butane-1,4-diamine were successfully catalyzed with either CuI/L1 (L1 = L-proline) or CuI/L2 (L2 = 2isobutyrylcyclohexanone) systems while pentane-1,5-diamine demonstrated better results with CuI/L2 system. Cs2CO3 was taken as a base in all cases.
Selective N1,N3-diarylation of triamine and N1,N4-diarylation of tetraamine turned to be a more complicated task, and target compounds were obtained in moderate yields using CuI/L2 catalytic system.
Acknowledgement: The work was financially supported by the RFBR grant N 12-03-00796.
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P9 NITRATING AND NITROSATING REAGENTS IN NOVEL HETEROCYCLIZATION REACTIONS. READY ACCESS TO HIGHLY SUBSTITUTED PYRIMIDINE AND ISOXAZOLE DERIVATIVES E.B. Averina, K.N. Sedenkova, D.A. Vasilenko, T.S. Kuznetsova, N.S. Zefirov Lomonosov Moscow State University, Department of Chemistry
Recently we have elaborated novel synthetic approaches to five- and six-membered N- and N,Oheterocycles basing on the heterocyclization of electrophilic alkenes or three-membered carbocycles under the treatment with nitrating or nitrosating reagents. The reaction of tetranitromethane with electrophilic alkenes in presence of triethylamine was found to afford 5-nitroisoxazoles 1 – highly reactive and versatile compounds which may be used as precursors of diverse functionalized compounds [1]. Employing the reduction of nitroisoxazoles 2 we suggested the regioselective method of synthesis of 5-aminoisoxazoles 2 that was used to accomplish a structure design of biologically active compounds. The series of compounds 2 was obtained in good yields (50-90%) and their antiviral activity was investigated. A series of previously unknown 4-fluoropyrimidine 1-oxides 4 was obtained via three-component heterocyclization involving gem-bromofluorocyclopropanes 3, nitrosating or nitrating agent and organic nitrile [2]. Preparative method of synthesis of 4-fluoropyrimidines 5 from corresponding Noxides under the treatment with PCl3 was elaborated. F R2
EWG N 1
O
C(NO2)4 -Et3N
NO2
SnCl2 EtOH R2
EWG N
O 2
:CBrF R1
R2
R1 = EWG (C(O)R', CO2R", P(O)(OEt)2 NO2, CO2R"); R2 = H, Alk
R1 R2
F
[NO+] Br RCN R2 3
R,R1,R2: Alk, Ar; [NO+]: NOBF4, NO2BF4, NO2OTf
NH2
R1
N N 4 O
R PCl3
F R1 R2
N N 5
R
4-Fluorosubstituted pyrimidine N-oxides 4 and pyrimidines 5 demonstrate high reactivity in aromatic nucleophilic substitution with various O-, N-, P-nucleophiles. In particular, a series of 4aminopyrimidines and pyrimidine N-oxides, potent as compounds with antiviral activity, was obtained via this reaction. In conclusion, simple and efficient synthetic methods allowing polyfunctionalized isoxazoles, pyrimidines and pyrimidine N-oxides, including those with valuable properties, from readily available starting materials were developed. We thank the Russian Foundation for Basic Research (Projects 14-03-31989-mol_а, 14-03-00469a) and Presidium RAS (program №8P) for financial support of this work. [1] (a) Y.A. Volkova, E.B. Averina, Y.K. Grishin, P. Bruheim, T.S. Kuznetsova, N.S. Zefirov J. Org. Chem., 2010, 75, 3047-3052; (b) E.B. Averina, Y.A. Volkova, Y.V. Samoilichenko, Y.K. Grishin, V.B. Rybakov, A.G. Kutateladze, M.E. Elyashberg, T.S. Kuznetsova, N.S. Zefirov Tetrahedron Lett., 2012, 53, 1472–1475. [2] (a) K.N. Sedenkova, E.B. Averina, Yu.K. Grishin, A.G. Kutateladze, V.B. Rybakov, T.S. Kuznetsova, N.S. Zefirov J. Org. Chem., 2012, 77, 9893–9899; (b) K.N. Sedenkova, E.B. Averina, Yu.K. Grishin, T.S. Kuznetsova, N.S. Zefirov Tetrahedron Lett., 2014, 55, 483–485.
120
P10 TRANSFER HYDROGENATION OF ACETOPHENONE OVER BIS-IMINE RHODIUM(I) COMPLEX. DFT STUDY N.M. Badyrova1, Z. Lin2, L.O. Nindakova1 1 - Irkutsk State Technical University, Physical and Technical Institute, Irkutsk, Russia 2 - The Hong Kong University of Science and Technology, Department of Chemistry, Hong Kong (P. R. China)
There are two reaction mechanisms for asymmetric transfer hydrogenation reactions of ketones over a diamine rhodium(I) complex leading to optically active secondary alcohols: a stepwise process through an intermediate hydride complex derived from an alkoxy complex via -hydride elimination and a concerted process where the hydrogen is directly transferred from the alkoxy complex to the coordinated substrate [1]. Here, we investigated mechanism of hydrogen transfer reaction (Scheme 1) from 2-propanol to acetophenone over a bis-imine-rhodium(I)-chloride complex with optical active bis–imine ligand R,R-1 on the basis of DFT theoretical calculations.
Scheme 1
Based on the mechanism proposed by Guiral et al [1], we designed a catalytic cycle (Scheme 2). This cycle starts with the hydride complex 1. The first step is reversible dissociation of a Rh-N bond in the 18-electron hydride complex leading to a 16-electron intermediate (the hydride complex 2). From 2, there are two possible pathways to achieve hydride transfer to acetophenone, an external pathway vial 3a and an internal pathway via 3b (Scheme 2). Both the two hydride transfer pathways give the alkoxy complex 4, which leads to 5 after with a metathesis with 2-propanol to release the product molecule. Next step involves -H elimination to give 6 followed by release of the sideproduct (acetone) to regenerate the starting hydride complex 1. H3 C N N N
N
H
Rh
Rh
N
N
N
H
3a
N
N
1
N N
Scheme 2
H
H3 C
C O
Rh N
CH3 N N
N
6
CH
N N
N 4
Ph
N
Ph (CH3)2CHOH N
H3C
CH
Rh
Rh
O
H N
3b (CH3)2CO
C
Rh
N
H3C
O N
CH3 O
N
Rh
H N
2 N
Ph
C
O N
CH3
(CH3)PhCHOH
N
5
Geometry optimizations of all species have been performed by means of the DFT M06 hybrid method [2]. The 6-31G(d) basis set was chosen to describe C, N, O, H atoms and the LanL2DZ basis set was used for Rh. All of the calculations were performed with the Gaussian 09 program [3]. 1. Guiral V., Delbecq F., Sautet P. Organometallics, 2000, 19, 1589-1598. 2. Zhao Y., Truhlar D. G., Theor Chem Account, 2008, 120, 215-241. 3. Frisch, M. J.; et al. Gaussian 09, Revision A.1; Gaussian Inc., Wallingford, CT, 2009.
121
P11 RHODIUM(II) CATALYZED REACTIONS FOR SYNTHESIS OF NOVEL AND DIVERSE FURO[2,3-D]PYRIMIDINEDIONES AND THIOXOFURO[2,3-D]PYRIMIDINEONES E.R. Baral, K.B. Somai Magar, Y.R. Lee School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of Korea
Furopyrimidines, the derivatives of pyrimidine and analog of purine have been demonstrated to have antimalarial, antifolate, antitumor, antiviral, antibacterial and antifungal, and antihypertensive properties.1-2 Accordingly, several methods have been devised to synthesize furopyrimidines.3-4 The general methods for the synthesis of furo[2,3-d]pyrimidinediones by ceric ammonium nitrate mediation involving ionic (non-carbenoid) mechanism is limited with the substrate scope in terms of olefins and alkynes with low yields,5 while three component reactions of N,N’-dimethylbarbituric acid with benzaldehydes, and isocyanides, provided 2,3-disubstituted furans.6 However, there is a need for more convenient and efficient synthetic methods for the preparation of furo[2,3d]pyrimidinedione derivatives, and in particular, the synthesis of thioxofuro[2,3-d]pyrimidinedione derivatives has not been reported to date. In this conference, we present the rhodium (II)-catalyzed reactions of cyclic diazo compounds derived from barbituric acid or thiobarbituric acid with arylacetylenes and styrenes. These reactions provide a rapid synthetic route to the preparation of a variety of novel and diverse furo[2,3d]pyrimidine-2,4-diones, 2-thioxodihydrofuro[2,3-d]pyrimidin-4-ones, dihydrofuro[2,3d]pyrimidine-2,4-diones, and 2-thioxotetrahydrofuro[2,3-d]pyrimidin-4-ones. O
O R X
R
Y'
N N R
O
Y'
X Rh 2(OPiv) 4 toluene reflux
N2
N N R
O
X=O, S R=Me, Et
O Y Rh2(OPiv)4 PhF rt - 60 oC
R X
N N R
O
Y
References 1. G. Jähne, H. Kroha, A. Müller, M. Helsberg, I. Winkler, G. Gross, T. Scholl, Angew. Chem. Int. Ed. Engl. 1994, 33, 562-563. 2. Q. Dang, Y. Liu, M. D. Erion, J. Am. Chem. Soc. 1999, 121, 5833-5834. 3. A. Sniady, M. D. Sevilla, S. Meneni, T. Lis, S. Szafert, D. Khanduri, J. M. Finke, R. Dembinski, Chem. Eur. J. 2009, 15, 7569-7577. 4. A. Sniady, A. Durham, M. S. Morreale, A. Marcinek, S. Szafert, T. Lis, K. R. Brzezinska, T. Iwasaki, T. Ohshima, K. Mashima, R. Dembinski, J. Org.Chem. 2008, 73, 5881-5889. 5. K. Kobayashi, H. Tanaka, K. Tanaka, K. Yoneda, Synth. Commun. 2000, 30, 4277-4291. 6. M. B. Teimouri, R. Bazhrang , Bioorg. Med. Chem. Lett. 2006, 16, 3697-3701.
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P12 DUAL REACTIVITY OF NTROARENES IN [4+2]-CYCLOADDITION REACTIONS M.A. Bastrakov, A.M. Starosotnikov, S.A. Shevelev N.D. Zelinsky Institute of Organic Chemistry RAS, Laboratory of Nitrogen-containing Aromatic Compounds, Moscow, Russia
[4+2]-Cycloaddition is one of the fundamental protocols for the construction of a new ring, which accompanies the formation of two bonds. This reaction is known for nitroalkenes1a, as well as for few highly electrophilic (low aromatic) benzoazoles1b-c. These compounds readily undergo DielsAlder reactions at C-C double bond activated by the nitro group. Also they form anionic σ-adducts with very weak nucleophiles1b. As a part of our research on highly electrophilic heterocyclic systems we have found that 4,6dinitroanthranil reacts with dienes and nucleophilic dienophiles in mild conditions2.
Moreover we have proposed methods for the synthesis of new policyclic heteroaromatic compounds on the nitroarenes basis consisting in annelation of a furoxan ring to different dinitrobenzoazoles and azines3. Some of these compounds readily undergo [4+2]-cycloaddtition with dienes and dienophiles.
This work was supported by the Russian Foundation for Basic Research, Projects No. 13-03-00452, 14-03-31508 mol_a and Grant of the President of the Russian Federation for State Support to young Russian scientists, Grant MK-3599.2013.3. 1. (a) S.E. Denmark, A. Thorarensen, Chem Rev., 1996, 96, 137; (b) S. Lakhdar, R. Goumont, T. Boubaker, M. Mokhtari, F. Terrier, Org. Biomol. Chem., 2006, 4, 1910; (c) S. Kurbatov, R. Goumont, S. Lakhdar, J. Marrot, F. Terrier, Tetrahedron, 2005, 61, 8167; 2. A.M. Starosotnikov, M.A. Leontieva, M.A. Bastrakov, A.V. Puchnin, V.V. Kachala, I.V. Glukhov, S.A. Shevelev, Mendeleev Commun, 2010, 20, 165. 3. M.A. Bastrakov, A.M. Starosotnikov, I.V. Glukhov, S.A. Shevelev, Russ. Chem. Bull. Int. Ed., 2009, 58, 426.
123
P13 UNEXPECTED FORMATION OF N-ALKYLIMIDES IN REACTION OF MALEOPIMARIC AND CITRACONOPIMARIC ACIDS WITH SECONDARY AMINES M.P. Bei1, A.P. Yuvchenko1, A.V. Baranovsky2 1 - The Institute of Chemistry of New Materials, 36 F.Skoriny st., Minsk 220141, Belarus 2 - The Institute of Bioorganic Chemistry, 5/2 Kuprevich st., Minsk 220141, Belarus
The Diels-Alder reaction of levopimaric acid with active dienophiles produces adducts (maleo-, fumaro-, quinopimaric acids) which are useful precursors in the synthesis of chiral ligands, terpenoquinones, biologically active compounds. Recently, we have reported the synthesis of isomer of citraconopimaric acid (2), an analog of well-known maleopimaric acid (1), bearing methyl group at C-15.1 The method includes preparation of the adduct of pine rosin with citraconic anhydride (formed in situ from itaconic acid) followed by recrystallization of the product from carbon tetrachloride and benzene. We have initiated the investigation of the reaction of citraconopimaric acid (2) with some secondary aliphatic amines in order to study the steric influence of the CH3 group at C-15 of the acid (2) on regioselectivity of anhydride ring opening by nucleophilic agents. It was established that the heating of citraconopimaric acid (2) solution in diethylamine, dipropylamine in autoclave, dibutylamine at 135ºC for 30h leads to the formation of N-ethyl-, N-propyl-, N-butylimides of citraconopimaric acid (3−5). Unlike citraconopimaric acid (2), reactions of maleopimaric acid (1) with diethyl-, dipropylamine at 135ºC gave N-ethyl-, N-propylimides of maleopimaric acid (6, 7; yields 60−80%) and amidodiacids (9, 10; yields 10−15%), and the reaction with dibutylamine gave only maleopimaric acid N-butylimide (8).2 O
R' = CH3
O O R' O
o
+ R2NH
135 C
NR O COOH (3, 4, 5) R = C2H5 (3), n-C3H7 (4), n-C4H9 (5) O
COOH R' = H (1), CH3 (2)
NR O +
R' = H
COOH (6-8)
COOH NR2 O * COOH (9, 10)
R = C2H5 (6, 9), n-C3H7 (7, 10), n-C4H9 (8) * The exact structure of regioisomer is not established
The formation of N-alkylimides (3−8) in the above transformations could be result of a thermal degradation of intermediate amidoacids giving stable cyclic imides. Would this assumption be true, the formation of mixture of two imides should be observed in the reaction of acids (1, 2) with unsymmetrical secondary amines. Thus, when acids (1, 2) were treated with methyl- or ethyl-(2-hydroxyethyl)amine, the formation of a mixture of two imides indeed was observed.2 O (1, 2) +
R
H N
O
NR
135oC
R' O
OH
+
N R' O
OH
COOH COOH R = CH3, C2H5, R' = H, CH3
[1] M.P. Bei, A.P. Yuvchenko. Patent of the Republic of Belarus 13,646, 2009. [2] M.P. Bei, A.P. Yuvchenko, A.V. Baranovsky. Proceed. Nat. Acad. Sci. Belarus. 2013, N 4, 104
124
P14 SYNTHESIS OF TRYPTAMINES FROM CYCLOPROPYLKETONES ARYLHYDRAZONES AND THEIR BIOLOGICAL STUDIES A.Yu. Belyy1, R.F. Salikov2, Yu.V. Tomilov2 1 - Higher Chemical College of Russian Academy of Sciences 2 - N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
Tryptamine derivatives are psychoactive compounds and are widely used as 5-HT agonists. We have found that cyclopropyl methyl ketone hydrazones rearrange into a mixture of tetrahydropyridazines and tryptamines, the best yield of tryptamine being observed in the case of generated in situ bromophenylhydrazone. The rearrangement of cyclopropyl ketones with a bulky group in most cases gives tetrahydropyridazines exclusively.
The tryptamine derivatives obtained demonstrated their antitumor activity against human neuroblastoma cell line SH-SY5Y. The best result was shown by 2-methyl-5-bromotryptamine (IC50 = 5,06 µМ) with the therapeutic index of 4, determined from the toxicity against human embryonic kidney cells (HEK 293). In order to investigate the biological activity of this interesting class of compounds we derived the tryptamines in three different ways: substitution of bromine, indole nitrogen alkylation and primary amine nitrogen. The biological studies are under performance.
125
P15 DEHYDROGENATION OF LOW ALIPHATIC ALCOHOLS ON COPPER SUPPORTED STRUCTURED CATALYST D.A. Bokarev1, E.A. Ponomareva2, E.V. Egorova2 1 - N.D. Zelinsky Institute of Organic Chemistry RAS, Moscow, Russia 2 - Lomonosov Moscow State University of Fine Chemical Technologies, Moscow, Russia
The important direction of the chemical industry development is engineering of new alternative manufactures based on renewable sources of raw materials. These materials could be methanol and ethanol, especially applied for synthesis of methylformiat and acetaldehyde respectively. 2CH3OH → HCOOCH3+2H2 C2H5OH → CH3CHO +H2 To realize the process of dehydrogenation with high technical parameters new catalytic systems must be worked out. Recently new classes of heterogeneous catalysts based on structured carbon fibers were developed. They possess a number of advantages - homogeneous distribution of a stream, low pressure drop. Moreover, fibers structured catalysts offer flexibility and endless forms that allow using them in reactors of a various constructions. It was shown that 5 wt.% of copper supported by impregnation appeared to be optimal in the process of alcohol dehydrogenation. Compared to powder and granular carbon materials used earlier, catalysts based on structural carbon fibers showed higher activity and selectivity due to better distribution of active component on the surface of the carrier (fig.1).
Activity – 126 gMeOH/gCu*h and 237 gEtOH/gCu*h
Activity – 24 gMeOH/gCu*h and 68 gEtOH/gCu*h
Fig. 1. Distribution of copper particles on the surface of carbon structured fiber (left) and granular carbon material Sibunit (right) Thus, application of structured carbon fibers as a support of copper catalytic system leads to increase of activity in comparison with known literature data. That allows to make a conclusion about appropriateness of using it in the process of dehydrogenation of low aliphatic alcohols.
126
P16 ARYLAMINATION OF 1,3,7-TRIAZAPYRENES I.V. Borovlev, O.P. Demidov, N.A. Saigakova, G.A. Amangasieva North Caucasus Federal University, Department of Chemistry, Stavropol, Russia
In our previous reports we have shown that 1,3,7-triazapyrene displays peculiar properties due to the unique fusion of the carbocyclic and heterocyclic rings. Specifically these properties include the unusual ease of oxidative nucleophilic substitution of hydrogen, such as amination [1] and alkylamination [2], which proceed in aqueous media. The aim of this work is the synthesis of arylamino derivatives of this heterocycle. In spite of a common mechanism, the conditions mentioned above are not suitable for arylamination reaction due to the low nucleophilicity of aryl amines and their high sensitivity towards oxidation. This is why SNH-arylamination reactions are still rare. We have found that the interaction of 1,3,7-triazapyrenes 1 with an excess of sodium arylamides obtained in situ in absolute DMSO proceeds at room temperature to form the 6-aryl(hetaryl)amino1,3,7-triazapyrenes 2 in 32-97 % yields. It was shown that the decisive factor for rearomatization of σH-adducts is crucial access to the air oxygen. R
R N
N
N
N
1 . A rN H - N a + DM SO, RT, O2 2 . H 2O
X
X
N
N
N H Ar
2
1
R = H, Me; X = H, Ar, NR2 Under the same conditions (DMSO, room temperature) the reaction of the rather accessible 6,8dialkoxy-1,3,7-triazapyrenes 3 with sodium aryl amide has resulted to a product of nucleophilic ipso substitution of one of the two RO groups - 6-alkoxy-8-aryl(hetaryl)amino-1,3,7-triazapyrenes 4. N
N
N
N
1 . A rN H - N a +
1 . A rN H - N a + re flu x in g to lu e n e
DM SO, RT
2 . H 2O
2 . H 2O RO
N 4
N H Ar
N
N
RO
N 3
OR
ArN H
N
N H Ar
5
R = Me, Et Products of double ipso substitution – 6,8-bis(aryl(hetaryl)amino)-1,3,7-triazapyrenes 5 were synthesized by refluxing of the compounds 3 with excess of the sodium arylamides in toluene for a long time. Consecutively replacing one methoxy group in 6,8-dimethoxy-1,3,7-triazapyrene in DMSO, and the second - in toluene, we obtained asymmetrically substituted diamine - 6phenylamino-8-(pyridin-4-ylamino)-1,3,7-triazapyrene. This project received financial support from the Ministry of Education and Science of the Russian Federation in the framework of the State Assignment to the Higher Education Institutions № 4.141.2014/K. [1]. O. P. Demidov, I. V. Borovlev, N. A. Saigakova, O. A. Nemykina, N. V. Demidova, and S. V. Pisarenko, Khim. Geterotsikl. Soedin., 142 (2011). [Chem. Heterocycl. Compd., 47, 114 (2011).] [2]. I. V. Borovlev, O. P. Demidov, N. A. Saigakova, S. V. Pisarenko, O. A. Nemykina, J. Heterocycl. Chem., 48, No. 5, 1206 (2011). 127
P17 SUSTAINABLE APPROACHES FOR ORGANIC SYNTHETIC PROCESSES L.C. Branco, K. Zalewska, G. Carrera, M.N. Da Ponte REQUIMTE, Departamento de Quнmica, Faculdade de Ciкncias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
For many synthetic approaches the incorporation of CO2 as alternative reagent or green solvent can improve significantly the efficiency (yields, purity, reaction conditions) for several organic processes. In recent years, the use and capture of Carbon Dioxide (CO2) became a hot research topic including their application for organic and pharmaceutical chemistry.1 The possibility to use carbon dioxide as useful reagent for different synthetic approaches or supercritical CO2 for efficient extraction and separation processes has been reported.1 The combination of ionic liquids and supercritical fluids has been reported for many organic transformations in particular catalytic reactions.2 The possibility to use scCO2 in order to extract the pure products without IL or catalyst contamination is one of the advantages for these processes. Several publications proof the advantages for ILs and scCO2 combinations in order to recycle the catalytic media during many reaction cycles without loss of efficiency. In this communication, we described the applicability of carbon dioxide approaches in two different organic synthetic processes:3 a) The use of CO2 as reagent for the preparation of reversible chiral and non-chiral carbamate salts by the reaction with different amines (e.g. primary alkyl and aryl amines or polyamines), aminoacids and pharmaceutical compounds in the presence of an organic superbase (e.g. DBU or tetramethylguanidine). According with the optimized reaction conditions, it´s possible to tune the chemical and thermal stability as well as potential application of the final salts. b) The potential use of scCO2 for extraction and separation processes in the case of three asymmetric catalytic reactions in the presence of ionic liquids and/or chiral ionic liquids as solvent or chiral media respectively. In particular, Sharpless asymmetric dihydroxylation of olefins (in the presence of osmium catalyst), asymmetric Aldol and Michael reactions (in the presence of chiral organocatalysts based on chiral ILs) will be presented. The peculiar properties of carbon dioxide including as supercritical fluid open excellent perspectives for the application in novel organic synthetic transformations as well as their use in industrial processes. Acknowledgements: We thank the Fundação para a Ciência e Tecnologia for financial support (PEst-C/EQB/LA0006/2011 and PTDC/CTM/103664/2008 projects and SFRH/BD/67174/2009 for KZ PhD grant). References: 1. a) Goodrich, B. F.; de la Fuente, J. C.; Gurkan, B. E.; Zadigian, D. J.; Price, E. A.; Huang, Y; Ind. Eng. Chem. Res. 2011, 50, 111. b) Camper, D.; Bara, J. E.; Gin, D. L.; Noble, R. D.; Ind. Eng. Chem. Res. 2008, 47, 8496. 2. Afonso, C. A. M.; Branco, L. C.; Candeias, N. R.; Gois, P. M. P.; Lourenço, N. M. T.; Mateus, N. M. M.; Rosa, J. N.; Chem. Commun. 2007, 2669. 3. a) Carrera, G. V. M.; da Ponte, M. N.; Branco, L. C.; Tetrahedron, 2012, 68, 7408. b) Branco, L. C.; Serbanovic, A.; da Ponte, M. N.; Afonso, C. A. M.; ACS Catalysis 2011, 1, 1408. c) Carrera, G. V. S.M.; Costa, A.; Ponte, M. N.; Branco, L.C., Synlett 2013, 24, 2525. 128
P18 1
H AND 13C ASSIGNMENTS OF THREE SERIES BIOACTIVE IMIDAZO[2,1-B]THIAZOLE DERIVATIVES A.S. Bunev, E.V. Sukhonosova, G.I. Ostapenko, P.P. Purygin Togliatti State University, Togliatti, Russia
The complete 1H and 13C NMR assignments of three series bioactive imidazo[2,1-b]thiazoles were achieved by combination of one and two-dimensional NMR experiments, and the NMR signals of these compounds were analyzed and compared.
The authors are grateful to the Ministry of Education and Science of the Russian Federation (State job No. 426)
129
P19 SYNTHESIS OF 1,4,5-TRISUBSTITUTED IMIDAZOLES CONTAINING TRIFLUOROMETHYL GROUP A.S. Bunev, M.A. Vasiliev, G.I. Ostapenko, V.E. Statsyuk Togliatti State University, Togliatti, Russia
A new synthetic protocol for the synthesis of 1,4,5-trisubstituted imidazoles (2a-i) containing trifluoromethyl group has been developed using van Leusen reaction, which incorporates twocomponent condensation reaction trifluoroacetimidoyl chlorides (1a-i) with tosylmethylisocyanide. This protocol provides a novel and improved method for obtaining trifluoromethyl containing 1,4,5trisubstituted imidazoles in good yields.
The authors are grateful to the Ministry of Education and Science of the Russian Federation (State job No. 426)
130
P20 THE QUANTUM-CHEMICAL STUDY OF THE KEY STEP OF THE CYCLIZATION OF 4,11-DIMETHOXY-5,10-DIOXO-2- ANTHRA[2,3-B]FURAN-3-CARBOXYLATES E.E. Bykov, A.S. Tikhomirov, A.E. Shchekotikhin, M.N. Preobrazhenskaya Gause Institute of New Antibiotics RASM, Moscow, Russia
Highly active inhibitors of topoisomerase I, capable of blocking the growth of tumor cells with activated mechanisms of multiple drug resistance, were discovered in the series of derivatives 4,11dihydroxy-5,10-dioxoanthra[2,3-b]furan-3-carboxylic acids [1]. Previously, a scheme of preparation of 2-substituted derivatives of 4,11-dimethoxy-5,10-dioxoanthra[2,3-b]furan-3-carboxylic acids was developed. However yields of anthrafurandiones by this method seriously depended on a substituent in position 2 [2]. To understand this, a quantum-chemical estimations of the key step of the intermolecular cyclization of the intermediate enol forms of ethyl 2-(3-bromo-1,4-dimethoxy-9,10dioxo-9,10-dihydroanthracene-2-yl)-3-hydroxypropanoates 1a-c to the corresponding anthra[2,3b]furan-5,10-diones 2a-c were carried out.
