Download PDF
Synlett 2019; 30(12): 1469-1473
DOI: 10.1055/s-0037-1611847
letter
© Georg Thieme Verlag Stuttgart · New York

Copper Acetate Aerobic Oxidative Synthesis of Pyrido[1,2-a]benzimidazoles from Aminopyridines and Phenylboronic Acids

Hao Yan*
a   College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China   Email: yanhao@sntcm.edu.cn
b   State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. of China
,
Hui Guo
a   College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China   Email: yanhao@sntcm.edu.cn
,
Xiaoqiang Zhou
b   State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. of China
c   College of Chemistry and Materials, Weinan Normal University, Chaoyang Road, Weinan 714099, P. R. of China
,
Zhenyu Zuo
a   College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China   Email: yanhao@sntcm.edu.cn
,
Jingli Liu
a   College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China   Email: yanhao@sntcm.edu.cn
,
Guanghui Zhang
a   College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China   Email: yanhao@sntcm.edu.cn
,
Shuan Zhang
a   College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, P. R. of China   Email: yanhao@sntcm.edu.cn
› Author AffiliationsWe acknowledge financial support from the Research Funds for the Shaanxi University of Chinese Medicine (2016PY19), Youth Talent Support Project of Shaanxi Association for Science and Technology (20170406). University Students’ Innovative Undertaking of Shaanxi Province (201823033), University Students’ Innovative Undertaking of Shaanxi University of Chinese Medicine (201807028), the Chinese Medicine Project of Shaanxi Province (ZYMS005) and the National Natural Science Foundation of China (81001669).
Further Information

Publication History

Received: 06 April 2019

Accepted after revision: 13 May 2019

Publication Date:
06 June 2019 (online)

    Permissions and Reprints All articles of this category


Abstract

Pyrido[1,2-a]benzimidazoles, which show interesting and potentially useful biological activities, have drawn extensive attention from chemists. A straightforward copper acetate-oxidative one-pot synthesis of these compounds from 2-aminopyridines and phenylboronic acids through C–N bond formation and C–H bond activation was developed as a simple and convenient method.

Key words

oxidation - cyclization - N–H coupling - C–H activation - pyridobenzimidazoles

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611847.
  • Supporting Information
 

