J Chem Crystallogr (2010) 40:391–395 DOI 10.1007/s10870-010-9742-6
COMMUNICATION
Crystal Structure of Diethyl[(4chlorophenyl) (dibenzylamino)methyl]propanedioate I. Meskini • L. Toupet • M. Akkurt • M. Daoudi A. Kerbal • Z. H. Chohan • T. Ben Hadda
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Received: 2 November 2009 / Accepted: 12 February 2010 / Published online: 25 February 2010 Springer Science+Business Media, LLC 2010
Abstract The titled new functionalized N,O,O-ligand of type diethyl[(4-chlorophenyl)(dibenzylamino)methyl]propanedioate (4) is prepared in good yield through condensation of dibenzylamine, with 2-arylidene-malonic acid diethyl esters 3. The structure of 4 was determined by spectral (IR, 1H NMR), elemental analyses and X-ray diffraction data. The molecular conformation shows two possible pockets ready to coordinate two metal atoms. Keywords N,O,O-ligand b-Amino dicarbonyl Malonate Michael reaction Mechanism study
I. Meskini M. Daoudi A. Kerbal Laboratoire de Chimie Organique, Universite´ Sidi Mohammed Ben Abdellah, Fe`s, Morocco L. Toupet Institut de Physique - IPR - UMR CNRS 6251, Universite´ de Rennes 1, Rennes, France e-mail:
[email protected] Z. H. Chohan Department of Chemistry, Bahauddin Zakariya University, Multan 60800, Pakistan T. Ben Hadda (&) Laboratoire de Chimie des Mate´riaux, Universite´ Med. 1ier, Oujda, Morocco e-mail:
[email protected] M. Akkurt Department of Physics, Faculty of Arts and Sciences, Erciyes University, 38039 Kayseri, Turkey e-mail:
[email protected]
Introduction The rational design of new HIV-1 Integrase (H-I) inhibitors, one validated target for chemotherapeutic intervention [1], is fundamentally based on intermolecular coordination between H-I/chemical inhibitor/metals (Mg?2 and Mn?2, co-factors of the enzyme), leading in the formation of bimetallic complexes [2, 3]. Thereby, several bimetallic metal complexes, in many cases exploring the known-well polydentate ligands, appear in this scenario as the most promising concept to employ in either enzyme/drug interaction or electron transfer process, in the last case involving the biological oxygen transfer [4–6]. Another exciting example of application for such polydentate ligand involves the synergic water activation, that occurs via the so-called ‘‘remote metallic atoms’’. Such organometallic compounds are structurally deemed to promote or block the H-I activity [7]. These explanations above detailed clearly demonstrate that polydentate ligands are of special interest in the bioorganometallic chemistry field [8]. Looking for the design of new bimetallic coordinating ligands to further explore in the building of intermolecular system involving H-I/inhibitor/metal complexation, we have targeted to study the crystallographic structure of polydendate malonate N,O,O-Ligand (4). To prepare such polydentate ligands, aza-Michael reactions appear to be key-step to lead the b-amino esters. In fact, this kind of reaction has been largely employed to generate structurally diverse b-amino dicarbonyl compounds, where the undoubtedly importance of this azaMichael step it is viewed by the large number of unconventional methodologies as well as the broadened of applications [9–11]. Not only from a drug design and synthetic point of view, but also from a mechanistic point of view the study of
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structure of the Michael reaction products is of considerable interest on mechanism analysis and poses a significant challenge. To this end, we decided to investigate the feasibility of applying the aza-Michael reactions to the more challenging substituted alkene derivatives. Our plan also included the application of this key-step to the synthesis of a novel set of polydentate ligands, in order to highlight the versatility of the procedure as well as to generate some insights regarding the 3D crystalline structure of compounds (4).
J Chem Crystallogr (2010) 40:391–395
The treatment of 2-(4-chloro-benzylidene)-malonic acid diethyl esters (3) in the presence of dibenzylamine, in an aqueous medium at room temperature brings about highly and efficient regioselective aza-Michael addition to produce the corresponding b-amino dicarbonyl compound 4 (Scheme 1).