The quantum-chemical calculations by DFT method B3LYP/6-31+G(d) by means program package Gaussian-09 [3] confirmed that the activation barriers (ΔE# ) of cyclization of enol form 1a-c depend on the nature of the substituent R. The groups R that have different electronic properties influence actively on the electron density of the internal nucleophile what is enolic oxygen atom (see Table, QO and ΕHOMO). The calculated values of ΔE# correlate with the yield of the anthra[2,3b]furan-5,10-diones 2a-c [2]. Thus quantum-chemical evaluation of the key step of cyclization confirmed that the electron-withdrawing substituents reduce the reactivity of enol intermediates 1ac in the cyclization to the corresponding anthra[2,3-b]furan-5,10-diones 2a-c. Table. Parameters for the reaction of cyclization of anthra[2,3-b]furan-5,10-diones 2a-c. Derivative 2a 2b 2c R -CH3 -Ph -CF3 ΔE#, (kcal/mol) 21.84 22.7 25.86 ΕHOMO, (ev) -2.01 -2.23 -2.45 QO -0.687 -0.577 -0.567 The yield, % [2] 72 40 3 References 1. Shchekotikhin, A. E. et. al, Patent RU № 2412166 (2011). 2. Tikhomirov, A. S.; Shchekotikhin, A. E.Chem. Heterocycl. Compd. 2014, 50, 271. 3. http://www.gaussian.com
131
P21 MACROPOLYCYCLIC COMPOUNDS COMPRISING DIAZACROWN ETHER MOIETIES AND FLUOROPHORE GROUPS N.M. Chernichenko, A.D. Averin, I.P. Beletskaya M.V. Lomonosov Moscow State University, Department of Chemistry, Moscow, Russia
Macrobicyclic compounds comprising structural fragments of diazacrown ethers and oxadiamines were synthesized using Pd-catalyzed amination reactions using Pd(dba)2/BINAP system [1]. They were further modified with various fluorophore substituents using catalytic and non-catalytic approaches to create promising fluorescent chemosensors and molecular probes for metal cations. Modification was carried out at N atoms of the cryptand and at C atoms of the benzyl spacer.
Macrotricycles and isomeric trismacrocycles were obtained via Pd-catalyzed macrocyclization reactions of N,N’-bis(3,5-dibromobenzyl) diazacrown ether derivatives with oxadiamines using either BINAP or RuPhos ligands and were further modified with dansyl fluorophores.
Acknowledgement: The work was financially supported by the RFBR grant N 12-03-93107. [1] A.A. Yakushev, N.M. Chernichenko, M.V. Anokhin, A.D. Averin, A.K. Buryak, F. Denat, I.P. Beletskaya. Molecules, 2014, 19, 940-965.
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P22 SYNTHESIS OF 1Н-IMIDAZOLECARBOXAMIDES I.V. Zavarzin, V.N. Yarovenko, S.L. Semenov, E.I. Chernoburova, M.M. Krayushkin N. D. Zelinsky Institute of Organic Chemistry, Laboratory for Chemistry of Steroid Compounds, Moscow, Russia
We earlier proposed the method for synthesis of 4,5-dihydro-1Н-imidazolecarboxamides (1) by the reaction of chloroacetamides with aliphatic diamines in the presence of sulfur1,2 (Scheme 1) O
O Cl
H 2 N ( C H 2) n2 N H 2
N
RNH
RNH
1
N H
( C H 2)
n
n = 1 ,2
Scheme 1 In this work we propose the method for the transformation of products 1 into 1Нimidazolecarboxamides 2. We found that the interaction of 1а-с with Ni/Al alloy in aqueous methanol at 20оС results in the dehydrogenation of dihydroimidazole fragments to form imidazoles 2а-с. N
H N
N
N O
N
H Ni/ A l, K O H
H
M e O H/ H 2 O
R
N O
H
R 1 a -c
2 a -c R = 2 -F ; 3 -O M e ; 2 ,4 -M e
Scheme 2 References 1. V.N. Yarovenko, S.A. Kosarev, I.V. Zavarzin, M.M. Krayushkin, Russ. Chem. Bull. (Int. Ed.) 1999, No. 4, p. 753. 2. M.M. Krayushkin, V.N. Yarovenko, I.V. Zavarzin, Russ. Chem. Bull. (Int. Ed.) 2004, No. 3, p. 491.
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P23 FEP/MD PROTOCOL TO MODEL SELECTIVITY OF KINASE INHIBITORS G.G. Chilov, O.V. Stroganov, F.N. Novikov, A.A. Zeifman, V.S. Stroylov, I.Yu Titov, I.V. Svitanko ND Zelinsky Institute of Organic Chemistry RAS
With over 500 different kinase enzymes encoded in a human genome and appreciation the role of kinases as promising therapeutic targets, the selectivity profile of a kinase inhibitor is an important indicator of its potential off-target effects including adverse effects, which sometimes might be quite severe and even preclude application of a drug in clinical practice. One of the recent examples of how the lack of selectivity of a kinase inhibitor drug may restrict its clinical application because of abundant life-threatening adverse effects is presented by Ponatinib - a potent inhitor of Abl kinase (primary therapeutic target) as well as over 40 off-target kinases. With the intent to overcome adverse effcts of Ponatinib we designed a PF-114 molecule, which appeard to be comparable to Ponatinib with respect to Abl suppression, but inhibited only 10 off-target kinases. In order to rationalize enhanced selectivity we established a FEP/MD protocol in which for each kinase Ponatinib molecule was transformed to PF-114 and the dG of such transition was recorded. The modeled system consisted of a full atom kinase domain with inhibitor docked into ATP-bindin site and immersed in a box of explicit solvent. FEP transition was split into 3 steps: decharging initial molecule (Ponatinib), converting Van der Waals parameters to another molecule (PF-114) and then charging the resulting molecule. Each transition was split in its turn into 10 windows, each taking 2 ns of MD simulation. Totally 15 kinases were modeled for the selectivity of inhibition. It appeared that calculated selecivities correlaeted with experimental data with R of 0,63. Structural findings from FEP/MD simulations uncovered 2 factors contributing to the enhanced selectivity of PF-114: its unfavorable (compared to Ponatinib) interaction with main chain carbonyl oxygen present in the active site of BRAF, Src, ERBB4, FGFR1, VEGFR2, TRKC, TRKB; and unfavorable interaction with water molecule in the active sites of BRAF, EPHA7, FGFR1, FLT1, MAPK11, MAPK14 kinases. Current results suggests that full atomic FEP/MD modeling may be a valuable instrument in the design of kinase inhibitors with improved selectivity.
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P24 FEATURES OF NATURAL POLYSACCHARIDE BASED THIN FILMS FORMATION Y.V. Chudinova2, D.V. Kurek2 1 - M.V.Lomonosov Moscow State University, Moscow, Russia 2 - Centre «Bioengineering», RAS, Moscow, Russia
Natural polysaccharide based thin films are promising biomaterials for using in different fields of science. Thin films were prepared by layer-by-layer (LbL) technique via alternately dipping the substrate into polycation and polyanion solutions to form polyelectrolyte multilayers. During each adsorption cycle one a monolayer is built up and the surface charge is reversed. This assembly process allows obtaining films with desired characteristic. Layer-by-layer method offers several advantages over other thin film deposition techniques, for example it is simple, rapid and inexpensive. Polyelectrolyte LbL films can be assembled from chitosan, pectin and other natural polymers. Pectin is one of the basic components of plant cell wall. It has a complex structure and contained linear and branched regions. Chitosan is produced by deacetylation of chitin, which is the structural element in the exoskeleton of crustaceans and cell walls of fungi. Chitosan and pectin are considered as some of the most attractive natural polyelectrolytes, because they are nontoxic, biodegradable, and biocompatible polymers. Their oppositely charged surface permits to use them for generating biocompatible surfaces via multilayer assembly. The main characteristic of biofilms, such as surface topography, roughness, thickness, molecular structure, adhesion forces were determined by atomic force microscopy (AFM). Influence of polyelectrolyte type and number of layers on the film buildup were investigated. Pectin covers mica surfaces very well and filling degree is nearly 100 %. Chitosan forms heterogeneous structures on the mica surface with a lesser filling degree. Chitosan with different molecular weight was studied. Results showed that in all cases were formed particles and aggregates. Influence of substrate type and its possible modifications was considered. Surface topography, height, roughness of the films which formed on the substrates with different properties were varied. Further, effect of the concentration and the presence of other polysaccharide were observed. Pectinchitosan and chitosan-pectin coatings which formed via layer-by-layer technique had different morphological characteristics. The adhesion of the polyelectrolyte multilayer films has been investigated by contact mode of AFM. Adhesion is the attraction forces between the AFM tip and the film surfaces by force-curves mode [1]. Obtained data demonstrated relationship between adhesion forces and surfaces properties. Understanding of the molecular structure and pathways of formation such thin films allows to predict the characteristics and produce coating materials for use in various fields of biology and medicine. References: 1. Guo Y.-B., Wang D.-G, Adhesion and friction of nanoparticles/polyelectrolyte multilayer films by AFM and micro-tribometer / Tribology International.- N 44. - P. 906–915. - 2011.
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P25 SYNTHESIS OF N-(PICRYLAMINO)NITROPYRAZOLES I.L. Dalinger, I.A. Vatsadze, T.K. Shkineva, A.V. Kormanov, S.A. Shevelev N.D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, Laboratory of Nitrogen-containing Aromatic Compounds, Moscow, Russian Federation
One of the directions of modern design of nitroazole-based high-energy compounds consists in the introduction of an N-amino group to the endocyclic nitrogen atom of the nitroazole ring. This results in the preparation of N-amino derivatives of nitrotetrazole [1], nitrotriazoles [1-3], nitroimidazoles [4], and nitropyrazoles [3, 5-8]. However, the possibility functionalization N-aminonitroazoles additional energy-rich groups with saving of nitro groups in azole cycle poorly understood and limited only N-nitration [4a], Ntrinitroethylation [3, 4c] and the introduction of a fragment of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine [9]. In continuation of our works on chemistry of polynitropyrazoles [10] and for the purpose of broadening of synthetic potential of N-aminonitroazoles as versatile building-blocks for constructing new energy-rich compounds we developed method functionalization N-amino group using picryl fragment on the example of N-aminonitropyrazoles 1.
This method is based on arylation N-aminonitropyrazoles 1 under the action of picrylchlorid (PicCl) in the presence of base (К2СО3) when heated in MeCN within 2-6 h. The result is synthesized representatives of a previously unknown type of energy-rich compounds - N(picrylamino)nitroazoles 2, which are isomers well known C-(picrylamino)nitroazoles [11]. Compounds 2 with two nitro groups in the pyrazole ring are organic NH-acids medium strength (рКа 4.0 - 4.5, in MeCN-Н2О). [1] T.M. Klapötke, D.G. Piercey, J. Strierstorfer, Dalton Trans., 2012, 41, 9451. [2] P. Yin, Y. Zhang, D.A. Parrish, J.M. Shreeve, J. Mater. Chem. A, 2013, 1, 585. [3] Y. Zhang, D.A. Parrish, J.M. Shreeve, J. Mater. Chem. A, 2014, 2, 3200 [4] (a) R. Duddu., P.R. Dave, R. Domavarapy, N. Gelber, D. Parrish, Tetrahedron Letters, 2010, 51, 399; (b) M.M. Breiner, D.E. Chavez, D.A. Parrish, Synlett, 2013, 24, 519; (c) P. Yin, Y. Zhang, Y. Zhang, D.A. Parrish, J.M. Shreeve, J. Mater. Chem. A, 2013, 1, 7500. [5] G. Hervé, C. Roussel, H. Graindorge, Angew. Chem., Int. Ed. Engl., 2010, 49, 3177 [6] C. He, J. Zhang, D.A. Parrish, J.M. Shreeve, J. Mater. Chem. A, 2013, 1, 2863. [7] V.M. Vinogradov, I.L. Dalinger, S.A. Shevelev, Mendeleev Commun., 1993, 111. [8] X. Zhao, C. Qi, L. Zhang, Y. Wang, S. Li, F. Zhao, S. Pang, Molecules, 2014, 19, 896. [7] N.V. Palysaeva, K.P. Kumpan, M.I. Struchkova, I.L. Dalinger, A.V. Kormanov, N.S. Aleksandrova, V.M. Chernyshev, D.F. Pyreu, K.Yu. Suponitsky, A.B. Sheremetev, Оrg. Lett., 2014, 16, 406. [10] (a) I.L. Dalinger, I.A. Vatsadze, T.K. Shkineva, G.P. Popova, S.A. Shevelev, Synthesis, 2012, 44, 2058; (b) I.L. Dalinger, I.A. Vatsadze, T.K. Shkineva, G.P. Popova, S.A. Shevelev, Y.V. Nelyubina, J. Heterocycl. Chem., 2013, 59, 911. [11] (a) P.N. Neuman, J. Heterocycl. Chem., 1970, 7, 1159; (b) M.D. Coburn, J. Heterocycl. Chem., 1970, 7, 345 and 1971, 8, 153.
The research was supported by the Division of Chem. and Material Sciences of the RAS (OKh-4).
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P26 MeLaOX/ZrO2 CATALYSTS FOR CO OXIDATION N.A. Davshan, A.L. Kustov, O.P. Tkachenko, L.M. Kustov IOC RAS, Lab.14, Moscow, Russia Mixed metal oxides with a composition АВО3 known as perovskites exhibit the high thermal stability and enhanced catalytic activity in CO and hydrocarbon oxidation. The perovskite-type materials are less expensive as compared to supported noble metals. The materials can be significantly improved by supporting the perovskites onto porous carriers with a developed surface area. The goal of our work was to prepare, characterize and test in CO oxidation a series of MeLaO3 perovskites (Me = Co, Fe, Ni) supported onto a mesoporous zirconia as a robust and durable carrier. The synthesis of mesoporous ZrO2 was carried out according to the previously developed and modified procedure [1]. A glycine complex of lanthanum and cobalt or iron or nickel was prepared by the recipe described in [2, 3]. The samples of supported lanthanum-metal perovskites were prepared by impregnation of the precalcined mesoporous carrier (ZrO2) with a solution of the prepared La-Co/Fe/Ni glycine complex. The chemical analysis of the samples for the contents of the metals (Zr, Co, Ni, Fe, and La) was carried out by atomic emission spectroscopy. Diffuse-reflectance FTIR spectra were recorded at room temperature in the frequency range of 6000-400 cm-1 with a resolution of 4 cm-1 using а NICOLET “Protege” 460 spectrometer supplied with a diffuse-reflectance attachment. The following probe molecules were used to test surface sites of different nature: СО as a probe for Lewis acid sites and low-coordinated metal ions, CD3CN as a probe for both Lewis and Broensted (if present) acid sites. The probe molecules were adsorbed at room temperature and equilibrium pressures of 5 Torr for СО, 96 Torr for CD3CN (saturated pressures). The phase composition of the samples and the particle size of the supported metal were examined by X-ray diffraction (XRD) analysis. X-ray absorption (XANES + EXAFS) spectra (Co K edge at 7709 eV and Ni K edge at 8333 eV) were measured at the Hasylab X1 station (DESY,Germany) using a Si(111) double crystal monochromator. The EXAFS data analysis was performed using the software VIPER [4]. Reference spectra were taken using standard reference compounds: CoO, Co3O4, Co-foil, NiO, and Ni -foil. The required scattering amplitudes and phase shifts were calculated by the ab initio FEFF8.10 code [6]. X-ray photoelectron spectra were recorded by XSAM 800 spectrometer with Mg Kα X-ray (1253.6 eV) source. Catalyst testing was carried out in a laboratory scale fixed bed quartz reactor (internal diameter 3 mm), operating at an atmospheric pressure. The feed gas mixture consisted of 4.5 vol. % CO, 22.5 vol. % O2 and He balance. The total feed flow rate was held constant at 10 cm3/min, with a volume hourly space velocity (VHSV) of 6000 h−1. The following order of the activity in CO oxidation, as the temperature of the 50% conversion (T50), was found in the temperature range from 50 to 400°C: LaCoO3/ZrO2 (200oC) > LaFeO3/ZrO2 (275oC) > LaNiO3/ZrO2(300oC). [1] V. A. Sadykov, L. A. Isupova, I. A. Zolotarskii, L. N. Bobrova, A. S. Noskov, V. N. Parmon, E. A. Brushtein, T. V. Telyatnikova, V. I. Chernyshev, V. V. Lunin, Appl. Catal.A 204 (2000) 59. [2] E.V. Makshina, Thesis of Cand. Sci. Dissertation, Moscow State Univ., 2008. [3] L.M. Kustov, Top. Catal. 4 (1997) 131. [4] K.V. Klementiev, www.cell.es/Beamlines/CLAESS/software/viper.html [5] A.L. Ankudinov, B. Ravel, J.J. Rehr, S.D. Conradson, Phys. Rev. B, 58 (1998) 7565. 137
P27 SELECTIVE FUNCTIONALIZATION OF ALKYNES WITH NATURALLY OCCURRING ORGANOSULFUR COMPOUNDS E.S. Degtyareva, V.P. Ananikov Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
Nowadays crude oil remains one of the most important resources in the industry. Crude oil is a complex mixture mostly of hydrocarbons with small amounts of sulfur- and nitrogen-containing impurities. To produce more valuable fuels, oil fractions are subject to catalytic processes, like reforming, isomerization, and cracking. For ecological as well as technological reasons organosulfur components should be removed before the petroleum refining. However, it would be much more interesting to utilize these sulfur species as a naturally-occurring source of chemical reagents, for example for functionalization of hydrocarbons. The promising and efficient way to create a C-S bond is an addition reaction of thiols and disulfides to unsaturated hydrocarbons [1,2]. A convenient and selective metal-catalyzed methods for the addition of thiols and disulfides to alkynes have been recently reported. The present study is dedicated to the development of such catalytic system in order to involve crude oil as a reagent in organic synthesis. As the first step in our study we describe analytic approach for high sensitivity mass spectrometric measurements with ability to detect trace amount of products. Since most of the components in the crude oil are nonpolar, special polar tags were introduced for electrospray ionization (ESI) detection. To achieve this aim the alkynes with easily polarizable groups were synthesized. Good results were achieved using 1-(pentyn-4)-1H-imidazole, and in the model reaction involving the mixture of C6H5SH, C6H11SH and C6H13SH all products were clearly detected (Figure 1). Detailed study of the catalytic system and ESI-MS characterization will be presented and discussed.
Figure 1. An example of ESI spectrum registered for the reaction mixture in the crude oil. (1) Ananikov, V. P.; Kabeshov, M. A.; Beletskaya, I. P.; Khrustalev, V. N.; Antipin, M. Y. Organometallics 2005, 24, 1275–1283. (2) Ananikov, V. P.; Orlov, N. V; Zalesskiy, S. S.; Beletskaya, I. P.; Khrustalev, V. N.; Morokuma, K.; Musaev, D. G. J. Am. Chem. Soc. 2012, 134, 6637–6649.
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P28 PLATINUM GROUP METALS COMPLEXES OF HYBRID CHALCOGEN LIGANDS: SYNTHESES, STRUCTURES AND CATALYSTS IN C-C COUPLING REACTIONS S. Dey Chemistry Division, Bhabha Atomic Research Centre, Mumbai- 400 085, India
The chemistry of chalcogenated platinum group metal complexes has been of considerable interest for several years due to their fascinating structural features, their relevance in catalysis [1] and lately in materials science [2,3]. These complexes are mostly non-volatile, insoluble or poorly soluble oligomeric species in organic solvents, thus limiting their utility as precursors for the synthesis of metal chacogenides for electronic devices or making them inconvenient for any homogeneous catalysis reaction. To inhibit polymerization of metal chalcogenolates and to develop phosphine free Pd-catalysts, internally functionalized ligands, containing both soft chalcogen and hard N donor atoms has been quite successful, such as pyridine chalcogenolates [4] or aliphatic amine chalcogenolate ligands [5,6]. We have designed and developed several internally functionalized ligands (N E)2, N EAr (E = S, Se, Te; N E = Me2NCH2CH2E, Me2NCH2CH2CH2E; Ar = Ph, tol, Mes) and bis(4pyridyl)dichalcogenide and synthesized their palladium(II) and platinum(II) complexes. Versatile coordination behaviour of these ligands are shown in their complexes (Chart 1). The unusual colour of [MCl(E N)(PR3)] (blue-violet: Pd, red: Pt) has been attributed due to metal mediated ligand (E) – to – ligand (PR3) charge transfer transitions. The cationic complexes [Pt(PEt3)2(py2E2)]2(CF3SO3)4 with Pt pyridyl bond have been isolated via self-assembly reaction. The complexes [PdCl2(N EAr)]n exist in monomer and dimer forms, their ratio depends on the size of chelate ring and chalcogen atom. The catalytic activity of [PdX(N E)]n (X = Cl, OAc), [PdCl2(N EAr)]n and trans-[PdCl(4-Sepy)(PPh3)2] in Suzuki C C cross coupling reaction will also be discussed. Chart E
N
E M
M
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+4
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Acknowledgement: Dilip Paluru, K. V. Vivekananda, A. Wadawale, N. Bhuvanesh, B. M. Bhanage and V. K. Jain are acknowledged for collaborations. References 1. Q. Yao, E. P. Kinney, C. Zheng, Org. Lett. 2004, 6, 2997 2999. 2. S. Dey, V. K. Jain, Platinum Met. Rev. 2004, 48, 16 29. 3. B. Radha, G. U. Kulkarni, Adv. Funct. Mater. 2010, 20, 879 884. 4. K. V. Vivekananda, S. Dey, A. Wadawale, N. Bhuvanesh, V. K. Jain, Dalton Trans., 2013, 42, 14158 14167. 5. D. K. Paluru, S. Dey, A. Wadawale , V. K. Jain, J. Organomet. Chem. 2013, 728, 52 56. 6. B. J. Khairnar, S. Dey, V. K. Jain, B. M. Bhanage, Tetrahedron Lett. 2014, 55, 716 719. 139
P29 THE REACTIONS OF 1,3-DIARYL-3-CYCLOHEXANONILPROPANE-1ONE WITH HYDROGEN SELENIDE IN SITU IN CONDITIONS OF ACID CATALYSIS D.Yu. Direnko1, Ya.B. Drevko2, B.I. Drevko2 1 - Penza branch of the military Academy of logistics 2 - FGU VPO Saratov State Agrarian University named after N.I. Vavilov
It is known that when arylaliphatic 1,5-dicetones interacts with hydrogen selenide in conditions of acid catalysis the corresponding 4H-selenopyran structures can be formed 1, which are used as veterinary and healthcare products. However, dicyclic diaryl-4H-selenopyrans have not been described until today. We have studied the chemical reaction of 1-paramethoxy-3-phenyl-3-cyclohexanonilpropane-1-one 1 with hydrogen selenide in situ in conditions of acid catalysis. The reaction has been conducted in the presence trimethoxyphosphine 1. In the result of the compound 1 was obtained in 2paramethoxy-4-phenyl-5,6,7,8-tetrahydro-4H-selenochromen 2 with quantitative output – 80% (Melting point = 108-1090С). Ph
Ph C H 3OH
O O
Ph - OCH
3
PCl3
ZnSe
Se
p
Ph - OCH p 3
2
1
In the course of reaction settled crystal compounds and mother solution were analyzed by method of the capillary gas-liquid partition chromatography with mass-selective detector HP 5890/5972: Tinj=200оС, tset=3 min; Tset=50 оС; Tend=280 оС; Т = 10 оС/min; carrier gas – helium, = 1 ml/min. It was found that every molecular ion or fragment which contained selenium presented in the form of six signal intensities conforming to the content of the selenium isotopes in the nature: Se74 (0,87%), Se76 (9,02%), Se77 (7,58%), Se78 (23,52%), Se80 (49,82%), Se82 (9,19%). The compound 2 is subjected to isomerisation at high temperature. So, there are signals of four compounds with retention time 27,03 min, 29,06 min, 29,3 min, 40,08 min on the chromatogram (m/z = 381, the output of this molecular ion is accompanied by loss of one hydrogen’s isotope). As well as, one compound was identified and its molecular ion was conformed to dehydroselenochromen (m/z = 380, retention time is 33,35 min). This ion also was identified through GH-MS that confirmed the received mass spectrum. Therefore formation of product (dehydroselenochromen (m/z = 380)) demonstrates the new direction of disproportionation of dehydroselenochromen structures on alicyclic fragment. Literature 1. Drevko Ya.B., Fedotova O.V. The synthesis of the first representatives of benzenediamine dehydroselenochromens // CHC.2006.№10.P.1586-1587.
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P30 SYNTHESIS OF UNNATURAL PROLINE DERIVATIVES USING THE AZACOPE-MANNICH-REACTION D.S. Belov, N.K. Ratmanova, A.V. Kurkin, I.A. Andreev Lomonosov Moscow State University
Oxygenated bicyclic amino acids constitute an important class of secondary metabolites. Many of these nonproteinogenic amino acids are subunits of structurally diverse natural products. Various methods to access these biologically important compounds were advised by synthetic community and subsequently used by pharmaceutical companies. However pharmaceutical industry usually relies on the most robust and reliable reactions. Aza-Cope-Mannich rearrangement is a powerful reaction which was successfully used in academia settings, was however largely overlooked by medicinal chemists.1 We have shown recently that it can be routinely scaled up to 1 mole.2,3 In this work we demonstrated that a number of proline analogs can be efficiently prepared with full control of stereochemistry.
Scheme 1. The aminoalcohols required for the rearrangement were effectively prepared in several steps form commercially available oxiranes (Scheme 1). The aza-Cope-Mannich reaction provided both cis and trans fused unnatural proline analogs 2, 3 or 4 in high yields. The ratio of products was dependent upon the reaction conditions and the nature of substituents R1 and R2. The reaction also proved to be scalable (>1 g). This study was supported by the Russian Foundation for Basic Research. (Projects No. 14-0331685, 14-03- 31709, 14-03-01114). 1. Overman, L. E.; Humphreys, P. G.; Welmaker, G. S. Org. React. 2011, 75, 747-820. 2. Belov, D. S.; Lukyanenko, E. R.; Kurkin, A. V.; Yurovskaya, M. A. Tetrahedron 2011, 67, 9214–9218. 3. Belov, D. S.; Lukyanenko, E. R.; Kurkin, A. V.; Yurovskaya, M. A. J. Org. Chem. 2012, 77, 10125–10134.
