G
V. S. C. de Andrade, M. C. S. de Mattos
Paper
Synthesis
Quinoxaline Derivatives 3; General Procedure
Espíndola, J. W. P.; Oliveira e Silva, D. A.; Ferreira, R. S.; Coelho, P.
L.; Anjos, P. S.; dos Santos, E. S.; Meira, C. S.; Moreira, D. R. M.;
Soares, M. B. P.; Leite, A. C. L. Eur. J. Med. Chem. 2017, 141, 346.
(5) Łączkowski, K. Z.; Sałat, K.; Misiura, K.; Podkowa, A.;
Malikowska, N. J. Enzyme Inhib. Med. Chem. 2016, 3, 1576.
(6) Bell, F. W.; Cantrell, A. S.; Högberg, M.; Jaskunas, S. R.;
Johansson, N. G.; Jordan, C. L.; Kinnick, M. D.; Lind, P.; Morin, J.
M.; Noréen, R. J. Med. Chem. 1995, 38, 4929.
(7) Li, J. J. Heterocyclic Chemistry in Drug Discovery; Wiley: Hobo-
ken, 2013.
(8) De Souza, M. V. N. J. Sulfur Chem. 2005, 26, 429.
(9) Hantzsch, A.; Weber, J. H. Ber. Dtsch. Chem. Ges. 1887, 20, 3118.
(10) (a) Robinson, R. J. Chem. Soc. 1909, 95, 2167. (b) Gabriel, S. Ber.
Dtsch. Chem. Ges. 1910, 43, 1283.
(11) Cook, A. H.; Heilbron, I.; MacDonald, S. F.; Mahadevan, A. P.
J. Chem. Soc. 1949, 1064.
(12) (a) Nagarajaiah, H.; Mishra, A. K.; Moorthy, J. N. Org. Biomol.
Chem. 2016, 14, 4129. (b) Khan, K. M.; Ambreen, N.; Karim, A.;
Saied, S.; Amyn, A.; Ahmed, A.; Perveen, S. J. Pharm. Res. 2012, 5,
651.
To a solution of the respective 1,3-dicarbonyl compound (1 mmol) in
H2O (7 mL) held at 70 °C was added TBCA (146 mg, 0.4 mmol) in small
portions and the mixture was stirred at 70 °C for 20 min. Then, o-
phenylenediamine (108 mg, 1 mmol) was added and the mixture was
stirred at 70 °C for an additional 3 h. After the completion of the reac-
tion, the resulting mixture was extracted with EtOAc (3 × 10 mL). The
combined organic layers were washed with brine (2 × 10 mL) and
dried (Na2SO4). The solvent was removed under reduced pressure and
the residue obtained was purified by column chromatography using
EtOAc/hexanes as eluent to give the corresponding quinoxaline.
Ethyl 3-Methylquinoxaline-2-carboxylate (3a)
Yield: 173 mg (80%); white solid; mp 65–67 °C (Lit.37 mp 67 °C).
1H NMR (DMSO-d6, 400 MHz): δ = 8.20 (d, J = 8.3 Hz, 1 H), 8.07 (d, J =
8.2 Hz, 1 H), 7.86–7.76 (m, 2 H), 4.57 (q, J = 7.1 Hz, 2 H), 1.51 (t, J = 7.1
Hz, 3 H).
13C NMR (DMSO-d6, 100 MHz): δ = 165.64, 152.76, 144.50, 142.37,
139.93, 131.82, 129.83, 128.38, 62.47, 23.64, 14.25.
MS (70 eV): m/z = 216 (M+), 187, 172, 144 (100%), 102.
(13) Meng, G.; Wang, M.; Zheng, A.; Dou, J.; Guo, Z. Green Chem. Lett.
Rev. 2014, 7, 46.
(14) (a) Zhao, R.; Gove, S.; Sundeen, J. E.; Chen, B. C. Tetrahedron Lett.
2001, 42, 2101. (b) Zhu, Y. P.; Yuan, J. J.; Zhao, Q.; Lian, M.; Gao,
Q. H.; Liu, M. C.; Yang, Y.; Wu, A. X. Tetrahedron 2012, 68, 173.
(15) (a) Donohoe, T. J.; Kabeshov, M. A.; Rathi, A. H.; Smith, I. E. D.
Org. Biomol. Chem. 2012, 10, 1093. (b) Ma, C.; Miao, Y.; Zhao, M.;
Wu, P.; Zhou, J.; Li, Z.; Xie, X.; Zhang, W. Tetrahedron 2018, 74,
3602.
(16) Castagnolo, D.; Pagano, M.; Bernardini, M.; Botta, M. Synlett
2009, 2093.
(17) Yadav, J. S.; Reddy, B. V. S.; Rao, Y. G.; Narsaiah, A. V. Tetrahedron
Lett. 2008, 49, 2381.
1-(3-Methylquinoxalin-2-yl)ethanone (3b)
Yield: 145 mg (78%); white solid; mp 77–79 °C (Lit.37 mp 78–80 °C).
