Y. Suzuki et al. / Tetrahedron 69 (2013) 470e473
473
4.2.1. 2-(4-Chlorophenyl)-3-phenylquinoxaline
(7ae). Colorless
(Mþ1)þ: 297.0795, found: 297.0791; 1H NMR (400 MHz) CDCl3
d:
powder, 65%; mp 142e143 ꢀC; HRMS (FAB) calcd for C20H14N2Cl
3.73 (3H, s), 6.90 (1H, dd, J¼8.3, 2.2 Hz), 6.96 (1H, d, J¼8.3 Hz), 7.02
(Mþ1)þ: 317.0846, found: 317.0862; 1H NMR (400 MHz) CDCl3
d:
(1H, t, J¼2.2 Hz), 7.20 (1H, t, J¼8.3 Hz), 7.28(2H, d, J¼8.3 Hz), 7.41
7.30e7.38 (5H, m), 7.46e7.52 (4H, m), 7.75e7.79 (2H, m), 8.15e8.19
(2H, d, J¼8.3 Hz), 8.59 (1H, d, J¼2.4 Hz), 8.60 (1H, d, J¼2.2 Hz); 13
C
(2H, m); 13C NMR (125 MHz) CDCl3
d: 128.5, 128.6, 129.0, 129.1,
NMR (125 MHz) CDCl3 d: 55.3, 114.7, 115.2, 122.2, 128.7, 129.6, 130.1,
129.8, 129.9, 130.1, 130.2, 131.3, 135.1, 137.7, 138.8, 141.2, 141.3, 152.1,
153.2.
131.1, 135.0, 137.0, 139.6, 142.3, 151.6, 152.7, 159.7.
4.3.4. 2-(4-Chlorophenyl)-3-(3-chlorophenyl)pyrazine
(10ab). Yellow oil, 75%; HRMS (FAB) calcd for C16H11Cl2N2 (Mþ1)þ:
301.0299, found: 301.0325; 1H NMR (400 MHz) CDCl3 d: 7.18e7.23
(2H, m), 7.27e7.34 (3H, m), 7.40 (2H, d, J¼8.8 Hz), 7.58 (1H, t,
J¼1.2 Hz), 8.60 (1H, d, J¼2.4 Hz), 8.61 (1H, d, J¼2.4 Hz); 13C NMR
4.2.2. 2-(3-Chlorophenyl)-3-phenylquinoxaline
(7be). Colorless
powder, 48%; mp 112e113 ꢀC; HRMS (FAB) calcd for C20H14N2Cl
(Mþ1)þ: 317.0846, found: 317.0872; 1H NMR (500 MHz) CDCl3
d:
7.17e7.37 (6H, m), 7.50e7.52 (2H, m), 7.32 (1H, s), 7.76e7.79 (2H,
m), 8.16e8.18 (2H, m); 13C NMR (125 MHz) CDCl3
d: 128.0, 128.6,
(125 MHz) CDCl3 d: 127.9, 128.7, 129.1, 129.6, 129.7, 131.0, 134.7,
128.8,129.0,129.1,129.2,129.5,129.7,130.1,130.4,131.1,134.6,135.3,
137.0, 140.5, 141.1, 151.4, 151.6.
135.3, 136.6, 140.1, 142.4, 142.6, 151.3, 151.7.
4.3.5. 2-(3-Chlorophenyl)-3-(4-methoxyphenyl)pyrazine
4.2.3. 2-(3-Chlorophenyl)-3-(4-chlorophenyl)quinoxaline
(10bf). Yellow oil, 55%; HRMS (ESI) calcd for C17H14OClN2 (Mþ1)þ:
(7ab). Colorless powder, 65%; mp 95e97 ꢀC; HRMS (FAB) calcd for
297.0795, found: 297.0799; 1H NMR (400 MHz) CDCl3
d: 3.80 (3H,
C
20H13N2Cl2 (Mþ1)þ: 351.0456, found: 351.0455; 1H NMR
s), 6.84 (2H, d, J¼8.8 Hz), 7.16e7.32 (3H, m), 7.39 (2H, d, J¼8.8 Hz),
(500 MHz) CDCl3 d: 7.09e7.48 (5H, m), 7.47e7.49 (2H, m), 7.62 (1H,
7.58 (1H, t, J¼1.7 Hz), 8.54 (1H, d, J¼2.4 Hz), 8.57 (1H, d, J¼2.4 Hz);
s), 7.75e7.79 (2H, m), 8.14e8.22 (2H, m); 13C NMR (125 MHz) CDCl3
13C NMR (125 MHz) CDCl3
d: 55.8, 113.8, 128.8, 129.5, 129.6, 130.4,
d: 128.0, 128.3, 128.4, 128.8, 128.9, 129.0, 129.1, 129.2, 129.6, 129.7,
131.0, 131.1, 134.5, 140.8, 141.6, 142.6, 151.0, 125.6, 160.3.
129.8, 130.1, 130.2, 134.3, 138.5, 140.7, 140.9, 141.2, 151.7, 153.1.