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P31 SYNTHESIS OF OXYGENATES OF DIFFERENT CLASSES ON HETEROGENIOUS KCOMOS-CATALYSTS V.S. Dorokhov, O.L. Eliseev, A.L. Lapidus, V.M. Kogan N. D. Zelinsky institute of organic chemistry, Moscow, Russia
Heterogeneous catalytic systems based on alkali-modified molybdenum disulphide are promising for alcohols synthesis from СО and Н2 [1,2]. The model of dynamic nature of the active sites of transition metal sulphide catalysts was taken as a conceptual basis for the work [3]. We conducted investigations of structure and functioning mechanism of MoS2-based catalysts active phase in oxygenates synthesis reaction. We found out that alkali metal (potassium) forms unite phase with MoS2 and significantly changes it structure. Addition of potassium increases average number of layers and average linear size of MoS2 crystallites. As it follows from our catalytic experiments, both Co and K increases selectivity of alcohols formation. Besides addition of potassium suppresses hydrogenation and hydrodesulphurisation reactions [4]. We suggested that formation of alcohols from СО and Н2 occurs on active sites located on the "edges" of the MoS2 slabs. It is likely that active sites responsible for alcohols synthesis consist of a combination of two MoS2 clusters, one of which is promoted with Co, and K is intercalated between the crystallite layers. Formation of alcohol molecule depends on accessibility of alkali ion to coordination of alcoxyl intermediate oxygen. The scheme of possible mechanism of synthesisgas conversion on KCoMoS catalyst was published in [5]. The addition of ethanol or ethylene to synthesis gas substantially changes the reaction rate and composition of the products [5]. Presence of these components in the gas feed can significantly increase CO conversion. According to our results alcohols can adsorb on KCoMoS-catalysts active sites and enter a series of side reactions, which leads to formation of ethers, esters, aldehydes, ketones and organic acids. Therefore, the use of additives to syngas makes it possible to obtain a wide range of oxygenates of different classes. The further development of this approach can be efficient for controlling selectivity in processes of simultaneous synthesis of various classes of organic compounds. Acknowledgment. This work was financially supported by the Russian Foundation for Basic Research (Project No. 14-03-31769 mol_a). References: 1) Surisetty V.R. et al. App. Cat. A 404 (2011) 1-11. 2) Feng M. Recent Patents Catal. 1 (2012) 13-26. 3) Kogan V.M., Nikulshin P.A., Rozhdestvenskaya N.N. Fuel 100 (2012) 2–16. 4) Dorokhov V.S. et al. Kinetics and Catalysis 54 N 2 (2013) 243–252. 5) Kogan V.M. et al. Russ. Chem. Bull. № 2 (2014) in press.
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P32 THE MECHANISM OF ALCOHOL FORMATION OVER TMS CATALYSTS V.S. Dorokhov1, E.A. Permyakov1, O.L. Eliseev2, V.M. Kogan1 1 - N.D. Zelinsky Institute of Organic Chemistry, RAS, Laboratory of catalysis by trasition metals and their compounds, Moscow, Russia 2 - N.D. Zelinsky Institute of Organic Chemistry, RAS, Laboratory of catalytic reaction of carbon oxides, Moscow, Russia
The aim of this work is to investigate a structure of transitional metal sulfide (TMS) catalyst active sites in mixed alcohol synthesis (MAS) from synthesis gas and to develop possible mechanism of this reaction. The model of dynamic nature of the active sites of TMS catalysts was taken as a conceptual basis for the work [1,2]. As it follows from our catalytic experiments, both Co and K affect alcohol selectivity towards hydrocarbon (HC) formation. It is likely that the active sites responsible for alcohol formation are located on the "edges" of the MoS2 slabs. Besides, K poisons C-S hydrogenolysis sites and HDS activity decreases. Basing on the experimental data, we suggest the structure of the MAS site as a combination of two MoS2 clusters, one of which is promoted with Co, and K is intercalated between the crystallite layers and the scheme of possible mechanism of synthesis-gas conversion on K-Co-Mo-S catalysts (Fig. 1). H H 2C O Mo
e ffe c t o f K , C o a n d s u p p o rt
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ef fe an ct d of su K pp , C or o t
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S
Fig. 1: Suggested mechanism of alcohols and HC formation over KCoMoS active sites. Black rectangle defines the initial step of reaction.
As an initial step of the mechanism, CO adsorption on the vacancy was taken. After partial hydrogenation of carbon by dissociatively adsorbed hydrogen, the C=O bond lengthens allowing the oxygen atom to coordinate on K+ ion intercalated between the MoS2 crystallite layers. Coordination of the oxygen on the K+ ion stabilizes the alkoxylenated intermediate and prevents the C-O bond from breaking, which is necessary for the succeeding process of alcohol formation. Oxygen coordination onto the Mo atom of the neighboring cluster leads to hydrogenolysis of the CO bond. The alkyl fragment can either be hydrogenated to form HC or take part in the carbon-chain growth – next CO molecule is inserted between C and Mo. Oxygen of a newly inserted CO can coordinate on K or Mo determining formation of either alcohols or HC. It was found that the ratio of alcohols to HC yields decreases with an increase of reaction temperature. It means that alcohols formation becomes kinetically less favorable at higher temperatures than the C-O bond hydrogenolysis. This observation is in agreement with the suggested mechanism. [1] V.M. Kogan, P.A. Nikulshin, N.N. Rozhdestvenskaya, Fuel 100 (2012) 2–16. [2] V.M. Kogan, P.A. Nikulshin, Catal. Today 149 (2010) 224–231. 143
P33 CATALYTIC CYCLOMAGNESIATION OF 1,2-DIENES IN THE SYNTHESIS OF PHEROMONES AND ACETOGENINE’S PRECURSORS V.A. Dyakonov, A.A. Makarov, O.A. Trapeznikova, U.M. Dzhemilev Institute of Petrochemistry and Catalysis, Russian Academy of Sciences; Laboratory Catalytic Synthesys; Ufa; Russia An efficient method for the synthesis of valuable N-, О-, and Si-containing 1Z,5Z-diene compounds was developed. The method comprises Cp2TiCl2-catalyzed cross-cyclomagnesiation of 1,2-dienes by Grignard reagents (RMgR’) to give 2,5-dialkylidenemagnesacyclopentanes in up to 96% yields. This approach was successfully used in the synthesis of 5Z,9Z-dienoic acids, precursors of acetogenins and insect pheromones Q
()n
.
[ T i] , M g 1
+
E tM g B r
Q
.
R
Q
()n
Mg
3
R
H 3O +(D 3O +)
R
()n
4
2
[ T i] = C p 2 T iC l 2 ; n = 1 , Q = T M S : R = B n ( k ) , H e x ( l) ; n = 2 : Q = O B n , R = H e x ( a ) ; Q = O T H P , R = H e x ( b ) ; Q = O T H P , R = B n ( c ) ; Q = M o r p h , R = B n ( h ) ; Q = M o r p h , R = H e x ( i) n = 3 : Q = T H P , R = C 1 2 H 2 5 ( d ) ; n = 4 : Q = T H P , R = B u ( e ) ; Q = T H P , R = H e x ( f) ; n = 6 : Q = T H P , R = B u ( g ) .
Acylation of diene 4g with acetyl bromide gave hexadeca-7Z,11Z-dien-1-yl acetate 5, the pink bollworm Pectinophora gossypiella attractant, in a final yield of 89%.
.
T H P O -( C H 2) 6
E tM g B r [ T i] , M g
+
T H P O -( C H 2) 6
( C H 2) 3 M e
.
94%
Mg
3g
O ( C H 2) 3 M e
T H P O -( C H 2) 6
H 3O +
( C H 2) 3 M e
Me Br 89%
( C H 2) 3 M e
A c O -( C H 2) 6
4g
5
The same approach was used to obtain the key synthons in the preparation of some acetogenins exhibiting high antitumor, antimalarial, and immunosuppressive activities. Cross cyclomagnesiation of 1,2-hexadecane and 2-(4,5-hexadiene-1-yloxy)tetrahydropyran followed by hydrolysis furnished 2-(hexacosa-4Z,8Z-dien-1-yloxy)tetrahydropyran 4h (yield 84%), which is the key intermediate in the preparation of the acetogenin cis-Solamin 6. .
( )10 + THPO
( )2
E t M g B r , [ T i]
.
( )2
( )10
2 0 oC , E t 2 O
Mg
H 3O +
OTHP
87%
3h O
( )2
( )10
H 23 C 12
OTHP
4h
HO
H
O
( )11 H
OH
O
6
This work was performed under financial support from the Russian Science Fondation (Grant 1413-00263) and by Russian Foundation for Basic Research (Grant 14-03-97024) 144
P34 SYNTHESIS AND ANTIHELMINTIC ACTIVITY OF 5-O-DERIVATIVES OF IVERMECTIN I.V. Zavarzin1, M.Kh. Dzhafarov2, N.V. Krukovskaya1 1 - N.D. Zelinsky Institute of Organic Chemistry, RAS, Moscow, Russia 2 - K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, Russia
Ivermectin 1 and its derivatives are widely used as antihelmintic medical formulations. In this case, the parasites eventually develop resistance to these substances.1,2 It is therefore highly relevant to develop new antihelmintic agents. We were the first who obtained the 5-O-ivermectin derivatives 2 by acylation of an ivermectin 1 anhydrides of carboxylic acids. In addition to the carboxylic acids the corresponding esters and amides are also obtained.
R MeO
C H3
O
O
O
H3 C C H3
HO
H3 C O
OMe
OH
O
O
O
1: R =M e, Et R 1=H 2: R =M e, Et
C H3
O
O O
C H3
R1
O
O
C H3
R 1= OH
Carboxylic acid 2, as well as their esters and amides show high antihelmintic activity. Literature: 1. Tyrell К., Leo F., Veterinary Parasitology. - 2009. - №11. - Р. 98-102. 2. Varady M., Cobra J., Letkova V., Kovac G., Veterinary Parasitology. - 2009. - №2-3. – Р. 267271.
145
P35 TRENDS IN EVOLUTION OF ANTIPARASITIC CHEMICAL AGENTS M.Kh Dzhafarov K.I. Skryabin Moscow State Academy of Veterinary Medicine and biotechnology
Chemotherapy and prevention are of high priority in control of helminthoses and other dangerous parasitoses of humans, animals and plants [1]. However, the intensive administration of antiparasitic preparations leads to development of resistance, which is one of the ways of biochemical adaptation of helminths, insects and arthopods to the first- and second-order environmental changes (the host and ecological niche occupied by the host, where certain stages of the complex-cycle pest metamorphoses take place), which necessitates regular renewal of the range of chemical agents, among different measures [2]. Systematization of the data on the antiparasitic substances in the light of new discoveries and developments is an important step for a successful struggle against parasitic diseases. In particular, based on the systemic analysis of features of the chemical structure of anthelminthic substances, the hypothesis on the viability of the targeted search for such compounds among the derivatives of conditionally progenitor cyclic hydrocarbons – benzene, indene, naphthalene, 1Нcyclopenth [a]-naphthalene, anthracene and phenanthrene – by alternating absolutely unsaturated and saturated structures, including heterocyclic analogues containing nitrogen, oxygen and sulfur and different substitutes and functional groups, was voiced:
References 1. Dzhafarov M.Kh. Russian J. Agrobiology. Animal biology series. 2013, №4, p.26-44. 2. Dzhafarov M.Kh., Vasilevich F.I. Advances in Pharmacology and Pharmacy. 2014, 2: 30-45.
146
P36 RHODIUM-CATALYZED REDUCTIVE CARBONYLATION OF IODOBENZENE O.L. Eliseev, T.N. Bondarenko, T.N. Myshenkova, A.L. Lapidus N.D.Zelinsky Institute of organic chamistry, Moscow, Russia
Aromatic aldehydes is useful class of products because of diverse reactivity of formyl group. Usually they are synthesized by Gattermann–Koch, Reimer–Tiemann, Vielsmeier–Haag, and Duff reactions. However, these methods suffers from drawbacks like low yield, poor selectivity and generating waste and side products.1,2 Alternatively, catalytic formylation (reductive carbonylation) of aryl halides with synthesis gas in the presence of palladium phosphine complexes was firhst reported in 1974 by Schoenberg and Heck3 and lately by Beller4–6 and Nagarkar7 groups. Somewhat surprisingly, up to now rhodium was unexplored as a catalyst for reductive carbonylation of aryl halides. This encouraged us to test rhodium salts and complexes in reductive carbonylation of iodobenzene as a model substrate. I
CHO R h -c a t. + CO + H2
+ b aseH I base
Rhodium phosphine complexes such as HRh(CO)(PPh3)3 and RhCl(CO)(PPh3)2 were found to be excellent catalysts They surpass PdCl2(PPh3)2 in respect to activity and selectivity to benzaldehyde. Aromatic solvents such as toluene and o-xylene seems to be the most suitable medium Other solvents such as heptane, 1,4-dioxane, MEK, DMF and acetonitrile gave poor yield of benzaldehyde. In methanol solution, methyl benzoate was the main product. Reaction is highly sensitive to the nature of the base. Replacing NEt3 with NBu3 resulted in almost threefold reduction in benzaldehyde yield. Somewhat higher but still low yield was achieved with Hünig's base. Inorganic bases such as potassium and cesium carbonates gave poor iodobenzene conversion and benzaldehyde yield. Synthesis gas pressure renders effect on reaction. Iodobenzene conversion reaches 100% at a total pressure of about 1–1.5 MPa and slightly decreases at higher pressure. Both selectivity and yield of benzaldehyde increase with pressure increasing while selectivity to benzene decreased. Biphenyl is a main product at atmospheric pressure but it fully disappears at a pressure 1 MPa and higher. In conclusion, rhodium (I) triphenylphosphine complexes are good catalysts for reductive carbonylation of iodobenzene. The best catalyst formulation found: 0.5% RhCl(CO)(PPh3)2, 150% NEt3, toluene. At 110°C and 1.5 MPa (CO/H2 = 1/1) iodobenzene is totally converted within 2 hours giving benzaldehyde with the yield of 88%. References 1. F. Aldabbagh, Compr. Org. Funct. Group Transform. II, 2005, 3, 99. 2. L. P. Crawford, S. K. Richardson, Gen. Synth. Methods, 1994, 16, 37. 3. A. Schoenberg, R. F. Heck, J. Am. Chem. Soc., 1974, 96, 7761. 4. S. Klaus, H. Neumann, A. Zapf, D. Sturbing, S. Hubner, J. Almena, T. Riermeier, P. Groß, M. Sarich, W.-R. Krahnert, K. Rossen, M. Beller, Angew. Chem. Int. Ed., 2006, 45, 154. 5. A. Brennfuhrer, H. Neumann, St. Klaus, T. Riermeier, J. Almenab, M. Beller, Tetrahedron, 2007, 63, 6252. 6. H. Neumann, R. Kadyrov, Xiao-Feng Wu, M. Beller, Chem. Asian J., 2012, 7, 2213. 7. A. S. Singh, B. M. Bhanage, J. M. Nagarkar, Tetrahedron Letters, 2011, 52, 2383.
147
P37 MODELING OF THE ELECTROCHEMICAL IMPEDANCE IN ANODIC DISSOLUTION OF IRON USING A GENETIC ALGORITHM APPROACH A.R. Enikeev1, I.M. Gubaidullin2, M.A. Maleeva3 1 - Institute of petrochemistry and catalysis, Laboratory of mathematical chemistry, Ufa, Russia 2 - Institute of petrochemistry and catalysis Laboratory of mathematical chemistry 3 - A.N. Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Moscow, Russia
In order to predict the general corrosion damage to metals and alloys, development of deterministic models and the acquisition of values for various model parameters are of paramount importance. Now it is generally accepted that elucidating an intricate reaction mechanism by means of steadystate techniques alone is a very difficult task [1]. In fact, the steady-state approach provides too little information in comparison with the complexity of the process under investigation. In the present work, we used model with three adsorbed species it was possible to explain the iron dissolution in sulphate and chloride media. It was recently found that impedance diagrams reveal at least three time constants concerning the faradaic process in the iron-sulphate systems was proposed by Keddam [2].
Reaction mechanis. The reaction kinetic parameters was calculated by genetic algorithm. The experimental impedance diagrams showed one high-frequency capacitive arc and three time constant at lower frequencies appearing as inductive or capacitive loops. They are attributed in the models, respectively, to the double layer capacitance in parallel with the transfer resistance and to the relaxation of three reaction intermediates. 1. E J Kelly, J Electrochem Sot 112, 124. 2. M Keddam, R Mattos and H Takenoutl, J Electro-them Sot 128, 257, 266 (1981).
148
P38 KINETICS AND MECHANISM OF THE CATALYTIC OXIDATION OF 4TERT-BUTYLPHENOL BY AQUEOUS SOLUTIONS OF H2O2 IN THE PRESENCE OF TITANOSILICATES L.V. Enikeeva, I.M. Gubaydullin, N.F. Murzasheva Institute of petrochemistry and catalysis RAS, Laboratory of mathematical chemistry, Ufa, Russia
Selective oxidation of phenol is of great interest in terms of education practically valuable product hydroquinone and catechol . This work is part of studies on the oxidation of phenols in aqueous solutions of hydrogen peroxide in the presence of metallosilicates . For initial evaluation of the activity of titanosilicate catalysts in oxidation reactions of organic compounds , we used a decomposition reaction of H2O2 in the absence of substrate. We studied the catalytic activity in the decomposition reaction metallosilicates H2O2: apparent activation energy of the reaction in the presence of different samples metallosilicates were calculated; expression for the reaction rate, which shows good agreement with the experimental data, was proposed; model validation on the value is performed. A series of catalytic activity of the samples in the reaction of hydrogen peroxide decomposition was created. At the moment we study the oxidation reaction of tretbutilfenola by aqueous solutions of H2O2. The scheme of the reaction, the reaction kinetic parameters was calculated.
149
P39 NEW CHEMICAL TRANSFORMATIONS OF Ni(acac)2 WITH POSSIBLE INVOLVEMENT OF SUPERATOMIC Ni2O2 CORE AS REVEALED BY ESIMS AND MS/MS D.B. Eremin, V.P. Ananikov Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
More than twenty signals of nickel-containing ions were detected upon studying of electrospray ionization mass spectrum of the Ni(acac)2 sample prepared in a plastic tube. However, changing sample preparation procedure to a glass vial gave a clear spectrum with four signals corresponding to: m/z 257.0141, [Ni(acac)2 + Na]+; m/z 413.0040, [Ni2(acac)3] +; m/z 535.03838 [Ni2(acac)4 + Na]+; and m/z 669.0285, [Ni3(acac)5] + (Figure 1A). A prominent difference in the spectra was caused by various plastic-derived contaminants, that were coordinated to the metal center.
Figure 1. (A) ESI-MS spectra of solution of Ni(acac)2 in acetonitrile prepared under standard conditions (with contaminant signals marked by blue symbols) and prepared without a contact with plastic (m/z = 250 – 1000 range; acac = C5H7O2); (B) Experimental survival yield curves of most abundant ions. CID (Collision-induced dissociation) MS/MS experiments were carried out to estimate relative stability and to study reactivity during fragmentation process. Fragmentation of the bimetallic ion [Ni2(acac)3] + was of most interest. Eight fragment ions of different composition were detected. Seven of them were formed as a result of C–C, C–H and C–O bond cleavage; nevertheless, they retained the Ni2O2 core, a supposed superatomic structure, which caused exceptional behavior observed in the fragmentation. After the fragmentation at the applied collision energy of 40 eV, ketene, pentyn-3-on-2, buten-3-on-2, acetaldehyde, carbon monoxide, and hydroxide-anion were formed. Other bi-, tri- and monometallic species detected did not undergo such transformations under MS/MS conditions. Survival yields were calculated (Figure 1B), and a series of relative stability was proposed: Ni2 >> Ni1 ≈ Ni3. The signal of [Ni2(acac)3] + remained as most intensive after heating of the solution. Mass spectra with the similar ionic composition were obtained for vanadyl and copper(II) acetylacetonates as well as after the addition of two-fold excess of acetylacetone to the solution of the acetates M(OAc)2 (M = Ni, Cu, Pd). Chemical reactivity of detected ions and the role of bimetallic species are currently under investigation.
150
P40 FORMATION OF A COMPLEX WITH FLUOROGENE LABEL IS A RELIABLE WAY OF CREATION OF AN EXPRESS-METHOD OF ACETYLCHOLINESTERASE ACTIVITY ASSAY O.V. Fateenkova, E.T. Gainulina, D.K. Gulikova, S.B. Ryzhikov, V.N. Fateenkov I.M. Sechenov First Moscow State Medical University, Faculty of Pharmacy, Russia, Moscow Assay of erythrocyte acetylcholinesterase (AChE) activity of human is widely used for the successful decision of many problems facing to a modern science: development of effective antidots for treatment of defeats by toxic organophosphorus inhibitors, medicines for treatment of illness Alzheimer and Parkinson etc. In a lot of cases there is a necessity of express-analyses of defeat by toxic organophosphorus inhibitors. As an example it is possible to refer to events in the Tokyo underground in 1985 year and also in territory of several syrian cities in 2013 year, when in the terrorist purposes sarin has been applied and there was a necessity of urgent diagnostics of a degree of defeat of significant number of victims of this act of terrorism. Known methods of AChE activity assay do not correspond to modern requirements to correlation of parameters “sensibility - time of formation of an analytical signal». In the given work the express-method of acetylcholinesterase activity assay is offered on the basis of formation of an intensively fluorescing complex by the given enzyme with fluorogene label thioflavine T (TF). TF is reversible inhibitor of AChE and selectively binds to the peripheral site of this enzyme.
Figure. Dependence of fluorescence intensity of TF (15 М) from AChE activity. With increase of AChE activity at constant concentration of ТF (15 М) in the investigated interval of reagents concentrations the dependence of fluorescence intensity of system TF - AChE has linear character (fig.). At addition AChE to solution TF formation of an analytical signal (increase of fluorescence intensity) on a wave of 490 nm is observed within of several seconds, and the achieved of fluorescence intensity remains stable more than 15 min. The absence of influence of human butirylcholinesterase and bull whey albumin on fluorescence intensity of thioflavine T on length of a wave of 490 nm is confirms selective character of interaction of human erythrocyte acetylcholinesterase with TF. 1. De Ferrari G.V., Mallender W.D., Inestrosa N.C., Rosenberry T.L. J. Biol. Chem. 2001. 276, 23282. 2. Antokhin A.M., Gainullina E.T., Taranchenko V.F., Ryzhikov S.B., Yavaeva D.K. Russ. Chem. Rev. 2010. 79. № 8, 713.
151
P41 QUANTUM CHEMICAL MODELING OF CONFORMATIONS OF TERTBUTYL HYDROPEROXIDE G.T. Garaeva, V.I. Anisimova, I.A. Suvorova, N.N. Batyrshin Kazan National Research Technological University, 420015, Kazan, K.Marks 68
Data on internal rotation of tert-butyl hydroperoxide (TBHP) advance the field of conformational analysis and can be used for investigation of reactivity of industrially important hydroperoxides which are primary products of hydrocarbon oxidation processes. For TBHP, internal rotation only about C-O and O-O bonds is possible. Earlier it was demosntrated that TBHP has two conformations – gauche and trans [1]. Figure 1 (curves 1,2) shows that all possible equilibrium structures of TBHP have identical energy, while analysis of bond lengths and angles (Table 1) also supports identity of these structures, and, therefore, monomeric form of TBHP exsists only in one conformation (Fig. 2) [2]. Table 1 – Parameters of TBHP according to B3LYP/6-311++G(df,p) calculations. Bond length, Å С-О
О-О
О-Н
Angle, ° СОО ООН
1.450 1.456 0.966 109.5 100.2
Torsion angle,°
OH,
С2С1О1О2
С3С1О1О2
С4С1О1О2
С1ООН
sm-1
-60.1
-178.0
63.8
-122.6
3785
Fig. 1 – PES of internal rotation of BHP: 1- around О-О bond , 2 – around С-О bond
Fig. 2 – Molecule of TBHP
1 Suvorov, I. A Association and the thermal decomposition of tertiary hydroperoxides: Thesis Candidate. chem. sci./I.A. Suvorov. - Kazan, 2003 - 124 p. 2 Anisimov, V.I. Quantum-chemical study of the hydrogen bonds between molecules tertiary butyl hydroperoxide // V.I. Anisimova, I.A. Suvorov, N.N. Batirshin, V.I. Sokolov, K.E. Kharlampidi // Vestnik Bashkir University. - 2008 - v. 13. -№3 (1). - p. 793-797. The work was supported by Russian Ministry of Education and Science within the framework of basic part (PNIL 02.14). 152
P42 SUPRAMOLECULAR INTERACTION OF CAFFEINE MOLECULES WITH EACH OTHER, WATER MOLECULES AND OXYGEN ATOMS OF TETRAOXIDOANIONS IN THE NEW COMPOUND COBALT HEXAHYDRATE DIPERRHENATE CAFFEINE K.E. German1, M.S. Grigoriev1, G.V. Kolesnikov2, Yu.A. Ustynyuk2, O.I. Slyusar3, Ya.A. Obruchnikova3, O.S. Kryzhovets3, M.N. Glazkova3 1 - A.N. Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Moscow, Russia; Medical Institute REAVIZ, Moscow, Russia 2 - Lomonosov Moscow State University, Moscow, Russia 3 - Medical Institute REAVIZ, Moscow, Russia
Recently the antitumor and radiosensitizing drugs being caffeine derivatives that penetrate easily through blood brain barrier have been developed. They are effective with radiation and chemotherapy treatment for cases of brain tumors. Results of these studies has shown the caffeine derivatives as perspective source for receiving therapeutic agents to be used in a combined therapy for primary and metastatic brain tumors. Anyhow the mechanism of caffeine interaction was not clear. To provide the proper understanding of caffeine action the precise structural data are necessary. To increase the accuracy of the structural date and to simulate the interaction of caffeine with tetraoxidoanion and hydration water molecules the synthesis of caffeine cobalt hexahydrate perrhenate was carried out from saturated water solutions and the single crystal thus obtained were subjected to X-ray structural study at Bruker KAPPA APEX II diffractometer.
Supramolecular interactions of caffeine molecules with each other, water molecules and oxygen atoms of tetraoxidoanions as in a new compound of Co(H2O)6[ReO4]2 . caffeine are analyzed in these study through comparison of the new precise structural data with quantum chemical analyses. The reasons for alterable orientation of caffeine molecules to each other and for the H-bonds network formation has been evaluated. 1. Vartanyan L.P., Kolesova M.B., Gornaeva G.F., Pustovalov Yu.I. Caffeine derivatives — perspective method of the search for anticancer and radiomodifying drugs in combined therapy for malignant brain tumors // Psychopharmacol. Biol. Narcol. — 2005. — Vol. 5, N 4. — P. 1093–1095. Central Research Institute of Roentgenology and Radiology, Saint Petersburg
153
P43 EFFICIENT CONVERSION OF ALKENYNONES TO 2METHYLENEDIHYDROPYRROLONES P.R. Golubev, A.S. Pankova St. Petersburg State University, Institute of chemistry, St. Petersburg, Russia
Earlier we have developed a method for the synthesis of cross-conjugated ketones 2 and investigated their interaction with common binucleophiles – hydrazines and amidines [1,2]. Our next goal was to study the reaction of enynones 2 with amines.
