International E-publication: Publish Projects, Dissertation, Theses, Books, Souvenir, Conference Proceeding with ISBN.  International E-Bulletin: Information/News regarding: Academics and Research

Synthesis of Substituted Imidazoles via a Multi-Component Condensation Catalyzed by p-toluene Sulfonic Acid, PTSA

Author Affiliations

  • 1Department of Chemistry, Acharya Narendra Dev College (University of Delhi), New Delhi-110019, INDIA
  • 2 Department of Chemistry, Graphic Era University, Dehradun, Uttarakhand, INDIA

Res.J.chem.sci., Volume 2, Issue (4), Pages 18-23, April,18 (2012)


A robust and reliable one pot synthetic method has been developed for 2,4,5-trisubstituted and 1,2,4,5-tetra substituted imidazoles. The synthetic sequence, via a multi-component condensation catalyzed by p-toluenesulfonic acid (PTSA), provides good isolated yields under mild conditions. The structural features have been arrived at from their micro analytical, infra red, mass and 1H NMR spectral data. Short synthesis, mild reaction conditions, inexpensive reagents and high yield illustrate the utility of this approach.


  1. Lee J.C., Laydon J.T., McDonnell P.C., Gallagher T.F.,Kumar S., Green D., McNulty D., Blumenthal M. J., Keys J.R., Vatter S.W.L., Strickler J.E., McLaughlin M.M., Siemens I.R., Fisher S.M., Livi G.P., White J.R., Adams J.L. and Young P.R., A protein kinase involved in the regulation of inflammatory cytokine biosynthesis, Nature, 372, 739 (1994)
  2. Takle A.K., Brown M.J.B., Davies S., Dean D.K., Francis G., Gaiba A., Hird A.W., King F.D., Lovell P.J., Naylor A., Reith A.D., Steadman J.G. and Wilson D.M., The identification of potent and selective imidazole-based inhibitors of B-Raf kinase, Bioorg. Med. Chem. Lett., 16, 378 (2006)
  3. Khanna I.K., Weier R.M., Yu Y., Xu X.D., Koszyk F.J., Collins P.W., Koboldt C.M., Veenhuizen A.W., Perkins W.E., Casler J.J., Masferrer J.L., Zhang Y.Y., Gregory S.A., Seibert K. and Isakson P.C., 1, 2-Diarylpyrroles as Potent and Selective Inhibitors of Cyclooxygenase-2, J. Med. Chem., 40, 1619 (1997)
  4. Lange J.H.M., Van-Stuivenberg H.H., Coolen H.K.A.C., Adolfs T.J.P., McCreary A.C., Keizer H.G., Wals H.C., Veerman W., Borst A.J.M., de Loof W. Verveer P.C. and Kruse C.G., Bioisosteric replacements of the pyrazole moiety of rimonabant, synthesis, biological properties, and molecular modeling investigations of thiazoles, triazoles, and imidazoles as potent and selective CB1 cannabinoid receptor antagonists, J. Med. Chem., 48, 1823 (2005)
  5. Gallagher T.F., Fier-Thompson S.M., Garigipati R.S., Sorenson M.E., Smietana J.M., Lee D., Bender P.E., Lee J.C., Laydon J.T., Griswold D.E., Chabot-Fletcher M.C., Breton J.J. and Adams J.L., 2,4,5-triarylimidazole inhibitors of IL-1 biosynthesis, Bioorg Med Chem Lett., 5, 1171 (1995)
  6. De Laszlo S.E., Hacker C., Li B., Kim D., MacCoss M., Mantlo N., Pivnichny J.V., Colwell L., Koch G.E., Cascieri M.A. and Hagmann W.K., Potent, orally absorbed glucagon receptor antagonists, Bioorg. Med. Chem. Lett., 9, 641 (1999)
  7. Eyers P.A., Craxton M., Morrice N., Cohen P. and Goedert M., Conversion of SB 203580-insensitive MAP kinase family members to drug-sensitive forms by a single amino-acid substitution, Chem. Biol., 5, 321, (1998)
  8. Newman M.J., Rodarte J.C., Benbatoul K.D., Romano S.J., Zhang C., Krane S., Moran E.J., Uyeda R.T., Dixon R., Guns E.S. and Mayer L.D., Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance, Cancer Res., 60, 2964 (2000)
  9. Wang L., Woods K.W., Li Q., Barr K.J., McCroskey R.W., Hannick S.M., Gherke L., Credo R.B., Hui Y.H., Marsh K., Warner R., Lee J. Y., Zielinsky- Mozng N., Frost D., Rosenberg S. H. and Sham H. L., Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure–activity relationship, pharmacokinetics and in vivo antitumor activity evaluation, J. Med. Chem., 45, 1697 (2002)
  10. Antolini M., Bozzoli A., Ghiron C., Kennedy G., Rossi T. and Ursini A., Analogues of 4,5-bis (3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole as potential antibacterial agents, Bioorg. Med. Chem. Lett., 9, 1023 (1999)
  11. Maier T., Schmierer R., Bauer K., Bieringer H., Burstell H. and Sachse B., 1-Substituted imidazole-5--carboxylic acid derivatives, their preparation and their use as biocides, U.S. Patent 4820335, (1989)
  12. Schmierer R., Mildenberger H. and Buerstell H., Preparation of phenylimidazoles as plant growth regulators, German Patent 361464 (1987)
  13. Lantos I., Zhang W.Y., Shiu X. and Eggleston D.S., Synthesis of imidazoles via hetero-Cope rearrangements, J. Org. Chem., 58, 7092 (1993)
  14. Zhang C., Moran E.J., Woiwade T.F., Short K. M. and Mjalli A. M., Synthesis of tetrasubstituted imidazoles via α-(N-acyl-N-alkylamino)-β-ketoamides on Wang resin Tet. Lett. 37, 751, (1996)
  15. Wolkenberg S.E., Wisnoski D.D., Leister W.H., Wang Y., Zhao Z. and Lindsley C.W., Efficient synthesis of imidazoles from aldehydes and 1, 2-diketones using microwave irradiation, Org. Lett. 6, 1453 (2004)
  16. Sharma G.V.M., Jyothi Y. and Lakshmi P.S., Efficient Room‐Temperature Synthesis of Tri‐and Tetrasubstituted Imidazoles Catalyzed by ZrCl4, Synthetic Commun., 36, 2991 (2006)
  17. Heravi M.M., Bakhtiari K., Oskooie H.A. and Taheri S., Synthesis of 2,4,5-triaryl-imidazoles catalyzed by NiCl2. 6H2O under heterogeneous system, J. Mol. Cata. A: Chemical, 263, 279 (2007)
  18. Siddiqui S.A., Narkhede U.C., Palimkar S.S., Daniel T., Lahoti R.J. and Srinivasan K.V., Room temperature ionic liquid promoted improved and rapid synthesis of 2,4,5-triaryl imidazoles from aryl aldehydes and 1,2-diketones or α-hydroxyketone, Tetrahedron, 61, 3539 (2005)
  19. Mamgain R., Singh R., Rawat D.S., DBU-catalyzed three-component one pot synthesis of highly functionalized pyridines in aqueous ethanol, J. Heterocyclic Chem., 46, 69 (2009)