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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
Author(s) -
Remers William A.,
Gibs Gabriel J.,
Weiss Martin J.
Publication year - 1969
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570060611
Subject(s) - chemistry , nitration , thiadiazoles , moiety , amidine , nitro , imidazole , oxime , hydrolysis , medicinal chemistry , pyrrole , organic chemistry , alkyl
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.