It was shown earlier [1,2] that the ethoxymethylene group is the most active center of ketones 2 in reactions with nucleophiles. In line with this, enamines 3 were obtained on the first stage in reactions with amines. Various solvents were used successfully in this reaction, but diphenyl ether was considered to be the most convenient, since in this case both synthetic steps could be performed in a one-pot fashion without isolation of intermediate enamines 3. We proposed that thermolysis of enamines 3 could lead to their cyclization via Michael-type intramolecular addition of amine nitrogen atom to a triple bond. We have found that this reaction proceeds smoothly at 200 °C as a 5-exo-dig cyclization leading to pyrrolinones 4 as single products in good to excellent yields. Various amines with alkyl, aryl or heteroaryl substituents were used. Thus, monoalkylamines are predictably the most active coupling partners, but in this case steric factors play a crucial role. Nevertheless, even tert-butylamine was employed successfully in this reaction along with n-alkyl- and (hetero)benzylamines. In case of anilines the reaction outcome was fully consistent with nucleophilicity of the amine used. Generally, anilines with electron-donating substituents reacted more readily and provided higher yields than electron-deficient ones, and a slight decrease of yield was observed when para-substituted aniline was replaced with an ortho-substituted analogue. Finally, pyrrolidinones 4 with various heteroaromatic substituents at nitrogen atom can also be obtained. In conclusion, we offer a straightforward and high-yielding method for the synthesis of previously unknown 2-methylenedihydropyrrolones. [1] A.S. Pankova, P.R. Golubev, I.V. Ananyev, M.A. Kuznetsov, Eur. J. Org. Chem. 2012, 30, 5965-5971. [2] P.R. Golubev, A.S. Pankova, M.A. Kuznetsov, Eur. J. Org. Chem. 2014, 17, 3614-3621. Authors thank the Russian Scientific Fund for a research grant No. 14-13-00126. 154
P44 THEORETICAL INVESTIGATION OF PALLADIUM-CATALYZED DIMERIZATION OF ALKYNES: HYDROPALLADATION VS. CARBOPALLADATION PATHWAYS E.G. Gordeev, V.P. Ananikov N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences
Catalytic dimerization of terminal alkynes is a waste-free process that allows preparation of enynes within atom-economic transformation. The key question for practical utilization of the dimerization approach is to understand the factors responsible for rendering regioselective transformation and lead in a to a single poduct. The studied catalytic dimerization of terminal alkynes may involve two mechanisms: hydropalladation and carbopalladation, which results in two types of products - head-to-head and head-to-tail dimers. Experimentally it has been found that the presence in the reaction mixture of carboxylate anion direct the reaction to head-to-tail product only [1]. To reveal the mechanistic picture we have carried out the quantum-chemical modeling (B3LYP/6-311G (d) & SDD) of the catalytic dimerization of phenylacetylene including participation of the carboxylate anion. Theoretical calculations have shown that in the absence of carboxylate anion the reaction proceeds as hydropalladation and forms head-to-head product, since potential barrier of the hydropalladation rate-determining step is much smaller than the barrier of the carbopalladation rate-determining step. The predominant formation of head-to-head product was also determined by kinetic factor: the energy of the corresponding transition state was smaller as compared to the transition state of carpbopalladation pathway. When carboxylate anion (acetate ion was used for modeling) was added to the reaction mixture, the H lignad at the metal center was blocked that and only carbopalladation pathway become possible. Indeed, coordination of the carboxylate ion to the palladium atom, leading to the formation of the ion pair, destabilized head-to-head intermediate complex. As a result, the second phenylacetylene molecule was not able to enter into the metal coordination sphere. In the case of head-to-tail intermediate complex such destabilization did not take place. Theoretical study of complete potential energy surface and comparison with experimental data will presented and discussed. References. [1] Zatolochnaya O.V., Gordeev E.G., Jahier C., Ananikov V.P., Gevorgyan V., Carboxylate Switch between Hydro- and Carbopalladation Pathways in Regiodivergent Dimerization of Alkynes, Chem. Eur. J., 2014, DOI: 10.1002/chem.201402809. Acknowledgement. Cooperation with V. Gevorgyan (UIC, Chicago) and his group is greatly acknowledged in this project. The support of the Russian Foundation for Basic Research (RFBR 1403-31752) is gratefully acknowledged.
155
P45 CROSS-METATHESIS OF POLYNORBORNENE AND POLY(1OCTENYLENE) AS A NEW ROUTE TO NORBORNENE AND CYCLOOCTENE MULTIBLOCK COPOLYMERS M.L. Gringolts, Yu.I. Denisova, G.A. Shandryuk, L.B. Krentsel, A.D. Litmanovich, Ya.V. Kudryavtsev, E.Sh. Finkelshtein A.V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Russia
Norbornene (NB) and cyclooctene (COE) are well-known objects in ring-opening metathesis polymerization (ROMP). Their homopolymers synthesized by ROMP are important commercial products [1]. Polynorbornene (PNB), which is sold under the trademark Norsorex, has various special applications. Poly(1-octenylene) (PCOE), known as Vestenamer or polyoctenamer, possesses unusual properties for an elastomer. At the same time, the ROMP synthesis of NB-COE copolymers is rather difficult because of considerably different polymerization activities of the comonomers. This problem can be solved by catalyst modification [2] or using NB with substituents decreasing its activity [3]. We propose a new approach to the synthesis of NB-COE multiblock copolymers via interchain cross-metathesis of PNB and PCOE. That approach enabled us to obtain new copolymers using the 1st generation Grubbs’ catalyst Cl2(PCy3)2Ru=CHPh, which is not suitable for copolymerization of NB and COE. m COE
-
COE
PCOE [R u = C H P h ]
+
C H C l3
a
n N B -N B NB
-
6 N B -C O E
c
b C O E -C O E
NB
PNB
Cross-metathesis between PNB and PCOE has been successfully realized. New NB-COE multiblock copolymers were identified and characterized by NMR spectroscopy, GPC, and DSC methods. It was found that in the course of the reaction the average lengths of PNB and PCOE blocks were decreased, as well as the copolymer molecular weight and crystallinity. For copolymer of 1:1 composition, Tg, is about -30 oC, which is higher than for PCOE (- 80 oC) and lower than for PNB (39 oC). The exchange degree (conversion) reached approximately 40-50% in 24 h. Copolymer characteristics can be controlled by varying concentration of the catalyst. The work was supported by RFBR (project 14-03-00665) 1. KJ Ivin, JC Mol (1997) Olefin Metathesis and Metathesis Polymerization. Academic Press, London 2. Marc Bornand und Peter Chen Angew. Chem. 2005, 117, 8123 –8125 3. C.S. Daeffler and R.H. Grubbs Macromolecules 2013, 46, 3288−3292
156
P46 SELECTIVE C=O HYDROGENATION OF ENONES, ENALS, AND ENOATES D.G. Gusev, D. Spasyuk Wilfrid Laurier University, Department of Chemistry, Waterloo, Canada In the past three years,1-4 we developed catalysts 1 - 3 for the reduction of esters under hydrogen gas. Complexes 2 and 3 are today’s most efficeint catalysts for this process and have recently become commercially available (Aldrich catalogue numbers 746339 and 746347).
Here, we disclose the synthetic, structural, and catalytic details of our newest robust, practical, and efficient H2 hydrogenation catalyst, distinguished by excellent carbonyl selectivity. The air-stable osmium complex from our laboratory, OsHCl(CO)(NNNP-tBu) (4), is today's most successful general catalyst for production of unsaturated alcohols from enals, enones, and alkyl enoates under H2 at 25 - 100 °C, while using 0.01 - 0.05 mol% [Os] preferably without solvent.
References
1. Goussev, D. G.; Spasyuk, D. PCT Patent Application WO 2013/023307 A1. 2. Spasyuk, D.; Smith, S.; Gusev, D. G. Angew. Chem. Int. Ed. 2013, 52, 2538 - 2542. 3. Spasyuk, D.; Gusev, D. G. Organometallics 2012, 31, 5239-5242. 4. Spasyuk, D.; Smith, S.; Gusev, D. G. Angew. Chem. Int. Ed. 2012, 51, 2772-2775.
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P47 OVERCOMING SELF-DESTRUCTIVE REACTIVITY IN ORGANOLANTHANIDE COMPLEXES P.G. Hayes, K.R.D. Johnson, B.L. Kamenz University of Lethbridge, Department of Chemistry, Lethbridge, Canada
In an effort to prepare organometallic lanthanide complexes that feature new and unusual properties, we have designed and synthesized several families of pincer ligands comprised of phosphinimine donors attached to rigid aromatic cores. Rare earth complexes of the ligands have been prepared and notably, diverse reaction behavior, such as cyclometalative C–H bond activation, dearomatization and functionalization of ligand pyrimidine rings by 1,5-alkyl migration, and ringopening insertion has been observed. Notably, the evolution of the design of these pincer ligands has recently yielded a series of thermally stable organolanthanide species that are resistant to cyclometalation. The synthesis, as well as the reaction chemistry of the corresponding organometallic complexes, will be presented.
.
158
P48 METALLOPORPHYRIN-INCORPORATED DIPHOSPHINE LIGANDS FOR METAL ION-BINDING G.-A. Yu, K.-M. Wong, J.-S. Huang, N. Zhu, C.-M. Che The University of Hong Kong, Department of Chemistry, Hong Kong Diphosphine ligands have been widely used in organometallic chemistry and catalysis.1 By incorporation of functional units such as metallomacrocycles, the resulting functionalized diphosphines could exhibit unusual properties or binding behavior. In this study, we prepared several examples of ruthenium porphyrin phosphine complexes [RuII(Por)(dppm)2] (1; Por = TTP, 4-MeO-TPP, F20-TPP; dppm = bis(diphenylphosphino)methane) by a similar method to that previously reported for their congeners.2 Reaction of complexes 1 with a number of metal complexes MLn afforded [(LmM)( -dppm)RuII(Por)( -dppm)(MLm)] (2; M = Ag, Au), which have been characterized by spectroscopic methods including 1H NMR, 31P NMR, and UV/Vis spectroscopy, and also by X-ray crystal structure determination. The formation of complexes 2 from complexes 1 demonstrates the role of complexes 1 as a unique type of diphosphine ligands functionalized with metalloporphyrins (which constitute a large family of metal complexes that resemble heme cores in biological systems and exhibit a wide variety of applications3). Studies are underway to explore the properties of this new type of metalloporphyrin-incorporated diphosphine complexes of transition metals.
References 1 (a) Genet, J.-P.; Ayad, T.; Ratovelomanana-Vidal, V. Chem. Rev. 2014, 114, 2824. (b) Broda, H.; Hinrichsen, S.; Tuczek, F. Coord. Chem. Rev. 2013, 257, 587. (c) Birkholz, M.-N.; Freixa, Z.; van Leeuwen, P. W. N. M. Chem. Soc. Rev. 2009, 38, 1099. (d) Freixa, Z.; van Leeuwen, P. W. N. M. Coord. Chem. Rev. 2008, 252, 1755. (e) Tuczek, F. Adv. Inorg. Chem. 2004, 56, 27. (f) Bessel, C. A.; Aggarwal, P.; Marschilok, A. C.; Takeuchi, K. J. Chem. Rev. 2001, 101, 1031. 2 Ball, R. G.; Domazetis, G.; Dolphin, D.; James, B. R.; Trotter, J. Inorg. Chem. 1981, 20, 1556. 3 (a) Handbook of Porphyrin Science, Kadish, K. M.; Smith, K. M.; Guilard, R., Eds.; World Scientific, 2010. (b) The Porphyrin Handbook, Kadish, K. M.; Smith, K. M.; Guilard, R., Eds.; Academic Press, 2000.
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P49 SYNTHESIS OF NOVEL ACCEPTOR MOLECULES OF MONO- AND MULTIADDUCT FULLERENE DERIVATIVES FOR IMPROVING PHOTOVOLTAIC PERFORMANCE H.B. Liu, C. Liu Institute of Chemistry, Chinese Academy of Sciences,CAS Key Laboratory of Organic Solids, Beijing, P.R. China
Fullerene derivatives are extensively used in organic photovoltaics (OPVs) because of their high electron affinity and high mobility1 and remarkable properties on photoinduced electron transfer, in which [6,6]-phenyl C61-butyric acid methyl ester (PC61BM) is the most widely employed material.2 We have successfully synthesized and separated a series of tert-butyl 4-C61-benzoate (t-BCB) organofullerenes, including monoadduct, diadduct, and triadduct compounds, and investigated their photophysics, electrochemistry, thermal properties, and high-performance liquid chromatography analysis.3 The photovoltaic devices were fabricated based on monoadduct, diadduct, and triadduct products, and the devices based on them exhibited power conversion efficiencies of 2.43%, 0.48%, and 1.68%, respectively. Methyl 4-C61-benzoate series fullerene materials with low cost and high yield, including monoadduct and bisadduct compounds were also synthesized and the photovoltaic devices based on them showed power conversion efficiency of 3.48% and 0.16% respectively.4 This was the first time to study the dependent relationship on the device performance and the different isomer numbers. This work supplied new route to design fullerene materials as PCBM’s alternative.
References 1. Yu, G.; Gao, J.; Hummelen, J. C.; Wudl, F.; Heeger, A. J. Science, 1995, 270, 1789. 2. Liu, C.; Xiao, S.; Shu, X.; Li, Y.; Xu, L.; Liu, T.; Yu, Y.; Zhang, L.; Liu, H.; Li, Y. ACS Appl. Mater. Interfaces, 2012, 4(2),1065. 3. Liu, C.; Xu, L.; Chi, D.; Li, Y.; Liu, H.; Wang, J. ACS Applied Materials & Interfaces, 2013, 5, 1061. 4. Liu, C.; Li, Y. J.; Chi, D.; Chen, S. H.; Liu, T. F.; Wang, J. Z.; Liu, H. B.; Li, Y. L. Fullerenes, Nanotubes, and Carbon Nanostructures, 2014, 22, 277.
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P50 THE FIRST EXAMPLE OF THE SYNTHESIS AND STUDY OF 2-[(Z)-1(FERROCENYLMETHOXY)PROP-1-ENYL]-5-ETHENYLIDENE-4,5DIHYDRO-1,3-THIAZOLES BY METHOD OF MALDI MASS SPECTROMETRY O.V. Inozemtseva, O.A. Tarasova, N.A. Nedolya, L.V. Klyba, E.R. Sanzheeva, B.A. Trofimov A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky St., Irkutsk 664033, Russian Federation
Earlier unknown 2-[(Z)-1-(ferrocenylmethoxy)prop-1-enyl]-5-ethenylidene-4,4-dimethyl-4,5dihydro-1,3-thiazole (1), the first representative of ferrocenyl-substituted functionalized 2thiazolines, was obtained in two preparative steps from (ferrocenylmethoxy)allene, isopropyl isothiocyanate, and propargyl bromide (through synthesis and structural reorganization of conjugated 2-aza-1,3,5-triene 2 under action of t-BuONa) in 33% yield (not optimized).
Intens. [a.u.]
Intens. [a.u.]
It was shown that the matrix-assisted laser desorption/ionization (MALDI) mass spectrometry can be appropriate for the study of the low molecular weight thiazoles, in particular, such as compound 1 (with 2,5-dihydroxybenzoic acid as a matrix). In the gas phase under the experiment conditions, the generation of [2M] and [2M – H2O] ions (M is molecule of thiazole 1) was detected. The analysis of the fragmentation of these ions in field-free region showed that their decay was mainly due to both the degradation of thiazole ring and the formation of the ion [FcCH2]+ at m/z 199. 5000
x104
786.469
786.182
B
3
2M
2
4000
1
199.130 313.201 473.353 643.392
0 200
2000
2M - H2O
Intens. [a.u.]
3000
400
600
800
m/z
x104 199.044 1.25 768.338
A
1.00 0.75 0.50
768.312
0.25
313.149
1000
473.156
784.186
0.00 200
400
600
800 m/z
0 767.5
770.0
772.5
775.0
777.5
780.0
782.5
785.0
787.5
790.0
m/z
Mass spectrum MALDI (under the positive mode) of thiazole 1, registered in the mode reflectron. On the inserts: А – the МS2 spectrum of ion at m/z 768, B – the МS2 spectrum of ion at m/z 786. The authors are grateful for the financial support from the Russian Foundation for Basic Research (Grant No. 13-03-00691a). 161
P51 SYNTHESIS AND MASS SPECTRA OF ELECTRON AND CHEMICAL IONIZATION OF 2-[(Z)-1-METHOXYPROP-1-ENYL]-5-ETHENYLIDENE4,5-DIHYDRO-1,3-THIAZOLE O.V. Inozemtseva, L.V. Klyba, E.R. Sanzheeva, N.A. Nedolya, O.A. Tarasova, B.A. Trofimov A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky St., Irkutsk 664033, Russian Federation
The behavior of 2-[(Z)-1-methoxyprop-1-enyl]-5-ethenylidene-4,5-dihydro-1,3-thiazoles 1–4, synthesized for the first time from methoxyallene, isothiocyanates, and propargyl bromide,1 under electron ionization (EI, 70 eV) and positive ion chemical ionization (PICI, methane) has been studied.
Principal fragmentation routes of the 4,5-dihydro-1,3-thiazoles 1–4 after EI include a thiazole ring cleavage (pathway 1) and the loss of alkyl substituent, mainly at position 4 (pathway 2).
For PICI of the compounds 1–4 are typical processes of protonation and electrophilic addition followed by the loss of the 2-methoxybut-2-enenitrile molecule. The authors are grateful for the financial support from the Russian Foundation for Basic Research (Grant No. 13-03-00691a). 1. Nedolya, N. A.; Tarasova, O. A.; Albanov, A. I.; Trofimov, B. A. Tetrahedron Lett. 2014, 55, 2495–2498. 162
P52 FLUORESCENCE PHOTOSENSITIVE MATERIALS FOR INFORMATION OPTICAL RECORDING V.F. Traven, I.V. Ivanov, S.M. Dolotov, D.A. Cheptsov D. Mendeleev University of Chemical Technology of Russia
In the modern world, computer and information technology continue to develop with increasing speed, that increases the requirement for higher performance systems that are capable of preservation, reproduction and processing of information at very high speeds. An actively developing area, allowing to obtain a carrier with high density recorded information is to manufacture fluorescent multilayer disks (FMD). Use of the information recording FM-discs is based on photochemical conversion of compounds that change their fluorescent properties, whether it is shift of the maximum fluorescence, appearance of fluorescence or its attenuation. [1] R3
R3 N
h
N
N
N
+H R1
R2
CH3
H 3C
N
R1
C C l4
CH3
CH3
N
O
H 3C
CH3
+
R2
H
N
CH3
N
O
+
+
CH3
O
OH
O
O
Previously, we have studied new reaction photodehydrogenation 3-pyrazolinylcoumarines and found it be accompanied by increased acidity [2]. In this report, we consider an application of this reaction for opening of the lactone form of rhodamine dye. These two reactions are accompanied by the formation of the fluorophore with a high fluorescence quantum yield and high light resistance. As we have found both these reactions undergo easily both in organic solvents and in polymer matrixes. For example, the irradiation of the polymethylmethacrylate film which contain dissolved pyrazoline, hexachloroethane and lactone of Rhodamine B by light in a wavelength range of 360400 nm leads to the appearance coloration of the film with irradiated areas exhibits fluorescent properties. We have used these results for optical data recording with fluorescent readout. [3] 1). C. M. Rudzinski, D.G. Nocera, In Optical Sensors and Switches; K.S. Schaze, Ed.; Marcel Dekker: New York, USA, 2001 (Chap. 1). 2). I.V. Ivanov, S.M. Dolotov, O.I. Kobeleva, T.M. Valova, V. A. Barachevskii, V.F. Traven, Izv.RAN, Ser.khim. 2012, 2290-2300. 3). V. F. Traven´, S. M. Dolotov, I. V. Ivanov, V. A. Barachevsky, O. I. Kobeleva, T. M. Valova, I. V. Platonova, A. O. Ait, Patent application no. 3011109935 of March 17, 2011;
163
P53 RING OPENING OF DONOR-ACCEPTOR CYCLOPROPANES WITH AZIDE ION – STRAIGHTFORWARD ACCESS TO AZA-HETEROCYCLES K.L. Ivanov, E.V. Villemson, E.M. Budynina, O.A. Ivanova, I.V. Trushkov Moscow State University, Department of Chemistry, Moscow, Russia
Nucleophilic ring opening of donor-acceptor (DA) cyclopropanes is an efficient approach to various polyfunctional structures, including natural products and medicines.1-4 Currently, a wide range of nucleophiles was introduced into reactions with DA cyclopropanes; however, a number of nucleophilic reagents still remains unexplored. In this research, we have found optimal conditions for DA cyclopropanes 1 ring opening with azide ion leading to the formation of -azidocarbonyl compounds 2. Moreover, we developed one-pot process consisting of ring opening/Krapcho dealkoxycarbonylation which allowed us to achieve a simple approach to the GABA precursors 3.
The concurrent presence of azide function, activated methine or methylene group, EDG and EWG substituents in compounds 2 and 3 makes them convenient building blocks for the streamlined synthesis of wide range five- and six-membered N-heterocyclic frameworks which are ubiquitous structural units of numerous natural and synthetic bioactive molecules. We designed approaches to pyrrolidones, pyrroles, piperideines, triazolopyridines, tetrazolopyridines, etc. based on simple synthetic sequences including Staudinger/aza-Wittig cascade or [3+2] cycloaddition as key steps. These strategies were successfully used in formal syntheses of nicotine and atorvastatin.
1. 2. 3. 4.
Reissig H.-U., Zimmer R., Chem. Rev. 2003, 103, 1151-1196 Carson C.A., Kerr M.A., Chem. Soc. Rev. 2009, 38, 3051-3060 Cavitt M.A., Phun L.H., France S., Chem. Soc. Rev. 2014, 43, 804-818 Schneider T.F., Kaschel J., Werz D.B., Angew. Chem. Int. Ed. 2014, 53, 5504-5523
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P54 NATURAL GAS HYDRATE FORMATION IN THE PRESENCE OF SURFACTANTS I.K. Ivanova1, M.E. Semenov2, I.I. Rozhin2 1 - Ammosov North-Eastern Federal University 2 - Institute of Oil and Gas Problems, Siberian Branch, Russian Academy of Sciences
The aim of the work is determination of the temperature and pressure of formation and decomposition (melting) of the natural gas hydrate synthesized from natural gas of the Sredneviluy gas and condensate field (GCF) and distilled water also in the systems based on it: in the presence of sulfonic of 0,1% by weight, as well as with artificial nucleating agent (sand) by differential scanning calorimetry.
Fig. 1 Calculated equilibrium conditions of the gas hydrate formation for natural gas of the Sredneviluy GCF and methane The experimental data (Fig. 1) are identical to those calculated by the method of E. Dendy Sloan for the used natural gas hydrate equilibrium conditions. It should be noted that against the background stands out experimental points obtained by the decomposition of natural gas hydrate, which was synthesized from a 0,1% solution of sulfonic. Comparing the equilibrium conditions of the individual components of natural gas, it is found that this point corresponds to the equilibrium conditions of the methane hydrate. It is known that natural gas hydrates are a mixture of hydrates of different gases with complex structure. This study suggests the possibility of separation of this mixture on the hydrates of individual gases. Furthermore, it was found that the use of surfactants leads to an increased conversion of water into the gas hydrate (> 70%), compared with 2,3% of the gas hydrate formation in distilled water.
165
P55 CONTROL OF THE REACTION SELECTIVITY IN Pd AND NiCATALYZED HYDROPHOSPHORYLATION OF ALKYNES J.V. Ivanova1, L.L. Khemchyan1, S.S. Zalesskiy1, V.P. Ananikov1, I.P. Beletskaya2, Z.A. Starikova3 1 - Zelinsky Institute of Organic Chemistry RAS, Moscow, Russia 2 - Lomonosov Moscow State University, Chemistry Department, Moscow, Russia 3 - Nesmeyanov Institute of Organoelement Compounds RAS, Moscow, Russia
Nowadays, transition-metal-mediated carbon-heteroatom (C-E: E=S, Se, Si, P, Te, O) bond construction has drawn great attention due to well-recognized advantages: high selectivity, quantitative yields and mild reaction conditions. [1],[2],[3] The study of metal-catalyzed phosphorus-carbon (P-C) bond formation has led to significant progress in organic synthesis and established numerous synthetic procedures for the synthesis of new valuable compounds. [1] We developed two switchable synthetic protocols allowing us to obtain the products of choice via subtle change in the catalytic system (Scheme 1). The palladium-based catalyst demonstrated high sensitivity to the number and position of substituent in the aromatic rings of the phosphine ligand. Application of two different phosphines selectively directed the catalytic reaction either to linear or branched product formation. [4] The Ni(acac)2/DIBAL-H precatalyst was the first example of nickel-based system which allowed to synthesize vinylphosphonates, bisphosphonates or alkyltetraphosphonates without any ligands or solvents. [5],[6] Slight variations of Ni precatalyst loading routed the selectivity of the hydrophosphorylation reaction. Mechanistic study with ESI-MS and NMR methods revealed the key nickel intermediates involved into the catalytic cycle. [6]
Scheme 1 [1] V.P. Ananikov, M. Tanaka (Eds.), Hydrofunctionalization, Springer, 2013, Heidelberg. ISBN 978-3-642-33734-5; DOI: 10.1007/978-3-642-33735-2 [2] I.P. Beletskaya, V.P. Ananikov, Chem. Rev., 2011, 111, 1596. [3] F. Alonso, I.P. Beletskaya, M. Yus, Chem. Rev., 2004, 104, 3079. [4] V.P. Ananikov, J.V. Ivanova, L.L. Khemchyan, I.P. Beletskaya, Eur. J. Org. Chem., 2012, 3830. [5] Yu.V. Ivanova, L.L. Khemchyan, S.S. Zalesskii, V.P. Ananikov, I.P. Beletskaya Rus. J. Org. Chem., 2013, 49, 1099. [6] L.L. Khemchyan, J.V. Ivanova, S.S. Zalesskiy, V.P. Ananikov, I.P. Beletskaya, Z.A. Starikova, Adv. Synth. Catal., 2014, 356, 771.
166
P56 Cu-CATALYZED AEROBIC OXIDATIVE TRANSFORMATION OF KETONE-DERIVED N-TOSYL HYDRAZONES: A NEW ENTRY INTO ALKYNES X.-W. Li, W.-Q. Wu, H.-F. Jiang South China University of Technology, School of Chemistry and Chemical Engineering, Guangzhou, P. R. China
Alkyne moiety is a fundamental structural element and functional group occurring in various bioactive molecules, functional materials and natural products.1 Sonogashira reaction and electrophilic alkynylation2 are the most widely used methods for the construction of alkynes, still, some formidable challenges remained to be resolved.3 On the other hand, the field of alkyne retrohydration, that is, deprotonation of ketone derivatives for the alkynes synthesis, however, is still in its infancy. 4 In our continuing efforts toward the development of green chemistry on selective oxidation of unsaturated hydrocarbons,5 we have developed an efficient copper-catalyzed aerobic dehydrogenation of ketone-derived N-tosyl hydrazones which were carbene precursors, to the corresponding alkynes. Further cross-couplings of N-tosyl hydrazones with halides or terminal alkynes were also performed, delivering to functionalized alkynes or asymmertric diynes. A mechanism involved aerobic oxidation of Cu-carbene intermediate was proposed for this C-C triple bond formation.
