Convenient syntheses of 5-[(2-methyl-5-nitro-1H-imidazol-1-yl)methyl]-1,3,4-oxadiazole-2(3H)thione and N-substituted 2-amino-5-[(2-methyl-5-nitro-1H-imidazol-1-yl)methyl]-1,3,4-thiadiazoles

Oxidation of metronidazole (4) with sodium dichromate yielded the corresponding 2‐(2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)acetic acid (5) which was esterified with 1‐butanol to give butyl 2‐(2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)acetate (8). Reaction of the latter with hydrazine hydrate gave 2‐(2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)acetohydrazide (9). Compound 5‐[(2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)methyl]‐1,3,4‐oxa‐diazole‐2(3H)‐thione (10) could be obtained through the reaction of compound 9 with carbon disulfide in basic medium. Subsequent alkylation of compound 10 afforded alkyl 2‐(5‐[(2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)methyl]‐1,3,4‐oxadiazol‐2‐ylthio)acetate (11) in good yield. Reaction of hydrazide 9 with substituted isothiocynate yielded 1‐[2‐(2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)acetyl]‐4‐aryl(or ethyl)thiosemicarbazide (12) which was cyclized in acidic media to N‐substituted 2‐amino‐5‐[(2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)methyl]‐1,3,4‐thiadiazole (13).