Synthesis of 3- and 5-methylpyrazoles containing N-polyfluoroalkyl substituents, as well as their 4-bromo- or 4-iodo derivatives

Abstract

Preparative methods have been developed for the preparation of 3- and 5-methylpyrazoles containing 1-fluoroalkyl substituents. 3(5)-Methyl-1-(2-fluoroethyl)-1H-pyrazoles, 3(5)-methyl-1-(2,2-difluoroethyl)-1H-pyrazoles, 3(5)-methyl-1-(3,3,3-trifluoropropyl)-1H-pyrazoles were synthesized by alkylation of 3(5)-methylpyrazole with 2-bromofluoroethane or the corresponding fluoroalkyl tosylates. 1-(2,2,2-Trifluoroethyl)pyrazole derivatives were obtained by the reaction of 4,4-diethoxy-2-butanone with 2,2,2-trifluoroethylhydrazine in water in the presence of HCl. Despite the close boiling points of the isomeric pyrazole derivatives, they were successfully separated using an efficient distillation column. Bromination of the synthesized 3(5)-methyl-1-fluoroalkylpyrazoles in the Br₂—AcOH system and their iodination in the I₂—HIO₃—H₂SO₄/AcOH system produced the corresponding 4-halopyrazoles in high yields.