Reference: 1. Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.; VCH, Weinheim, Germany, 1995. 2. Dudnik, A. S.; Gevorgyan, V. Angew. Chem. Int. Ed. 2010, 49, 2096. 3. Negishi, E.; Anastasia, L. Chem. Rev. 2003, 103, 1979. 4. Negishi, E.; King, A. O.; Klima, W. L.; Patterson, W.; Silveira, A. J. Org. Chem. 1980, 45, 2526. 5. Wu, W.; Jiang, H. Acc. Chem. Res. 2012, 45, 1736.
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P57 [Co]-СATALYZED [6+2]-CYCLOADDITION OF 1,2-DIENES TO 1,3,5,7CYCLOOCTATETRAENE V.A. Dyakonov1, G.N. Kadikova1, G.F. Gazizullina2, U.M. Dzhemilev1 1 - Federal State Institution of Science Institute of Petrochemistry and Catalysis, Russian Academy of Sciences; Laboratory catalytic Synthesys; Ufa; Russia 2 - Ufa State University of Economics and Service; Ufa; Russia
Eight-membered carbocycles are found in many natural compounds exhibiting high biological activity [1]. The catalytic cycloaddition based on 1,3,5,7-cyclooctatetraene (COT) are an effective method for the synthesis of such carbocycles [2]. [Co]-Catalyzed cyclodimerization of COT with alkynes leading to the formation of bicyclo[4.2.2]deca-2,4,7,9-tetraenes 1 [3]. R C o I 2 /d p p e /Z n /Z n I 2 , 4 0 o C , C 2 H 4 C l2
R 1
It should be noted that in literature have no examples of catalytic codimerization of 1,3,5,7cyclooctatetraene with 1,2-dienes. In the development of this work and our ongoing research [4a,b] we carried out [6π+2π]-cycloaddition of COT with 1,2-dienes in the presence of 10 mol% CoI2/dppe/Zn/ZnI2 (C2H4Cl2, 40 ° C, 20 h). The corresponding bicyclo[4.2.2]deca-2,4,7-trienes 2 were obtained in high yields.
R C o I 2 /d p p e /Z n /Z n I 2 , 4 0 o C , C 2 H 4 C l2 R = P h , A lk
R 2
This work was performed under financial support from the Russian Foundation for Basic Research (Grant 13-03-00167 and Grant of RF President (Sci. Sh. – 2136.2014.3)). 1. Plemenkov V.V. Introduction to the chemistry of natural compounds. Kazan, 2001, 376 p. 2. Yu Z.X, Wang Y., Wang Y. Transition-metal-catalyzed cycloadditions for the synthesis of eightmembered carbocycles, Chem. Asian J., 2010, 1072-1088. 3. Achard M., Mosrin M., Tenaglia A., Buono G. Cobalt (ΙΙ)-Catalyzed [6+2] Cycloadditions of Cyclooctatetra(tri)ene with Alkynes, J.Org.Chem, 2006, 71, 2907 -2910. 4. a) Dyakonov V.A., Kadikova G.N., Dzhemilev U.M. Ti-catalyzed [6π +2 π]-cycloadditions of allenes with 1,3,5-cycloheptatriene, Tetrahedron Lett., 2011, 52, 2780-2782; b) Dzhemilev U.M., Kadikova G.N., Kolokoltsev D.I., Dyakonov V.A. Catalytic [6π+2π]-cycloaddition of alkynes, 1,2- and 1,3-dienes to 1,3,5-cycloheptatrienes involving Ti complexes, Tetrahedron, 2013 , 69, 4609-4611.
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P58 MOBILE NANODEFECTS AS COMPLEXING AGENTS IN SOLID PHASE CHEMISTRY A.M. Kaplan, N.I. Chekunaev N.N.Semenov Institute of Chemical Physics, Russian Academy of Sciences
Put forward by one of the authors, the idea about the possible role of mobile nanodefects as complexing agents, allowed to explain for the first time a number of non-trivial effects of solidphase chemistry. These are: 1. the effect of greatly acceleration of catalytic processes induced by high energy impacts on heterogeneous catalysts [1]; 2. the phenomena of "freezing" of polymer chains at constant temperatures and "reanimation" of such chains at temperatures increasing of investigated samples in solids [2]; 3. the effect of exceeding by several orders of the rate of affiliation of monomer molecules to the active centers in glass monomers samples compared to crystalline samples of the monomer [3]; 4. the phenomenon of the abnormal logarithmic time dependence of the polymer yield for unterminated solid-state polymerization at low conversions [4]. In contrast to gas and liquid phases, very low orientation mobility of microparticles in solid phase frequently does not allow to perform chemical interaction even particles of reagents which are in contact with each other for prolonged time. This effect is a consequence of unacceptable for chemical interaction starting mutual orientation of the particles and impossibility to improve the situation at insufficient space close to them. Furthermore, structural nanodefects (mobile vacancies, polyvacancies, dislocations, nanoincontinuity, etc) present in the real solid bodies may, in case of their sufficient mobility, lead to pair of potentially chemically capable, but unreacting due to orientational immobility of adjacent reagents particles, in quite dense areas of solid bodies sufficient free space. Remobing by this the steric barrier for the interactions of such particles. Consequently, as it was for the first time mention by the presenter, real (‘living’) active center (A*) of solid phase reactions should be considered not the experimentally detectable traditional active centers (A) (radical and ions), but a peculiar complex of such centers with the carrier of excess of volume — with mobile nanodefects. The concentration of [A*]0.3, the bunches undergo slow dissociation which rate is determined by the quantity of protonated amino groups. The time-dependency of dissolution degree (measured as an average distance between chains) is almost linear during 10 ns of simulations. The dissolution rate estimated as the time derivative of average distance between chains is also linearly dependent on PD, with threshold of dissolution about PD=0.3 (pH~6.8) which agrees well with available experimental data. The final structures of chitosan after 10 ns of dissolution in aqeous media of various acidity are shown in Figure.
[1] Pedroni V.I., Schulz P.C., Gschaider M.E., Andreucetti N. Colloid Polym Sci, 2003, 282, 100. [2] Franca E.F., Lins R.D., Freitas L.C.G., Straatsma T.P. J. Chem. Theory Comput, 2008, 4, 2141. [3] Franca E.F., Freitas L.C.G., Lins R.D. Biopolymers, 2011, 95, 448. [4] Yui T., Imada K., Okuyama K.,Obata Y.,Suzuki K.,Ogawa K. Macromolecules, 1994. 27, 7601. [5] Hansen H.S., Hünenberger P.H. J Comput Chem, 2011, 32, 998. This work was supported by the RFBR (Project No. 14-03-00585, 14-03-31981)
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P110 THE STEAM OSMOTIC ENGINE WITH THE INCREASED EFF TO 50% P.A. Nazarov Russian Chemical Technology University named after D.I. Mendeleev,Chair of Processes and devices of chemical technology position,Moscow.Russia
The evolution of heat osmotic engine [2] on the prototype[1] is to increase the temperature (T1=380С) of the left part of the circuit(fig.1) the engine in changing the phase state of the water from liquid to gas, but also adding a second stage of desalination by electrodialysis. Due to the process "steam" or osmosis process of rapid diffusion of water vapor molecules through the membrane into the liquid solution inside the reactor 3(fig.1) osmosis increases the specific power of the engine(W/kgengine), as well as its efficiency. Steam osmotic engine[2] repeats energy cycle thermal power plant, but through a process of "steam" osmosis and because of the lack of vapor condensation (in the cooler) its efficiency is much higher. Ideal efficiency manual 2-nd Carnot's theorem is(fig.1): EFF= [(T1–T2)/T1]х100% = [(380С–20С)/380С]х100%=[(653–293)/653]х100%=55% (1) Given the mechanical losses in the pump Pump1, 2; formula for calculating the efficiency takes the form. EFF мах ={(N–Wpumps)/∆Q}= [(T1–T2)/T1]–Wpumps= [(P1osmosis–P2reverse osmosis)/P1osmosis]–Wpumps (2) Where N [W] - output power of osmotic (hydraulic) flow ∆Pturbines=224,1at; ΔQ [W] - The amount of heat in heat generators 1,2 to keep the system in a given thermal regime (the left side of the technological scheme T1=380C=653k, right side T2=20C=293k); Wpumps [W] - power pumps1,2. Steady state operation of the scheme of steam osmotic engine T1=379-380C, T2=20-40C.
fig.1 References 1. Patent of USA №4193267 on 18.03.1980, Metod and apparatus for generating power utilizing pressure-retarted osmosis. Inventor Sydney Loeb, the Bulletin, №1877989, 15.02.1978. 2. The application for the patent of the Russian Federation №2014108948 from 11.03.2014, «Method of reception of mechanical energy and the steam osmotic engine for its realisation» / the applicant and the legal owner Nazarov P. A. 221
P111 THE UNSATURATED CARBON-CARBON BOND HYDROGENATION IN PRESENCE OF NANOPARTICLES OF THE Fe-Ni GROUP D.N. Nebykov, V.M. Mokhov, Yu.V. Popov Volgograd State Technical University, Chemical Technology Faculty, Volgograd, Russia
The hydrogenation of unsaturated substances and arenes is a widely used industrial process, but it proceeds in harsh conditions or requires using of expensive catalysts. We discovered some methods, giving an ability to carry out the reduction of different substituted alkenes and arenes without using of high temperatures and pressures or expensive materials by means of using ferrous, cobalt or nickel nanoparticles as catalysts. The advantage of methods is in combination of metal nanoparticles synthesis and organic substance hydrogenation. The nano-catalyst is formed from inexpensive metal salts by their reduction with complex borohydrides or alumohydrides or by hydrazine hydrate in solutions, in some cases proceeds in situ hydrogenation of unsaturated bonds. The essential interest deserves a method of liquid phase alkenes hydrogenation with gaseous hydrogen at atmospheric pressure, which is a widely used and inexpensive industrial reagent. Using of simply obtained from accessible and inexpensive substances metal nanoparticles is able to decrease the cost and energy losses comparing to traditional hydrogenation methods. The investigations showed an ability of the carbon-carbon unsaturated bond hydrogenation at very smooth conditions - atmospheric pressure and near room temperatures. Also was found that change of hydrogenating agent, catalyst and it's preparing conditions makes possible to direct the process selectivity and also to reduce some functional groups. As starting materials for hydrogenation were used different derivatives of norbornene, styrene, linear and cyclic alkenes, heterocyclic compounds. References 1. Colloid and nanodimensional catalysts in organic synthesis: I. Investigation of hydrogenation selectivity of unsaturated compounds with hydrazine hydrate and aluminum hydride / Popov Yu.V., Mokhov V.M., Nebykov D.N. // Russian Journal of General Chemistry. - 2014. - Vol. 84, No. 3. - C. 444-448. 2. Colloid and nanodimensional catalysts in organic synthesis: II. The hydrogenation of alkenes with hydrogen at atmospheric pressure / Popov Yu.V., Mokhov V.M., Nebykov D.N. // Russian Journal of General Chemistry. - 2014. - Vol. 84, No. 4. - C. 622-628. 3. Hydrogenation of unsaturated carboxylic acids/ Mohov V.N., Popov Y.V., Nebykov D.N.// Izvestiya VolGTU, Series “Chemsitry and technology of organoelemnt monomers and polymeric materials” Iss 12. Mezhvus.sb.nauch.st./VolGTU. – Volgograd, 2014, N7 (134) – C. 60-63.
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P112 SYNTHESIS AND INVESTIGATION OF FUNGICIDAL ACTIVITY OF 6BROMO-4-HYDROXY-2-PHENILINDOLE O.D. Neverova, M.D. Dutov, S.A. Shevelev, G.V. Bastrakova, O.V. Serushkina, K.E. Aisina, S.V. Popkov N. D. Zelinsky institute of organic chemistry, Leninsky prospekt, 47, 119991 Moscow, Russia
Recently, we showed high fungicidal activity of the 2-aryl-4-hydroxy-6-nitroindoles [1]. The presence of the nitro group in these compounds, of course, reduces their value as fungicides, as in the case of use as agricultural agents, and in the case of drugs. Therefore it is very important task to replace the nitro group to an appropriate electronegative substituent, as which, by analogy with Arbidol, we have chosen a bromine atom. Synthesis of the title compound (1) was carried out as follows:
It is shown that 6-bromo-4-hydroxy-2-phenylindole outperforms standard triadimefon by fungitoxicity with respect to all the examined fitopatagence not inferior nitro analog. Compound
Triadimefon
Mycelium growth inhibition, % (С = 30 μg mL-1) V.i.* R.s. F.o. F.m. B.s. S.s. 100
92
88
100
95
100
89
100
88
100
100
100
42
66
60
79
71
47
The authors thank the Russian Foundation for Basic Research (Grant No 13-03-01276) for financial support [1] G. V. Kokurkina, M. D. Dutov, S. A. Shevelev, S. V. Popkov, A. V. Zakharov and V. V. Poroikov, European Journal of Medicinal Chemistry, 2011, 46, 4374-4382.
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P113 THEORETICAL STUDY OF MULTISTEP MECHANISM OF THERMAL FRAGMENTATION OF O-NITRO TOLUENE E.V. Nikolaeva, A.G. Shamov, G.M. Khrapkovskii Kazan National Research Technological University, Catalisis Department, Kazan, Russia
A mechanism which is believed to be involved in thermodistruction of o-nitrotoluene (I) and other nitroarenes bearing hydrogen-containing substituent in ortho-position to nitro group, includes the formation of its aci-form at the first step. At the same time, significant differences in activation enthalpies ( H = Ea – RT) of thermodistruction of compound I were observed by different authors. Thus, in the temperature interval 300-350оС H equals 172,8 kJ/mol[4]; 350-420оС H = 201,6 3 kJ/mol; 797-907оС H = 206,2 kJ/mol. Results of theoretical investigation of the thermodistruction mechanism of compound I, can be presented as the following scheme:
The data on relative enthalpies of formation of transition states of reactions ( Hf , enthalpy of formation of o-nitrotoluene was selected as zero) for this scheme provided in the literature suggest that it should terminate at the limiting step of hydrogen atom transfer between two oxygens in the group =N(O)OH (process III VI). Possibility of further reactions remained unclear. The investigation of the specified sequence of transformation of o-nitrotoluene by B3LYP/631+G(2df,p) demonstrated that this scheme can be realized if isomerization III IV proceeds as a rotation of =N(O)OH around С=N bond. For this process, Hf equals 188 kJ/mol. The limiting steps are elimination of water (V VII) or hydroxyl radical (V VI) from 2,1-benzisoxazol2(3H)-ole (V), with barriers being equal 193,0 and 204,9 kJ/mol, respectively. That is, at lower temperatures, a more probable would be the realization of the process V VII, since for it Hf correlates well with experimental estimation of 201,6 3 kJ/mol. At higher temperatures, there is an opportunity for elimination of OH from compound V (V VI), since for it Hf correlates well with experimental estimation of 206.2 kJ/mol. In favor of this conclusion is the systematic character of deviations (1-9 kJ/mol decrease) of calculated values of activation enthalpies of primary act and specified steps from experimental data. 1. V.G. Matveev, V.V. Dubihin, G.M. Nazin, Izv. Acd. Nauk USSR. Ser. chem., 2, 474-476 (1978). 2. G.M.Khrapkovskii, A.G.Shamov, E.V.Nikolaeva, D.V.Chachkov, Russ.Chem.Rev., 78, 10, 903-943 (2009). 3. Y. Y. Maksimov, Zh. Phys. Chem., XLIII, 3, 725-729 (1969). 4. T.B. Brill, K.J. James, Chem. Rev., 93, 2667-2692 (1993). 5. W. Tsang, D. Robaugh, W.G. Mallard, J. Phys. Chem., 90, 5968-5973 (1986). 6. Y.V. Il’ichev, J. Wirz, J. Phys. Chem. A., 104, 7856-7870 (2000). 7. S.C. Chen, S.C. Xu, E. Duau, M.C. Lin, J. Chem. Phys. A., 110, 10130-10134 (2006). 8. G. Fayet, L. Joubert, P. Rotureau, C. Adamo, J. Phys. Chem. A., 113, 13621-13627 (2009). 9. E.V. Nikolaeva, D.V. Chachkov, A.G. Shamov, G.M. Khrapkovskii, Vestnik NovGU, 2, 73, 76-82 (2013).
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P114 OPTICAL ACTIVE BIS-IMINE RHODIUM(I) COMPLEXES IN TRANSFER HYDROGENATION OF PROCHIRAL C=O BONDS L.O. Nindakova, A.V. Khatashkeev, N.M. Badyrova, I.A. Ushakov, E.Kh. Sadykov Irkutsk State Technical University, Physical-technical Institute, Irkutsk, Russia
Rhodium (1+) complexes with bis-aldimine ligands on the basis of (R,R)-1,2-cyclohexanediamine (1) were tested in the asymmetric transfer hydrogenation of ketones and ketoacids, with isopropanol as hydrogen source under basic conditions. The catalyst:substrate ratio was 1/170-340.
Ligands (1а-1с) were synthesized by the condensation reaction of diamine 1 with aldehides: 2pyridinecarbaldehyde, 2-quinolinecarbaldehyde and 2-thiophene-carbaldehyde, following the scheme:
,
R’- = Rhodium complexes were used as catalysts for this reaction, it was confirmed by 1Н and 13С HMR that this complexes were formed in situ from the reaction of [Rh(1,5-COD)Cl]2 and ligands 1a-1с. TOF and TON values are higher for ligands that synthesize from 2-pyridinecarbaldehyde (250 h-1; 340) and from 2-quinolinecarbaldehyde (109 h-1; 170); the lowest values were obtained for bisaldimine based on 2-thiophene-carbaldehyde (16 h-1; 43). The excess formation of R-(+)enantiomer of 1-phenylethanol and R-(-)-methyl mandelate is observed for all Rhodium complexes. But the all used catalytic systems are slightly enantioselective (prior to 20 % of ee), similar result was obtained using Ir - and Ru -bis(oxazoline) catalytic system [1]. [1] Gömez M, Jansat S., Muller G., Bonnet M. C., Breuzard J. A.J., Lemaire M. J. Organomet. Chem, 2002, 659, 186-195
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P115 STRUCTURAL ANALYSIS OF IODINE ADDUCTS WITH HETEROAROMATIC N-OXIDES V.V. Romanov1, Y.P. Nizhnik1, A.V. Ryzhakov2, L.L. Rodina3 1 - Petrozavodsk State University, Petrozavodsk, Russia 2 - Karelian Research Center RAS, Petrozavodsk, Russia 3 - St. Petersburg State University, St. Petersburg, Russia
Heteroaromatic N-oxides contain two potential donor centers capable to interact with Lewis acids such as halogen bond donors: -system of the aromatic rings and the oxygen atom of N-oxide group. According to the HSAB principle, the iodine as a soft Lewis acid might interact on both donor centers, however the literature and our IR-spectroscopy data unambiguously indicate the oxygen atom as a donor center. Yet a half-century ago T. Kubota [1] questioned the exact geometry of iodine adducts of N-oxides due to potentially different hybridization types of oxygen atom. Actually, owing to an ambivalent character of the group N–O in the heteroaromatic N-oxides, the oxygen atom’s hybridization might be characterized by the two extreme cases – sp3 or sp2. Single X-ray data obtained by us for the adducts of iodine with pyridine, 4-methylpyridine and 4chloroquinoline N-oxides have clearly demonstrated the sp3-character of the oxygen atom in the complexes and the absence of any -interaction. In the both cases for pyridine N-oxides, the structure of the adducts includes infinite quasi one dimensional chains of alternating D and A moieties: ( I–I O I–I O ). In the case of the adduct of 4-chloroquinoline N-oxide with iodine (see the picture), the individual adduct molecule may be distinguished within the crystal lattice. To estimate the possibility of existing different conformations of the adduct (sp3 or sp2), on the base of its crystal structure the energy profile of the structure was calculated in Hyperchem program as the dependence of the potential energy on the dihedral angle (I–I–O–N) – (quinoline ring):
Two distinct barriers have been observed: at 0o ( E = 357 Kcal/mol, corresponds to the structure where iodine is in a close proximity to H8), and 180o ( E = 3.7 Kcal/mol, iodine is in a close proximity to H2). The real X-ray structure (dihedral angle 117 o, ( E = 0.25 Kcal/mol) is similar to the calculated conformer (dihedral angle 131 o, ( E = 0 Kcal/mol)). Obtained data indicate that potential “sp2-stereoisomers” are not favorable energetically due to probably the sterical factors and should not be observed at least in the case of “strong” adducts with bulky Lewis acids. [1] T. Kubota // J. Amer. Chem. Soc. 1965. 87(3). P.458-468.
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P116 COPPER CATALYZED CYCLOPROPYL-ALLYLIC RING-OPENING TRANSFORMATIONS OF GEM-CHLOROFLUORO- AND GEMBROMOFLUOROCYCLOPROPANES. PREPARATION OF 2FLUOROALLYL HALIDES M.A. Novikov, N.V. Volchkov, M.B. Lipkind, O.M. Nefedov N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation
Cyclopropyl-allylic ring-opening transformation of gem-chlorofluoro- and gem-bromofluorocyclopropanes widely available by carbene cyclopropanation of corresponding alkenes is an attractive tool for preparation of 2-fluoroallylic compounds that are known to possess a wide range of biological activities. Ability of copper(I) compounds to catalyze cyclopropyl-allylic isomerization of gem-chlorofluoroand gem-bromofluorocyclopropanes was found and an effective route to 2-fluoroallyllic chlorides and bromides was developed. F R1
R3
R2
R4
CFX
R1
R2
F
X R3
R4
C u X /M e C N or (N H C )C u X /d io x a n e
R1
X R2 R3
R4
8 0 -1 0 0 ° C
X = C l, B r; R 1 -R 4 = H , C H 3 , -(C H 2 ) n - (n = 2 -4 ), P h , -C H = C H 2 , c -C 3 H 5 , C l;
Thus, from alkyl-, aryl, chloro substituted gem-chlorofluoro- and gem-bromofluorocyclopropanes, their bicyclic and spiro-substituted derivatives, in presence of CuX or (NHC)CuX (NHC — Nheterocyclic carbene) in MeCN or 1,4-dioxane at elevated temperatures corresponding 2fluoroallyllic chlorides and bromides could be prepared. In the case of vinyl substituted gemchlorofluorocyclopropane 5-chloro-2-fluoropenta-1,3-diene forms as a major product. Isomerization of gem-chlorofluoro-1,1’-bi(cyclopropane) proceeds via successive opening of both cycles leading to 6-chloro-2-fluorohexa-1,3-diene as an only product. References 1) N. V. Volchkov, M. A. Novikov, M. B. Lipkind, and O. M. Nefedov, Mendeleev Commun., 2013, 23, 19–21; 2) M. A. Novikov, N. V. Volchkov, M. B. Lipkind, and O. M. Nefedov, Russ. Chem. Bull., 2013, 62, 71–82.
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P117 DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF PGLYCOPROTEIN INHIBITORS FOR MODULATION AND PREVENTION OF MULTIDRUG RESISTANCE M. Sagnou1, X. Alexiou1, E.S. Kolotova2, A.A. Shtil2, A.A. Zeifman3, I.J. Titov3, O.V. Stroganov3, V.V. Stroylov3, I.V. Svitanko3, F.N. Novikov3, G.G. Chilov3 1 - Demokritos National Research Center, Greece 2 - Russian Scientific Oncology Center RAS 3 - N. D. Zelinsky institute of organic chemistry, Russia
Multidrug resistance (MDR) mediated by P-glycoprotein (one of ATP-binding cassette (ABC) transporters) through efflux of antineoplastic agents from cancer cells is a major obstacle to successful cancer chemotherapy. The inhibition of P-glycoprotein (P-gp) is thus a logical approach to circumvent MDR. There has been intensive research effort to design and develop novel inhibitors for the P-gp and other ABC transporters to achieve this goal. Complex in silico P-gp inhibition model was developed in the present study using the pharmacophore ensemble/support vector machine scheme (to take into account the promiscuous nature of P-gp), molecular docking and molecular dynamics approach (to predict ligand binding pose in huge P-gp hydrophobic cavity) and free energy perturbation methods (FEP, to accurate estimation of ligand-binding affinities). Two series of novel P-gp inhibitors (based on curcumine scaffold) was designed, synthesized and evaluated in doxorubicin accumulation and cytotoxicity tests on chronic myeloid leukemia cell line К562/Dox with MDR phenotype. During the first round of optimization we discovered novel P-gp inhibitors that bind to the active site of the enzyme and have activity comparable to clinical P-gp blocker verapamil. We showed that that hydrogen bonds with residues T837 and Q737 and hydrophobic and stacking interactions with residues P770, Y307 and P994 play significant role in ligand binding. We demonstrated that for correct predictions of relative binding energy by FEP it is necessary to carry out an explicit account of the solvent, since the bridging water molecules significantly contribute to the energy of formation of the protein-ligand complex. In the second round of optimization we discovered P-gp inhibitors that were to verapamil and comparable with P-gp inhibitors in clinical trials. We demonstrated that these compounds do not exhibit the toxicity at concentrations up to 50 uM and have more than 100-fold lower IC50 in doxorubicin cytotoxicity tests on К562/Dox with MDR phenotype
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P118 SELECTIVE HYDROGENATION OF UNSATURATED ALDEHYDES ON THE COMPOSITE Pt-BASED NANOCATALYSTS. A QUANTUM CHEMICAL STUDY A.I. Okhapkin1, O.B. Gadzhiev1, A.E. Masunov2, S. Kunz3, M. Bäumer3, S.K. Ignatov1 1 - N.I. Lobachevsky State University of Nizhny Novgorod, Chemistry Department, Nizhny Novgorod, Russia 2 - University of Central Florida, Chemistry Department, Orlando, USA 3 - University of Bremen, Institute for Applied and Physical Chemistry (IAPC), Bremen, Germany
Selective hydrogenation of unsaturated aldehydes to alcohols is a key process in fabrication of fragrance components for the modern cosmetology and perfume industry. Since the selective oxogroup hydrogenation is thermodynamically unfavorable due to the presence of the C=C bond, the industrial process is indirect, complicated, and expensive. Recently, a novel type of catalyst was proposed that shows enhanced selectivity towards unsaturated alcohols. It is using metal-oxide supported Pt-nanoparticles with chemically modified surface. In a present work, the elementary steps of such a catalytic reaction, i.e., propenal and croton aldehyde hydrogenation, were studied within the cluster models of Pt surface using the DFT quantum chemical calculations (BLYP and PBE density functionals in conjunction with the CRENBS or LANL2DZ pseudopotentials for Pt atoms and 6-31G(d,p) basis set for the remaining atoms). The clusters Pt8, Pt13, and Pt25 consisting of two layers of Pt atoms were used as models for the Pt nanoparticle surface. The diameter of the Pt25 cluster is about 12 Å which is close to the size estimated for the experimentally studied Pt nanoparticles (18±3Å) [1]. The different spin states of the clusters were considered (spin multiplicity up to 11). The adsorption of reagents (H2 and aldehydes) and the organic ligands working as orienting agents ensuring the reaction selectivity (BuSH, Bu = n-C4H9) were studied as initial steps of the catalytic process. The various kinds of adsorption were studied: (1) physical adsorption of H2 on different sites of Ptn clusters; (2) dissociative chemisorption of H2 resulting in the Pt-adsorbed H atoms; (3) chemisorption of ligands forming the Ptn-SBu structures and the neighboring –SBu/H adsorbed pairs; (4) aldehyde adsorption on the neat Pt surface and the surface partially occupied by the H atoms and the –SBu and –SBu/H groups. For all these pre-reaction surface complexes, the molecular structures, adsorption energies, and vibrational frequencies were studied. It was found that the ground state of the Pt25 clusters is the quintet one with the typical spread of energies in lower spin states (M=1,3,5, and 7) of about 3 kcal mol-1. The H2 physical adsorption energy is about 0.6-1.8 kcal mol-1 depending on the adsorption site. The dissociative adsorption energy of H2 was estimated to be 5-9 kcal mol-1which is in reasonable agreement with experimental values (~16 kcal mol-1)[2]. At the same time, the –SBu group formation energy was estimated as 30-56 kcal mol-1 depending on the adsorption site. Their estimated surface coverage of about 4/9 monolayer is in reasonable agreement with the experimentally observed dependence of hydrogenation kinetics on the surface coverage [1]. The kinetic barriers of the surface migration of adsorbed H atoms and various hydrogenation pathways are discussed on the basis of the different theoretical estimates. 1. L. Altmann, S. Kunz, M. Bäumer, J. Phys. Chem. C 2014, 118, 8925-8932 2. P.R. Norton, J.A. Davies, T.E. Jackman, Surf. Sci., 1982, 121, 103-110 The work was partially supported by the Russian Foundation for Basic research (project No. 14-0300585). OBG and AIO are thankful to DAAD for the travel grants support.