1H NMR (DMSO-d6, 400 MHz): δ = 8.13 (d, J = 8.4 Hz, 1 H), 8.09 (d, J =
8.4 Hz, 1 H), 7.85 (t, J = 7.6 Hz, 1 H), 7.83 (t, J = 7.6 Hz, 1 H), 3.00 (s, 3
H), 2.86 (s, 3 H).
13C NMR (DMSO-d6, 100 MHz): δ = 201.21, 152.98, 147.27, 142.19,
139.89, 132.20, 129.87, 129.73, 128.17, 27.79, 24.25.
MS (70 eV): m/z = 186 (M+, 100%), 158, 144, 143, 117, 102, 77, 75.
(18) Zhao, D.; Guo, S.; Guo, X.; Zhang, G.; Yu, Y. Tetrahedron 2016, 72,
5285.
(19) Lei, W.-L.; Wang, T.; Feng, K.-W.; Wu, C.-Z.; Liu, Q. ACS Catal.
2017, 7, 7941.
(20) (a) Scalacci, N.; Pelloja, C.; Raddi, M.; Castagnolo, D. Synlett
2016, 27, 1883. (b) Jalani, H. B.; Pandya, A. N.; Pandya, D. H.;
Sharma, J. A.; Sudarsanam, V.; Vasu, K. K. Tetrahedron Lett. 2013,
54, 5403. (c) Golubev, V.; Zubkov, F.; Krasavin, M. Tetrahedron
Lett. 2013, 54, 4844. (d) Tang, X.; Zhu, Z.; Qi, C.; Wu, W.; Jiang, H.
Org. Lett. 2016, 18, 180.
Acknowledgment
We thank CNPq for financial support. We also thank Prof. Rafael Gar-
rett da Costa and LBCD-LADETEC/IQ-UFRJ for the HRMS analyses.
Supporting Information
Supporting information for this article is available online at
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(21) Hayashi, Y. Chem. Sci. 2016, 7, 866.
(22) For our recent work on trihaloisocyanuric acids, see:
(a) Sanabria, C. M.; Costa, B. B. S.; Viana, G. M.; de Aguiar, L. C. S.;
de Mattos, M. C. S. Synthesis 2018, 50, 1359. (b) Crespo, L. T. C.;
Nogueira, G. P.; de Mattos, M. C. S.; Esteves, P. M. ARKIVOC 2018,
(ii), 205. (c) Sanabria, C. M.; do Casal, M. T.; de Souza, R. B. A.; de
Aguiar, L. C. S.; de Mattos, M. C. S. Synthesis 2017, 49, 1648.
(d) Sindra, H. C.; de Mattos, M. C. S. J. Braz. Chem. Soc. 2016, 27,
1129. (e) de Andrade, V. S. C.; de Mattos, M. C. S. Synthesis 2016,
48, 1381. (f) de Almeida, L. S.; Esteves, P. M.; de Mattos, M. C. S.
Tetrahedron Lett. 2015, 56, 6843.
(23) For a review on the chemistry of tribromoisocyanuric acid, see:
de Almeida, L. S.; Esteves, P. M.; de Mattos, M. C. S. Curr. Green
Chem. 2014, 1, 94.
(24) de Almeida, L. S.; Esteves, P. M.; de Mattos, M. C. S. Synlett 2006,
1515.
References
(1) (a) Chhabria, M. T.; Patel, S.; Modi, P.; Brahmkshatriya, P. S. Curr.
Top. Med. Chem. 2016, 16, 2841. (b) Rouf, A.; Tanyeli, C. Eur. J.
Med. Chem. 2015, 97, 911. (c) Metwally, M. A.; Abdel-Latif, E.;
Amer, F. A.; Kaupp, G. J. Sulfur Chem. 2004, 25, 63. (d) Dondoni,
A. Phosphorus Sulfur Silicon Relat. Elem. 1985, 24, 1.
(2) Sharma, R. N.; Xavier, F. P.; Vasu, K. K.; Chaturvedi, S. C.;
Pancholi, S. S. J. Enzyme Inhib. Med. Chem. 2009, 24, 890.
(3) Gu, X. H.; Wan, X. Z.; Jiang, B. Bioorg. Med. Chem. Lett. 1999, 9,
569.
(4) (a) Gomes, P. A. T. M.; Barbosa, M. O.; Santiago, E. F.; Cardoso, M.
V. O.; Costa, N. T. C.; Hernandes, M. Z.; Moreira, D. R. M.; Da
Silva, A. C.; Dos Santos, T. A. R.; Pereira, V. R. A.; Dos Santos, F. A.
B.; Pereira, G. A. N.; Ferreira, R. S.; Leite, A. C. L. Eur. J. Med. Chem.
2016, 121, 387. (b) de Oliveira Filho, G. B.; Cardoso, M. V. O.;
(25) Mendonça, G. F.; de Almeida, L. S.; de Mattos, M. C. S.; Esteves, P.
M.; Ribeiro, R. S. Curr. Org. Synth. 2015, 12, 603.
(26) Tozetti, S. D. F.; de Almeida, L. S.; Esteves, P. M.; de Mattos, M. C.
S. J. Braz. Chem. Soc. 2007, 18, 675.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H