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, Email: dfokasarqule.com
D. Yang, D. Fokas, J. Li, L. Yu, C. M. Baldino, Synthesis, 2005, 47-56.
DOI: 10.1055/s-2004-834926
see article for more examples
Abstract
A highly efficient and versatile method for the synthesis of a series of 2-substituted N-H, N-alkyl, and N-aryl benzimidazoles containing a wide range of functional groups was achieved in one step via the Na2S2O4 reduction of o-nitroanilines in the presence of aldehydes.
see article for more examples
Details
The document describes a highly efficient and versatile method for synthesizing benzimidazoles from o-nitroanilines and aldehydes in one step via reductive cyclization using sodium dithionite (Na2S2O4). This method involves heating a solution of o-nitroaniline and an aldehyde in ethanol with Na2S2O4, resulting in the formation of 2-substituted N-H benzimidazoles. The process is applicable to a wide range of functional groups and substrates, including aliphatic and aromatic aldehydes, and can be scaled from high throughput synthesis to multi-gram production. Additionally, the method allows for the regioselective synthesis of N-alkyl and N-aryl benzimidazoles from corresponding N-substituted nitroanilines. The mild reaction conditions and the use of Na2S2O4 as a reducing agent make this approach advantageous over traditional methods, which often require harsh conditions and result in limited product diversity. The methodology has also been extended to synthesize other imidazole-containing heterocyclic ring systems, such as imidazopyridines and imidazoquinolines, demonstrating its broad applicability and efficiency.
Key Words
benzimidazoles, benzo-fused N-heterocycles, reductive cyclization, sodium dithionite, imidazopyridines, imidazoquinolines
ID: J54-Y2005-600