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P119 NMR DIFFERENTIATION OF CHIRAL ALCOHOLS AND AMINES USING SELENIUM-BASED CHIRAL PROBES N.V. Orlov, V.P. Ananikov Zelinsky Institute of Organic Chemistry RAS, Russia, Moscow, Leninsky pr. 47, 119991
Modern NMR spectroscopy is a powerful tool for structure elucidation of complex organic molecules including natural products1. An important issue in this field is analysis of complex mixtures of chiral compounds and determination of enantiomeric composition of each individual molecule. Utilization of chiral auxiliary reagents allows to efficiently differentiate enantiomers in NMR spectra2. Besides, continuous progress in development of chiral auxiliaries and derivatization protocols made it possible to obtain diastereomers suitable for NMR analysis within minutes directly in NMR tube excluding isolation and purification steps3. Nevertheless analysis of mixtures of several chiral compounds is still a complicated task4. Recently we have developed simple synthetic routes to several selenium-based chiral probes which readily react with chiral alcohols and amines directly in an NMR tube (Scheme 1, left) followed by determination of their enantiomeric composition using 77Se NMR spectroscopy5. In this case only signals of selenium-containing diastereomers formed are observed in the spectra thus simplifying assignment procedure.
Scheme 1. DCC-promoted "in tube" derivatization of chiral alcohols and amines with chiral probes R-ArSePA (left) and examples of spectral data - structure relationship using R-(4chlorophenylselanyl) propionic acid (right). Now we have revealed that the diastereomers formed can be efficiently differentiated in 77Se NMR spectra depending on the nature of substituents at stereogenic center of analyzed chiral aclohols and amines (Scheme 1, right). This observation gives possibility to perform preliminary structure elucidation in several minutes and to analyse complex mixtures using a single 1D NMR experiment. Scope and limitations of this approach to various chiral alcohols and amines will be presented in the poster. Acknowledgments: This work was supported by RFBR (project No. 12-03-01094). 1. Breton, R. C.; Reynolds, W.F. Nat. Prod. Rep. 2013, 30, 501. 2. Wenzel, T. J. Top. Curr. Chem. 2013, 341, 1. Chem. Rev. 2012, 112, 4603. 4. Novoa-Carballal, R.; Fernandez-Megia, E.; Jimenez, C.; Riguera, R. Nat. Prod. Rep. 2011, 28, 78. 5. Orlov, N. V.; Ananikov, V. P. Chem. Commun. 2010, 46, 3212. 230
P120 NEW LIFE FOR OLD REACTION. SYNTHESIS OF THIAZOLIDINES VIA REGIOSELECTIVE ADDITION OF UNSYMMETRIC THIOUREAS TO MALEIC ACID DERIVATIVES A.S. Pankova, M.A. Kuznetsov Saint Petersburg State University, Insitute of Chemistry, Saint Petersburg, Russia
Thiazolidine derivatives and, in particular, thiazolidinylacetic acids are highly valuable scaffolds for medicinal and bioorganic chemistry as can be exemplified by a central penicillin core that contains fused -lactam and thiazolidine rings. Various substituted thiazolidines feature exclusively broad range of biological activities that warrants a constant interest in preparing new thiazolidines and studying their properties. Addition of thiourea derivatives to maleic anhydride or maleimides is used to get a rich functionalized thiazolidinylacetic acid framework. This reactions is classical, but at the same time many questions concerning regioselectivity in case of unsymmetric thioureas remained unclear and there were problems to be solved. Some controversial data and surprising results can be found in the literature and therefore we decided to thoroughly investigate factors governing the regioselectivity of this process.
We have shown that addition of N-aryl-N’-ethyl(or methyl)thioureas to N-arylmaleimides proceeds regioselectively providing 2-(3-ethyl(methyl)-2-arylimino-4-oxo-1,3-thiazolidin-5-yl)-Narylacetamides in good yields. It is applicable for a wide range of substituents in aromatic rings and the product selectivity does not depend on the solvent used. A remarkable dependence of the reaction regioselectivity on the solvent polarity was revealed with more sterically hindered alkyl thioureas. In nonpolar benzene 3-alkyl-2-arylimino-4-oxo-1,3-thiazolidines are formed preferentially, whereas in polar isopropyl alcohol and acetonitrile the reaction regioselectivity changes in favor of 2-alkylimino-3-aryl-4-oxo-1,3-thiazolidines. In the case of the most bulky N-tert-butyl-N’-phenylthiourea, the isomer with exo-cyclic position of an alkyl group is formed exclusively. At the same time addition of sterically hindered N-alkyl-N’-arylthioureas to maleic anhydride leads only to 3-alkyl-2-arylimino-4-oxo-1,3-thiazolidinylacetic acids independent of the solvent used. We have unambiguously established the structures of all obtained thiazolidines (some of them using X-ray data) and demonstrated the utility of the 15N-1H HMBC spectroscopy for their unequivocal assignment. Authors thank the Russian Scientific Fund for a research grant no. 14-13-00126.
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P121 MECHANISTIC STUDY OF Cu2O AND CuO-CATALYZED C–S CROSS COUPLING REACTION Y.S. Panova1, V.P. Ananikov2 1 - Saint-Petersburg State University Institute of Chemistry, Russia, Petrodvorets, Universitetsky pr. 26 2 - N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Russia, Moscow, Leninsky pr. 47
C-S cross-coupling is a valuable synthetic tool to prepare a diversity of sulfur derivatives with high yields [1,2]. In spite of various synthetic applications, the mechanism of C-S cross-coupling was not clearly resolved. Catalytic reactions mediated with CuO and Cu2O nanoparticles represent a substantial challenge in this regard. In order to have a better insight of the reaction pathways, detailed FE-SEM, ESI-MS and NMR studies were carried out. Ligand-free copper oxides (I, II)-catalyzed reactions of thiophenol with 4iodotoluene were chosen as a model reaction. The role of copper centers on the surface of the nanoparticles and in solution was studied and compared to reported in the literature reaction pathways. It is interesting to note, DFT calculations revealed that strongly polar solvent (like DMSO) facilitates the formation of the anionic active species [Cu(SPh)2]- [3]. This type of intermediates is favored for halogen atom transfer mechanism as its activation energy barrier much lower (33.2 kcal/mol), then the activation energy barrier of the most often suggested oxidative addition mechanism (41.3 kcal/mol), according to theoretical study [3]. Based on calculations and experimental data we will discuss the following catalytic pathways: 1) generation of [Cu(SPh)2]- complex by reaction of thiophenol with the base and copper oxides; 2) iodine atom transfer from 4-iodotoluene to Cu-center to form the [Cu(SPh)I]- intermediate and phenyl radical; 3) attack by phenyl radical at S atom of Ph-thiolate affording the formation of coupling product. It is noteworthy, that in the absence a base, intermediate [CuI2]- was observed by ESI-MS analysis. References [1] S. Ganesh Babu, R. Karvembu Tetrahedron Lett., 2013, 54, 1677–1680. [2] S.-W. Cheng, M.-C. Tseng, K.-H. Lii, C.-R. Leec, and S.-G. Shyu Chem. Commun., 2011, 47, 5599–5601. [3] S.-L. Zhang, and H.-J. Fan Organometallics, 2013, 32, 4944-4951. Acknowledgment P.Y. acknowledges (12.50.1560.2013).
Saint-Petersburg
State
232
University
for
postdoctoral
fellowship
P122 TRANSFORMATIONS OF CYCLIC ORGANIC PEROXIDES IN THE PRESENCE OF TRANSITION METALS Z.Y. Pastukhova1, I.A. Yaremenko1, L.G. Bruk2, A.O. Terent’ev1 1 - N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences 2 - Lomonosov Moscow State University of Fine Chemical Technologies
Currently, organic peroxides are produced by dozens of the largest chemical companies in a largetonnage scale. Peroxides are the main source of free radicals in chemical practice. They are widely used to initiate radical including chain-radical processes, especially in the polymer manufacture. In the past decades, the chemistry of organic peroxides has attracted considerable attention from physicians and pharmacologists due to the detection of these compounds high antimalarial, anthelminthic and antitumor activities. Thermal instability of peroxides, because of the presence of weak O-O bonds, leads to decomposition at normal or elevated temperatures. Transition metals (Fe, Сu, Мn, Со, Сr) and their salts are effective catalysts of decomposition. Usually decomposition of organic peroxides is nonselective process. Decomposition reactions are not limited by the only homolytic decomposition of O-O bond resulting in a complex product mixture is generated. In our work we found the selective transformations of cyclic organic peroxides in the presence of transition metals (Scheme 1). Scheme 1. Transformations of Cyclic Organic Peroxides
O O
?
O O
Mn+
O
?
O O
?
O O This work is supported by RFBR №14-03-00237.
Terent’ev A.O., Yaremenko I.A., Chernyshev V.V., Dembitsky V.M., Nikishin G.I. // J. Org. Chem. 2012, 77, 1833-1842. Terent'ev A.O, Yaremenko I.A., Vil' V.A., Dembitsky V.M, Nikishin G.I. // Synthesis. 2013, 45 (2), 246-250. Ingram K., Yaremenko I.A., Krylov I.B., Hofer L., Terent'ev A.O., and Keiser J. // J. Med. Chem. 2012, 55 (20), 8700-8711.
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P123 ENANTIOSELECTIVE HYDROLYSIS OF 3-HYDROXY-1,4BENZODIAZEPIN-2-ONE ESTERS BY PIG LIVER MICROSOMES V.I. Pavlovsky1, E.A. Shesterenko1, I.I. Romanovska1, O.V. Sevastyanov1, T.A. Yurpalova1, S.A. Andronati1, V.Ch. Kravtsov2 1 - A.V. Bogatsky Physico-chemical Institute, National Academy of Sciences of Ukraine, Lustdorfska dor., 86, Odessa, Ukraine 2 - Institute of Applied Physics, Academy of Sciences of Moldova, Chisinau, Republic of Moldova The configuration of chiral biologically active compounds plays an important role in processes of their biotransformation and binding with biomembranes. Methods of asymmetric synthesis and resolution of enantiomers are fraught to difficulties, thus development of economical preparative biotechnological methods of enantiomers resolution is prospective. Carboxylesterase (EC 3.1.1.1) is the most studied enzyme, which catalyze the enantioselective hydrolysis of a wide range of acyclic, carbocyclic and heterocyclic compounds. But the number of publications, devoted to the enantioselective hydrolysis of benzodiazepine derivatives, which clinical effects include anxiolytic, anticonvulsant and hypnotic effects, muscle relaxation is quite limited. The aim of the present work was the development of a method of the enantioselective hydrolysis of 3hydroxy-1,4-benzodiazepin-2-one esters by pig liver microsomes and investigation of S-enantiomers binding affinity for central benzodiazepine receptors. Microsomal fraction was isolated by the low speed centrifugation method in the presence of Ca2+ ions. Protein yield was 38.0 mg/g of liver tissue and esterase activity was 17.25 U/mg protein. The method of enantioselective hydrolysis of 1-unsubstituted-(1), 1-methyl-(2), 1-ethyl-(3) 3-acetoxy-7bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones using pig liver microsomal fraction was 3 developed (esterase activity 130- U/cm ; pH 7,0; t 37 ºC; τ 2,5 h; DMSO concentration 40 % (v/v)). Enantiomers of 3-hydroxy-1,4-benzodiazepin-2-one esters were purified by silica gel column chromatography. Enantiomeric excesses of substrates (ees) were determined by HPLC using Shimadzu LC8A pump with a chiral column ChiraDex. It was shown, that the products of the reaction – 1-unsubstituted(4), 1-methyl-(5), 1-ethyl-3-hydroxy-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones (6) underwent racemization during hydrolysis and subsequent isolation, what is consistent with the literature data [1]. The S-enantiomers of three substrates 1S-3S were obtained with ees >97 % and yields 44-49 %, their absolute configurations were determined by X-ray crystallography (fig.).
3S(b) 1S 2S 3S(a) Fig. ORTEP view of molecular structure of 1S, 2S, and two conformers in the structure 3S (a and b) illustrates their absolute configuration. Values of specific rotation 20D of 1S-3S were +116.9º, +195.3º, +193.8º (c = 1.0, CHCl3), respectively. With a help of the radioligand binding methods, affinity of S-enantiomers 1S-3S and racemates 1-3 for the CBR of rat brain was determined and values of IC50 were evaluated. It was shown, that the S-enantiomers 1S-3S are 1.4-2.1 times more potent ligands of CBR than the corresponding racemates 1-3. References: 1. Oswald P., Desmet K., Sandra P. et al, 2002 Determination of the enantiomerization energy barrier of some 3hydroxy-1,4-benzodiazepine drugs by supercritical fluid chromatography. J. Chromatogr. B. 779, 283–295.
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P124 A SIMPLE TECHNIQUE FOR PRODUCING PALLADIUM NANOPARTICLES ON CARBON SUPPORT AS CATALYST FOR CROSS-COUPLING REACTIONS E.O. Pentsak, V.P. Ananikov N.D. Zelinsky Institute of Organic Chemistry RAS, Moscow, Russia
Recently, much attention has been paid to carbon materials, modified by metal nanoparticles, due to increasing interest in using of such systems in catalysis, material science optics and electronics. Successful application of palladium nanoparticles supported on carbon materials was facilitated many organic synthesis procedures. Efficiency and selectivity of these catalysts was determined by such characteristics as particles size, the uniformity of their distribution on the support surface and the range of particle size distribution. We have previously shown that the labile behavior in solution and the tendency to form palladium clusters are inherent in Pd2dba3 complex [1]. Thus, we were able to cover carbon material by nanoparticles with optimum sizes and high monodispersity under mild conditions without the need of stabilizers and reducing agents, using easily available Pd2dba3 complex as a precursor of palladium. In this study, we found that the variation of temperature and concentration of solution allowed tuning of coverage density of the supported nanoparticles, as well as control of diameter of the nanoparticles from 2 to 15 nm. This procedure was found scalable and well reproducible. Dispersion values of the nanoparticles sizes usually did not exceed 1-2 nm. Kinetics of the process was investigated by nuclear magnetic resonance spectroscopy NMR and scanning electron microscopy (FE-SEM). Study of deposition process by FE-SEM showed that the average particles size was stabilized quickly during the coating process. The particles size depended on the conditions of the process, while the increase of the coating density occurred gradually until complete consumption of the Pd precursor. The catalytic activity of prepared palladium nanoparticles supported on graphite has been studied utilizing model Suzuki and Heck reactions. The catalyst prepared by our method showed high efficiency for this type of reactions, 100% conversion of the Heck and Suzuki reactions was reached only in a few hours at low catalyst loadings (0.2-0.5 mol %).
[1] Zalesskiy S. S., Ananikov V. P. // Organometallics, 2012, V. 31, P. 2302–2309.
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P125 SELECTIVE CLEAVAGE OF GLYCOSIDIC LINKAGES USING SOLVOLYSIS WITH ANHYDROUS TRIFLUOROACETIC ACID S.N. Senchenkova, A.V. Perepelov, A.V. Filatov, A.S. Shashkov, Y.A. Knirel N.D.Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
A common approach in structural studies of polysaccharides is the selective cleavage of glycosidic linkages to give oligosaccharide fragments, which usually show better-resolved NMR spectra than the parent polymer and are readily amenable to MS analysis. One of the methods useful for this purpose is solvolysis with strong acids. For instance, solvolysis with anhydrous HF has been used in structural analysis of carbohydrates since early 1980s, and later trifluoromethanesulfonic (triflic) acid was introduced. However, these reagents have some disadvantages; e.g. HF handling requires special equipment, triflic acid is expensive, and both are highly hazardous. In search for a better solvolytic agent, we tested anhydrous CF3CO2H in selective cleavage O-polysaccharides of medically important bacteria Escherichia coli and Enterobacter cloacae and found it to be useful and convenient. CF3CO2H split selectively the α1→2- and α1→3-rhamno- and -fuco-pyranosidic linkages as well as the HexpNAc-(1→4)-Manp linkage, whereas other linkages were not affected. Below are structures of the cleaved O-polysaccharides (O68 at 50°C for 16 h; all others at 40°C for 5 h) with the glycosidic linkages sensitive to CF3CO2H shown in rectangles.
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P126 СROSS-COUPLING OF TEREPHTHALONITRILE DIANION AND AROMATIC NITRILE RESULTING IN SUBSTITUTED DICYANOBIARYLS R.Yu. Peshkov1, E.V. Panteleeva1, V.D. Shteingarts2 1 - Novosibirsk State University, Novosibirsk, Russia 2 - N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Novosibirsk, Russia
Cyanobiaryls have a wide area of practical utilization in technology (polymers, semiconductors, OLED) as well as in medicine [1]. Modern approaches to their synthesis are based on manifold cross-coupling reactions of preactivated arenes catalyzed by transition metals. We suggest a concise and inexpensive non-catalytic approach applying terephthalonitrile dianion 1 as cyanoarylating reagent for neutral aromatic nitriles. It was found that 1, generated by terephthalonitrile reduction with alkali metal in liquid ammonia, undergoes cross-coupling with benzonitrile as well as 2- and 3cyanobiphenyls providing 4,4`-dicyanobiphenyl and dicyanoterphenyls [2]. Present work is aimed on broadening the scope of neutral substrates applicable for such type of cross-coupling and study of its mechanism by revealing electronic and structural factors governing regioselectivity and efficiency of the reaction. For the purpose we varied the nature of substrate by introduction of an extra substituent into benzonitrile (Me, MeO, F, Cl, Br) as well as by alteration of aromatic moiety. (cyanonaphthalenes, 9-cyanoanthracene, 4-cyanopyridine). Besides nitriles, electron-deficient arenes: ethylbenzoate, 3-methylbenzophenone and nitrobenzene were tested. Also experimental and quantum-chemical modeling of possible reaction pathways were performed. We found out that benzonitriles substituted with o-, m-Me, -MeO and -F, both cyanonaphthalenes and 9cyanoanthracene undergo coupling with 1 providing subsequent cyanobiaryls (scheme). Towards all other substrates 1 acts as reducing reagent. The regularities revealed are interpreted in terms of the reaction scheme with the intermediacy of the charge-transfer complex 2 between 1 and cyanoarene [2], which further transforms into dimeric dianion 3 either by heterolytic pathway or by successive single electron transfer and recombination of primary generated radical anions. Subsequent decyanation of 3 forms long-living monoanion 4 capable to be converted into cyanobiarylic product either through oxidation or alkylation. CN
CN
CN
CN
X
CN CTC
1
X
CN
CN
X
CN
Bu X
CN F
NC
CN
-CNCN
CN
4
3 X
CN
F
X
[O]
Alk
NC Alk
heterolytic pathway (SNAr)
F
2-
CN
X X
X
primary RA-pair
2 + CN 2M ArX
in-cage recombination
ET
2-
2- +
CN
CN
CN CN *
CN
AlkB r -Br -
X
Bu
CN
X -H+ -CN-
CN
CN
CN
CN
NH3
CN
M: Li, Na, K X: H; 2-, 3-CH3; -OCH3; -F ArX:
CN CN
CN CN
CN
F
F F
CN
CN
F
X
CN
CN
F
F
cyanobiaryle yield 14-90%
CN NC
CN
CN
CN
CN
F
CN
CN
CN
CN CN
CN
X
F
The financial support of the CMSD of RAS (the project No 2.6) is acknowledged. [1] Corbet, J.-P., Mignani, G. Chem. Rev., 2006, 106, 2651. [2] a) Panteleeva, E.V. et al., Eur. J. Org. Chem., 2005, 2558; b) Panteleeva, E.V. et al., ARKIVOC, 2011, viii, 123. 237
P127 REARRANGEMENT OF CYCLIC 9-MEMBERS Si-PEROXIDES R.A. Pototskiy1, R.A. Novikov2, A.O. Terentev1, G.I. Nikishin1, A.V. Arzumanyan1 1 - N. D. Zelinsky Institute of Organic Chemistry, Laboratory for Studies of Homolytic Reactions, Moscow, Russia 2 - N. D. Zelinsky Institute of Organic Chemistry, Laboratory of Carbene Chemistry and SmallSized Cyclic Compounds, Moscow, Russia
Among organic peroxides, compounds with SiOO moiety are less known than their carbon analogues. As the result there are few examples of reaction of silicon containing peroxides in literature. In the previous works we reported about successful synthesis of different silicon containing cyclic peroxides [1,2]. Now we focused on investigation of treatment of such compounds with different reducers and Lewis acids (LA). It has been shown that treatment of the cyclic Si-peroxides with different Si Si reducers leads to contraction of peroxide cycle on two oxygen atoms. Notably O O each peroxide group lost one oxygen atom giving earlier unknown silylO O protecting diols. Reaction was carried out in diethyl ether medium at ambient R R' temperature in the presence of 3-fold access of a reducer. The best results were reached with triphenylphosphine. Yield of products were 60 to 75%, depending on structure of starting substance. Such products may be used as building blocks bin different bioactive compounds. Treatment of bis-sililperoxides under LA action was studied. The reaction was carried out in different reaction media with 2-fold excess of LA (SnCl4, TiCl4, AlCl3). It has been established that the way of reaction depends on nature LA catalyst. For example, formation of lactones yield of 80 – 95% was observed (Bayer-Villiger-like reaction) in the presence of SnCl4. In case of TiCl4 the combination of a regrouping and formation of an appropriate ketone was observed; with AlCl3 reaction did not flow past. Summary, in this work chemical reactions of cyclic Si-peroxide compounds have been investigated. Organic silicon peroxide compounds can enter various reactions leading to formation of lactones, diols with a trialkylsilyl group, depending on reaction conditions that point to their high synthetic potential. References: [1] Arzumanyan A.V., Terent’ev A.O., Nikishin G.I. et.al. Organometallics, 2014, 33, 2230-2246. [2] Platonov M.M., Terent’ev A.O., Nikishin G.I. et.al. J. Org. Chem., 2008, 73, 3169-3174.
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P128 EFFICIENT ONE-POT SYNTHESIS OF DIVERSE BENZO[C[CHROMENE6-ONES BY BASE-PROMOTED CASCADE REACTIONS T.N. Poudel, Y.R. Lee School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of Korea Molecules bearing benzo[c]chromen-6-one and its derivatives are extensively distributed in nature.1 Some of these molecules exhibit biologically and pharmacologically important antitumor and antibiotic activities,2 promote endothelial cell proliferation, and inhibit oestrogene receptor growth activities.3 Due to the importance of these biological and pharmacological activities, several synthetic methods have been devised to produce benzo[c]chromen-6-one derivatives. Of these methods, the most useful method involves a Suzuki-Miyaura cross-coupling reaction followed by metal or Lewis acid mediated lactonization of ester and methoxy groups.4 Recently, a new reaction involving a microwave-assisted Diels-Alder reaction betwee 4-cyanocoumarin and 1-oxygenated dienes followed by elimination and aromatization with a strong base was also described. 5 However, these synthetic approaches included two-step reactions and required purification of the intermediate. In addition, the starting materials used for these transformations were synthesized from corresponding materials in two or more steps. Thus, a mild, general, and efficient one-pot synthetic route for benzo[c]chromen-6-one derivatives using inexpensive catalysts and reagents is still in demand, especially a route that allows minimization of the steps and access to diverse products. We present herein a novel one-pot synthesis of a variety of benzo[c]chromen-6-one derivatives using Cs2CO3-promoted reactions of substituted 2-hydroxychalcones and β-ketoesters. These reactions involved cascade Michael addition/ intramolecular aldol/ oxidative aromatization/ lactonization and provided an efficient synthetic route for the production of biologically interesting novel benzo[c]chromen-6-one molecules bearing several different substituents on benzene rings. As an application of this methodology, several synthesized benzo[c]chromen-6-ones were transformed into highly functionalized novel terphenyls.
References: 1. (a) Ya. L. Garazd, A. S. Ogorodniichuk, M. M. Garazd andV. P. Khilya, Chem. Nat. Compd., 2002, 38, 424; (b) K. Ishiguro, M. Yamaki, M. Kashihara, S. Takagi and K. Isoi, Phytochemistry,1990, 29, 1010; (c) H. Abe, K. Nishioka, S. Takeda, M. Arai, Y. Takeuchi and T. Harayama, Tetrahedron Lett.,2005,46, 3197. 2. (a) T. Hosoya, E. Takashiro, T. Matsumoto and K. Suzuki, J. Am. Chem. Soc.,1994, 116, 1004;(b) C. A. James and V. Snieckus, Tetrahedron Lett.,1997, 38, 8149. 3. (a) J. M. Schmidt, G. B. Tremblay, M. Page, J. Mercure, M. Feher, R. Dunn-Dufault, M. G. Peter and P. R. Redden, J. Med. Chem., 2003, 46, 1289;(b) J. Pandey, A. K. Jha and K. Hajela, Bioorg. Med. Chem.,2004, 12, 2239. 4. (a) Q. J. Zhou, K. Worm and R. E. Dolle, J. Org. Chem.,2004, 69, 5147; (b) G. J. Kemperman, B. Ter Horst, D. Van de Goor, T. Roeters, J. Bergwerff, R. Van der Eem and J. Basten,Eur. J. Org. Chem.,2006, 14, 3169 5. M. E.Jung and D. A. Allen, Org. Lett., 2009, 11, 757.
