Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 66

Antineoplastics and Immunosuppressives/Cytotoxic and Adjuvant Medicines

A 2‐alkylbenzimidazole is often formed by the reaction of a 1,2‐phenylenediamine with an acid chloride, anhydride, ester or carboxylic acid.

Discussion. The carboxylic acid is formed by ester hydrolysis in the final step. The bis‐(2‐chloroethyl)amine is formed from the bis‐(2‐hydroxyethyl)amine. The bis‐(2‐hydroxyethyl)amine is formed by ring‐opening of ethylene oxide by the 5‐aminobenzimidazole.

The 5‐aminobenzimidazole is formed by reduction of the 5‐nitrobenzimidazole. The ester is formed from the carboxylic acid and ethanol (Fischer Esterification). The benzimidazole ring and the carboxylic acid both form in the reaction of N1‐methyl‐4‐nitro‐1,2‐phenylenediamine with glutaric anhydride. The phenylenediamine is formed by a selective reduction of N‐methyl‐2,4‐dinitroaniline. The dinitroaniline is formed by the displacement of chloride from 1‐chloro‐2,4‐dinitrobenzene by methylamine.