Preference of cis-Thioamide Structure in N-Thioacyl-N-methylanilines

The thioamide group represents a highly attractive isostere of the amide bond. We report a combined structural and computational study on cis -thioamide conformation of N -thioacyl- N -methylanilines. Amide to thioamide replacement in a class of anilides that are highly valuable as conformational locks results in a higher preference for cis conformation in a unique compacted template intrinsic to the thioamide structure. The study strongly supports the use of N -methylthioanilides as cis -conformational locks in various facets of chemistry.