Trifluoroacetic Acid‐Mediated Cyclization of α‐Mercapto Ketones with Trifluoromethyl <i>N</i> ‐Acylhydrazones for the Synthesis of 2‐Trifluoromethylthiazole Derivatives

Abstract A novel method for synthesizing fully substituted 2‐trifluoromethylthiazoles is reported, achieving yields up to 94% via trifluoroacetic acid (TFA)‐mediated intermolecular cyclization of α‐mercapto ketones with trifluoromethyl N ‐acylhydrazones under mild, open‐flask conditions. This reaction involves cleavage of the N–N bond in the acylhydrazone moiety, and efficiently constructs dual carbon‐heteroatom bonds of C─N and C─S in one step. The protocol features broad substrate scope, operational simplicity, and scalability, as demonstrated by a gram‐scale synthesis.