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Current Organic Synthesis, 2013, 10, 328-332
Copper-Catalyzed Synthesis of Isoquinolines by the Cyclocondensation of orthoAlkynyl Aromatic Aldehydes or Ketones with Urea Jia Ju,1 and Ruimao Hua1,2,* 1
Department of Chemistry, Tsinghua University, Key Laboratory of Organic Optoelectronics & Molecular Engineering of Ministry of Education, Beijing 100084, China
2
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China Abstract: A simple and efficient synthesis of isoquinoline derivatives by the condensation of ortho-alkynyl aromatic aldehydes/ketones with urea in the presence of copper salts is developed.
Keywords: o-Alkynyl aromatic aldehyde, o-Alkynyl aromatic ketone, cyclocondensation, isoquinoline derivative, urea. INTRODUCTION Substituted isoquinoline derivatives are considered as an important class of N-heterocyclic compounds, which show interesting physiological, biological and pharmacological activity [1]. Therefore development of the simple and efficient synthetic methods for constructing isoquinoline ring is one of the hot research topics in organic and medicinal chemistry. Some representative procedures for isoquinolines synthesis include: thermal imination/annulation of ortho-alkynylbenzaldehydes with ammonia [2], or under microwave irradiation [3], transition metal-catalyzed intramolecular cyclization of N-tert-butyl-2-(1-alkynyl)arylaldimines [4], palladiumcatalyzed cross-coupling reaction of 2-(1-alkynyl)benzaldimines with organic halides [5], intramolecular cyclization of orthoalkynylarenecarbaldehyde oximes in the presence of Lewis acids [6], iodine-mediated electrophilic cyclization [7] or gold-catalyzed cyclization [8] of ortho-alkynyl benzyl azides, nickel-catalyzed annulation of ortho-iodobenzaldimines with alkynes [9], and rhodium-catalyzed cyclocondensation of aryl ketone O-acyloximes with internal alkynes [10]. On the other hand, urea is a simple and cheap compound, which has been used as ligand in transition metal catalytic reactions [11] and nitrogen source in the synthesis of nitrogen heterocyclic compounds via its decomposition into ammonia [12]. Very recently, molten urea was applied as both a solvent and a reagent for the conversion of peri-alkynyl-9,10-anthraquinones into 2-substituted7H-dibenzo[de,h]quinolin-7-ones [13]. As a continuation of our interest in the exploration of synthetic strategies for the construction of N-heterocycles [12b, 14] and the extended application of copper salts as catalysts in the synthesis of cyclic compounds using alkynes as starting materials [14a-c, 15], in this paper we wish to report an efficient and general method for the formation of isoquinolines by copper-catalyzed cyclocondensation of ortho-alkynyl aromatic aldehydes/ketones with urea as the nitrogen source. RESULTS AND DISCUSSION Our first attempt was the reaction of 2-(phenylethynyl)benzaldehyde (1a) with urea (2.0 eq) at 120 °C in the presence of copper salts (10 mol%) for 12 h, and the results obtained are summarized in Table 1. Reaction without catalyst in toluene gave the desired *
Address correspondence to this author at the Department of Chemistry, Tsinghua University, Key Laboratory of Organic Optoelectronics & Molecular Engineering of Ministry of Education, Beijing 100084, China; Tel: +86-10-62792596; Fax: +86-1062771149; E-mail:
