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

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.