Preparation of halomethyl‐1,3,4‐thiadiazoles. Conversion to 2‐amino‐5‐(1‐methyl‐5‐nitro‐2‐imidazolyl)‐1,3,4‐thiadiazole, an important antimicrobial agent

Abstract

Abstract A new route for the synthesis of 2‐amino‐5‐(l‐methyl‐5‐nitro‐2‐imidazolyl)‐1,3,4‐thiadiazole ( 1 ) is described. This route was based upon the preparation of 2‐amino‐5‐halomethyl‐1,3,4‐thiadiazoles by condensation of haloacetic acids with thiosemicarbazide. One of these intermediates, 2‐acetamido‐5‐dichloromethyl‐1,3,4‐thiadiazole ( 4 ), was hydrolyzed to the corresponding 5‐amino‐2‐carboxaldehyde 6 , which was trapped as its oxime 5 . 5‐Acetamido‐1,3,4‐thiadiazole‐2‐carbonitrile ( 7 ), formed upon dehydration of 5 , was then converted into 2‐amino‐5‐(2‐imidazolyl)‐1,3,4‐thiadiazole ( 11 ) by a route based on the Pinner amidine synthesis. Methylation and nitration of the imidazole moiety then completed the preparation of 1.