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product of 3-phenylisoquinoline (2a) in 22% GC yield (entry 1). In the presence of cuprous halides, such as CuI, CuBr and CuCl, 2a was formed in a range of 63-68% yield (entries 2-4). In the cases of cupric salts used (entries 5-9), copper (II) sulfate pentahydrate showed the best catalytic activity to afford 2a in 88% yield (entry 9). Polar solvents, such as DMF and 1,4-dioxane retarded the reaction (entries 10 and 11). We investigated its generality with various ortho-alkynyl aromatic aldehydes and ortho-alkynyl aromatic ketones under the conditions indicated in entry 9 of Table 1, and the obtained results are presented in Table 2. As can be seen from the table, in the cases of ortho-alkynyl aromatic aldehydes used, alkyl-substituted alkynyl benzaldehydes showed higher reactivity than aryl-substituted alkynyl benzaldehydes to give the corresponding isoquinoline derivatives in high yields (2d-e vs 2b-c), indicating that electron-rich alkynyl groups favor the occurrence of cyclocondensation. These results are consistent with the results from the cyclocondensation of 2-(4-methoxyphenylethynyl)benzaldehyde (1b) to afford higher yield of 2b, and in the case of 2-(4-acetylphenylethynyl)benzaldehyde (1c) employed, 2c was formed in relatively low yield. In addition, the cyclocondensation of 2-ethynylbenzaldehyde (1f) with urea gave a low yield of isoquinoline (2f) with almost complete conversion of 1f after 6 h, accompanied with the formation of unidentified by-products. Although AgOTf-catalyzed reactions of ortho-alkynyl acetophenone with ammonia under microwave irradiation was well studied by Abbiati et al. a mixture of 1-methylisoquinoline derivatives and 1-aminonaphthalene derivatives was usually obtained [16]. Therefore we intended to expand the scope of the present cyclocondensation by the reactions of ortho-alkynyl aromatic ketones with urea, and the reaction afforded the desired 1,3-disubstituted isoquinolines 2g-j in good yields with excellent selectivity. The reaction is also applicable to ortho-alkynyl heteroaryl aldehydes or ketones under the similar conditions to give heterocyclefused pyridines. For examples, the reactions of 2-acetyl-3-(4methoxyphenylethynyl)thiophene (1k) and 2-acetyl-3-(nhexylethynyl)thiophene (1l) with urea afforded the expected thiophene-fused pyridine 2k and 2l in 51% and 78% yields, respectively (eqs 1 and 2). The yields of products are also dependent on the electron properties of substituents in alkynyl groups, and electron-donating character of substituent gave higher yield. Moreover, 7-aryl-1,6-naphthydrines showed interesting bioactivity [17], being usually synthesized by sequential reactions of conversion of 2-bromonicotinaldehyde into its N-tBu imine, © 2013 Bentham Science Publishers
Copper-Catalyzed Synthesis of Isoquinolines by the Cyclocondensation
Current Organic Synthesis, 2013, Vol. 10, No. 2 329
Table 1. Formation of 3-Phenylisoquinoline (2a) by the Reaction of 2-(Phenylethynyl)benzaldehyde (1a) and Ureaa CHO +
entry
NH2
H2N
N
solvent 120 oC, 12 h
2.0 equiv
Ph
1a
Cu catalyst (10 mol%)
O
catalyst
1c
Ph 2a
solvent
yield (%)b
toluene
22
2
CuI
toluene
63
3
CuBr
toluene
68
4
CuCl
toluene
66
5
CuCl2
toluene
72
6
CuBr2
toluene
76
7
Cu(OTf)2
toluene
72
8
Cu(OAc)2.5H2O
toluene
83
9
CuSO4.5H2O
toluene
88 (79)
10c
CuSO . 5H O
DMF
66
11c
. CuSO 5H O
1,4-dioxane
62
4
2
4
2
a
Unless otherwise noted, the reactions were carried out with 1.0 mmol of 1a, 2.0-3.0 equiv. of urea and 0.1 mmol of catalyst in 2.0 mL of solvent at 120 oC in a sealed tube under nitrogen atmosphere. b GC yield based on the amount of 1a. Number in parenthesis is isolated yield. c 24 h.
Table 2. Formation of 3-Substituted Isoquinoline Derivativesa O O
R'
R
+
H2N
R"
1
R'
CuSO4.5H2O (10 mol%)
N R
NH2
toluene 120 oC, 12 h
R"
2.0 equiv.
2 N
N
2b 73%
O
2c 54%
O N
N CN
n-C6H13
2d 86%
2e 86%
N
N
N
n-C6H13
Ph 2f
2g 74%
23%b
2h 79% n-C4H9
N
N Ph
F 2i 63%
Ph 2j 75%
reactions were carried out with 1.0 mmol of 1, 2.0 mmol of urea and 0.1 mmol of CuSO4. 5H2O in 2.0 mL of toluene in a sealed tube under nitrogen atmosphere at 120 oC for 12 h. The yields are Isolated yields based on the amount of 1 used. b For 6 h.
a The
330 Current Organic Synthesis, 2013, Vol. 10, No. 2
Ju and Hua
O S
.
