Russian Journal of Bioorganic Chemistry

, Volume 40, Issue 3, pp 343–349 | Cite as

A green synthetic approach to the synthesis of Schiff bases from 4-amino-2-thioxo-1,3-diazaspiro[5.5]undec-4-ene-5-carbonitrile as potential anti-inflammatory agents

  • Sh. A. Abdel-Mohsen
  • E. M. Hussein


A green, novel, rapid, and efficient protocol is developed for the synthesis of various Schiff bases from 4-amino-2-thioxo-1,3-diazaspiro[5.5]undec-4-ene-5-carbonitrile using ammonium chloride as a very inexpensive and readily available reagent in refluxing ethanol. High yields, easy work-up, and short reaction times are advantages of this environmentally benign procedure. The prepared compounds were screened for their anti-inflammatory activity “at a dose of 10 mg/kg body weight,” which revealed promising activities relative to indomethacin used as a reference standard in this study.


green synthesis Schiff bases anti-inflammatory rapid procedure 4-amino-2-thioxo-1,3-diazaspiro[5.5]undec-4-ene-5-carbonitrile 


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  1. 1.
    Kappe, C.O., Tetrahedron, 1993, vol. 49, pp. 6937–6963.CrossRefGoogle Scholar
  2. 2.
    Studer, A., Jeger, P., Wipf, P., and Curran, D.P., J. Org. Chem., 1997, vol. 62, pp. 2917–2924.PubMedCrossRefGoogle Scholar
  3. 3.
    Kappe, C.O., Acc. Chem. Res., 2000, vol. 33, pp. 879–888.PubMedCrossRefGoogle Scholar
  4. 4.
    Atwal, K.S., Rovnyak, G.C., O’Reilly, B.C., and Schwartz, J., J. Org. Chem., 1989, vol. 54, pp. 5898–5907.CrossRefGoogle Scholar
  5. 5.
    Rovnyak, G.C., Atwal, K.S., Hedberg, A., Kimball, S.D., Moreland, S., Gougoutas, J.Z., O’Reilly, B.C., Schwartz, J., and Malley, M.F., J. Med. Chem., 1992, vol. 35, pp. 3254–3263.PubMedCrossRefGoogle Scholar
  6. 6.
    Kappe, C.O., Fabian, W.M.F., and Semons, M.A., Tetrahedron, 1997, vol. 53, pp. 2803–2807.CrossRefGoogle Scholar
  7. 7.
    Barrow, J.C., Nantermet, P.G., Selnick, H.G., Glass, K.L., Rittle, K.E., Gilbert, K.F., Steele, T.G., Homnick, C.F., Freidinger, R.M., Ransom, R.W., Kling, P., Reiss, D., Broten, T.P., Schorn, T.W., Chang, R.S.L., O’Malley, S.S., Olah, T.V., Ellis, J.D., Barrish, A., Kassahun, K., Leppert, P., Nagarathnam, D., and Forray, C., J. Med. Chem., 2000, vol. 43, pp. 2703–2718.PubMedCrossRefGoogle Scholar
  8. 8.
    Marchand, J.R. and Chotia, D.S., J. Med. Chem., 1970, vol. 13, pp. 335–338.Google Scholar
  9. 9.
    Singare, M.S. and Ingle, D.B., J. Indian Chem. Soc., 1976, vol. 53, pp. 1036–1037.Google Scholar
  10. 10.
    Huneck, S., Joseph, R., and George, K.E., Int. J. Polym. Matter, 1993, vol. 23, pp. 17–26.CrossRefGoogle Scholar
  11. 11.
    Kozlov, N.S., Korolyshova, G.P., and Rozhkova, N.G., Chem. Abstr., 1987, vol. 106, p. 155955.Google Scholar
  12. 12.
