Development of Safe One-Pot Synthesis of N-1- and C-2-Substituted Benzimidazole via Reductive Cyclization of o-Nitroarylamine Using Na₂S₂O₄

Abstract

We report that the reductive cyclization of o-nitroarylamine with aldehyde using sodium dithionite (Na2S2O4) could be accelerated by addition of H2O, which made it possible to control the heat release of the reaction by semibatch-type operation. Safety evaluation was performed using DSC, ARSST, in situ IR analysis, and Multimax.

Synthetic Approaches to 2-Arylbenzimidazoles: A Review

“…The reaction was accelerated by addition of H 2 O for the one-Pot Synthesis of N-1-and C-2-substituted benzimidazole (Scheme 17) [196].…”

“…In addition 2-arylbenzimidazoles were also synthesized by replacing aryl acids with aryl chlorides [60][61][62][63][64][65][66][67][68][69][70][71]. Efficient one-pot syntheses of 2-arylbenzimidazoles starting from 2-nitroaniline have been also reported [191][192][193][194][195][196]. A large number of reagents with different combination of solvents under different reaction conditions were explored from time to time in order to find an economical and efficient method for the synthesis of 2-arylbenzimidazoles.…”

2-(3,4-Dimethoxyphenyl)-N-(4-methoxyphenyl)-1-propyl-1H-benzo[d]imidazole-5-carboxamide

“…'One-pot' synthesis of benzimidazole has gained much attraction in synthetic organic chemistry as it reduces the number of steps involved and the reaction time, and increases the yield of the product [31]. 'One-pot' reductive cyclization was found to be highly efficient using sodium dithionite as reductive cyclizing agent compared to other reagents [32][33][34][35]. Thus, in this paper we describe the efficient synthesis and characterization (by IR, 1 H-NMR, 13 C-NMR, and LC-MS spectral data) of new benzimidazole coupled carboxamide.…”

Direct conversion of alkyl halides into benzimidazoles using pyridine-N-oxide and 1,2-diaminobenzenes

“…Reductive cyclization of o-nitroarylamines with aldehydes using sodium dithionite 32,33 or formic acid, iron powder and NH4Cl 34 leads to benzimidazole derivatives. These procedures use a large amount of reducing agent which leads to waste at the end of the synthesis.…”