Chemistry of Heterocyclic Compounds

, Volume 55, Issue 8, pp 783–787 | Cite as

The First Example of Palladium(II)-Catalyzed Oxidative C–N Cross Coupling of 2H-Imidazole 1-Oxide with Azoles

  • Alexey A. Akulov
  • Mikhail V. Varaksin
  • Valery N. Charushin
  • Oleg N. ChupakhinEmail author

We report the first example of the direct nucleophilic C–H functionalization of cyclic aldonitrone, a derivative of 2H-imidazole 1-oxide, with 1H-imidazole and 3,5-dimethylpyrazole rings using oxidative C–N cross-coupling reactions in the presence of palladium(II) catalyst. The obtained new bisheterocyclic N-oxides may be of interest as molecules with potential biological activity and as functional organic materials.


imidazoles nitrones N-oxides palladium pyrazoles C–H functionalization cross-dehydrogenative coupling 


This study received financial support from the Russian Science Foundation (grant No. 18-73-00088).

Supplementary material

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  1. 1.
    Thomas, C. E.; Ohlweiler, D. F.; Carr, A. A.; Nieduzak, T. R.; Hay, D. A.; Adams, G.; Vaz, R.; Bernotas, R. C. J. Biol. Chem. 1996, 271, 3097.CrossRefGoogle Scholar
  2. 2.
    Rosselin, M.; Poeggeler, B.; Durand, G. Curr. Top. Med. Chem. 2017, 17, 2006.CrossRefGoogle Scholar
  3. 3.
    Oliveira, C.; Benfeito, S.; Fernandes, C.; Cagide, F.; Silva, T.; Borges, F. Med. Res. Rev. 2018, 38, 1159.CrossRefGoogle Scholar
  4. 4.
    Dicks, A. P.; Hent, A. In Green Chemistry Metrics: A Guide to Determining and Evaluating Process Greenness (SpringerBriefs in Molecular Science); Springer: Cham, 2015, 1st ed., Ch. 2, p. 17.Google Scholar
  5. 5.
    Lancaster, M. Green Chemistry. An Introductory Text; RSC Publishing: Cambridge, 2010, 2nd ed.Google Scholar
  6. 6.
    C−H Bond Activation and Catalytic Functionalization I and II; Dixneuf, P. H.; Doucet, H., Eds.; Springer: Berlin, 2016.Google Scholar
  7. 7.
    Varaksin, M. V.; Utepova, I. A.; Chupakhin, O. N.; Charushin, V. N. J. Org. Chem. 2012, 77, 9087.CrossRefGoogle Scholar
  8. 8.
    Akulov, A. A.; Varaksin, M. V.; Charushin, V. N.; Chupakhin, O. N. ACS Omega 2019, 4, 825.CrossRefGoogle Scholar
  9. 9.
    Varaksin, M. V.; Utepova, I. A.; Chupakhin, O. N. Chem. Heterocycl. Compd. 2012, 48, 1213. [Khim. Geterotsikl. Soedin. 2012, 1301.]Google Scholar
  10. 10.
    Varaksin, M. V.; Utepova, I. A.; Chupakhin, O. N.; Charushin, V. N. Tetrahedron 2015, 71, 7077.CrossRefGoogle Scholar
  11. 11.
    Smyshliaeva, L. A.; Varaksin, M. V.; Slepukhin, P. A.; Chupakhin, O. N.; Charushin, V. N. Beilstein J. Org. Chem. 2018, 14, 2618.CrossRefGoogle Scholar
  12. 12.
    Li, M.; Liang, F. Tetrahedron Lett. 2016, 57, 3823.CrossRefGoogle Scholar
  13. 13.
    Janzen, E. G.; Zhang, Y.-K. J. Org. Chem. 1995, 60, 5441.CrossRefGoogle Scholar
  14. 14.
    Voinov, M. A.; Grigor'ev, I. A. Tetrahedron Lett. 2002, 43, 2445.CrossRefGoogle Scholar
  15. 15.
    Lobo, A. M.; Prabhakar, S.; Rzepa, H. S.; Skapski, A. C.; Tavers, M. R.; Widdowson, D. A. Tetrahedron 1983, 39, 3833.CrossRefGoogle Scholar
  16. 16.
    Demory, E.; Farran, D.; Baptiste, B.; Chavant, P. Y.; Blandin, V. J. Org. Chem. 2012, 77, 7901.CrossRefGoogle Scholar
  17. 17.
    Zhao, H.; Wang, R.; Chen, P.; Gregg, B. T.; Min Hsia, M.; Zhang, W. Org. Lett. 2012, 14, 1872.CrossRefGoogle Scholar
  18. 18.
    Guo, X.; Hu, J.; Zhang, M.; Wang, L. Asian J. Org. Chem. 2019, 8, 417.CrossRefGoogle Scholar
  19. 19.
    Li, G.; Jia, C.; Sun, K. Org. Lett. 2013, 15, 5198.CrossRefGoogle Scholar
  20. 20.
    Sun, K.; Wang, X.; Liu, L.; Sun, J.; Liu, X.; Li, Z.; Zhang, Z.; Zhang, G. ACS Catal. 2015, 5, 7194.CrossRefGoogle Scholar
  21. 21.
    Xie, L.-Y.; Qu, J.; Peng, S.; Liu, K.-J.; Wang, Z.; Ding, M.-H.; Wang, Y.; Cao, Z.; He, W.-M. Green Chem. 2018, 20, 760.CrossRefGoogle Scholar
  22. 22.
    Wei, W.; Wang, L.; Bao, P.; Shao, Y.; Yue, H.; Yang, D.; Yang, X.; Zhao, X.; Wang, H. Org. Lett. 2018, 20, 7125.CrossRefGoogle Scholar
  23. 23.
    Bariwal, J.; Van der Eycken, E. Chem. Soc. Rev. 2013, 42, 9283.CrossRefGoogle Scholar
  24. 24.
    Henry, M. C.; Mostafa, M. A. B.; Sutherland, A. Synthesis 2017, 4586.Google Scholar
  25. 25.
    Barra, C. V.; Rocha, F. V.; Netto, A. V. G.; Shimura, B.; Frem, R. C. G.; Mauro, A. E.; Carlos, I. Z.; Ananias, S. R.; Quilles, M. B. J. Therm. Anal. Calorim. 2011, 106, 483.CrossRefGoogle Scholar
  26. 26.
    Chen, S.-S. CrystEngComm 2016, 18, 6543.CrossRefGoogle Scholar
  27. 27.
    Xu, L.; Li, T.; Wang, L.; Cui, X. J. Org. Chem. 2019, 84, 560.CrossRefGoogle Scholar
  28. 28.
    Kirilyuk, I. A.; Grigor'ev, I. A.; Volodarskii, L. B. Bull. Acad. Sci. USSR, Div. Chem. Sci. 1991, 40, 1871. [Izv. Akad. Nauk SSSR, Ser. Khim. 1991, 2113.]Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Alexey A. Akulov
    • 1
  • Mikhail V. Varaksin
    • 1
    • 2
  • Valery N. Charushin
    • 1
    • 2
  • Oleg N. Chupakhin
    • 1
    • 2
    Email author
  1. 1.Ural Federal University named after the first President of Russia B. N. YeltsinYekaterinburgRussia
  2. 2.Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of SciencesYekaterinburgRussia

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