Skip to main content

Advertisement

SpringerLink
Log in

Different synthetic routes to 4-(1H-benzo[d]imidazol-2-yl)aniline

  • Published:
Research on Chemical Intermediates Aims and scope Submit manuscript

Abstract

The benzimidazole nucleus is an important pharmacophore in drug discovery, being a good bioisostere of naturally occurring nucleotides. This heterocycle may represent a type of privileged substructure which can interact with proteins and enzymes; it has, hence, been extensively utilized as a drug scaffold in medicinal chemistry. The connection between wide ranging biological activity and compounds containing the benzimidazole nucleus is known, and well documented in the literature. Benzimidazole derivatives have a multitude of interesting pharmacological activity, including antiviral, antitumor, antihypertensive, proton pump inhibitory, anthelmintic, antimicrobial, and anti-inflammatory activity. Accordingly, a brief survey is given below covering the synthesis of 2-phenybenzimidazole derivatives and their biological importance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Scheme 6
Scheme 7
Scheme 8

Similar content being viewed by others

References

  1. M. Alamgir, D.C. Black, N. Kumar, Synthesis, reactivity and biological activity of benzimidazoles. Top. Heterocycl. Chem. 9, 87–118 (2007)

    Article  CAS  Google Scholar 

  2. N. Dege, M. Şekerci, S. Servi, M. Dinçer, Ü. Demirbaş, Structure of 1-(thiophen-2-ylmethyl)-2-(thiophen-2-yl)-1H-benzimidazole. Turk. J. Chem. 30, 103–108 (2006)

    CAS  Google Scholar 

  3. G. Ayhan-Kılcıgil, N. Altanlar, Synthesis and antimicrobial activities of some new benzimidazole derivatives. IL Farm. 58, 1345–1350 (2003)

    Article  Google Scholar 

  4. B. Miklaszewski, S. Niememtowski, Vergleichendes studium der drei isomeren (b)-amino-phenylbenzimidazole. Chem. Ber. 34, 2953–2974 (1901)

    Article  CAS  Google Scholar 

  5. C. Kus, G. Ayhan-Kılcıgil, M. Tunçbilek, N. Altanlar, T. Çoban, B. Can-Eke, M. Iscan, Synthesis, antimicrobial and antioxidant activities of some benzimidazole derivatives. Lett. Drug Des. Discov. 6, 374–379 (2009)

    CAS  Google Scholar 

  6. Y.S. Chhonker, B. Veenu, S.R. Hasim, N. Kaushik, D. Kumar, P. Kumar, Synthesis and pharmacological evaluation of some new 2-phenyl benzimidazoles derivatives and their Schiff’s bases. E. J. Chem. 6, 342–346 (2009)

    Article  Google Scholar 

  7. K. Sreena, R. Ratheesh, M. Rachana, M. Poornima, C. Shyni, Synthesis and anthelmintic activity of benzimidazole derivatives. Hygeia 1, 21–22 (2009)

    Google Scholar 

  8. C. Mei-Sze, S. Dong-Fang, W. Samantha, D.B. Tracey, H. Ian, P.N. Shaw, A.B. David, A.S. Lesley, F.G. Stevens, Antitumor benzothiazoles. 7. Synthesis of 2-(4-acylamino phenyl)benzothiazoles and investigations into the role of acetylation in the antitumor activities of the parent amines. J. Med. Chem. 42, 381–392 (1999)

    Article  Google Scholar 

  9. N.S. Moorthy, R. Dubey, Comparative studies on conventional and microwave assisted synthesis of benzimidazole and their 2-substituted derivative with the effect of salt form of reactant. Chem. Pharm. Bull. 55, 115–117 (2007)

    Article  Google Scholar 

  10. K. Niknam, A. Fatehi-Raviz, Synthesis of 2-substituted benzimidazoles and bis-benzimidazoles by microwave in the presence of alumina-methanesulfonic acid. J. Iran. Chem. Soc. 4, 438–443 (2007)

    Article  CAS  Google Scholar 

  11. J.H. Clark, Solid acids for green chemistry. Acc. Chem. Res. 35, 791–797 (2002)

    Article  CAS  Google Scholar 

  12. A. Corma, Inorganic solid acids and their use in acid-catalyzed hydrocarbon reactions. Chem. Rev. 95, 559–614 (1995)

    Article  CAS  Google Scholar 

  13. A. Corma, H. Garcia, Lewis acids: from conventional homogeneous to green homogeneous and heterogeneous catalysis. Chem. Rev. 103, 4307–4365 (2003)

    Article  CAS  Google Scholar 

  14. T. Okuhara, Water-tolerant solid acid catalysts. Chem. Rev. 102, 3641–3665 (2002)

    Article  CAS  Google Scholar 

  15. M.A. Hamer, Q. Sun, Solid acid catalysis using ion-exchange resins. Appl. Catal. A 221, 45–62 (2001)

    Article  Google Scholar 

  16. R.V. Shingalapur, K.M. Hosamani, An efficient and eco-friendly tungstate promoted zirconia (WOx/ZrO2) solid acid catalyst for the synthesis of 2-aryl benzimidazoles. Catal. Lett. 137, 63–68 (2010)

