Chemistry of Heterocyclic Compounds

, Volume 50, Issue 10, pp 1388–1403 | Cite as

Reactions of 2-Mono- and 2,6-Disubstituted 4-Pyrones with Phenylhydrazine as General Method for the Synthesis of 3-(N-Phenylpyrazolyl)Indoles

  • D. L. ObydennovEmail author
  • B. I. Usachev
  • V. Ya. Sosnovskikh

Phenylhydrazine reacted regioselectively with 6-substituted 4-pyrone-2-carboxylic acids (or esters) in protic and aprotic solvents, leading to phenylhydrazones of 3-(3-R-1-phenylpyrazol-5-yl)- or 3-(5-R-1-phenylpyrazol-3-yl)pyruvic acids (or esters), respectively. 6-Di(tri)fluoromethylcomanic acids (or esters) reacted analogously, forming the corresponding phenylhydrazones with RF group in the side chain. The obtained phenylhydrazones underwent Fischer reaction under acidic conditions, forming the respective 3-(N-phenylpyrazolyl)indoles. In contrast to comanic acid and its ester, the reactions of 2-substituted 4-pyrones occurred non-selectively and gave mixtures of regioisomeric pyrazoles with phenylhydrazone group in the side chain or 3-(N-phenylpyrazolyl)indoles. A mechanism was proposed to explain the effect of solvent on the course of reaction.


comanic acid indoles phenylhydrazine pyrazoles 4-pyrones Fischer reaction regio-selectivity 


This work received financial support from the Russian Foundation for Basic Research (project No. 14-03-31925) and the development program at Ural Federal University for the winners of competition "Young scientists of Ural Federal University".

Supplementary material

10593_2014_1603_MOESM1_ESM.pdf (566 kb)
ESM 1 Supplementary information file, containing synthetic procedures and spectral data for compounds Z- 2c, 3a,c, E- 4d, 5d, E- 10a,b, 11a,b, E- 12a,b, 13a,b, E-15b, E-16b, 17b, 18b is available to authorized users. (PDF 565 kb)


