Advertisement

Chemistry of Heterocyclic Compounds

, Volume 52, Issue 11, pp 952–957 | Cite as

Preparation of benzimidazole N-oxides by a two-step continuous flow process

  • Fabrizio Politano
  • Elba I. Buján
  • Nicholas E. Leadbeater
Article

A continuous flow process for the synthesis of nitrobenzimidazole N-oxides from 2,6-dinitrochlorobenzene and amines or amino acids is reported. The process, performed in a two-step sequence, is faster than previously reported batch processes and avoids some of the isolation and purification steps.

Keywords

benzimidazoles N-oxides cyclization flow chemistry green chemistry nucleophilic aromatic substitution 

Notes

Fabrizio Politano is thankful to Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina, for a PhD fellowship and to Bec.Ar – Fulbright Commission, for an exchange fellowship.

References

  1. 1.
    DeSimone, R. W.; Currie, K. S.; Mitchell, S. A.; Darrow, J. W.; Pippin, D. A. Comb. Chem. High Throughput Screening 2004, 7(5), 473.Google Scholar
  2. 2.
    Leeson, P. D.; Springthorpe, B. Nat. Rev. Drug Discov. 2007, 6, 881.CrossRefGoogle Scholar
  3. 3.
    Kobayashi, M.; Uneyama, K. J. Org. Chem. 1996, 61, 3902.CrossRefGoogle Scholar
  4. 4.
    Cundy, D.; Simpson, G. Aust. J. Chem. 1996, 49, 199.Google Scholar
  5. 5.
    Demirayak, S.; Kayagil, I.; Yurttas, L. Eur. J. Med. Chem. 2011, 46, 411.CrossRefGoogle Scholar
  6. 6.
    Wang, H.; Xu, S.; Zhang, B.; Zhang, Q.; Yang, H. Mater. Res. Bull. 2009, 44, 619.CrossRefGoogle Scholar
  7. 7.
    Rida, S. M.; El-Hawash, S. A. M.; Fahmy, H. T. Y.; Hazzaa, A. A.; El-Meligy, M. M. M. Arch. Pharm. Res. 2006, 29, 826.CrossRefGoogle Scholar
  8. 8.
    Agents, A.; Boiani, M.; Denicola, A.; Ortiz, S. T. De; Serna, E.; Bilbao, N. V. De; Sanabria, L.; Yaluff, G.; Arias, A. R. De; Vega, C.; Rolan, M.; Go, A.; Cerecetto, H.; Gonza, M. Chart 2006, 3215.Google Scholar
  9. 9.
    Yang, D.; Fokas, D.; Li, J.; Yu, L.; Baldino, C. M. Synthesis 2005, 47.Google Scholar
  10. 10.
    Szczeciński, P.; Bartusik, D. J. Chem. Res. 2002, 5, 84.CrossRefGoogle Scholar
  11. 11.
    Cafiero, P. A. C.; French, C. S.; MacFarlane, M. D.; Mackie, R. K.; Smith, D. M. J. Chem. Soc., Perkin Trans, 1 1997, 1375.Google Scholar
  12. 12.
    Sheldon, R. A. Chem. Soc. Rev. 2012, 41, 1437.CrossRefGoogle Scholar
  13. 13.
    Malet-Sanz, L.; Susanne, F. J. Med. Chem. 2012, 55, 4062.CrossRefGoogle Scholar
  14. 14.
    Reddy, G. S.; Reddy, N. S.; Manudhane, K.; Rama Krishna, M. V.; Ramachandra, K. J. S.; Gangula, S. Org. Process Res. Dev. 2013, 17, 1272.CrossRefGoogle Scholar
  15. 15.
    Chen, J.; Przyuski, K.; Roemmele, R.; Bakale, R. P. Org. Process Res. Dev. 2014, 18, 1427.CrossRefGoogle Scholar
  16. 16.
    Buján de Vargas, E.; Cañas, A. I. Tetrahedron Lett. 1996, 37, 767.Google Scholar
  17. 17.
    Buján, E. I.; Salum, M. L. Can. J. Chem. 2004, 82, 1322.CrossRefGoogle Scholar
  18. 18.
    Buján, E. I.; Salum, M. L. J. Phys. Org. Chem. 2006, 19, 187.CrossRefGoogle Scholar
  19. 19.
    Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford University Press: New York, 1998.Google Scholar
  20. 20.
    Alfonsi, K.; Colberg, J.; Dunn, P. J.; Fevig, T.; Jennings, S.; Johnson, T. A.; Kleine, H. P.; Knight, C.; Nagy, M. A.; Perry, D. A.; Stefaniak, M. Green Chem. 2008, 10, 31.CrossRefGoogle Scholar
  21. 21.
    Prat, D.; Pardigon, O.; Flemming, H. W.; Letestu, S.; Ducandas, V.; Isnard, P.; Guntrum, E.; Senac, T.; Ruisseau, S.; Cruciani, P.; Hosek, P. Org. Process Res. Dev. 2013, 17, 1517.CrossRefGoogle Scholar
  22. 22.
    Prat, D.; Hayler, J.; Wells, A. Green Chem. 2014, 16, 4546.CrossRefGoogle Scholar
  23. 23.
    Prat, D.; Wells, A.; Hayler, J.; Sneddon, H.; McElroy, C. R.; Abou-Shehada, S.; Dunn, P. J. Green Chem. 2016, 18, 288.Google Scholar
  24. 24.
    Cherng, Y.-J. Tetrahedron 2000, 56, 8287.CrossRefGoogle Scholar
  25. 25.
    Salum, M. L.; de Rossi, R. H.; Buján, E. I. Eur. J. Org. Chem. 2007, 2164.Google Scholar
  26. 26.
    Buján, E. I.; Cañas, A. I.; de Rossi, R. H. J. Chem. Soc., Perkin Trans. 2 2001, 1973.Google Scholar
  27. 27.
    Henderson, R. K.; Hill, A. P.; Redman, A. M.; Sneddon, H. F. Green Chem. 2015, 17, 945.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Fabrizio Politano
    • 1
    • 2
  • Elba I. Buján
    • 2
  • Nicholas E. Leadbeater
    • 1
  1. 1.Department of ChemistryUniversity of ConnecticutStorrsUSA
  2. 2.Instituto de Investigaciones en Físico Química de Córdoba (INFIQC)-CONICET, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad UniversitariaCórdobaArgentina

Personalised recommendations