+
S
CuSO4 5H2O (10 mol%)
O H2N
NH2
(1)
toluene 120 oC, 12 h
2k 51%
2.0 equiv. 1k
N
OMe
OMe
O S
.
CuSO4 5H2O (10 mol%)
O +
H2N
n-C6H13
1l
NH2
S
N
toluene 120 oC, 12 h
(2) n-C6H13
2.0 equiv.
2l 78%
O
+ N
H2N
Ph
1m
CuSO4. 5H2O (10 mol%)
O
H
NH2
(3)
toluene 120 oC, 12 h
N
2.0 equiv.
ate 3 is formed in situ by the reaction of 1 with low concentration of ammonia, which occurs from the gradual decomposition of urea initiated by the presence of trace amount of water; (2) intermediate 3 undergoes subsequent intramolecular hydroamination of carboncarbon triple bond in the presence of copper to yield isoquinoline derivative 2. Note that there is another possible mechanism including a first step of Cu-catalyzed addition of urea to C=O bond reported by Vasilevsky and Alabugin [13].
Because starting materials 1 are usually prepared from Sonogashira cross-coupling reaction of ortho-iodo or bromo aromatic aldehydes with terminal alkynes, we designed a three-component reaction of ortho-bromobenzaldehyde, phenylacetylene and urea in the presence of CuI, and 2a could be obtained in 47% yield (eq. 4), providing a potential one-pot procedure for the formation of isoquinoline derivatives from simple and commercial starting materials.
CONCLUSION In summary, an efficient and simple method for the synthesis of isoquinoline derivatives and heterocycle-fused pyridines by the cyclocondensation of ortho-alkynyl aromatic aldehydes/ketones with urea catalyzed by copper (II) sulfate pentahydrate has been developed. The present procedure has the advantages of including cheap catalyst, urea as nitrogen source, wide substrate scope, and high chemoselectivity.
The formation of isoquinolines by the cyclocondensation of ortho-alkynyl aromatic aldehydes or ketones with urea is assumed to involve two main steps: (1) ortho-alkynyl benzaldimines intermediCHO
CuI (30 mol%) Et3N (2.0 equiv)
O Ph
+
Br 1.5 equiv.
Ph
2m 62%
Sonogashiro coupling with aryl acetylenes catalyzed by PdCl2(PPh3)2/CuI, and final CuI-mediated cyclocondensation [4f, 17]. The application of the present procedure provides an alternatively efficient method for the formation of 7-phenyl-1,6naphthydrine (2m) from the reaction of 2-phenylethynyl-3formylpyridine (1m) with urea under the standard conditions as shown in Eq. 3.
+
N
H2N
NH2
2a
toluene, N2 120 oC, 24 h
5.0 equiv.
47%
O
R' R'
R
+ 1
dehydration
NH3
R"
NH
R
3 R'
intramolecular hydroamination
N
R
R" 2 Scheme 1. Proposed Mechanism for Copper-Catalyzed Formation of Isoquinolines.
