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.