4.3. General procedure for the one-pot synthesis of pyrazines
Acknowledgements
To
a
mixture of the N-phenylbenzimidoyl chlorides
1
We are very appreciative of the funding received via a Grant-in-
Aid for Scientific Research (C) and a Grant-in-Aid for Scientific
Research on Innovative Areas ‘Advanced Molecular Trans-
formations by Organocatalysts’ from the Japan Society for the
Promotion of Science and MEXT, Japan.
(1.0 mmol), aromatic aldehyde
2
(1.5 mmol), and 1,3-
dimethylimidazolium iodide 3 (6.7 mg, 0.03 mol) in THF (20 mL),
NaH (60% in oil, 52 mg, 1.3 mmol) was added with stirring under an
argon atmosphere. The reaction mixture was refluxed for 6 h, and
cooled. After the addition of concd H2SO4 (0.6 mL), the reaction
mixture was stirred at room temperature for 3 h, and then ethyl-
enediamine (104 mg, 1.0 mmol) was added. The reaction mixture
was refluxed for 12 h, and then sulfur (63 mg, 2.0 mmol) was added.
The reaction mixture was refluxed for another 12 h, and then
poured into water. The products were extracted with diethyl ether,
washed with brine, and dried over MgSO4. The solvent was evap-
orated and the residue was purified by silica gel column chroma-
tography (n-hexane/ethyl acetate) to obtain pyrazines 10.
References and notes
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Med. Chem. 2007, 15, 4077e4084; (b) Singh, S. K.; Saibaba, V.; Ravikumar, V.;
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Appl. WO 2003052850, 2003.
2. (a) Shipe, W. D.; Yang, F.; Zhao, Z.; Wolkenberg, S. E.; Nolt, M. B.; Lindsley, C. W.
Heterocycles 2006, 70, 655e689; (b) Katritzky, A. R.; Zhang, D.; Kirichenko, K. J.
Org. Chem. 2005, 70, 3271e3274.
4.3.1. 2-(4-Chlorophenyl)-3-(4-methoxyphenyl)pyrazine
3. Barta, T. E.; Stealey, M. A.; Collins, P. W.; Weier, R. M. Bioorg. Med. Chem. Lett.
1998, 8, 3443e3448.
(10af). Brown oil, 56%; HRMS (FAB) m/z calcd for C17H14OClN2
(Mþ1)þ: 297.0795, found: 297.0779; 1H NMR (500 MHz) CDCl3
d:
4. (a) Harada, T.; Nakagawa, Y.; Wadkins, R. M.; Potter, P. M.; Wheelock, C. E. Bi-
oorg. Med. Chem. 2009, 17, 149e164; (b) Edwards, C. C.; Hyatt, J. L.; Tsurkan, L.;
Bai, F.; Fraga, C.; Morton, C. L.; Howard-Williams, E. L.; Potter, P. M.; Redinbo, M.
R. J. Mol. Biol. 2005, 352, 165e177; (c) Wadkins, R. M.; Hyatt, J. L.; Wei, X.; Yoon,
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4710e4715.
3.81 (3H, s), 6.84 (2H, d, J¼8.5 Hz), 7.28 (2H, d, J¼8.3 Hz), 7.37 (2H, d,
J¼8.5 Hz), 7.40 (2H, d, J¼8.3 Hz), 8.57 (1H, d, J¼2.2 Hz), 8.62 (1H, d,
J¼2.2 Hz); 13C NMR (125 MHz) CDCl3
d: 55.4, 114.0, 128.7, 130.6,
131.0, 131.2, 134.9, 137.4, 141.7, 142.4, 151.3, 152.5, 160.3.
4.3.2. 2-(4-Chlorophenyl)-3-(2-naphthyl)prazine (10ag). Yellow oil,
61%; HRMS (ESI) calcd for C20H14ClN2 (Mþ1)þ: 317.0846, found:
317.0871; 1H NMR (500 MHz) CDCl3
d: 7.25 (2H, d, J¼8.9 Hz),
7.40e7.52 (6H, m), 7.76 (1H, d, J¼8.9 Hz), 7.78e7.80 (2H, m), 8.10
(1H, s), 8.61 (1H, d, J¼2.3 Hz), 8.64 (1H, d, J¼2.3 Hz); 13C NMR
(125 MHz) CDCl3 d: 126.5, 126.8, 127.0, 127.1, 127.7, 128.1, 128.7,
128.8, 129.6, 131.1, 133.4, 135.1, 135.8, 137.0, 142.2, 142.6, 151.7, 152.7.
9. Our former co-workers Miyashita and co-workers reported the first example of
NHC-catalyzed aroylation of N-phenylbenzimidoyl chloride 1, see Miyashita, A.;
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4.3.3. 2-(4-Chlorophenyl)-3-(3-methoxyphenyl)pyrazine
(10ai). Yellow oil, 57%; HRMS (FAB) m/z calcd for C17H14OClN2