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

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.