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Synlett 2018; 29(11): 1447-1450
DOI: 10.1055/s-0037-1609846
letter
© Georg Thieme Verlag Stuttgart · New York

One-Pot Selective Synthesis of Multisubstituted Quinoxalin-2(1H)-ones by a Ugi 4CR/Catalytic Aza-Wittig Sequence

Yan-Mei Yan*
a   Department of Chemistry, Taiyuan Normal University, Jinzhong, 030619, P. R. of China   Email: yanyanmei1019@126.com
b   Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Central China Normal University, Wuhan 430079, P. R. of China   Email: mwding@mail.ccnu.edu.cn
,
Hao-Yang Li
a   Department of Chemistry, Taiyuan Normal University, Jinzhong, 030619, P. R. of China   Email: yanyanmei1019@126.com
,
Jing Ren
a   Department of Chemistry, Taiyuan Normal University, Jinzhong, 030619, P. R. of China   Email: yanyanmei1019@126.com
,
Song Wang
a   Department of Chemistry, Taiyuan Normal University, Jinzhong, 030619, P. R. of China   Email: yanyanmei1019@126.com
,
Ming-Wu Ding*
b   Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Central China Normal University, Wuhan 430079, P. R. of China   Email: mwding@mail.ccnu.edu.cn
› Author Affiliations
We gratefully acknowledge financial support of this work by the ­National Natural Science Foundation of China (No. 21572075 and 21172085).
Further Information

Publication History

Received: 07.02.2018

Accepted after revision: 05 April 2018

Publication Date:
23 May 2018 (online)

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Abstract

A facile, one-pot synthesis of multisubstituted quinoxalin-2(1H)-ones via a Ugi 4CR/catalytic aza-Wittig sequence has been developed. In the presence of a catalytic amount of 3-methyl-1-phenyl-2-phospholene 1-oxide, the reaction of 2-aminobenzoyl azides, aldehydes, ketoacids, and isocyanides selectively produces quinoxalin-2(1H)-ones as the sole products in high yields.

Key words

quinoxalin-2(1H)-ones - 2-aminobenzoyl azide - Ugi reaction - catalytic aza-Wittig reaction

Supporting Information

    1H and 13C NMR spectra of compounds 5h, 5k, and 7a–o for this ­article are available free of charge via the Internet at https://doi.org/10.1055/s-0037-1609846.

