Chemistry of Heterocyclic Compounds

, Volume 54, Issue 3, pp 351–354 | Cite as

Efficient copper-catalyzed synthesis of 2-arylbenzimidazole derivatives by reaction of 1-fluoro-2-nitrobenzene with benzamidine hydrochlorides

  • Mohammad Hosein SayahiEmail author
  • Mehdi Khoshneviszadeh
  • Mehdi Soheilizad
  • Seyyed Jafar SaghanezhadEmail author
  • Mohammad Mahdavi

A novel and efficient approach to the preparation of 2-arylbenzimidazoles is described. Heating a mixture of 1-fluoro-2-nitrobenzene and benzamidine hydrochlorides in the presence of CuBr and K2CO3 in DMSO afforded 2-arylbenzimidazoles in good to excellent yields. The reaction was initiated by nucleophilic aromatic substitution and further proceeded by intramolecular nucleophilic copper-catalyzed cyclization reaction of benzamidine.


2-arylbenzimidazoles benzamidine hydrochloride 1-fluoro-2-nitrobenzene copper-catalyzed reactions 


The authors wish to thank the support of the Vice-Chancellor for Research of Shiraz University of Medical Sciences (grant No. 1396-01-12-14909).


  1. 1.
    (a) Singla, P.; Luxami, V.; Paul, K. RSC Adv. 2014, 4, 12422. (b) Bansal, Y.; Silakari, O. Bioorg. Med. Chem. 2012, 20, 6208.Google Scholar
  2. 2.
    (a) Singh, N.; Pandurangan, A.; Rana, K.; Anand, P.; Ahamad, A.; Tiwari, A. K. Int. Curr. Pharm. J. 2012, 1, 119. (b) Ansari, K. F.; Lal, C. Eur. J. Med. Chem. 2009, 44, 4028.Google Scholar
  3. 3.
    (a) Denny, W. A.; Rewcastle, G. W.; Baguley, B. C. J. Med. Chem. 1990, 33, 814. (b) Gaba, M.; Singh, S.; Mohan, C. Eur. J. Med. Chem. 2014, 76, 494 and references therein.Google Scholar
  4. 4.
    Elokdah, H. M.; Chai, S.-Y.; Sulkowski, T. S. US Patent 5654436A (1995).Google Scholar
  5. 5.
    Aliyan, H.; Fazaeli, R.; Fazaeli, N.; Mssah, A. R.; Naghash, H. J.; Alizadeh, M.; Emami, G. Heteroat. Chem. 2009, 20, 202.CrossRefGoogle Scholar
  6. 6.
    Stevenson, C.; Davies, R. J. H. Chem. Res. Toxicol. 1999, 12, 38.CrossRefPubMedGoogle Scholar
  7. 7.
    (a) Greenlee, W. J.; Siegl, P. K. S. Ann. Rep. Med. Chem. 1992, 27, 59. (b) Shilcrat, S. C.; Mokhallalati, M. K.; Fortunak, J. M. D.; Pridgen, L. N. J. Org. Chem. 1997, 62, 8449.Google Scholar
  8. 8.
    (a) Hornberger, K. R.; Adjabeng, G. M.; Dickson, H. D.; Davis-Ward, R. G. Tetrahedron Lett. 2006, 47, 5359. (b) Wang, R.; Lu, X.-X.; Yu, X.-Q.; Shi, L.; Sun, Y. J. Mol. Catal. A: Chem. 2007, 266, 198.Google Scholar
  9. 9.
    (a) Mukhopadhyay, C.; Tapaswi, P. K. Tetrahedron Lett. 2008, 49, 6237. (b) Lin, C.; Lai, P.-T.; Liao, S. K.-S.; Hung, W.-T.; Yang, W.-B.; Fang, J.-M. J. Org. Chem. 2008, 73, 3848.Google Scholar
  10. 10.
    (a) Yang, D.; Fokas, D.; Li, J.; Yu, L.; Baldino, C. M. Synthesis 2005, 47. (b) Surpur, M. P.; Singh, P. R.; Patil, S. B.; Samant, S. D. Synth. Commun. 2007, 37, 1375.Google Scholar
  11. 11.
    Yadav, G.; Ganguly, S. Eur. J. Med. Chem. 2015, 97, 419.CrossRefPubMedGoogle Scholar
  12. 12.
    Kulagowski, J. J.; Rees, C. W. Synthesis 1980, 215.Google Scholar
  13. 13.
    Zhu, Y. F.; Lin, G. Q.; Chen, Y. Q. Synthesis 1990, 430.Google Scholar
  14. 14.
    Xu, Z.-B.; Lu, Y.; Guo, Z.-R. Synlett 2003, 564.Google Scholar
  15. 15.
    Kim, Y. M.; Yu, S. J. Am. Chem. Soc. 2003, 125, 1696.Google Scholar
  16. 16.
    Sayahi, M. H.; Saghanezhad, S. J.; Mahdavi, M. Res. Chem. Intermed. 2018, 44, 739.CrossRefGoogle Scholar
  17. 17.
    Gupta, S.; Agarwal, P. K.; Kundu, B. Tetrahedron Lett. 2010, 51, 1887.CrossRefGoogle Scholar
  18. 18.
    Mirza, B.; Zeeb, M. Synth. Commun. 2015, 45, 524.CrossRefGoogle Scholar
  19. 19.
    Sunke, R.; Venkat Shivaji Ramarao, E. V.; Nallapati, S. B.; Medisetti, R.; Kulkarni, P.; Kapavarapu, R. K.; Bankala, R.; Parsa, K. V. L.; Pal, M. Adv. Synth. Catal. 2016, 358, 3201.Google Scholar
  20. 20.
    Ghafuri, H.; Joorabchi, N.; Emami, A.; Esmaili Zand, H. R. Ind. Eng. Chem. Res. 2017, 56, 6462.CrossRefGoogle Scholar
  21. 21.
    Bahrami, K.; Khodaei, M. M.; Nejati, A. Green Chem. 2010, 12, 1237.CrossRefGoogle Scholar
  22. 22.
    Khan, A. T.; Parvin, T.; Choudhury, L. H. Synth. Commun. 2009, 39, 2339.CrossRefGoogle Scholar
  23. 23.
    Du, L.-H.; Wang, Y.-G. Synthesis 2007, 675.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mohammad Hosein Sayahi
    • 1
    Email author
  • Mehdi Khoshneviszadeh
    • 2
  • Mehdi Soheilizad
    • 3
  • Seyyed Jafar Saghanezhad
    • 4
    Email author
  • Mohammad Mahdavi
    • 5
  1. 1.Department of ChemistryPayame Noor University (PNU)TehranIran
  2. 2.Medicinal & Natural Products Chemistry Research CenterShiraz University of Medical SciencesShirazIran
  3. 3.CinnaGen Medical Biotechnology Research CenterAlborz University of Medical SciencesKarajIran
  4. 4.ACECR-Production Technology Research InstituteAhvazIran
  5. 5.Endocrinology and Metabolism Research Center, Endocrinology and MetabolismClinical Sciences Institute Tehran University of Medical SciencesTehranIran

Personalised recommendations