    Article  CAS  Google Scholar 

  17. Q. Su, B. Gatto, C. Yu, A. Liu, L.F. Liu, E.J. LaVoie, Synthesis and evaluation of terbenzimidazoles as topoisomerase I inhibitors. J. Med. Chem. 38, 3638–3644 (1995)

    Article  Google Scholar 

  18. Z. Xiao-Kang, G. Jian, T. Yoko, F.B. Kenneth, J.C. Sung, C. Huey-Hwa, C. Yung-Chi, G. Marc, L. Kuo-Hsiung, Antitumor agents. 194. Synthesis and biological evaluations of 4-β-mono-, -di-, and -trisubstituted aniline-4′-o-demethyl-podophyllotoxin and related compounds with improved pharmacological profiles 1. J. Med. Chem. 42, 2441–2446 (1999)

    Article  Google Scholar 

  19. S. Gowda, B.K.K. Gowda, D.C. Gowda, Hydrazinium monoformate: a new hydrogen donor. Selective reduction of nitro compounds catalyzed by commercial zinc dust. Synth. Commun. 33, 281–289 (2003)

    Article  CAS  Google Scholar 

  20. M.A. Pagano, M. Andrzejewska, M. Ruzzene, S. Sarno, L. Cesaro, J. Bain, M. Elliott, F. Meggio, Z. Kazimierczuk, L.A. Pinna, Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J. Med. Chem. 47, 6239–6247 (2004)

    Article  CAS  Google Scholar 

  21. M. Tonelli, M. Simone, B. Tasso, F. Novelli, V. Boido, F. Sparatore, G. Paglietti, S. Pricl, G. Giliberti, S. Blois, C. Ibba, G. Sanna, R. Loddo, P. La Colla, Antiviral activity of benzimidazole derivatives. II. Antiviral activity of 2-phenylbenzimidazole derivatives. Bioorg. Med. Chem. 18, 2937–2953 (2010)

    Article  CAS  Google Scholar 

  22. S. Alper, Ö.T. Arpaci, E.Ş. Aki, I. Yalcin, Some new bi- and ter-benzimidazole derivatives as topoisomerase I inhibitors. IL Farm. 58, 497–507 (2003)

    Article  CAS  Google Scholar 

  23. T. Shunya, K. Hiroyoshi, N. Montowo, Design and synthesis of a heparanase inhibitor with pseudodisaccharide structure. Tetrahedron 57, 6915–6926 (2001)

    Article  Google Scholar 

  24. C.P. Jeffrey, C. Murty, C. Josh, F. Irene, G. Lloyd, G. Daniel, H. Diane, H. Christine, J. James, K. Wenling, S.K. Gregory, T.L. Joseph, M. Charles, M. John, R. John, S. Linda, W. Jay, 2-Phenyl-4-piperazinylbenzimidazoles: orally active inhibitors of the gonadotropin releasing hormone (GnRH) receptor. Bioorg. Med. Chem. 16, 6617–6640 (2008)

    Article  Google Scholar 

  25. E.B. Skibo, W.G. Schulz, Pyrrolo[1,2-a]benzimidazole-based aziridinyl quinones. A new class of DNA cleaving agent exhibiting G and A base specificity. J. Med. Chem. 36, 3050–3055 (1993)

    Article  CAS  Google Scholar 

  26. A.R. Katritzky, D.A. Dobchev, D.C. Fara, M. Karelson, QSAR studies on 1-phenyl benzimidazoles as inhibitors of the platelet derived growth factor. Bioorg. Med. Chem. 13, 6598–6608 (2005)

    Article  CAS  Google Scholar 

  27. A. Rao, A. Chimirri, E. De Clercq, A.M. Monforte, P. Monforte, C. Pannecouque, M. Zappalà, Synthesis and anti-HIV activity of 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole structurally-related 1,2-substituted benzimidazoles. IL Farm. 57, 819–823 (2002)

    Article  CAS  Google Scholar 

  28. J.R. Hwu, R. Singha, S.C. Hong, Y.H. Chang, A.R. Das, I. Vliegen, E. De Clerq, J. Neyts, Synthesis of new benzimidazole-coumarin conjugates as anti-hepatitis C virus agents. Antivir. Res. 77, 157–162 (2008)

    Article  CAS  Google Scholar 

  29. D.L. Evers, G. Komazin, D. Shin, D.D. Hwang, L.B. Townsend, J.C. Drach, Interactions among antiviral drugs acting late in the replication cycle of human cytomegalovirus. Antivir. Res. 56, 61–72 (2002)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, Cairo, 12622, Egypt

    Muhammad Khattab, Shadia A. Galal & Hoda I. El Diwani

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Fatma A. F. Ragab

Authors
  1. Muhammad Khattab
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shadia A. Galal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fatma A. F. Ragab
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hoda I. El Diwani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Muhammad Khattab.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khattab, M., Galal, S.A., Ragab, F.A.F. et al. Different synthetic routes to 4-(1H-benzo[d]imidazol-2-yl)aniline. Res Chem Intermed 39, 2917–2923 (2013). https://doi.org/10.1007/s11164-012-0843-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11164-012-0843-z

Keywords

Search

Navigation