  • Supporting Information
 

  • References and Notes

  • 1 Isambert N. Lavilla R. Chem. Eur. J. 2008; 14: 8444
    CrossrefPubMedSearch in Google Scholar
  • 3 Zhu J. Bienayme H. Multicomponent Reactions . Wiley-VCH; Weinheim: 2005
    Search in Google Scholar
  • 4 Dömling A. Wang W. Wang K. Chem. Rev. 2012; 112: 3083
    CrossrefSearch in Google Scholar
  • 5 Ramon DJ. Yus M. Angew. Chem. Int. Ed. 2005; 103: 1602
    Search in Google Scholar
  • 6 Ugi I. Meyr R. Fetzer U. Steinbrückner C. Angew. Chem. 1959; 71: 386
    Search in Google Scholar
  • 7 Che C. Yang B. Lin S. J. Org. Chem. 2014; 79: 436
    CrossrefPubMedSearch in Google Scholar
  • 8 Zeng XH. Wang HM. Ding MW. Org. Lett. 2015; 17: 2234
    CrossrefSearch in Google Scholar
  • 9 Cheng GS. He X. Tian L. Li J. J. Org. Chem. 2015; 80: 11100
    CrossrefPubMedSearch in Google Scholar
  • 11 Marsden SP. McGonagle AE. McKeever-Abbas B. Org. Lett. 2008; 10: 2589
    CrossrefPubMedSearch in Google Scholar
  • 12 Yan YM. Rao Y. Ding MW. J. Org. Chem. 2016; 81: 1263
    CrossrefSearch in Google Scholar
  • 14 EI-Sabbagh OI. EI-Sadek ME. Lashine SM. Yassin SH. EI-Nabtity SM. Med. Chem. Res. 2009; 18: 782
    CrossrefSearch in Google Scholar
  • 15 Ajani OO. Obafemi CA. Ikpo CO. Ogunniran KO. Nwinyi OC. Chem. Heterocycl. Compd. 2009; 45: 1370
    CrossrefSearch in Google Scholar
  • 16 Gupta D. Ghosh NN. Chandra R. Bioorg. Med. Chem. Lett. 2005; 15: 1019
    CrossrefSearch in Google Scholar
  • 17 Rösner M. Billhardt-Troughton U.-M. Kirsh R. Kleim JP. Meichsner C. Riess G. Winkler I. US Patent 5723461, 1998
  • 18 Carta A. Piras S. Loriga G. Mini-Rev. Med. Chem. 2006; 6: 1179
    CrossrefPubMedSearch in Google Scholar
  • 20 Carta A. Sanna P. Gherardini L. Usai D. Zanetti S. Il Farmaco 2001; 56: 933
    CrossrefPubMedSearch in Google Scholar
  • 21 Mossetti R. Pirali T. Saggiorato D. Tron GC. Chem. Commun. 2011; 6966
  • 22 Erb W. Neuville L. Zhu JP. J. Org. Chem. 2009; 74: 3109
    CrossrefPubMedSearch in Google Scholar
  • 23 Haridas KR. Pajalingam P. Radhakrishna G. J. Elastomers Plast. 1991; 23: 104
    CrossrefSearch in Google Scholar
  • 24 General procedure for the preparation of Ugi intermediates 5: A mixture of 2-aminobenzoyl azide 1 (1 mmol), aldehyde 2 (1 mmol), ketoacid 3 (1 mmol), and isocyanide 4 (1 mmol) was stirred in methanol (5 mL) at room temperature for 8–12 h, after the reaction was complete, the precipitate was filtered to give 5
  • 25 Compound 5h: Yield: 90%; white solid; mp 115–117 °C; 1H NMR (CDCl3, 600 MHz): δ = 7.99–6.69 (m, 12 H, Ar-H), 6.53–6.13 (m, 1 H, NH), 6.04–5.97 (m, 1 H, CH), 2.26–2.05 (m, 3 H, CH3), 1.38–1.36 (m, 9 H, 3CH3); 13C NMR (CDCl3, 100 MHz): δ = 189.3, 170.7, 168.6, 166.1, 139.2, 134.5, 134.2, 134.1, 133.6, 133.2, 132.3, 131.3, 130.9, 129.8, 129.6, 128.6, 128.4, 128.0, 65.1, 51.5, 28.2, 20.7; IR (KBr): 2142, 1707, 1690, 1675, 1638 cm–1. Anal. Calcd for C28H26ClN5O4: C, 63.22; H, 4.93; N, 13.16; Found: C, 63.00; H, 4.98; N, 13.26
  • 26 General procedure for the preparation of quinoxalin-2(1H)-ones 7: A mixture of 2-aminobenzoyl azide 1 (1 mmol), aldehyde 2 (1 mmol), ketoacid 3 (1 mmol), and isocyanide 4 (1 mmol) was stirred in methanol (5 mL) at room temperature for 8–12 h, then the solvent was removed under reduced pressure at room temperature. Toluene (5 mL) and 3-methyl-1-phenyl-2-phospholene 1-oxide (0.01 g, 0.05 mmol) were added to the reaction vessel and the reaction mixture was heated to 110 °C for 2–3 h to form quinoxalin-2(1H)-ones 7. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel (ether/petroleum ether, 1:4, v/v) to give 7. Compound 7a: Yield: 75%; white solid; mp 220–223 °C. 1H NMR (CDCl3, 600 MHz): δ = 8.20–8.19 (m, 2 H, Ar-H), 7.90 (s, 1 H, Ar-H), 7.49–7.41 (m, 4 H, Ar-H), 7.31–7.21 (m, 5 H, Ar-H), 6.75 (s, 1 H, NH), 6.09 (s, 1 H, CH), 2.22 (s, 3 H, CH3), 1.30 (s, 9 H, 3CH3); 13C NMR (CDCl3, 150 MHz): δ = 166.0, 154.9, 136.9, 135.4, 134.4, 132.4, 132.3, 131.4, 131.3, 130.6, 129.5, 129.4, 129.1, 128.1, 127.7, 126.9, 117.2, 61.6, 52.0, 28.3, 19.5; MS (EI, 70 eV): m/z (%) = 459 (5) [M+], 386 (12), 360 (75), 331 (28), 104 (100). Anal. Calcd for C27H26ClN3O2: C, 70.50; H, 5.70; N, 9.14; Found: C, 70.58; H, 5.64; N, 9.20