asymmetric unit of (4), (4a) and (4b), are shown in Figs. 1 and 2. The asymmetric unit in the crystal structure of 4 consists of two independent molecules (4a and 4b). The bond lengths are almost identical in both molecules and are comparable with those in related structures [14, 15]. In molecule (4a), the dihedral angles between the rings A(C9– C14), B(C16–C21) and C(C23–C28) are A/B = 15.61 (8), A/C = 69.93 (8) and B/C = 67.48 (8). In molecule (4b), the equivalent planes are A0 (C39–C44), B0 (C46–C51) and C0 (C53–C58), and the angles between them are A0 / B0 = 85.62 (8), A0 /C0 = 16.47 (8) and B0 /C0 = 79.47 (8). The dihedral angles between the planes of similar rings of the two molecules of (4) are not identical, with values of A/ A0 = 81.01(7), B/B0 = 64.58(8) and C/C0 = 4.17(8). In the molecular structure of (4a), the torsion angles O1–C6C3–O3, O1–C6C1–N1 and O3–CC1–N1 are 165.12 (2), -157.35 (1) and 45.42 (3), respectively. In (4b), the values of the corresponding angles O31– C33C36–O33, O31–C33C31–N31 and O33– C36C31–N31 are 165.00 (2), -161.68 (1) and 43.02 (3), respectively (Table 3).
X-ray Structure Setermination of N,O,O-ligand (4)
Supplementary Information
Suitable single crystal of malonate derivative 4 was obtained by recrystallization from ethanol. A white-transparent crystal of C28H30ClNO4 having approximate dimensions of 0.18 9 0.12 9 0.12 mm was mounted on a glass fibre. All measurements were made in the x-scan technique on a CCD Saphire 3 Xcalibur diffractometer (Oxford Diffraction) with graphite monochromatized MoKa radiation. The details of the data collection and refinement are given in Table 1. The structure was solved by direct methods using the program SIR-97 [12] and the non-hydrogen atoms were refined anisotropically by the full-matrix least-square techniques using the program SHELXL97 [13]. All the hydrogen atoms bonded to C atoms were located geometrically and treated using a riding ˚ and Uiso(H) = 1.2 or model, with C–H = 0.95–1.00 A 1.5Ueq(C). The details of the crystal and experimental data were listed in Table 1. Selected bond distances and bond angles are given in Table 2. The two molecules in the
Crystallographic data for the structural analysis has been deposited with the Cambridge crystallographic Data Centre, CCDC No. 734201 for compound (4). Copies of this information can be obtained free of charge from The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: ?44-1223-336033; e-mail:
[email protected]. uk or http://www.ccdc.cam.ac.uk).
Results and Discussion Chemistry
Scheme 1 (i) piperidine, CH3CO2H, EtOH/D; (ii) NH(benzyl)2, H2O/RT
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Experimental Section All materials and solvents used were of reagent grade as received from commercial sources. The starting material 2-(4-chloro-benzylidene)-malonic acid diethyl ester (3) was synthesized and transformed to the malonate derivative as described in our previous work [14]. 1H NMR spectra were recorded on AC 250 MHz NMR Bruker Spectrometer at ambient temperature and chemical shifts were reference to the internal tetramethylsilane. Infrared
J Chem Crystallogr (2010) 40:391–395 Table 1 Crystal data and structure refinement for 4
