296
T.-Q. Huang, W.-Y. Qu, J.-C. Ding, M.-C. Liu, H.-Y. Wu, and J.-X. Chen
Vol 50
Na2SO4 and concentrated. The crude product was separated and
purified by column chromatography on silica gel (300–400
mesh) using an ethyl acetate/petrol mixture as the eluent to
Scheme 4
afford
a pure product of 3 and 5. Here, the selected
characterization data is given for the representative known
products 3a, 5a, and unknown product 3t. For analytical data
and spectra of other compounds, see Supporting Information.
2,3‐Diphenylquinoxaline (3a).
This compound was
obtained as white solid, m.p. 128–129°C (Table 2, entry
1); 1H‐NMR (300 MHz, CDCl3): δ 8.18–8.21 (2H, m),
7.74–7.78 (2H, m), 7.53–7.55 (4H, m), 7.34–7.36 (6H, m);
13C‐NMR (75 MHz, CDCl3) δ 153.4, 141.2, 139.0, 123.0,
Scheme 5
129.8, 129.2, 128.8, 128.3.
2,3‐Bis(4‐bromophenyl)‐6,7‐dimethylquinoxaline (3t).
This compound was obtained as colorless needles solid, m.p.
175–176°C (Table 2, entry 20); IR: 1716, 1673, 1587, 1483.6,
1446, 1420, 1392, 1364, 1224, 1207, 1073, 1010, 971, 872, 831
1
cm−1; H‐NMR (300 MHz, CDCl3): δ 7.86 (s, 2H), 7.46 (d, J =
6.2 Hz, 4H), 7.34 (d, J = 8.4 Hz, 4H), 2.49 (s, 6H); 13C‐NMR
(125 MHz, CDCl3): δ 150.9, 141.1, 140.2, 138.0, 131.6, 131.5,
128.2, 123.4, 20.5; Anal. Calcd. for C22H16Br2N2: C, 56.44; H,
3.44; N, 5.98. Found: C, 56.35; H, 3.51; N, 6.06.
Finally, we investigated the recycling of PEG‐400 in a
subsequent reaction, for example, the synthesis of 3a from
the reaction of benzil 1a with 1,2‐diaminobenzene 2a
(Scheme 5). PEG‐400 was reused for five runs without
any appreciable loss of activity (with the yield of the
corresponding product being 98, 96, 94, 93, and 93%
yield, respectively).
2,3‐Diphenylpyrazine (5a). This compound was obtained as
1
white solid, m.p. 121–122°C (Table 3, entry 1); H‐NMR (300
MHz, CDCl3): δ 8.59 (s, 2H), 7.45–7.49 (m, 4H), 7.28–7.34
(m, 6H); 13C‐NMR (75 MHz, CDCl3): δ 152.8, 142.1, 138.6,
129.6, 128.7, 128.3.
In conclusion, we developed a highly efficient and
eco‐friendly synthesis of quinoxalines and pyrazines in
PEG‐400 under catalyst‐free condition. Compared to
previous reported methodologies, the present protocol
features simple workup, broad substrates scope, no
requirement of catalysts, and environmentally benign.
Further investigations on the reaction mechanism,
scope, limitations, and biological‐activity evaluation of
these new classes of compounds are under way.
Acknowledgments. The authors are grateful to the National
Natural Science Foundation of China (No. 21072153) and
Wenzhou Science and Technology Bureau Program (G20100065)
for financial support.
REFERENCES AND NOTES
[1] (a) Sakata, G.; Makino, K.; Kuraswa, Y. Heterocycles 1988,
27, 2481; (b) He, W.; Meyers, M. R.; Hanney, B.; Spada, A.; Blider, G.;
Galzeinski, H.; Amin, D.; Needle, S.; Page, K.; Jayyosi, Z.; Perrone, H.
Bioorg Med Chem Lett 2003, 13, 3097; (c) Kim, Y. B.; Kim, Y. H.;
Park, J. Y.; Kim, S. K. Bioorg Med Chem Lett 2004, 14, 541.
[2] (a) Dell, A.; William, D. H.; Morris, H. R.; Smith, G. A.;
Feeney, J.; Roberts, G. C. K. J Am Chem Soc 1975, 97, 2497; (b) Bailly,
C.; Echepare, S.; Gago, F.; Waring, M. Anti‐Cancer Drug Des 1999, 15,
291; (c) Sato, S.; Shiratori, O.; Katagiri, K. J. Antibiot 1967, 20, 270.
[3] (a) Katoh, A.; Yoshida, T.; Ohkanda, J. Heterocycles 2000, 52,
911; (b) Thomas, K. R. J.; Velusamy, M.; Lin, J. T.; Chuen, C. H.; Tao, Y.
T. Chem Mater 2005, 17, 1860; (c) Dailey, S.; Feast, W. J.; Peace, R. J.;
Sage, I. C.; Till,S.; Wood, E. L. J Mater Chem 2001, 11, 2238; (d) Sascha,
O.; Rüdiger, F. Synlett 2004,1509; (e) Sessler, J. L.; Maeda, H.; Mizuno,
T.; Lynch, V. M.; Furuta, H. J Am Chem Soc 2002, 124, 13474; (f)
Crossley, M. J.; Johnston, L. A. Chem Commun 2002,1122.
[4] (a) Porter, A. E. A. In Comprehensive Heterocyclic Chemistry;
Katritsky, A. R.; Rees, C. W., Eds.; Pergamon: Oxford, 1984,157; (b)
Woo, G. H. C.; Snyder, J. K.; Wan, Z. K. Prog Heterocycl Chem 2002,
14, 279.
[5] Heravi, M. M.; Tehrani, M. H.; Bakhtiari, K.; Oskooie, H. A.
Catal Commun 2007, 8, 1341.
[6] Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.; Shankar, K. S.
Synthesis 2008,3787.
[7] Darabi, H. R.; Mohandessi, S.; Aghapoor, K.; Mohsenzadeh,
F. Catal Commun 2007, 8, 389.
[8] Cai, J. J.; Zou, J. P.; Pan, X. Q.; Zhang, W. Tetrahedron Lett
2008, 49, 7386.
EXPERIMENTAL
Chemicals and solvents were either purchased or purified by
standard techniques. The melting points were uncorrected and
were recorded on Digital Melting Point Apparatus WRS‐1B.
IR spectra were recorded on an AVATAR 370 FI infrared
spectrophotometer. NMR spectroscopy was performed on a
Bruker‐300 spectrometer or Bruker‐500 spectrometer using
DMSO‐d6 or CDCl3 as the solvent with tetramethylsilane
(TMS) as an internal standard at room temperature. The mass‐
spectrometric identification of the products was performed on
Thermo Finnigan LCQ‐Advantage or SHIMADZU GCMS‐
QP2010 system. Elemental analysis was determined on a
Carlo‐Erba 1108 instrument.
General procedure for synthesis of quinoxalines (3) and
pyrazines (5).
To a mixture of 1,2‐diketones 1 (0.5 mmol)
and 1,2‐diamine 2 or 4 (0.7 mmol), PEG‐400 (5 mL) was
added, and the mixture was stirred for the respective time at
120°C. The reaction was monitored by TLC. After completion
of the reaction, water (10 mL) was added, and the mixture was
extracted with ethyl acetate (3 × 10 mL), the organic layer
washed with brine (3 × 10 mL), then dried over anhydrous
[9] (a) More, S. V.; Sastry, M. N. V.; Wang, C.‐C.; Yao, C.‐F.
Tetrahedron Lett 2005, 46, 6345; (b) Bhosale, R. S.; Sarda, S. R.;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet