The current dye intermediate market - A cautionary tale and detective story; characterization and unambiguous synthesis of 5-amino-4-chloro-2,7-dimethyl-1H-benzimidazole

Abstract

Commercially delivered 2-chloro-5-methyl-1,4-phenylenediamine (1 metric ton) was not identical to the commonly used dye intermediate; it was found that the material was a pure but not yet described molecule. 1H, 13C NMR, MS, microanalysis and X-ray diffraction showed that the substance was in fact 5-amino-4-chloro-2,7-dimethyl-1H-benzimidazole. The manufacturer's mistake was explained by independent synthesis, which revealed that the key step was nitration of N-(5-chloro-2-methyl-4-nitrophenyl)acetamide giving N-(5-chloro-2-methyl-4,6-dinitrophenyl)acetamide, which requires Fe(III) catalysis. Subsequent reduction of N-(5-chloro-2-methyl-4,6-dinitrophenyl)acetamide with hydrogen and Pd/C catalyst exclusively gives N-(2,4-diamino-3-chloro-6-methylphenyl)acetamide. The ring closure reaction giving 5-amino-4-chloro-2,7-dimethyl-1H-benzimidazole takes place during the reduction with iron.