393 ˚ ) and angles () for 4 Table 2 Bond lengths (A
Empirical formula
C28H30ClNO4
Cl1–C12
1.7415 (17)
O32–C34
1.4584 (17)
Formula weight
479.98
Cl31–C42
1.7416 (17)
O33–C36
1.2104 (19)
Temperature
110(2) K
O1–C6
1.195 (2)
O34–C37
1.455 (2)
Wavelength
˚ 0.71073 A
O2–C6
1.3384 (18)
O34–C36
1.3314 (19)
Crystal system, space group
Triclinic, P-1
O2–C7
1.458 (2)
N1–C15
1.4700 (18)
O3–C3
1.2055 (19)
N1–C22
1.471 (2) 1.482 (2)
Unit cell dimensions ˚ a = 11.6913 (3) A
a = 81.995 (2)
O4–C4
1.454 (2)
N1–C1
˚ b = 11.7021 (3) A ˚ c = 19.5116 (6) A
b = 87.387 (2)
O4–C3
1.334 (2)
N31–C52
1.472 (2)
c = 71.779 (2)
O31–C33
1.200 (2)
N31–C45
1.4769 (19)
Volume
˚3 V = 2510.87 (12) A
O32–C33
1.3380 (18)
N31–C31
1.4832 (19)
Z
4
C6–O2–C7
116.94 (12)
O2–C7–C8
107.15 (14)
Calculated density
1.270 Mg/m3
C3–O4–C4
116.21 (12)
Cl1–C12–C13
118.94 (13)
F(000)
1088
C33–O32–C34
116.22 (12)
Cl1–C12–C11
120.02 (12)
Absorption coefficient
l = 0.186 mm-1
C36–O34–C37
116.06 (13)
N1–C15–C16
113.25 (12)
Crystal size Theta range for data collection
0.18 9 0.12 9 0.12 mm 2.79 to 27.00
C1–N1–C22 C1–N1–C15
114.43 (12) 111.55 (11)
N1–C22–C23 N31–C31–C32
112.72 (13) 109.02 (12)
Limiting indices
-14 B h B 14, -14 B k B 14, -24 B l B 23
C15–N1–C22
111.37 (12)
N31–C31–C39
113.98 (11)
C31–N31–C52
111.46 (11)
O31–C33–O32
124.58 (13)
Measured reflections
22331
C45–N31–C52
111.31 (11)
O31–C33–C32
125.77 (13)
Independent reflections
10915 [R(int) = 0.026]
C31–N31–C45
114.27 (11)
O32–C33–C32
109.64 (13)
Reflections with I [ 2r (I)
7545
N1–C1–C2
109.73 (12)
O32–C34–C35
109.77 (13)
Completeness to h = 27.00
99.7%
N1–C1–C9
115.81 (12)
O33–C36–O34
124.54 (14)
Absorption correction
None
O3–C3–O4
125.06 (15)
O33–C36–C32
124.58 (14)
Refinement method
Full-matrix least-squares on F2
O4–C3–C2
110.45 (13)
O34–C36–C32
110.87 (13)
Parameters
613
O3–C3–C2
124.49 (15)
O34–C37–C38
109.23 (16)
Goodness-of-fit on F2
0.904
O4–C4–C5
110.41 (15)
Cl31–C42–C41
120.19 (12)
Final R indices [I [ 2r(I)]
R1 = 0.0376, wR2 = 0.0889
O2–C6–C2
109.36 (13)
Cl31–C42–C43
118.53 (13)
R indices (all data) Weighting scheme
R1 = 0.0614, wR2 = 0.0937 w = 1/[r2(F2o) ? (0.0525P)2] where P = (F2o ? 2F2c )/3
O1–C6–O2
124.62 (15)
N31–C45–C46
111.05 (12)
O1–C6–C2
126.02 (14)
N31–C52–C53
112.63 (11)
(D/r)max
0.001
Largest diff. peak and hole
˚ -3 0.31 and -0.38 e A
spectra were recorded in KBr pellets using a Perkin–Elmer 1310 spectrophotometer. Mass spectra were determined by platform II Micromass (ESI?, CH3CN/H2O: 50/50) and elemental analyses were performed by CNRST and Service Central d’Analyse CURI (Fe`s, Morocco). Synthesis of (3): to a solution of ethyl malonate 2 (15 g, 93 mmol) in 40 mL of ethanol, were added the 4-chlorobenzaldehyde 1 (15 g, 107 mmol)] and 1.5 mL of piperidine and 1 mL of glacial acetic acid. Then the mixture was stirred at refluxing temperature of ethanol for 12 h, until thin-layer chromatography indicated the complete consume of the starting material. After removing solvent, the crude product was washed with a saturated solution of sodium bisulfite (20 mL). The product was extracted by diethyl ether (2 9 20 mL), dried with sodium sulphate and evaporated to give the pure oil.
