Chemistry of Heterocyclic Compounds

, Volume 50, Issue 11, pp 1547–1558 | Cite as

Alkylation and Aminomethylation of 1,3-Dihydro-2Н-Benzimidazole-2-Thione

  • A. Ya. Bespalov
  • T. L. Gorchakova
  • A. Yu. Ivanov
  • M. A. Kuznetsov
  • L. M. Kuznetsova
  • A. S. Pankova
  • L. I. Prokopenko
  • M. S. Avdontceva

Alkylation of 1,3-dihydro-2Н-benzimidazole-2-thione (2-mercaptobenzimidazole) with bromoethane and chloroacetic acid derivatives occurrs at the sulfur atom, leading to the corresponding 2-sulfanylbenz-imidazole derivatives. Aminomethylation of 1,3-dihydro-2Н-benzimidazole-2-thione with piperidine and 4-methylpiperidine gives reaction products at both nitrogen atoms, while reaction with morpholine gives derivative at only one nitrogen atom, which is in an equilibrium with the starting compound and bis-adduct in DMSO solution.


1,3-dihydro-2Н-benzimidazole-2-thione 2-mercaptobenzimidazole 2-sulfanylbenzimid-azole alkylation aminomethylation 


This work received financial support from the Russian Science Foundation (grant No. 14-13-00126). The experiments were performed by using equipment at the Saint Petersburg State University Resource Centers "Center for Magnetic Resonance Research", "Center for X-ray Diffraction Studies", "Center for Chemical Analysis and Material Research".