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P129 PRACTICAL SYNTHESIS OF 1,2,4-THIADIAZOLES VIA` COPPER-MEDIATED HOMO-COUPLING OF THIOAMIDES Y.-D. Sun, C.-R. Qi, H.-F. Jiang South China University of Technology, College of Chemistry & Chemical Engineering, Guangzhou, P. R. China
Thiadiazoles are regarded as an important class of five-membered heterocycles for many bioactive molecules. One general method for the preparation of 1,2,4-thiadiazoles containing the same groups in 3- and 5-positions was oxidative dimerization of the corresponding thioamides using oxidizing agents. One the other hand, the transition metal-mediated oxidative transformations to construct heterocycles have attracted great interest over the past decade. In particular, copper salts have been successfully applied in the formation of C-hetero or hetero-hetero bonds, which exhibit great potential for the construction of various heterocycles. On the basis of our recent developed Cucatalyzed method for synthesis of heterocycles1-5 and increasing interest of oxidative cross-coupling reactions of two nucleophiles, herein, we disclose a novel method for 3,5-disubstituted 1,2,4thiadiazoles via copper(II)-mediated homo-coupling of thioamides involving C-N and N-S bond formations (Scheme 1).
Scheme 1. Synthesis of 1,2,4-thiadiazoles References 1. Huang, L.; Jiang, H.; Qi, C.; Liu, X. J. Am. Chem. Soc. 2010, 132, 17652. 2. Li, X.; Huang, L.; Chen, H.; Wu, W.; Huang, H.; Jiang, H. Chem. Sci. 2012, 3, 3463. 3. Gao, Y.; Yin, M.; Wu, W.; Huang, H.; Jiang, H. Adv. Synth. Catal. 2013, 355, 2263. 4. Zeng, W.; Wu, W.; Jiang, H.; Huang, L.; Sun, Y.; Chen, Z.; Li, X.; Chem. Commun. 2013, 49, 6611. 5. Sun, Y., Jiang, H.; Wu, W.; Zeng, W.; Wu, X. Org. Lett. 2013, 15, 1598.
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P130 HIGHLY EFFICIENT SYNTHESIS OF TERTIARY α-HYDROXY KETONES VIA CO2-PROMOTED REGIOSELECTIVE HYDRATION OF PROPARGYLIC ALCOHOLS H.-T. He, C.-R. Qi, H.-F. Jiang South China University of Technology, College of Chemistry & Chemical Engineering, Guangzhou, P. R. China
-Hydroxy ketones have attracted tremendous interest in biologically active natural product research and synthetic chemistry. However, few of methodologies could be applicable for efficient hydration of propargylic alcohols to form -hydroxy ketones except the Kucherov reaction using mercury(II) salts as catalysts. A wide range of transition metals including Pd, Pt, Fe, Au, Ag, Ir and Ru have been investigated for the hydration of alkynes, however, these catalytic systems either showed low activity or led to side reactions such as Meyer-Schuster and Rupe rearrangements. Therefore, the development of novel processes for the hydration of propargylic alcohols to produce -hydroxy ketones with high efficiency is highly desirable. Using CO2 as the feedstock, a great deal of work in many different fields, has been undertaken to produce cyclic carbonates. In our previous work1, 2, we found that secondary amine was able to attack the carbonyl group of the α-methylene cyclic carbonate to give the ring-opening product. Recently, we set out to study whether water was capable to proceed the nucleophilic attack instead of the secondary amines to furnish useful -hydroxy ketone derivatives (Scheme 1).
Scheme 1
References [1] Qi C.; Jiang, H. Green Chem., 2007, 9, 1284. [2] Qi C.; Huang, L.; Jiang, H. Synthesis, 2010, 9, 1433.
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P131 UNEXPECTED DIRECT CONVERSION OF FUSED 1,2,5SELENADIAZOLES INTO 1,2,5-THIADIAZOLES L.S. Konstantinova, E.A. Knyazeva, O.A. Rakitin N.D. Zelinsky Institute of Organic Chemistry RAS
Fused 1,2,5-thiadiazoles have attracted much attention because of their interesting chemical properties and various possibilities for use as antibacterial and antiviral agents, agrochemicals and as π-type building blocks for organic electronics, particularly for both low- and high-molecular organic light-emitting diodes (OLEDs).1 Recently 1,2,5-thiadiazole derivatives were recognized as efficient electron acceptors and successfully used in the preparation of radical-anion salts revealing antiferromagnetic exchange interactions in their spin systems and conductive charge-transfer complexes.2 Although methods for the preparation of fused 1,2,5-thiadiazoles are numerous and well elaborated, there is still a lack of syntheses of derivatives containing electron-deficient heterocycles. We have found that treatment of 1,2,5-selenadiazoles fused with nitrogen heterocycles, such as piperazine and thia(selena)diazole with S2Cl2 in DMF gave unexpectedly corresponding 1,2,5thiadiazoles in high yields. This is the first case of direct substitution of the selenium to sulfur atom in 1,2,5-selenadiazoles. The driving force of this reaction is the precipitation of elemental selenium which was isolated from the reaction mixtures in practically quantitative yield.
We gratefully acknowledge financial support from the Russian Foundation for Basic Research (Project 13-03-00072), from the Presidium of the Russian Academy of Sciences (Programme No. 8) and from the Leverhulme Trust (Project IN-2012-094). 1. Todres Z.V., Chalcogenadiazoles: Chemistry and Applications, CRC Press/Taylor & Francis: Boca Raton, 2012, 290 pp. 2. N. A. Semenov, N. A. Pushkarevsky, E. A. Suturina, E. A. Chulanova, N. V. Kuratieva, A. S. Bogomyakov, I. G. Irtegova, N. V. Vasilieva, L. S. Konstantinova, N. P. Gritsan, O. A. Rakitin, V. I. Ovcharenko, S. N. Konchenko, A. V. Zibarev Inorg. Chem., 2013, 52, 6654.
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P132 ACTIVATION OF HYDROPEROXIDES BY TETRAALKYLAMMONIUM BROMIDES E.V. Raksha1, Yu.V. Berestneva1, N.A. Turovskij1, M.Yu Zubritskij2 1 - Donetsk National University, Physical chemistry Department, Donetsk, Ukraine 2 - L.M. Litvinenko Institute of Physical Organic and Coal Chemistry National Academy of Sciences of Ukraine, Donetsk, Ukraine
The investigation of supramolecular catalysis of organic peroxides decomposition is the actual direction in the development of peroxide initiators chemistry. There are a wide range of catalytic systems for the radical decomposition of hydroperoxides and quaternary ammonium salts are occupied an important place among of them. The key feature of supramolecular hydroperoxides decomposition in the presence of Alk4NBr is the complex formation between the reactants [1]. Systematic kinetic investigations of the interaction between hydroperoxides and Alk4NBr have been carried out [1]. Activation energies of the hydroperoxides thermolysis and catalytic decomposition have shown to be change simbatically. Kinetic parameters of the hydroperoxide-catalyst complex decomposition have been determined. Lowering of the activation barrier for the complex-bonded hydroperoxide decomposition as compared with its thermolysis in acetonitrile is 40 kJ·mol-1. The interaction of tert-butyl as well as 1,1,3-trimethyl-3-(4-methylphenyl)butyl hydroperoxides with tetraalkylammonium bromides (Alk4NBr) has been studied by NMR spectroscopy. The complexation between reactants was observed by relative change of the chemical shifts in the NMR 1 H spectra. The complex formation between the hydroperoxide molecule and corresponded quaternary ammonium salt has been proved. Thermodynamic parameters of complex formation have been determined. The equilibrium constants of complex formation (KС) between tert-butyl hydroperoxide and Alk4NBr have been determined both by NMR 1H and 13C spectroscopy. The values of the ΔcompH for the hydroperoxide complex with investigated salts are negative and lie are within -20 ÷ -9 kJ·mol-1 7 in CDCl3 solution that corresponds to the formation of weak hydrogen bonds. Similar effect has been observed in CD3CN solution for the hydroperoxide-Alk4NBr systems. The equilibrium constant values as well as complexation enthalpies decrease with intrinsic tetraalkylammonium cation volume increasing and this effect is observed over the temperature range 297-313 K. Complexation enthalpies defined by kinetic and NMR spectroscopy methods coincide. The structural model has been proposed for the complex of hydroperoxides with Alk4NBr. It includes the hydroperoxide molecule, salt cation and anion, as well as solvent molecule. Structural reorganization of the hydroperoxide fragment is the key factor of the chemical hydroperoxide activation in the presence of Alk4NBr. [1] N.А. Тurovskij, E.V. Raksha, Yu.V. Berestneva, et al. in: Polymer Products and Chemical Processes. Techniques, Analysis, and Applications, Editors: R.A. Pethrick, E.M. Pearce, G.E. Zaikov. – Toronto, New Jersey: Apple Academic Press, 2013. – 323 p. – P. 269-284. [2] N.А. Тurovskij, Yu.V. Berestneva, E.V. Raksha, et al. Polymers Research Journal. – 2014. – Vol. 8, No. 2. – P. 85 – 90. [3] N.А. Тurovskij, E.V. Raksha, Yu.V. Berestneva, M.Yu. Zubritskij. Russian Journal of General Chemistry – 2014. – Vol. 84, Iss. 1. - P. 16-17. [4] N.А. Тurovskij, Yu.V. Berestneva, E.V. Raksha, et al. Monatshefte für Chemie - Chemical Monthly DOI 10.1007/s00706-014-1234-5. 243
P133 THE AZA-COPE-MANNICH REACTION: APPLICATION TO THE SYNTHESIS OF UNNATURAL L-ALANINE DERIVATIVES N.K. Ratmanova, D.S. Belov, I.A. Andreev, A.V. Kurkin Lomonosov Moscow State University, Department of Chemistry, Moscow, Russia
Unnatural amino acids represent a nearly infinite array of diverse structural elements for the development of new leads in peptidic and non-peptidic compounds. Due to their seemingly unlimited structural diversity and functional versatility, they are widely used as chiral building blocks and molecular scaffolds in constructing combinatorial libraries. Herein we report the synthesis of the enantiopure unnatural L-alanine derived transoctahydrocyclohepta[b]pyrroles 5a and 5b via the aza-Cope-Mannich reaction (Scheme 1). Epoxide 2 (the source of chirality) was prepared according to the literature procedures from commercially available alcohol 1 applying Shi epoxidation protocol.1 The LiClO4-meditated epoxide ring-opening of 2 with L-alanine ethyl ester gave the diastereomeric mixture of amino ethanols 3a and 3b. After the chromatographic separation the compounds 3a and 3b were obtained as single isomers with high enantiomeric purity (ee = 99% and 86% respectively, chiral HPLC). The hydrogenation of 3a and 3b on the Lindlar catalyst gave desired alkenes 4a and 4b and unexpected side products (S)– and (R)–ethyl 2–(4,5,6,7–tetrahydro–1H–indol–1–yl)propanoates. Finally, carrying out the azaCope-Mannich reaction under previously optimized conditions2 gave the target enantiopure products 5a and 5b without epimerization.
Scheme 1. Synthesis of target compounds 5a and 5b. As a result, two diastereomeric unnatural L-alanine analogues 5a and 5b were synthesized in 5 steps from commercially available materials. The study showed that conditions of the aza-CopeMannich reaction are mild enough to be applied in the complex settings, for example, to the synthesis of molecules with several stereocenters which are prone to racemization.3 This study was supported by the Russian Foundation for Basic Research (RFBR), Russia (Projects No. 14-03-31685, 14-03-31709, 14-03-01114). References: 1. Wang, Z.-X.; Cao, G.-A.; Shi, Y. J. Org. Chem. 1999, 64, 7646–7650. 2. Belov, D. S.; Lukyanenko, E. R.; Kurkin, A. V.; Yurovskaya, M. A. J. Org. Chem. 2012, 77, 10125–10134. 3. Ratmanova, N. K.; Belov, D. C.; Andreev, I. A.; Kurkin, A. V. Tetrahedron: Asymmetry 2014, 25, 468–472. 244
P134 MECHANISTIC STUDIES OF PALLADIUM-MEDIATED ALKYNE INSERTION REACTION USING ELECTROSPRAY IONIZATION TANDEM MASS SPECTROMETRY K.S. Rodygin1, L.L. Khemchyan2, V.P. Ananikov2 1 - Saint Petersburg State University, Institute of Chemistry, Stary Petergof, Russia 2 - N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
Rapid development of transition metal catalysis allows rational design of a new methodology to carry out three-component coupling. To achieve this aim challenging question concerning mechanistic features of insertion reaction should be resolved.[1] Oxidative addition of an aryl halide to Pd in Pd(PPh3)4 (a common source of Pd in cross-coupling reactions) is the first step in the catalytic cycle. Addition of an alkyne to the mixture containing Pd(PPh3)2ArX results in the formation of another intermediate, Pd(Ar)(PPh3)2(alkyne)X. The intermediate containing the alkyne-unit has three possibilities to evolve: π-complex, acetylide or vinyl complex (insertion product). For development of the present project it was important to reveal the nature of transition metal intermediates and their role in the catalytic cycle in order to improve selectivity and scope of three-component coupling reaction. The questions of key importance in this regard (see Scheme): how facile is the insertion reaction? And what types of complexes – π-complex, acetylide or vinyl complex – are formed?
Few important features of the studied system deserve a note. Oxidative addition proceeds with formation of Pd complex, the corresponded ion was detected as [Pd(PPh3)2Ph]+. The elimination of PPh3-containing species is typical and expected under these conditions. More interesting series of alkyne insertions into Pd-C bond starting from initial complex lead to the formation of Pd-containing vinyl complexes. Reductive elimination results in formation of corresponded substituted alkenes, dienes, triene and tetraene. Note, formation of these Pd-free olefinic species provides an evidence for the fact of alkyne insertion into Pd-C bonds. On the next stage ESI-(+MS/MS) experiment via collision-induced dissociation (CID) was performed. The detected fragment ions serve as an additional evidence for the investigated alkyne insertion step. In the present study we were able to distinguish π-complex and insertion intermediate using ESI-(MS/MS) experiment. K.R. gratefully acknowledges Saint Petersburg State University for a postdoctoral fellowship (№ 12.50.1560.2013). References [1] Hydrofunctionalization, V.P.Ananikov, M.Tanaka (Eds.), Springer, 2013, Heidelberg. ISBN 978-3-642-33734-5.
245
P135 FACILE AND EFFICIENT SYNTHESIS 2-AMINO-4H-CHROMENES VIA SOLVENT-FREE CASCADE ASSEMBLING OF SALICYLALDEHYDES AND CYANOACETATES F.V. Ryzhkov, R.F. Nasybullin, M.N. Elinson N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation
2-Amino-4H-chromenes (or 2-amino-4H-benzo[b]pyranes) are of particular interest as they belong to privileged medicinal scaffolds serving for generation of small-molecule ligands with highly pronounced spasmolitic-, diuretic-, anticoagulant-, and antianaphylactic activities [1]. The current interest in 2-amino-4H-chromenes bearing nitrile functionality arises from their potential application in the treatment of human inflammatory TNFα-mediated diseases, such as rheumatoid and psoriatic arthritis, and in cancer therapy [2]. The development of solvent-free organic synthesis has become an important research area. This is not only due to the need for the more efficient and less labour-intense methodologies for the synthesis of organic compounds, but also because of the increasing importance of the environmental considerations in chemistry. The elimination of volatile organic solvents in organic synthesis is also the most important goal in ‘green chemistry’. We were prompted to use a convenient and facile solvent-free cascade methodology for the synthesis of 2-amino-4H-chromene scaffold from salicylaldehydes and cyanoacetates. We have found that potassium fluoride as catalyst can produce, under solvent-free mild conditions, a fast and selective cascade trasformation of salicylaldehydes and cyanoacatates into substituted at ambient temperature 2-amino-4H-chromenes chromenes in 88–98% yields.
The catalytic procedure utilizes simple equipment; it is easily carried out and is valuable from the viewpoint of environmentally benign diversity-oriented large-scale processes. This efficient potassium fluoride catalyzed solvent-free approach to substituted 2-amino-4H-chromenes represents a new synthetic concept for cascade reactions, and allows for the combination of the synthetic virtues of conventional cascade processes with ecological benefits and convenience of solvent-free procedure. 1. H. Aryapour, M. Mahdavi, S.R. Mohebbi, Frch. Pharm. Res., 2012, 35, 9, 1573-1582. 2. J. Skommer, D. Wlodkowic, M. Matto, M.Eray, J. Pelkonen, Leukemia Res., 2006, 30, 322-333.
246
P136 A NEW 3D CHEMICAL FORMULAS FOR ANALYZING OF GEOMETRICAL STRUCTURES OF ACTIVE BIOMOLECULES IN «STRUCTURE-ACTIVITY» PROBLEM E.A. Smolenskii, A.N. Ryzhov, P.O. Guskov, I.V. Chuvaeva N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia We suggest a new way (“the method of triangles”) to describe 3D molecule structures and solid surfaces with account their spatial geometry making the difference between stereo and conformational isomers. The new formulas allow using well-known procedures of the “structure-property” and “structure-activity” problems for large molecules. Furthermore, the method clears the novel ways of circumscribing solid surfaces and in “structure-catalytic activity” problems. The approach is based on taking into account every of the spatialorientated atom triples i , j , k , designating triangle. Let us to consider vertex i of the triangle and vectors V ij
Vi
V j , V ik
Vi
V k being the entries of the i-row of the Matrix of Geometrical Distances (MGD). And
now we proceed to description in terms of the triangles matrix:
ijk
: i
j
k
1 V ij 2
ijk
V jk
ijk
n ijk ;
ijk
1 V ij V jk sin 2
; n ijk
V ij V ij
V jk V jk
.
Since a vectors product determines the triangle, it automatically means an orientation of the triangle surface in space. There are 3 sets of indexes with the same direction of normal vectors n ijk and 3 ones in opposite. One can
selects internal or external triangles from the triangle matrix by following rule: triangle m
i , j , k and
i, j, k :
n ijk V
is external, if
ijk
0 ; for triples of atoms placed on one line n ijk is determined as vector
m
that is perpendicular to and finished on this line and started from the mass center of molecule.
Changing internal triangles in the matrix
by zeros, we get the external triangles matrix
ijk
contains the same external triangle i , j , k
ex ijk
. This matrix
three times. Thus, we define geometrical structure of a molecule.
Usually a biomolecule activity is defined by small site being complimentary to its natural substrates. The site (“kcomplex”) is consisted of k inter-oriented triangles. Vector F m of entry numbers a lm for every type of the kcomplex triangles in molecule with number m may be called as “3D chemical formula” of this molecule. One can M k
selects the triangles of k-complex considering the matrix ( M
CN
m
dimension) of entry numbers a lm for
m 1
every type of the k-complex triangles in each compound of the set Pm ( m
(1, M ) ) of active and non-active
M
substances. Here a lm ( m
1, M
, l
k
C N ) ) is the entry number of k-complex with number l in m -
(1,
m
m 1
compound, taking into account conformational isomerism, M – the number of compounds, N m - the number of M
triangles in m-compound, N
N m - the general number of triangles in all substances. This matrix is based on m 1
3D chemical formulas. Here we must using rule: any triangle being among type of triangles contained in inactive substances cannot be contained in k-complex. Remaining triangles (approximately, they are contained in kcomplex; their number, as show on example of set of castanospermines tested by anti-HIV activity [G.W.J. Fleet et al. FEBS Letters. 1988. V. 237. № 1-2. P. 128-132], as a rule, less than number of active compounds) is used for making of additive scheme for calculating of biological activity. So, 3D chemical formulas can be used for describing genes, catalyst surfaces, proteins and other biomolecules.
247
P137 A PROBLEM OF DEFINITION OF CHEMICAL EQUILIBRIUM IN CONTEMPORARY CHEMISTRY A.N. Ryzhov, E.A. Smolenskii, P.O. Guskov, M.S. Molchanova N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
Unfortunately, a many definitions of chemical equilibrium of systems exist and are used now. In process of our investigation, we find that principle of detailed equilibrium is sufficient but not necessary condition of chemical equilibrium from the viewpoint of formal kinetics. We propose a new definitions: 1. Steady-state chemical system is called chemical system with constant temperature, pressure, volume and activities of compounds. 2. Equilibrium chemical system is called steady-state and adiabatically isolated system. 3. System with detailed equilibrium is called equilibrium system with equilibrium in all elementary reactions. 4. Quasiequilibrium chemical system is open system with time of parameter stabilization been more less than time of changing of external conditions. Necessary and sufficient condition of chemical equilibrium is equality between sum of velocities of elementary reactions with getting of some compound and sum of velocities of elementary reactions with expenses of this compound for all compounds of system. For system with three compounds A vBA vAC
B
vAB
vCA C vBC vCB
in the case of detailed equilibrium (S=[A]+[B]+[C])
k
AC
k
CB
k
BA
k
AB
k
BC
k
CA
,
Sk
A k
Sk
B k
AB
k
CB
k
AB
BA
k
k
CB
CB
k
AB
k
BC
,
Sk
C k
BC
k
AC
k
BC
CB
k
k
AC
AC
For this system in the common case of equilibrium
248
k
BC
k
CA
.
BA
k
CA
k
BA
AB
k
k
CA
CA
k
BA
k
AC
,
P138 SYNTHESIS, STRUCTURE AND THERMAL PROPERTIES OF PROPYLENE OXIDE, CARBON DIOXIDE AND L-LACTIDE TERPOLYMERS Z.N. Nysenko1, E.E. Said-Galiev1, Ya.E. Belevtsev2, S.I. Daineko2, M.I. Buzin3, G.G. Nikiforova4, A.M. Sakharov1 1 - N.D.Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Moscow, Russia 2 - A.N.Nesmeyanov Institute of Organoelement Compounds of Rusian Academy of Sciences, Physical Chemistry, Moscow, Russia 3 - A.N.Nesmeyanov Institute of Organoelement Compounds of Rusian Academy of Sciences, Academy of sciences, Polymer Physics, Moscow, Russia 4 - A.N.Nesmeyanov Institute of Organoelement Compounds of Rusian Academy of Sciences, Polymer Physics, Moscow, Russia
Poly(propylene carbonate) (PPC) is a sustainable polymer that undergoes complete ash-free incineration accompanied by the formation of CO2 and H2O. PPC is prepared by copolymerization of propylene oxide (PO) with CO2 and it exhibits attractive physical and mechanical properties responsible for its potential practical applications. It is known that ester units introduction into a polymer chain promotes increasing its biodegradability. Copolymers with different L-lactide concentrations were synthesized in the presence of zinc adipate The combination of 1Н, 13С, and 2D {1Н-13С}HMBC NMR, DSC, FT-IR spectroscopy, and GPC study results allows one to assume that copolymerization of СО2, PO and L-lactide yields to partially crystalline terpolymers composed of propylene carbonate blocks combined with L-lactic acid blocks and may be depicted by segment II of structure represented onto Scheme.
The synthesis of the terpolymers is not aggravated by side reactions. No inversion of the configuration of L-lactide occurs during its addition to the polymer chain and the copolymer possesses optic activity that depends on the L-lactide concentration in its chain. All possible types of the PO addition (head-to-head, head-to-tail, and tail-to-tail), where head-to-tail addition predominates, are found in the propylene carbonate blocks. L-Lactic acid content increase was shown to be accompanied with elevation of terpolymers onset degradation temperature values. The research was supported by the Russian Ministry of Education and Science (Contract No. 14.513.11.0139).
249
P139 SIMPLE PRECURSORS FOR THE REGIOSELECTIVE SYNTHESIS OF METHYLENE-EXPANDED ANALOGUES OF C-NUCLEOSIDES V.K. Brel1, A.V. Samet2, L.D. Konyushkin2, V.V. Semenov2 1 - A.N. Nesmeyanov Institute of Organoelement Compounds 2 - N. D. Zelinsky Institute of Organic Chemistry
Nucleosides with heterocyclic base linked to sugar through C–C bond instead of C–N attachment in natural nucleosides attract much attention because of their chemical and enzymatic stability. Compounds with methylene group inserted between the ring oxygen and the carbon atom linked to the base moiety are considered as ring-expanded (six-membered ring) analogues of nucleosides (Figure 1, A). Several of these molecules showed potent antiviral and antitumor activity. F ig u re 1
We have developed the synthesis of C2 chiral derivatives of dihydrolevoglucosenone 1a, 2a, and 3–7 as simple precursors for preparation of methylene-expanded C-nucleosides (A), using pyrolysis of cellulose as a key step followed by hydrogenation of LG and introduction of vinyl and ethynyl fragments to 2-position.
6
O
5
Cellulose
stainless steel autoclave 2% Pd/C (Sibunit)
1
O
6
2 4
HO
5
3
O o
EtOAc, 40
4 3
2
O
O
20 bar, 8 h
DLG
LG
85%
O HC
H2C
CMgBr o
OH
O
R 3: Ph
C
A
O
1
O
Het
Et2O, rt, 2 h
THF, 40 , 2 h +
RC
N
CMgBr
-
O
O R
N
4: p-Me-Ph 5: p-F-Ph
o
54-75%
6: Ac
O
Et2O, -40 , 3 h
1a CH
Cu(OAc)2 OH
O
OH
O
PhCH2N3
O
O OH
O
63%
42%
2a
+
+
O
O
H2O, rt, 1 h
CH2
CH
N
N N
84%
7
OH
OH
CH2Ph
CH2
O
O
1b
4.8%
3.8%
2b
The opening of 1,6-anhydrohexitols acetal ring could be used for transformation of derivatives 3–7 into methylene-expanded C-nucleosides (Figure 1, A). 250
P140 SYNTHESIS AND BIOLOGICAL EVALUATION OF FURANOALLOCOLCHICINOIDS E.S. Schegravina1, Yu.V. Voitovich1, N.S. Sitnikov1, V.I. Faerman1, V.V. Fokin1, H.-G. Schmalz2, S. Combes3, D. Allegro4, P. Barbier4, I.P. Beletskaya5, E.V. Svirshchevskaya6, A.Yu. Fedorov1 1 - Department of Organic Chemistry, Nizhny Novgorod State University, Gagarina av. 23, Nizhny Novgorod 603950, Russian Federation 2 - University of Cologne, Department of Chemistry, Koln, Germany 3 - Institut Paoli-Calmettes, Aix-Marseille Universite, Laboratory of Integrative Structural and Chemical Biology, Marseille, France 4 - Aix-Marseille Universit, INSERM UMR_S 911, CRO2 F-13005, Marseille, France 5 - M.V.Lomonosov Moscow State University, Department of Chemistry, Moscow, Russian Federation 6 - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russian Federation
A series of conformationally flexible furan-derived allocolchicinoids was prepared from commercially available colchicine in good to excellent yields using a three-step reaction sequence1.