Yellow oil. 77% yield, Rf 0.73 (ether/hexane, 1/1). IR (KBr, m cm-1): 2906–2982 (CH), 1724 (CO), 1591/1631 (C=C), 1254/1308 (C–O). 1H-NMR (300 MHz, CDCl3) d ppm: 7.7 (s, 1H, C=CH–ph), 7.45–7.30 (m, 4H, Ph), 4.31– 4.4 (2 q, 4H, 2CH2–CH3, 3J = 7.12 Hz), 1.31–1.25 (2 t, 6H, 2H2C–CH3, 3J = 7.11 Hz). 13C-NMR (300 MHz, CDCl3) d ppm: 166.36–163.86 (2C=O); 140.01 (ClPh– CH=), 132.90 (Cquat, C–Cl–Ph), 130.30 (2Cmeta), 130.49 (Cquat, para/Cl), 129.07 (2Cortho), 125.40 (C=C–(CO2Et)2), 61.44–61.79 (2CH2–CH3), 13.74–13.88 (2CH3–CH2). MS (IE): Calcd for [M]? C14H15ClO4: 282.07; Found [M ? H]•? = 283 (100%). Synthesis of (4): to a solution of the 2-(4-chloro-benzylidene)-malonic acid diethyl ester 3 (8.1 mmol) in water (25 mL) was added the respective dibenzylamine (6 mmol) and the mixture and the stirring was continued at room temperature until the complete consume of the starting material. After removing solvent, the crude products were dissolved in diethyl ether (2 9 40 mL) and washed with water until the pH became neutral. The organic solvent was
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J Chem Crystallogr (2010) 40:391–395 Table 3 Torsion angles () for 4 N1–C1–C2–C3
-39.23 (17) N31–C31–C32– C33
-163.05 (12)
N1–C1–C2–C6
-162.44 (12) N31–C31–C32– C36
-42.47 (15)
N1–C1–C9–C10
101.96 (17) N31–C31–C39– C40
91.56 (16)
N1–C22–C23– C24
-47.48 (19) N31–C52–C53– C54
-52.53 (18)
C1–C2–C3–O3
108.75 (17) C31–C32–C36– O33
110.21 (16)
C1–C2–C6–O1 C1–N1–C15–C16
Fig. 1 An ORTEP view of the molecule 4a of two crystallographically independent molecules in the asymmetric unit, with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level
-5.5 (2)
C36–C32–C33– O31
-131.24 (16)
-71.66 (16) C31–N31–C45– C46
166.25 (12)
2CHPh, 3J = 13 Hz), 3.98 (dq, 2HAB, OCH2CH3, 2JAB = 14.10 Hz, 3J = 7.10 Hz), 4.20–4.40 (dq, 2HAB, OCH2CH3, 2 JAB = 14,11 Hz, 3J = 7.10 Hz), 1.30 (t, 3H, OCH2CH3, 3 J = 7.10 Hz), 1.01 (t, 3H, OCH2CH3, 3J = 7.10 Hz), 1.25 (t, 3H, OCH2CH3, 3J = 7.10 Hz). 13C-NMR (250 MHz, CDCl3) d (ppm): 166.74/167.26 (2CO), 138,71 (Cquat, CCl, Ph), 133.68 (Cquat, para–Cl–Ph), 130.47 (Ctert, 2Cmeta, para–Cl–Ph), 128.91 (Ctert, 2Cortho, para–Cl–Ph), 128.29 (Cquat, 2C, 2Ph), 128.34 (Ctert,, 4Cmeta, 2Ph) 128.29 (Ctert, 4Crtho, 2Ph), 127.15 (Ctert, 2Cpara, 2Ph), 61.73 (Csec, 2CH2, ester), 61.04 (Ctert, C3HPhCl), 55.26 (Ctert, C2H(CO2Et)2), 13.75 (C, OCH2CH3, ester), 13.92 (C, OCH2CH3, ester), 61.31 (Csec, 2CH2Ph). MS (IE) Calcd for [M]? : 479.99, [M ? H]•? = 481, [M-CH(CO2Et)2]•? = 320 (100%). Elemental analysis for C28H30NO4Cl Calcd (Found): C 70.06 (69.98), H 6.30 (6.27), N 2.92 (2.91). Acknowledgements This work was supported by grants from Project PGR-UMP-BH-2005 and the Centre National de Recherche Scientifique, Universite´ de Rennes 1 (France).
References Fig. 2 An ORTEP view of the molecule 4b of two crystallographically independent molecules in the asymmetric unit, with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level
dried with sodium sulphate and then evaporated to give the pure compound (4). White crystals. 67% yield. Rf = 0.42 (ether/hexane:1/ 1). Mp = 110–112 C. IR (KBr, m cm-1): 2811/2980 (CH), 1722 (C=O), 1591 (C=C), 1257/1301(C–O), 1181, 1092, 822, 747, 416. 1H-NMR (250 MHz, CDCl3) d (ppm): 7.24– 7.44 (m, 4H, aromat, Ph–Cl, 3J = 6.60 Hz), 7.23–7.31 (m, 10H, aromat, Ph,3J = 4.15 Hz), 4.56 (d, 1H, ClPhC3H, 3 J = 12.12 Hz), 4.33 (d, 1H, C2H(CO2Et)2, 3J = 12.12 Hz), 3.0 (d, 1H, 2CHPh, 3J = 13.50 Hz), 3.9 (d, 1H,
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