  1. 1.
    K.-L. Yu, Y. Zhang, R. L. Civiello, A. K. Trehan, B. C. Pearce, Z. Yin, K. D. Combrink, H. B. Gulgeze, X. A. Wang, K. F. Kadow, C. W. Cianci, M. Krystal, and N. A. Meanwell, Bioorg. Med. Chem. Lett., 14, 1133 (2004).CrossRefGoogle Scholar
  2. 2.
    D. L. Evers, G. Komazin, D. Shin, D. D. Hwang, L. B. Townsend, and J. C. Drach, Antiviral Res., 56, 61 (2002).CrossRefGoogle Scholar
  3. 3.
    A. D. Jordan, A. H. Vaidya, D. I. Rosenthal, B. Dubinsky, C. P. Kordik, P. J. Sanfilippo, W. N. Wu, and A. B. Reitz, Bioorg. Med. Chem. Lett., 12, 2381 (2002).CrossRefGoogle Scholar
  4. 4.
    A. Orjales, R. Mosquera, L. Labeaga, and R. Rodes, J. Med. Chem., 40, 586 (1997). A. P. Thomas, C. P. Allot, K. H. Gibson, J. S. Major, B. B. Masek, A. A. Oldham, A. H. Ratchiffe, D. A. Russell, and D. A. Thomason, J. Med. Chem., 35, 877 (1992).Google Scholar
  5. 5.
    F. R. Basford, F. H. S. Curd, and F. L. Rose, GB Pat. Appl. 593499.Google Scholar
  6. 6.
    J. L. H. van Gelder, A. H. M. Raeymaekers, and L. F. C. Roevens, DE Pat. Appl. 2029637.Google Scholar
  7. 7.
    K. M. Hosamani and R. V. Shingalapur, Arch. Pharm., 344, 311 (2011).CrossRefGoogle Scholar
  8. 8.
    V. A. Mauro, H. C. Silvia, V. A. Joao, and V. N. S. Marcus, J. Sulfur Chem., 28, 17 (2007).CrossRefGoogle Scholar
  9. 9.
    M. Andrzejewska, L. Yepez-Mulia, A. Tapia, R. Cedillo-Rivera, A. E. Laudy, B. J. Starosciak, and Z. Kazimierczuk, Eur. J. Pharm. Sci., 21, 323 (2004).CrossRefGoogle Scholar
  10. 10.
    R. Dahiya and R. Kaur, Biosci., Biotechnol. Res. Asia, 4, 561 (2007).Google Scholar
  11. 11.
    M. Marco, B. F. S. Claudia, S. Rivara, Z. Valentina, V. Federica, R. Mirko, B. Elisabetta, B. Simona, B. Vigilio, M. Francesca, and I. Mariannina, V. P. Pier, Bioorg. Med. Chem., 12, 663 (2004).CrossRefGoogle Scholar
  12. 12.
    M. S. Reddy, R. N. Anisetti, K. D. Prasad, S. Sannigrahi, and P. A. Reddy, Pharm. Chem. J., 44, 642 (2011).CrossRefGoogle Scholar
  13. 13.
    E. V. Bakhareva, M. G. Voronkov, M. S. Sorokin, V. A. Lopyrev, S. B. Seredenin, and G. M. Gaidarov, Pharm. Chem. J., 30, 89 (1996). [Khim.-Farm. Zh., No. 2, 20 (1996).]Google Scholar
  14. 14.
    K. Anandrajagopal, R. N. Tiwari, K. G. Bothara, J. A. J. Sunilson, C. Dineshkumar, and P. Promwichit, Adv. Appl. Sci. Res., 1, 132 (2010).Google Scholar
  15. 15.
    G. Sach, Scand. J. Gastroenterol. Suppl., 21, 1 (1986).CrossRefGoogle Scholar
  16. 16.
    D. Carcanague, Y. K. Shue, M. A. Wuonola, M. U. Nickelsen, C. Joubran, J. K. Abedi, J. Jones, and T. C. Kuhler, J. Med. Chem., 45, 4300 (2002).CrossRefGoogle Scholar
  17. 17.
    E. V. Ryaskina, M. V. Voronin, and S. B. Seredenin, Pharm. Chem. J., 46, 334 (2012). [Khim.-Farm. Zh., No. 6, 12 (2012).]Google Scholar
  18. 18.
    Ya. M. Vakhrushev and N. A. Khokhlacheva, Eksperim. i Klin. Gastroenterol., No. 4, 105 (2010).Google Scholar
  19. 19.
    I. Szanyi, L. Lujber, I. Gerlinger, J. Pytel, M. Bauer, A. Csejtey, E. Szele, K. Gombos, I. Kiss, S. Seredenin, M. Yarkova, and I. Ember, In Vivo, 21, 1059 (2007).Google Scholar
  20. 20.
    G. Absalan and A. Aghaei Goudi, J. Korean Chem. Soc., 51, 141 (2007).CrossRefGoogle Scholar
  21. 21.
    H. Bagheri and A. Gholami, Talanta, 55, 1141 (2001).CrossRefGoogle Scholar
  22. 22.
    D. M. Manohar, K. Anoop Krishnan, and T. S. Anirudhan, Water Res., 36, 1609 (2002).CrossRefGoogle Scholar
  23. 23.
