Solid-phase synthesis of substituted 1,3,4-thiadiazoles

Two novel and facile syntheses strategies for the synthesis of substituted 1,3,4-thiadiazoles on solid support are described based on a resin-bound thiosemicarbazide: (a) treatment with aldehydes to form immobilised thiosemicarbazones, and oxidative cyclodehydration with iron(III) chloride forms resin-bound 1,3,4-thiadiazoles; and (b) treatment with di-(2-pyridyl)thionocarbonate affords immobilised 1,3,4-thiadiazole-2-thione which is selectively mono-S-alkylated to yield resin-bound 2-alkylthio-1,3,4-thiadiazoles. Acidic cleavage with trifluoroacetic acid yields the products from both studies in good yield and excellent purity.