R"
(4)
Copper-Catalyzed Synthesis of Isoquinolines by the Cyclocondensation
EXPERIMENTAL SECTION (1) General Method All organic starting materials are analytically pure and used without further purification. 1H-, 13C-NMR spectra were recorded on JOEL JNM-ECA300 or JNM-ECA600 spectrometers at 300 MHz or 600 MHz and 75 MHz or 150 MHz, respectively. 1 H chemical shifts () were referenced to TMS, and 13C NMR chemical shifts () were referenced to internal solvent resonance. GC analyses of organic compounds were performed on an Agilent Technologies 1790 GC (with a SGE-OV1701 25m capillary column) instrument. Mass spectra were obtained on a Shimadzu GCMS-QP2010S, and HRMS was obtained on a micrOTOF-Q 10142. (2) Typical Experimental Procedures A Typical experimental procedure for the reaction of 2(phenylethynyl)- benzaldehyde (1a) with urea (2.0 eq) affording 3phenylisoquinoline (2a) (Table 1, entry 9): A mixture of 2(phenylethynyl)benzaldehyde (206.0 mg, 1.0 mmol), urea (120.0 mg, 2.0 mmol), CuSO4·5H2O (24.9 mg, 0.1 mmol) in toluene (2.0 mL) in a screw-capped thick-walled Pyrex tube was heated at 120 o C (oil bath temperature) with stirring for 12 h under nitrogen atmosphere. After the reaction mixture was cooled to room temperature, CH2Cl2 (4.0 mL) and n-docosane (155.2 mg, 0.5 mmol, as an internal standard for GC analysis) were then added. After GC and GC-MS analyses of the reaction mixture, volatiles were removed under reduced pressure, and the residue was subjected to silica gel column chromatography, and eluted with a mixture of solvents of ethyl acetate and petroleum ether (2:100 in volume) to afford 2a (162.0 mg, 0.79 mmol, 79%) as a white solid. The GC analysis of reaction mixture disclosed that the formation of 2a was in 88% GC yield. (3) Characterization Data of Products 2i, 2k and 2l are new compounds and characterized by 1H-, 13CNMR, mass spectrum and HRMS. Other products are known compounds, which were characterized by 1H-, 13C-NMR and mass spectra. 3-Phenylisoquinoline (2a) [9]: White solid, m.p. 94-96 oC (lit. o 93 C); 1H NMR (300 MHz, CDCl3) 9.32 (s, 1H), 8.12 (d, J = 7.9 Hz, 2H), 8.04 (s, 1H), 7.95 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.71-7.62 (m, 1H), 7.59-7.45 (m, 3H), 7.45-7.38 (m, 1H); 13C NMR (75 MHz, CDCl3) 152.5, 151.4, 139.7, 136.7, 130.6, 128.9, 128.6, 127.9, 127.6, 127.14, 127.11, 127.0, 116.6; GCMS m/z (% rel. inten.) 205 (M+, 100), 204 (63), 128 (2), 102 (22), 77 (4). 3-(4-Methoxyphenyl)isoquinoline (2b) [6b]: Yellow solid, m.p. 104-105 oC (lit. 97-99 oC); 1H NMR (600 MHz, CDCl3) 9.26 (s, 1H), 8.06 (d, J = 8.9 Hz, 2H), 7.91 (s, 1H), 7.89 (d, J = 8.3 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.47 (ddd, J = 8.3 Hz, 6.9 Hz, 1.4 Hz, 1H), 7.00 (d, J = 8.9 Hz, 2H), 3.82 (s, 3H); 13C NMR (150 MHz, CDCl3) 160.2, 152.3, 151.0, 136.8, 132.3, 130.4, 128.2, 127.5, 127.4, 126.8, 126.7, 115.3, 114.2, 55.4; GCMS m/z (% rel. inten.) 235 (M+, 100), 220 (32), 204 (2), 191 (22), 128 (2).
Current Organic Synthesis, 2013, Vol. 10, No. 2 331
