N-acyl-3,3-difluoro-2-oxoindoles as versatile intermediates for the preparation of different 2,2-difluorophenylacetic derivatives

Abstract

This paper describes the versatility of N-Acyl-3,3-difluoro-2-oxoindoles, obtained from the the reaction of N-acylisatins with (diethylamino)sulphur trifluoride (DAST) which, on opening of the heterocyclic ring by reactions with nucleophiles, lead to the formation of a variety of products: reaction with water yields 2-(2-amidoacyl)-2,2-difluoroacetic acids, with alcohols yields alkyl 2-(2-amidoacyl)-2,2-difluoroacetates, with amines and glycine yields 2-(2-amidoacyl)-2,2-difluoroacetamides and with thiosemicarbazides yields difluorothiosemicarbazide derivatives. The latter undergo acid-catalysed cyclizations to yield N-(2-((5-aminoaryl-1,3,4-thiadiazol-2-yl)difluoromethyl)- 4-(R)-phenyl)acetamide. The X-ray structure of N-(2-((5-amino-1,3,4-thiadiazol- 2-yl)difluoromethyl)-4-methylphenyl)acetamide has been determined. ©2008 Sociedade Brasileira de Química.