PAPER	Synthesis 2005: 47-56   DOI: 10.1055/s-2004-834926
© Georg Thieme Verlag Stuttgart · New York
A Versatile Method for the Synthesis of Benzimidazoles from o-Nitroanilines and Aldehydes in One Step via a Reductive Cyclization
Donglai Yang*, Demosthenes Fokas*, Jingzhou Li, Libing Yu, Carmen M. Baldino
Department of Chemistry, ArQule Inc, 19 Presidential Way, Woburn, MA 01801, USA Fax: +1(781)3766019; e-Mail: dfokas@arqule.com;
Received 26 April 2004

Abstract

A highly efficient and versatile method for the synthesis of benzimidazoles was achieved in one step via the Na₂S₂O₄ reduction of o-nitroanilines in the presence of aldehydes. Heating a solution of o-nitroaniline (1c) and an aldehyde in EtOH or another appropriate solvent, in the presence of aqueous or solid Na₂S₂O₄, provided facile access to a series of 2-substituted N-H benzimidazoles 5a-m containing a wide range of functional groups not always compatible with the existing synthetic methods. This methodology has also been applied to the regioselective synthesis of N-alkyl and N-aryl benzimidazoles 6a-f via the cyclization of the corresponding N-substituted nitroanilines 13a-e, respectively. In addition, the method was applied successfully to the synthesis of other imidazole containing heterocyclic ring systems such as 1H-imidazo[4,5-b]pyridines 14a,b and 1H-imidazo[4,5-f]quinoline 15.

Key words

benzimidazoles - reductive cyclization - sodium dithionite - imidazopyridines - imidazoquinolines