(d, J = 8.3 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.66 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.50 (s, 1H), 3.07 (t, J = 7.2 Hz, 2H), 2.38 (t, J = 6.9 Hz, 2H), 2.20 (pentet, J =7.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) 152.7, 152.4, 136.3, 130.5, 127.5, 127.3, 126.8, 126.1, 119.6, 118.8, 36.3, 25.2, 16.5; GCMS m/z (% rel. inten.) 196 (M+, 5), 156 (24), 143 (100), 128 (7). 3-Hexylisoquinoline (2e) [6b]: Brown oil; 1H NMR (300 MHz, CDCl3) 9.19 (s, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.60 (dt, J = 7.6 Hz, 1.4 Hz, 1H), 7.47 (dt, J = 7.6 Hz, 1.4 Hz, 1H), 7.43 (s, 1H), 2.92 (t, J = 7.7 Hz, 2H), 1.81 (pentet, J =7.5 Hz, 2H), 1.45-1.24 (m, 6H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) 155.9, 152.0, 136.5, 130.2, 127.5, 127.1, 126.2, 126.1, 117.9, 38.2, 31.8, 30.0, 29.2, 22.6, 14.1; GCMS m/z (% rel. inten.) 213 (M+, 3), 198 (1), 184 (4), 170 (11), 156 (19), 143 (100), 142 (10), 128 (5). Isoquinoline (2f) [18]: Brown oil; 1H NMR (300 MHz, CDCl3) 9.26 (s, 1H), 8.53 (d, J = 4.8 Hz, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.3 Hz, 1H), 7.72-7.55 (m, 3H); 13C NMR (75 MHz, CDCl3) 152.6, 143.1, 135.9, 130.4, 128.8, 127.7, 127.3, 126.6, 120.5; GCMS m/z (% rel. inten.) 129 (M+, 100), 128 (19), 102 (33), 51 (22). 1-Methyl-3-phenylisoquinoline (2g) [16]: Brown solid, m.p. 58-60 oC (lit. brown oil); 1H NMR (300 MHz, CDCl3) 8.13 (d, J = 8.6 Hz, 2H), 8.07 (d, J = 7.9 Hz, 1H), 7.88 (s, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.65-7.58 (m, 1H), 7.55-7.44 (m, 3H), 7.42-7.34 (m, 1H), 3.01 (s, 3H); 13C NMR (75 MHz, CDCl3) 158.6, 150.1, 139.9, 136.8, 130.1, 128.8, 128.4, 127.7, 127.1, 126.8, 126.7, 125.7, 115.3, 22.8; GCMS m/z (% rel. inten.) 219 (M+, 100), 204 (4), 115 (11), 108 (12). 3-Hexyl-1-methylisoquinoline (2h) [16]: Yellow oil; 1H NMR (300 MHz, CDCl3) 8.05 (d, J = 8.6 Hz, 1H), 7.71 (d, J = 8.3 Hz, 1H), 7.63-7.56 (m, 1H), 7.52-7.45 (m, 1H), 7.30 (s, 1H), 2.94 (s, 3H), 2.88 (t, J = 7.7 Hz, 2H), 1.79 (pentet, J =7.6 Hz, 2H), 1.481.23 (m, 6H), 0.88 (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) 158.1, 154.7, 136.7, 129.8, 126.9, 126.0, 125.9, 125.6, 116.5, 38.4, 31.9, 30.1, 29.3, 22.7, 22.5, 14.2; GCMS m/z (% rel. inten.) 227 (M+, 3), 184 (9), 170 (15), 157 (100), 115 (10). 6-Fluoro-1-methyl-3-phenylisoquinoline (2i): Yellow solid, m.p. 39-41 oC; 1H NMR (300 MHz, CDCl3) 8.13-8.04 (m, 3H), 7.80 (s, 1H), 7.52-7.44 (m, 2H), 7.43-7.36 (m, 2H), 7.31-7.22 (m, 1H), 2.98 (s, 3H); 13C NMR (75 MHz, CDCl3) 63.2 (d, J 1C-F = 252.2 Hz), 158.5, 151.1, 139.5, 138.5 (d, J 3C-F = 10.1 Hz), 128.9, 128.7, 127.1, 123.8, 117.0 (d, J 2C-F = 25.3 Hz), 114.9 (d, J 4C-F = 5.1 Hz) 110.8 (d, J 2C-F = 20.2 Hz), 22.8; GCMS m/z (% rel. inten.) 238 (18), 237 (M+, 100), 236 (24), 222 (4); 133 (12); HRMS (ESI): Calcd. For C16H13FN [M+H]+: 238.1027; Found: 238.1031. 1-Butyl-3-phenylisoquinoline (2j) [7d]: Yellow oil; 1H NMR (300 MHz, CDCl3) 8.19-8.11 (m, 3H), 7.90 (s, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.66-7.59 (m, 1H), 7.57-7.44 (m, 3H), 7.42-7.34 (m, 1H), 3.36 (t, J = 7.9 Hz, 2H), 1.94 (pentet, J = 7.7 Hz, 2H), 1.54 (sextet, J = 7.5 Hz, 2H), 1.01 (t, J = 7.4 Hz, 3H); 13C NMR (75 MHz, CDCl3) 162.2, 150.0, 140.1, 137.2, 129.9, 128.8, 128.4, 127.9, 127.1, 126.8, 126.2, 125.5, 115.0, 35.3, 31.7, 23.1, 14.2; GCMS m/z (% rel. inten.) 261 (M+, 6), 246 (7), 232 (13), 219 (100).
