Facile preparation of difluoromethyl- and monofluoromethyl-containing amides via Ritter reaction

Both secondary and tertiary difluoromethylated carbinols were found to readily react with acetonitrile under the catalysis of concentrated sulfuric acid to give the corresponding difluoromethylated acetamides in good yields, which is remarkably more efficient than the previously reported Ritter reactions with corresponding trifluoromethylated carbinols. Similarly, monofluoromethylated and (benzenesulfonyl)difluoromethylated carbinols have shown good reactivity in the Ritter reactions. Since the acetamides can be mildly deacetylated to give amines, the present methodology provides a convenient way for the synthesis of both difluoromethyl- and monofluoromethyl-containing amines starting from simple carbonyl compounds.

Graphical abstractDownload full-size image