    Verma, M., Pandeya, S.N., Singh, K.N., and Sable, J.P., Acta Pharm., 2004, vol. 54, pp. 49–56.PubMedGoogle Scholar
  13. 13.
    Gupta, J.K., Biplab, D.E., and Saravanan, V., Indian J. Chem., 2006, vol. 42B, pp. 2580–2582.Google Scholar
  14. 14.
    Shah, S., Vyas, R., and Mehta, R.J., J. Indian Chem. Soc., 1992, vol. 69, pp. 590–596.Google Scholar
  15. 15.
    Nair, S.M., and Bhattacharya, I.R.A., Asian J. Chem., 2009, vol. 21, pp. 509–510.Google Scholar
  16. 16.
    Wadher, S.J., Puranik, M.P., Karande, N.A., and Yeole, P.G., Int. J. Pharm. Tech. Res., 2009, vol. 1, pp. 22–33.Google Scholar
  17. 17.
    Cravotto, G., and Cintas, P., Chem. Soc. Rev., 2006, vol. 35, pp. 180–196.PubMedCrossRefGoogle Scholar
  18. 18.
    Ralls, J.W., Lundin, R.E., and Bailleg, G.F., J. Org. Chem., 1963, vol. 28, pp. 3521–3226.CrossRefGoogle Scholar
  19. 19.
    Shaabani, A., Bazgir, A., and Thimouri, F., Tetrahedron Lett., 2003, vol. 44, pp. 857–859.CrossRefGoogle Scholar
  20. 20.
    Chen, W.G. and Shi, L., Catal. Commun., 2008, vol. 9, pp. 1079–1081.CrossRefGoogle Scholar
  21. 21.
    Azizian, J., Thimouri, F., and Mohammadizadeh, F.M., Catal. Commun., 2007, vol. 8, pp. 1117–1121.CrossRefGoogle Scholar
  22. 22.
    Darabi, H.R., Tahoori, F., Aghapoor, K., Taala, F., and Mohsenzaeh, F., J. Brazil. Chem. Soc., 2008, vol. 19, pp. 1646–1652.CrossRefGoogle Scholar
  23. 23.
    Seela, F. and Peng, X., Current Topics Med. Chem., 2006, vol. 6, pp. 867–892.CrossRefGoogle Scholar
  24. 24.
    Hussein, E.M., Heterocycl. Lett., 2012, vol. 2, pp. 19–26.Google Scholar
  25. 25.
    Hussein, E.M., Z. Naturforsch., 2012, vol. 67b, pp. 231–237.CrossRefGoogle Scholar
  26. 26.
    Hussein, E.M. and El-Khawaga, A.M., J. Heterocycl. Chem., 2012, vol. 49, pp. 1296–1301.CrossRefGoogle Scholar
  27. 27.
    Hussein, E.M., Monatsh. Chem., 2013, vol. 144, pp. 1691–1697.CrossRefGoogle Scholar
  28. 28.
    Hussein, E.M. and Abdel-Monem, M.I., Arkivoc, 2011, vol. 10, pp. 85–98.CrossRefGoogle Scholar
  29. 29.
    Hussein, E.M. and Abdel-Monem, M.I., Int. Res. J. Pharm. Pharmacol., 2012, vol. 2, pp. 45–51.Google Scholar
  30. 30.
    Maleki, B. and Salehabadi, H., Eur. J. Chem., 2010, vol. 1, pp. 377–380.CrossRefGoogle Scholar
  31. 31.
    Winter, C.A., Risley, E.A., and Nus, G.N., Proc. Soc. Exp. Biol., 1962, vol. 111, pp. 544–547.PubMedCrossRefGoogle Scholar
  32. 32.
    Sztaricskai, F., Takacs, I.E., Pusztai, F., Szabo, G., and Csipo, I., Arch. Pharm., 1999, vol. 332, pp. 321–326.CrossRefGoogle Scholar

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© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  1. 1.Department of Chemistry, Faculty of ScienceAssiut UniversityAssiutEgypt

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