  • References and Notes

  • 1 Bagdi AK, Santra S, Monir K, Hajra A. Chem. Commun. 2015; 51: 1555
    CrossrefPubMed
    • 2a Rupert KC, Henry JR, Dodd JH, Wadsworth SA, Cavender DE, Olini GC, Fahmy B, Siekierka J. Bioorg. Med. Chem. Lett. 2003; 13: 347
      CrossrefPubMed
    • 2b Moraski GC, Markley LD, Hipskind PA, Boshoff H, Cho S, Franzblau SG, Miller MJ. ACS Med. Chem. Lett. 2011; 2: 466
      CrossrefPubMed
  • 3 Bae J.-S, Lee D.-W, Lee D.-H, Jeong D.-S. WO 2007011163, 2007
  • 4 Takeshita H, Watanabe J, Kimura Y, Kawakami K, Takahashi H, Takemura M, Kitamura A, Someya K, Nakajima R. Bioorg. Med. Chem. Lett. 2010; 20: 3893
    CrossrefPubMed
  • 5 Refaat HM. Med. Chem. Res. 2012; 21: 1253
    Crossref
  • 6 Ndakala AJ, Gessner RK, Gitari PW, October N, White KL, Hudson A, Fakorede F, Shackleford DM, Kaiser M, Yeates C, Charman SA, Chibale K. J. Med. Chem. 2011; 54: 4581
    CrossrefPubMed
  • 7 Jardosh HH, Sangani CB, Patel MP, Patel RG. Chin. Chem. Lett. 2013; 24: 123
    Crossref
  • 8 Rasheed S, Rao DN, Das P. J. Org. Chem. 2015; 80: 9321
    CrossrefPubMed
    • 9a Qian G, Liu B, Tan Q, Zhang S, Xu B. Eur. J. Org. Chem. 2014; 4837
    • 9b Rao DN, Rasheed S, Vishwakarma RA, Ras P. RSC Adv. 2014; 4: 25600
      Crossref
  • 10 Yan CG, Wang QF, Song XK, Sun J. J. Org. Chem. 2009; 74: 710
    CrossrefPubMed
  • 11 Wu Z, Huang Q, Zhou X, Yu L, Yu L, Li Z, Wu D. Eur. J. Org. Chem. 2011; 5242
  • 12 Barolo SM, Wang Y, Rossi RA, Cuny GD. Tetrahedron 2013; 69: 5487
    Crossref
  • 13 Panda K, Suresh JR, Ila H, Junjappa H. J. Org. Chem. 2003; 68: 3498
    CrossrefPubMed
  • 14 Liang D, He Y, Liu L, Zhu Q. Org. Lett. 2013; 15: 3476
    CrossrefPubMed
  • 15 Ibrahim MA. Tetrahedron 2013; 69: 6861
    Crossref
  • 16 Chen J, Natte K, Man NY. T, Stewart SG, Wu X.-F. Tetrahedron Lett. 2015; 56: 4843
    Crossref
  • 17 Wang H, Wang Y, Peng C, Zhang J, Zhu Q. J. Am. Chem. Soc. 2010; 132: 13217
    CrossrefPubMed
  • 18 Masters K.-S, Rauws TR. M, Yadav AK, Herrebout WA, Van der Veken B, Maes BU. W. Chem. Eur. J. 2011; 17: 6315
    CrossrefPubMed
    • 19a Yan H, Yang SZ, Gao XA, Zhou K, Ma C, Yan RL, Huang GS. Synlett 2012; 2961
      Article in Thieme Connect
    • 19b Yan H, Yan R, Yang S, Gao X, Wang Y, Huang G, Liang Y. Chem. Asian J. 2012; 7: 2028
      CrossrefPubMed
    • 19c Yan R.-L, Yan H, Ma C, Ren Z.-Y, Gao X.-A, Huang G.-S, Liang Y.-M. J. Org. Chem. 2012; 77: 2024
      CrossrefPubMed
    • 19d Yan H, Ma Y, Sun Y, Ma C, Wang Y, Ren X, Huang G. Tetrahedron 2014; 70: 2761
      Crossref
    • 19e Yan H, Wang Y, Pan C, Zhang H, Yang S, Ren X, Li J, Huang G. Eur. J. Org. Chem. 2014; 2754
    • 19f Hu T, Yan H, Liu X, Wu C, Fan Y, Huang J, Huang G. Synlett 2015; 26: 2866
      Article in Thieme Connect
    • 19g Zhou X, Yan H, Ma C, He Y, Li Y, Cao J, Yan R, Huang G. J. Org. Chem. 2016; 81: 25
      CrossrefPubMed
  • 20 Pyrido[1,2-a ]benzimidazole (3aa); Typical Procedure An oven-dried Schlenk tube was charged with 2-aminopyridine (1a; 0.32 mmol), PhB(OH)2 (2a; 0.38 mmol), and Cu(OAc)2 (29 mg, 0.16 mmol). The Schlenk tube was sealed and then evacuated and backfilled with O2 (three cycles). DMSO (2 mL) was added, and the mixture was stirred at 120 °C for 36 h then cooled to r.t. The solvent was diluted with EtOAc (10 mL), and the mixture was washed with brine (5 mL) then dried (Na2SO4) and concentrated under vacuum. The residue was purified by column chromatography (silica gel, PE–EtOAc) to give a yellow solid; yield: 43 mg (80%); mp 174–176 °C. IR (neat): 3057, 3018, 1641, 1502, 1466, 1356, 1258, 1226, 1144, 756, 723 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.42 (dd, J = 6.8, 1.2 Hz, 1 H), 7.94 (d, J = 8.4 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 1 H), 7.68 (dd, J = 9.2, 0.8 Hz, 1 H), 7.54–7.51 (m, 1 H), 7.42–7.34 (m, 2 H), 6.82 (t, J = 6.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 148.4, 144.5, 129.2, 128.6, 125.6, 125.1, 120.9, 119.9, 118.0, 110.3, 110.2. HRMS (ESI): m/z [M + H]+ calcd for C11H9N2: 169.0760; found: 169.0757.
  • 21 Han Y, Zhang M, Zhang Y.-Q, Zhang Z.-H. Green Chem. 2018; 20: 4891
    Crossref
    • 22a Ley SV, Thoms AW. Angew. Chem. Int. Ed. 2003; 42: 5400
      CrossrefPubMed
    • 22b Zhang M. Appl. Organomet. Chem. 2010; 24: 269
    • 22c King AE, Huffman LM, Casitas A, Costas M, Ribas X, Stahl SS. J. Am. Chem. Soc. 2010; 132: 12068
      CrossrefPubMed