    N. Pourreza and K. Ghanemi, J. Hazard. Mater., 161, 982 (2009).CrossRefGoogle Scholar
  24. 24.
    F. Zavarise, D. Merli, and A. Profumo, Anal. Chim. Acta, 668, 177 (2010).CrossRefGoogle Scholar
  25. 25.
    O. L. Humenyuk, O. I. Syza, and O. M. Krasovs'kyi, Mater. Sci., 43, 91 (2007).CrossRefGoogle Scholar
  26. 26.
    M. Finšgar, Corros. Sci., 72, 90 (2013).CrossRefGoogle Scholar
  27. 27.
    L. Wang, J.-X. Pu, and H.-C. Luo, Corros. Sci., 45, 677 (2003).CrossRefGoogle Scholar
  28. 28.
    M. Mahdavian and S. Ashhari, Electrochim. Acta, 55, 1720 (2010).CrossRefGoogle Scholar
  29. 29.
    H. Zinner, O. Schmitt, W. Schritt, and G. Rembarz, Chem. Ber., 90, 2852 (1957).CrossRefGoogle Scholar
  30. 30.
    A. M. Gazaliev, M. K. Ibraev, M. B. Isabaeva, and Zh. A. Ibataev, Russ. J. Gen. Chem., 83, 1098 (2013). [Zh. Obsch. Khim., 83, 967 (2013).]Google Scholar
  31. 31.
    W. S. Hamama, J. Chem. Res., Synop., 269 (2000).Google Scholar
  32. 32.
    B. Stanovnik and M. Tišler, Arch. Pharm., 298, 357 (1965).CrossRefGoogle Scholar
  33. 33.
    R. S. Varma and D Chatterjee, J. Ind. Chem. Soc., 60, 1077 (1983).Google Scholar
  34. 34.
    R. S. Varma, S. Chauhan, and C. R. Prasad, Ind. J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 22B, 705 (1983).Google Scholar
  35. 35.
    R. S. Varma, S. Chauhan, and C. R. Prasad, Ind. J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 27B, 438 (1988).Google Scholar
  36. 36.
    A. A. Hassan, Phosphorus, Sulfur Silicon Relat. Elem., 106, 55 (1995).CrossRefGoogle Scholar
  37. 37.
  38. 38.
    V. Yu. Vvedenskii and E. D. Shtefan, Russ. Chem. Rev., 65, 307 (1996). [Usp. Khim., 65, 326 (1996).]Google Scholar
  39. 39.
    Y.-M. Guo and B.-Z. Li, Acta Chim. Sinica, 65, 1561 (2007).Google Scholar
  40. 40.
    S. Vijayaraghavan, R. R. Somani, P. Y. Shirodkar, and V. J. Kadam, Int. J. PharmTech. Res., 1, 811 (2009).Google Scholar
  41. 41.
    H. P. Narkhede, U. B. More, D.S. Dalal, and P. P. Mahulikar, J. Sci. Ind. Res., 67, 374 (2008).Google Scholar
  42. 42.
    S. Ram, D. S. Wise, and L. B. Townsend, J. Heterocycl. Chem., 22, 1269 (1985).CrossRefGoogle Scholar
  43. 43.
    S. A. Nevade, S. G. Lokapure, and N. V. Kalyane, J. Korean Chem. Soc., 57, 755 (2013).CrossRefGoogle Scholar
  44. 44.
    A. L. Misra, J. Org. Chem., 23, 897 (1958).CrossRefGoogle Scholar
  45. 45.
    K. B. Wiberg and Y. Wang, ARKIVOC, v, 45 (2011).Google Scholar
  46. 46.
    M. R. Truter, Acta Crystallogr., 22, 556 (1967).CrossRefGoogle Scholar
  47. 47.
    G. M. Sheldrick, Acta Crystallogr., Sect. A: Found Crystallogr., A64, 112 (2008).Google Scholar
  48. 48.
    O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, and H. Puschmann, J. Appl. Crystallogr., 42, 339 (2009).CrossRefGoogle Scholar
  49. 49.
    CrysAlisPro, Agilent Technologies, Version (release 27-06-2012).Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • A. Ya. Bespalov
    • 1
  • T. L. Gorchakova
    • 1
  • A. Yu. Ivanov
    • 2
  • M. A. Kuznetsov
    • 2
  • L. M. Kuznetsova
    • 2
  • A. S. Pankova
    • 2
  • L. I. Prokopenko
    • 1
  • M. S. Avdontceva
    • 3
  1. 1.Institute of ToxicologyFederal Medical-Biological Agency of the Russian FederationSaint PetersburgRussia
  2. 2.Saint Petersburg State UniversitySaint PetersburgRussia
  3. 3.Research Center for X-ray Diffraction StudiesSaint Petersburg State UniversitySaint PetersburgRussia

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