N-methyl-N-(2-nitrophenyl)acetamide → 1,2-Dimethylbenzimidazole

Participants

Reaction Conditions

One-pot sequence: nitro reduction to aniline -> intramolecular cyclization of the aniline nitrogen onto the acetyl carbonyl -> dehydrative aromatization to the benzimidazole. Fe(0) powder (100 mesh, 6-8 equiv), glacial acetic acid as solvent, 95-100 degC, 2-4 h (2 h for model substrate 8a-acetyl -> product 10). Per general methods, reactions were run under N2.

Reaction Steps

Step 3 (reductive cyclization) of a three-step synthesis. A solution of N-methyl-N-(2-nitrophenyl)acetamide (8a, 150 mg) in glacial acetic acid (6 mL) was heated to 90 degC; 100-mesh iron powder (6-8 equiv) was added with vigorous stirring and a condenser fitted, then heated at 95-100 degC for 2-4 h (2 h for the model substrate 8a-acetyl). After cooling, the stir bar and unreacted iron were removed, the mixture concentrated under vacuum, the residue taken up in EtOAc and washed with H2O, 1 M aq. NaOH and sat. aq. NaCl, then dried (MgSO4) and concentrated to give 1,2-dimethyl-1H-benzo[d]imidazole (10). (Experimental Section 3.3, Molecules 2026, 31(12), 2150.)

Provenance & Evidence