Compounds containing a hydroxyl group in the pseudo-benzylic position of the furan side chain exhibited high cytotoxicity toward epithelial and lymphoid cell lines (AsPC-1, HEK293 and Jurkat) in the nanomolar concentration range. In vivo studies also demonstrated significant activity of compounds bearing a hydroxymethyl fragment in the α-position of the furan ring against the tumor growth without symptoms of neurotoxicity. Acknowledgment We thank the Russian Foundation for Basic Research (projects 14-03-91342 and 12-03-00214-a), The Ministry of Education and Science of The Russian Federation (project 4.619.2014/K). The research is partly supported by the grant №02.В.49.21.0003 of The Ministry of Education and Science of the Russian Federation to Lobachevsky State University of Nizhni Novgorod. References 1. Voitovich, Yu.V., Sсhegravina, E.S., Sitnikov, N.S. Faerman, V.I., Fokin, V.V., Schmalz, H.-G., Comes, S., Allegro, D., Barbier, P., Beletskaya, I.P., Svirshchevskaya, E.V., Fedorov, A.Yu. Synthesis and biological evaluation of furanoallocolchicinoids. J. Med. Chem. 2014 (submitted)
251
P141 TETRAMETHYLENECYCLOOCTANE – A BASIS FOR POLYSPIROCYCLIC SMALL RING ARCHITECTURES K.N. Sedenkova, E.B. Averina, S.G. Bakhtin, T.S. Kuznetsova, N.S. Zefirov Lomonosov Moscow State University, Department of Chemistry, Moscow, Russia 1,3,5,7-Tetrakis(methylidene)cyclooctane (1, TMCO) – a symmetric tetraene with highly reactive exo-cyclic double bonds – represents a promising starting compound for the synthesis of polyspirocyclic small ring structures, including rotanes and heterorotanes. Nevertheless, up to date the synthesis of TMCO was mentioned in one short communication without an experimental procedure [1]. We developed a straightforward synthesis of TMCO from commercial adamantane1,3-dicarboxylic acid (2). The key stage of the synthesis is fragmentation of adamantane pattern of tetrabromide 3 under the treatment with zinc. CH2Br
COOH
Zn, NaI, Na2CO3
4 steps COOH
74%
Br
CH2Br Br
2
DMF, 60% 1 (TMCO)
3
TMCO was shown to demonstrate high reactivity toward diazomethane, dihalocarbenes and epoxidizing reagents, undergoing multiple cyclopropanations or epoxidations of four double bonds to yield polyspirocyclic products 4–6. X
X
[1+2]-cycloaddition or epoxydation
X
1
X
4, X=CH2, 80% 5a, X=CCl2, 95% 5b, X=CBr2, 65% 5c, X=CBrF, 50% 6, X=O, 50%
Stereochemical features of polyspirocyclopropanated compounds 5,6 have been thoroughly examined in experimental (NMR) and theoretical (DFT) studies. Comprehensive stereochemical assignment of TMCO adducts with dihalocarbenes and polyspiroepoxy products was achieved. In course of the work we have found that carrying out the fragmentation of adamantane derivative 3 in presence of traces of water leads to the formation of bis(methylidene)bicyclononane 7. The addition of dihalocarbenes to diene 7 was shown to be stereoselective, giving solely the products of exo-addition to double bonds 8a–c, that was by unambiguously proved by RSA for 8a. CXY 3
CHX2Y, NaOHaq
Zn, NaI, Na2CO3 DMF/H2O, 160oC, 25%
CH3 TEBA, CH2Cl2 7
CH3
8a, X=Y=Cl, 87% 8b, X=Y=Br, 72% 8c, X=Br, Y=F, 43%
CXY
In conclusion, we elaborated a preparative gram-scale approach to TMCO and obtained a series of unique polyspirocyclic structures starting from this highly reactive tetraene. We thank the Russian Foundation for Basic Research (Projects 14-03-31989-mol_а, 14-03-00469a) and Presidium RAS (program №8P) for financial support of this work. [1] Stepanov, F. N.; Sukhoverkhov, V. D.; Baklan, V. F.; Yurchenko, A. G. Zh. Org. Khim. 1970, 6, 884–885; J. Org. Chem. USSR (Engl. Transl.) 1970, 6, 278–284.
252
P142 USING HAuCl4 AS A SINGLE SOURCE OF METAL TO PRODUCE SOLUBLE Au(Pr3)Cl COMPLEXES AND Au(0) PARTICLES A.E. Sedykh1, S.S. Zalesskiy2, A.S. Kashin2, V.P. Ananikov2 1 - Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia; Higher Chemical College, Russian Academy of Sciences, Moscow, Russia 2 - Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
A simple approach was developed for the synthesis of homogeneous and heterogeneous gold catalysts. One of the most common gold compounds – HAuCl4 was used as a single source of metal. Efficient one-pot synthesis procedure was created for preparation of gold complexes with various phosphine or phosphite ligands Au(PR3)Cl (90 – 99% yield). The developed method gives excellent results even for electron-deficient ligands and sterically hindered Buchwald-type phosphines. Various gold(0) nanoparticles were prepared using simple and available reductants. The morphology of metal particles was studied and characterized with high-resolution field-emission scanning electron microscopy (FE-SEM). It was found that the size and shape of the growing particles can be controlled simply by selecting a reducing agent. Several unique types of structured gold materials were prepared, such as particles arranged in a well-developed porous network, hierarchical agglomerates and metal mirror composed of ultrafine particles.[1]
. [1] Zalesskiy, S.S.; Sedykh, A.E.; Kashin, A.S.; Ananikov, V.P J. Am. Chem. Soc. 2013, 135, 3550.
253
P143 MOLECULAR INTERACTIONS AND EXTRACTION OF PEPTIDES IN IONIC LIQUIDS SYSTEMS M.M. Seitkalieva, V.V. Kachala, K.S. Egorova, V.P. Ananikov N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
In past decade, ionic liquids (ILs) have been weightiest matter because of their well-favored properties for variety of physical, chemical and biological application. [1] The technologies of ILs mediated extraction have shown the good prospects for replacing traditional methods in separating natural bioactive homologues. They widely have been investigated as extracting phases in liquid-liquid and aqueous two-phase systems for amino acids and proteins. For peptides no such large achievement were reached and the mechanisms of peptide – IL interactions remain to be established. Recently, we have studied interactions of imidazolium-based ILs with peptides built from L-alanine and L-valine by NMR spectroscopy. [2] High sensitivity of ILs to the nature of peptides and remarkably capability to distinguish a small change in the amino acid sequence was demonstrated, that allowed further to study the molecular nature of the separation process. Hereinafter the back extraction of peptides in a two-phase ‘ionic liquid – organic solvent’ system was performed and mechanism of peptide transition was studied. The slice-selective NMR experiments were applying for effectively monitoring extraction process that allowed discovering the molecular mechanism of peptide transition from the ionic liquid to organic phase. The results suggested that the extraction occurred by molecular diffusion of individual peptide molecules, which passed from IL to the organic solvent without structural changes. The selection of the extraction system was carried out, and imidazolium-based ILs: ethyl acetate petroleum ether system was used for effective partition of structurally similar peptides. Was demonstrated that the extraction efficiency and selectivity increased with increasing the molecular concentration of peptides. Obtained results have potential application in separation and analysis of biomolecules. [1] (a) V. P. Ananikov, Chem. Rev., 2011, 111, 418; (b) K. S. Egorova and V. P. Ananikov, ChemSusChem, 2014, 7, 336. [2] M. M. Seitkalieva, A. A. Grachev, K. S. Egorova and V. P. Ananikov, Tetrahedron, 2014, 10.1016/j.tet.2014.02.025s.
254
P144 SYNTHESIS AND BIOLOGICAL EVALUATION OF ANALOGS OF NATURAL ANTIMITOTIC PRODUCTS USING PARSLEY AND DILL SEED EXTRACTS D.V. Tsyganov1, N.B. Chernysheva1, D.V. Demchuk1, A.V. Samet1, L.D. Konyushkin1, M.N. Semenova2, V.V. Semenov1 1 - N. D. Zelinsky Institute of Organic Chemistry 2 - N. K. Kol’tsov Institute of Developmental Biology
Analogs of antimitotic natural products podophyllotoxin (PT) and combretastatin A-4 (CA4) as well as plant-derived glaziovianin A were synthesized using allylpolyalkoxybenzenes from dill and parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and microtubule destabilizing activity. Structure–activity relationship studies identified CA4 analogs with 3,4,5-trimethoxyphenyl and 3,4-methylenedioxy-5-methoxyphenyl ring A and 4-methoxyphenyl ring B as potent antiproliferative agents with high cytotoxicity against a panel of 60 human cancer cell lines including multi-drug resistant cells. The most active aza- and oxa-PTs featured myristicin-derived ring E. Cytotoxic effect of tested compounds was attributed to microtubule destabilization resulted in cell cycle arrest followed by apoptotic cell death. The effective threshold concentrations (EC) resulting in mitotic abnormalities in the sea urchin embryos are presented in Figure.
Considering these encouraging data from phenotypic and mechanistic studies, some compounds may prove to be lead candidates for further in vivo studies to assess its potential as an anti-tumor agents. 255
P145 STRUCTURES OF CAPSULAR POLYSACCHARIDES OF NOSOCOMIAL PATHOGEN ACINETOBACTER BAUMANNII AND THEIR CLEAVAGE BY SPECIFIC BACTERIOPHAGE TAIL-SPIKE DEPOLYMERASES A.S. Shashkov1, S.N. Senchenkova1, Y.A. Knirel1, M.M. Shneider2, K.A. Miroshnikov2, A.V. Popova3, N.V. Volozhantsev3 1 - N.D.Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia 2 - M.M. Shemyakin & Y.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia 3 - State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, Russia
Nosocomial infections due to multidrug-resistant pathogen Acinetobacter baumannii have become increasingly common. Phage therapy is promising for their treatment. A prerequisite of bacteriophage adsorption on the bacterial cell surface necessary for the infection and the following lysis of the cell is the cleavage of the protecting bacterial capsular polysaccharide (CPS) by a specific structural depolymerase (phage tail spike). To develop the biochemical basis for phage therapy of A. baumannii infections we studied structures of the CPSs of these bacteria and mechanisms of the CPS depolymerisation by bacteriophage tail spikes. CPS structures of 5 strains of A. baumannii (28, 1053, 1432, 5075 and ACICU) were established using chemical methods along with 1H и 13С NMR spectroscopy. Degradation of the CPSs from A. baumannii 28 and 1053 was performed with recombinant tail-spike depolymerases of bacteriophages Fri1 and AP22, respectively. Structures of the CPSs and degradation products were established by 1H and 13C NMR spectroscopy and high-resolution ESI MS. FriI glycosidase hydrolysed the CPS of strain 28 at one of the glycosidic linkage to give mainly a nonasaccharide composed of three CPS repeats (Scheme 1). AP22 lyase cleaved the CPS of strain 1053 by -elimination in a hexuronic acid residue to give unsaturated trisaccharide (major) and hexasaccharide (minor) (Scheme 2).
Scheme 1. Depolymerisation of CPS of A. baumannii 28 by phage FriI tail-spike hydrolase. QuiNAc4NAc, 2,4-diacetamido-2,4,6-trideoxy-D-glucose; n = 1 (major), 0, 2-4 (all minor).
Scheme 2. Depolymerisation of CPS of A. baumannii 1053 by phage AP22 tail-spike lyase. 4,5HexNAcA, 2-acetamido-2,4-dideoxy-L-erythro-hex-4-еnuronic acid. 256
P146 ON PHOTOLUMINESCENCE PROPERTIES OF INDIUM-EXCHANGED ZSM-5 ZEOLITE A.I. Serykh Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences
Optical properties of indium-exchanged ZSM-5 zeolite with different indium content have been studied. It has been found for the first time that reduced In-ZSM-5, containing low-valence In+ cations exhibits strong photoluminescence emission both in UV and visible light region. The intensity of visibly light luminescence strongly increases with increase of indium content in InZSM-5. The emission spectrum of low-indium loaded In-ZSM-5 is represented mainly by an intense UV band at 350 nm (Fig.1). The excitation spectrum consists of three irregularly-shaped bands at about 220-230 nm, 260 nm and 308 nm. Lifetime measurements show that the UV emission of this sample has a single component (approximately 5×10-3 ms). The emission spectrum of In-ZSM-5 with high indium content (Fig. 2) is represented by two intense emission bands both in UV and visible-light regions. The visible light emission decay is complex and has a fast (10-3 ms or faster) and at least two slow components (0.05 ms and 0.2 ms). The excitation spectra of both UV and visible-light emission bands are represented by three irregular shaped peaks at 220-230 nm, 260 nm and 308-314 nm. These peaks can be induced by the electronic excitations transitions similar to those X 1Σ+(0+)C 1 (1), X 1Σ+(0+)B 3 1(1) and X 1Σ+(0+)A 3 0(0+) in indium halides or 1 S01P1, 1S03P2 and 1S03P1 transitions in indium-doped alkali halides (C, B and A transitions). The emission in In-ZSM-5 occur due to irradiative transition from the lowest excited state (which is a triplet state according to its lifetime) The UV luminescence most probably is associated with isolated In+ cations, while the visible-light emission can be related to the formation of In+ oligomers or clusters in the excited state. Fig.1. Emission and excitation spectra of lowindium-loaded In-ZSM-5 (4 wt.% In) reduced in hydrogen at 823 K and evacuated at the same temperature for 2 h. E m is s io n
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P147 CATALYTIC OXIDATION OF OLEFINS BY TBHP IN THE PRESENCE OF TRANSITION METALS M.Y. Sharipov, A.O. Terent’ev N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences 119991 Moscow, Leninsky prospekt, 47, Russia
The transition metal catalyzed selective oxidation of organic compounds with the aim of organic peroxides preparation is a demanded field of the oxidative processes chemistry. The publications of recent years show that organic peroxides possess a high antimicrobial, antiparasitical and fungicidal activity. It was discovered that cyclic diperoxides reveal a high antischistosomal activity (IC50 4 form cocrystals instead of salts5. ΔpKa equals to 7.14 for the cocrystal under consideration. According to single crystal X-Ray, the salicylamide cocrystal possesses an unusually short O-H...O intramolecular H-bond with O...O distance of 2.493 Å. The pattern of noncovalent interactions has been quantified using the solid-state DFT computations (B3LYP/6-31G**) followed by the Bader analysis of the periodic electron density. The lattice energy of the cocrystal is evaluated in a way described in Ref. 6 to be equal to 314.7 kJ/mol. It is found that O-H...O and N-H...O hydrogen bonds provide nearly 70% of all lattice energy in crystal. The IR spectrum computed in the harmonic approximation using solid-state DFT agrees with the experimental spectrum of the crystal. The IR intensive band around 2400 cm-1 is caused by the stretching vibration of the OH group, involved into formation of the short (strong) H-bond. [1] a) A.V. Trask, W.D.S. Motherwell, W. Jones. Physical stability enhancement of theophylline via cocrystallization. Int. J. Pharm. 2006, 320, 114–123. b) N. Schultheiss, A. Newman. Pharmaceutical cocrystals and their physicochemical properties. Cryst Growth Des., 2009, 9(6), 2950–2967. [2] F. Lara-Ochoa, G. Espinosa-Pérez. Cocrystals Definitions. Supramol. Chem., 2007, 19(8), 553–557. [3] T. Steiner, The Hydrogen Bond in the Solid State, Angew. Chem. Int. Ed. 2002, 41, 48–76. [4] C.B. Aakeroy, M.E. Fasulo, J. Desper. Cocrystal or salt: does it really matter? Mol. Pharm., 2007, 4(3), 317–322. [5] A.J. Cruz-Cabeza. Acid-base crystalline complexes and the pKa rule. CrystEngComm, 2012, 14, 6362– 6365. [6] A.N. Manin, A.P. Voronin, N.G. Manin, M.V. Vener, A.V. Shishkina, A.S. Lermontov, G.L. Perlovich, Salicylamide Cocrystals: Screening, Crystal Structure, Sublimation Thermodynamics, Dissolution and Solid-State DFT Calculations, J. Phys. Chem. B, 2014, 118, 6803–6814.
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P182 OXYPALLADATION-HECK TANDEM REACTIONS OF INTERNAL ALKYNES WITH ALLYLIC ALCOHOLS: A NEW APPROACH TO ISOCOUMARINS AND BENZOPYRANS M.-F. Zheng, W.-Q. Wu, H.-F. Jiang South China University of Technology, School of Chemistry and Chemical Engineering, Guangzhou, P. R. China
Transition metal-catalyzed cascade reactions have emerged as a valuable approach for the synthesis of complex molecular structures and attracted great attention.1 In this regard, the electrophilic activation of the alkynes by coordination to palladium continues to be a fascinating arena due to its high efficiency in constructing multiple new chemical bonds in one step.2 Recently, a new approach for isocoumarins and benzopyrans between internal alkynes and allylic alcohols is developed. This one-pot cascade cyclization is supposed to go through a sequential intramolecular C−O bond cyclization, olefin insertion, β-H elimination and isomerization to afford the isocoumarin products, all occurring in a single operation. Remarkably, benzopyran derivatives could be also constructed efficiently via this cascade transformation (Scheme 1).
Scheme 1 Reference: 1. (a) Waslike, J.-C.; Obrey, S. J.; Bake, R. T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001. (b) Tietze, L. F. Chem. Rev. 1996, 96, 115. (c) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem. Int. Ed. 2006, 45, 7134. 2. (a) Frühauf, H.-W. Chem. Rev. 1997, 97, 523. (b) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. Rev. 1996, 96, 635.
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P183 EFFICIENT SYNTHESIS OF PYRAZOLES VIA COPPER-CATALYZED RELAY OXIDATION STRATEGY X.-D. Tang, W.-Q. Wu, H.-F. Jiang South China University of Technology, School of Chemistry and Chemical Engineering, Guangzhou, P. R. China
Pyrazoles are an important heteroaromatic ring for pharmaceutical industry. Selected pharmaceutical examples include the well-known drugs Mavacoxib, Celebrex, and Acomplia. Many methods have developed for this attractive scaffold, and the classical preparation method is the condensation of 1,3-dicarbonyl compounds and their 1,3-dielectrophilic equivalents with hydrazines. However, they often suffer from some drawbacks such as multi-step synthesis, long reaction time, use of expensive reagents, and the limitation of the substrates. In the past several years, oxime esters have become powerful tool for N-heterocycles in presence of Cu catalysts. Based on our continue interest in oxime esters, herein, we present a Cu-catalyzed synthesis of 1,3- and 1,3,4-substituted pyrazoles from oxime acetates, anilines and formaldehyde (Scheme 1c). This process involves Cu-catalyzed N-O bond cleavage, C-C/C-N/N-N bond formation and oxidative dehydrogenation process, which is a relay oxidation process and the oxidants are oxime acetates and O2.
Scheme 1 References [1] Tang, X.; Huang, L.; Qi, C.; Wu, W.; Jiang, H. Chem. Commun., 2013, 49, 9597. [2] Huang, H.; Ji, X.; Tang, X.; Zhang, M.; Li, X.; Jiang, H. Org. Lett. 2013, 15, 6254. [3] Tang, X.; Huang, L.; Qi, C.; Wu, X.; Wanqing Wu, W.; Jiang, H. Chem. Commun. 2013, 49, 6102. [4] Tang, X.; Huang, L.; Xu, Y.; Yang, J.; Wu, W.; Jiang, H. Angew. Chem. Int. Ed. 2014, 53, 4205.
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P184 SELECTIVE SYNTHESIS OF CYCLIC PEROXIDES FROM TRIKETONES AND H2O2 I.A. Yaremenko, V.A. Vil`, I.B. Krylov, A.O. Terent`ev N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation
In the past decades, the chemistry of organic peroxides has attracted considerable attention from physicians and pharmacologists because these compounds were found to have antimalarial, antihelmintic, and antitumor activities. The interest in the synthesis of radical polymerization initiators and drugs gave impetus to the development of methods for the synthesis of peroxides with the use of carbonyl compounds, their derivatives, and H2O2 as the starting reagents. A method for the assembly of tricyclic structures containing the peroxide, monoperoxyacetal, and acetal moieties was developed based on the acid-catalyzed reaction of β,δ-triketones with H2O2. The tricyclic compounds are produced in 39−90% yields and can be easily isolated from the reaction mixture. The reaction is scaled up to several grams. The resulting tricyclic compounds are unusual in that they contain one acetal and two monoperoxyacetal moieties, which are as a rule unstable and can undergo peroxidation in the presence of water and hydrogen peroxide under acidic conditions, and acetals are susceptible to hydrolysis (Scheme 1). Scheme 1. Synthesis of Tricyclic Peroxides
To assess the resistance of tricyclic peroxides to reagents used in organic synthesis and to determine the structures, which are interesting to test for biological activity, we performed the oxidation, alkaline hydrolysis, amidation, and reduction (Scheme 2). Scheme 2. Reactions of Tricyclic Peroxides
Tricyclic monoperoxides showed high antischistosomal activity against Schistosoma mansoni. This work is supported by RFBR №14-03-00237. Reference Terent’ev A.O., Yaremenko I.A., Chernyshev V.V., Dembitsky V.M., Nikishin G.I. // J. Org. Chem. 2012, 77, 1833-1842. Terent'ev A.O, Yaremenko I.A., Vil' V.A., Dembitsky V.M, Nikishin G.I. // Synthesis. 2013, 45 (2), 246-250. Ingram K., Yaremenko I.A., Krylov I.B., Hofer L., Terent'ev A.O., and Keiser J. // J. Med. Chem. 2012, 55 (20), 8700-8711. 295
P185 NEW LIGANDS BASED ON OXAMINIC ACID THIOHYDRAZIDES V.N. Yarovenko, E.S. Zayakin, I.V. Zavarzin, M.M. Krayushkin N.D. Zelinsky Institute of Organic Chemistry, RAS, Moscow, Russia
Convenient methods for the synthesis of poorly studied thiohydrazides of oxaminic acids 1 were developed. Compounds 1 are of special interest as complexing structures as containing donor atoms with both high (N,O) and low (S) electronegativity, due to which they can form fairly stable coordination compounds with both “hard” and “soft” Pearson’s acids. New ligands 2-7 were synthesized from oxaminic acid thiohydrazide derivatives.
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P186 SYNTHESIS OF 8-H-PYRIMIDO[ 5,4-B] [1,4]-THIAZINE-5,5-DIOXIDE DERIVATIVES M.A. Prezent, I.V. Zavarzin N. D. Zelinsky Institute of Organic Chemistry, Laboratory for Chemistry of Steroid Compounds, Moscow, Russia
We showed for the first time that methanesulfonylacetonitrile 1 can interact with two molecules of dimethylformamide acetal. The reaction proceeds at both methylene and methyl groups of 1 to form condensation product 2. The latter smoothly reacts with binucleophiles, such as acetamidine and guanidine to form new representatives of the pyrimidine series: 4-amino-5-sulfonylpyrimidines 3а,в,с. N
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R = H (a); Me (b); NH2 (c) Heating of 3а,в,с in acetic acid results in heterocyclization to form bicyclic systems 4а,b,c. New 4-amino-5-sulfonylpyrimidines 3а,в,с were thus obtained, as well as derivatives of earlier undescribed system 8H-pyrimido[4,5-b] [1,4]-thiazine-5,5-dioxide 4а,b,c.
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P187 A CRUCIAL ROLE FOR THE ESCHERICHIA COLI S4 O-ANTIGEN OACETYLATION IN THE BACTERIOPHAGE G7C RECEPTION E.L. Zdorovenko1, N.S. Prokhorov2, O.G. Ovchinnikova1, A.S. Shashkov1, A.V. Letarov2, Y.A. Knirel1 1 - N.D.Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia 2 - S.N. Vinogradsky Institute of Microbiology, Russian Academy of Sciences, Moscow, Russia
The phage–host system E. coli 4s–bacteriophage G7C was isolated from horse feces in 2006. Despite an extremely narrow host range, E. coli 4s being the only known G7C host, the phage persisted in the same horse population for several years. Evaluation of the fine mechanisms of the G7C interactions with the host cell is important for understanding this ecological phenomenon. Studies of G7C adsorption proteins suggested that the bacterial lipopolysaccharide is the primary phage receptor. In this work, we studied structure and genetics of biosynthesis of the polysaccharide chain of the lipopolysaccharide (O-antigen) in wild type E. coli 4s and its G7C-resistant mutants 4sI-2 and 4sI-4 that kept the ability to produce a long-chain O-antigen. The 4s O-antigen was found to be related to that of E. coli O22 differing only in decoration of the linear polysaccharide with an -D-Glc group on GlcA. The O-antigen of both mutants had the same structure as that of the wildtype strain but lacked O-acetylation on GalNAc.
E. coli 4s and O22 possessed essentially identical O-antigen gene clusters, which included all genes that were necessary for biosynthesis of the E. coli O22 polysaccharide, including a gene for the O-acetylation of GalNAc called wclK. In addition, E. coli 4s, but not E. coli O22, had a three-gtr gene operon that was putatively responsible for the glucosylation of the O-antigen. In both 4sI-2 and 4sI-4 mutants, the wclK gene was inactivated by an insertion of a IS1-like element, the genetic basis that accounted for the lack of the O-antigen O-acetylation. Complementation of the mutants with the wclK gene from E. coli 4s restored the phase-sensitive phenotype. The data obtained demonstrated that the O-antigen of E. coli 4s is the specific receptor of bacteriophage G7C and the O-antigen O-acetylation is necessary for the phage reception.
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P188 NEW WAYS TO HALOPEROXIDES A.T. Zdvizhkov, A.N. Kulakova, R.A. Pototskiy, P.S. Radulov, A.O. Terentev, G.I. Nikishin N.D. Zelinsky Institute of Organic Chemistry, RAS, Laboratory for Studies of Homolytic Reactions, Moscow, Russia
Organic peroxides are one of the most useful classes of organic compounds in different part of human life. The most common application of these substances is polymer chemistry. Moreover, the high anticancer and antihelminthic activities have been discovered recently. It makes researchers invent new types of peroxides and new ways to them. Substitution of halide atom seems huge part of organic synthesis. So we focused on synthesis of halide-substituted peroxide. The system of I2/hydroperoxide was examined in addition to double C=C bond reaction. It was found that type of product depends on I2-hydroperoxide ratio. Noteworthy target iodoperoxides were obtained with huge excess of iodine. However, iodoalcohol as side product formed inevitably. This fact may be complained by cleavage of O-O moiety under iodide-anion action. To avoid degradation of target product we suggested use N-halosuccinimides as halogenations agents. The decision allows decrease of haloalcohol percentage. However, it have been founded employment of N-halosuccinimides initiate a new reaction of radical halogenations of double C=C bond. The problem was solved with adding of catalytic amounts of phosphomolibdic or phosphotungstic acids. Described results have extremely value. Developed methods allow to synthesis wide number of structures containing different halogen atoms and peroxide moiety. This work was supported by the Russian Science Foundation (Grant 14-23-00150).
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P189 MODELING METAL-CATALYZED CROSS-COUPLING AND ADDITION REACTIONS USING COMBINED QUANTUM AND MOLECULAR MECHANICS METHODS A.A. Zeifman, F.N. Novikov, O.V. Stroganov, V.S. Stroylov, I. Yu. Titov, G.G. Chilov, I.V. Svitanko, V.P. Ananikov N. D. Zelinsky Insitiute of Organic chemistry, Moscow, Russia
We have developed a combined QM + MM FEP (free energy perturbation) protocol for modeling metal-catalyzed reactions in explicit solvent media. First, QM calculations are employed to handle reagent, transition state and product in vacuum, and then MM FEP is used to account for solvation effects. In contrast to commonly used PCM, MM FEP allows to obtain a “true” solvation free energy by accounting for all solvent-solute interaction at atomic level and by thermodynamic averaging over entire statistical ensemble and thus potentially offers great advantages in precision of calculations (standard error