1-(4-(Isoquinolin-3-yl)phenyl)ethanone (2c) [7d]: Yellow solid, m.p. 164-166 oC (lit. 148-150 oC); 1H NMR (600 MHz, CDCl3) 9.32 (s, 1H), 8.20 (d, J = 8.3 Hz, 2H), 8.09 (s, 1H), 8.06 (d, J = 8.3 Hz, 2H), 7.96 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.69 (ddd, J = 8.3 Hz, 6.9 Hz, 1.4 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 2.63 (s, 3H); 13C NMR (150 MHz, CDCl3) 197.8, 152.6, 149.8, 143.9, 136.8, 136.5, 130.8, 128.9, 128.1, 127.7, 127.6, 127.1, 127.0, 117.5, 26.8; GCMS m/z (% rel. inten.) 247 (M+, 57), 232 (100), 204 (51), 128 (3).
5-(4-Methoxyphenyl)-7-methylthieno[2,3-c]pyridine (2k): Brown solid, m.p. 76-78 oC; 1H NMR (300 MHz, CDCl3) 7.98 (d, J = 8.9 Hz, 2H), 7.82 (s, 1H), 7.55 (d, J = 5.5 Hz, 1H), 7.29 (d, J = 5.5 Hz, 1H), 6.98 (d, J = 8.9 Hz, 2H), 3.81 (s, 3H), 2.82 (s, 3H); 13C NMR (75 MHz, CDCl3) 160.0, 152.4, 151.6, 146.0, 133.6, 132.7, 131.1, 128.3, 124.0, 114.1, 111.6, 55.4, 23.8; GCMS m/z (% rel. inten.) 256 (17), 255 (M+, 100), 240 (41), 212 (33), 105 (12); HRMS (ESI): Calcd. For C15H14NOS [M+H]+: 256.0791; Found: 256.0792.
3-Isoquinolinebutanenitrile (2d) [9]: White solid, m.p. 103105 oC (lit. 98 oC); 1H NMR (300 MHz, CDCl3) 9.19 (s, 1H), 7.92
4-Hexyl-7-methylthieno[2,3-c]pyridine (2l): Brown oil; 1H NMR (300 MHz, CDCl3) 7.58 (d, J = 5.5 Hz, 1H), 7.37 (s, 1H),
332 Current Organic Synthesis, 2013, Vol. 10, No. 2
Ju and Hua
7.26 (d, J = 5.5 Hz, 1H), 2.86 (t, J =7.9 Hz, 2H), 2.78 (s, 3H), 1.831.69 (m, 2H), 1.47-1.22 (m, 6H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) 156.1, 152.0, 145.7, 133.0, 130.9, 123.5, 114.0, 38.3, 31.9, 30.6, 29.2, 23.6, 22.7, 14.2 ; GCMS m/z (% rel. inten.) 233 (M+, 3), 190 (11), 176 (16), 163 (100), 162 (9); HRMS (ESI): Calcd. For C14H20NS [M+H]+: 234.1311; Found: 234.1312. 7-Phenyl-1,6-naphthyridine (2m) [4g]: Yellow solid, m.p. 147-149 oC (lit. 135-137 oC); 1H NMR (300 MHz, CDCl3) 9.35 (s, 1H), 9.09 (d, J = 4.1 Hz, 1.7Hz, 1H), 8.35 (s, 1H), 8.32-8.26 (m, 1H), 8.21-8.15 (m, 2H), 7.59-7.40 (m, 4H); 13C NMR (75 MHz, CDCl3) 155.3, 155.1, 152.8, 151.5, 139.0, 135.7, 129.3, 129.0, 127.3, 122.8, 122.3, 117.9; GCMS m/z (% rel. inten.) 206 (M+, 100), 205 (65), 178 (9), 150 (12), 103 (16), 102 (11), 76 (12).
[5]
[6]
[7]
CONFLICT OF INTEREST The author(s) confirm that this article content has no conflict of interest. ACKNOWLEDGEMENTS This project was supported by the National Natural Science Foundation of China (21032004, 20972084), the Specialized Research Fund for the Doctoral Program of Higher Education (20110002110051) and the Bilateral Scientific Cooperation between Tsinghua University & K. U. Leuven.
[8] [9] [10]
SUPPORTING INFORMATION Charts of 1H-, 13C-NMR for all products are included (Supplementary material is available on the publishers Web site along with the published article).
[11]
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Revised: November 05, 2012
Accepted: November 26, 2012