  1. 1.
    D. Zhang, G. Wang, G. Zhao, W. Xu, and L. Huo, Eur. J. Med. Chem., 46, 5868 (2011).CrossRefGoogle Scholar
  2. 2.
    L. T. Pierce, M. M. Cahill, and F. O. McCarthy, Tetrahedron, 67, 4601 (2011).CrossRefGoogle Scholar
  3. 3.
    P. Diana, A. Carbone, P. Barraja, A. Martorana, O. Gia, L. DallaVia, and G. Cirrincione, Bioorg. Med. Chem. Lett., 17, 6134 (2007).CrossRefGoogle Scholar
  4. 4.
    M. V. R. Reddy, V. K. Billa, V. R. Pallela, M. R. Mallireddigari, R. Boominathan, J. L. Gabriel, and E. P. Reddy, Bioorg. Med. Chem., 16, 3907 (2008).CrossRefGoogle Scholar
  5. 5.
    D. Zhang, G. Wang, C. Tan, W. Xu, Y. Pei, and L. Huo, Arch. Pharm. Res., 34, 343 (2011).CrossRefGoogle Scholar
  6. 6.
    S. K. Singh, V. Saibaba, K. S. Rao, P. G. Reddy, P. R. Daga, S. A. Rajjak, P. Misra, and Y. K. Rao, Eur. J. Med. Chem., 40, 977 (2005).CrossRefGoogle Scholar
  7. 7.
    V. P. Gorbunova, G. S. Grekova, N. N. Suvorov, T. A. Gus'kova, T. S. Kukushkina, and G. N. Pershin, Pharm. Chem. J., 11, 897 (1977). [Khim. Farm. Zh., 11, № 7, 21 (1977).]Google Scholar
  8. 8.
    H. Abdel-Gawad, H. A. Mohamed, K. M. Dawood, and F. A.-R. Badria, Chem. Pharm. Bull., 58, 1529 (2010).CrossRefGoogle Scholar
  9. 9.
    M. Sechi, A. Innocenti, N. Pala, D. Rogolino, M. Carcelli, A. Scozzafava, and C. T. Supuran, Bioorg. Med. Chem. Lett., 22, 5801 (2012).CrossRefGoogle Scholar
  10. 10.
    I. Stansfield, M. Pompei, I. Conte, C. Ercolani, G. Migliaccio, M. Jairaj, C. Giuliano, M. Rowley, and F. Narjes, Bioorg. Med. Chem. Lett., 17, 5143 (2007).CrossRefGoogle Scholar
  11. 11.
    T. A. Khan, S. Kumar, C. Venkatesh, and H. Ila, Tetrahedron, 67, 2961 (2011).CrossRefGoogle Scholar
  12. 12.
    V. P. Gorbunova and N. N. Suvorov, Chem. Heterocycl. Compd., 9, 1374 (1973). [Khim. Geterotsikl. Soedin., 1519 (1973).]Google Scholar
  13. 13.
    V. P. Gorbunova, K. F. Turchin, and N. N. Suvorov, Chem. Heterocycl. Compd., 6, 1406 (1970). [Khim. Geterotsikl. Soedin., 1508 (1970).]Google Scholar
  14. 14.
    T. V. Stupnikova, T. V. Nuzhnaya, N. A. Klyuev, and A. Yu. Chervinskii, Chem. Heterocycl. Compd., 18, 164 (1982). [Khim. Geterotsikl. Soedin., 212 (1982).]Google Scholar
  15. 15.
    S. H. Kim, S. Lee, S. H. Kim, K. H. Kim, and J. N. Kim, Bull. Korean Chem. Soc., 34, 3415 (2013).CrossRefGoogle Scholar
  16. 16.
    M. Jukić, M. Cetina, G. Pavlović, and V. Rapić, Struct. Chem., 10, 85 (1999).CrossRefGoogle Scholar
  17. 17.
    B. I. Usachev, D. L. Obydennov, and V. Ya. Sosnovskikh, Russ. Chem. Bull., Int. Ed., 59, 300 (2010). [Izv. Akad. Nauk, Ser. Khim., 291 (2010).]Google Scholar
  18. 18.
    B. I. Usachev, D. L. Obydennov, M. I. Kodess, and V. Ya. Sosnovskikh, Tetrahedron Lett., 50, 4446 (2009).CrossRefGoogle Scholar
  19. 19.
    B. I. Usachev, D. L. Obydennov, and V. Ya. Sosnovskikh, J. Fluorine Chem., 135, 278 (2012).CrossRefGoogle Scholar
  20. 20.
    B. I. Usachev, D. L. Obydennov, M. I. Kodess, G.-V. Röschenthaler, and V. Ya. Sosnovskikh, Russ. Chem. Bull., Int. Ed., 58, 1248 (2009). [Izv. Akad. Nauk, Ser. Khim., 1213 (2009).]Google Scholar
  21. 21.
    B. I. Usachev, D. L. Obydennov, G.-V. Röschenthaler, and V. Ya. Sosnovskikh, J. Fluorine Chem., 137, 22 (2012).CrossRefGoogle Scholar
  22. 22.
    C. Ainsworth and R. G. Jones, J. Am. Chem. Soc., 76, 3172 (1954).CrossRefGoogle Scholar
  23. 23.
    A. S. Afridi, A. R. Katritzky, and C. A. Ramsden, J. Chem. Soc., Perkin Trans. 1, 12, 1428 (1977).CrossRefGoogle Scholar
  24. 24.
    M. P. Sammes, C. W. F. Leung, C. K. Mak, and A. R. Katritzky, J. Chem. Soc., Perkin Trans. 1, 1585 (1981).Google Scholar
  25. 25.
    B. I. Usachev, S. A. Usachev, G.-V. Röschenthaler, and V. Ya. Sosnovskikh, Russ. Chem. Bull., Int. Ed., 59, 845 (2010). [Izv. Akad. Nauk, Ser. Khim., 827 (2010).]Google Scholar
  26. 26.
    C. Hansch, A. Leo, and R. W. Taft, Chem. Rev., 91, 165 (1991).CrossRefGoogle Scholar
  27. 27.
    J. Kóña, P. Zahradnık, and W. M. F. Fabian, Theor. Chem. Acc., 109, 176 (2003).CrossRefGoogle Scholar
  28. 28.
    D. L. Obydennov and B. I. Usachev, J. Fluorine Chem., 141, 41 (2012).CrossRefGoogle Scholar
  29. 29.
    G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., A64, 112 (2008).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • D. L. Obydennov
    • 1
    Email author
  • B. I. Usachev
    • 1
  • V. Ya. Sosnovskikh
    • 1
  1. 1.Institute of Natural SciencesUral Federal University named after the First President of Russia B. N. YeltsinYekaterinburgRussia

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