Efficient synthesis of tri- and difluoroacetyl hydrazides as useful building blocks for non-symmetrically substituted, fluoroalkylated 1,3,4-oxadiazoles

摘要

A convenient and efficient approach to 2-arylamino-5-fluoroalkyl-1,3,4-oxadiazoles has been established via heterocyclization of tri- and difluoroacetylated thiosemicarbazides using dicyclohexylcarbodiimide. A heterocyclization performed with selected thiosemicarbazides under basic conditions led to 4-aryl-5-fluoroalkyl-2,4-dihydro-3H-1,2,4-triazole-3-thiones in moderate yields. The starting fluoroacetylated thiosemicarbazides were prepared by fluoroacetylation of benzyloxycarbonyl-protected hydrazine with a corresponding anhydride, followed by hydrogenolytic deprotection and reaction with arylisothiocyanates. Fluoroacetylated semicarbazides were prepared similarly, but all attempts to achieve their heterocyclization were unsuccessful.