Facile Acid-Catalyzed Route to Thiazoles from Propargylic Alcohols and Thioamides

Significance

Reported is a PTSA-catalyzed ­cyclization of trisubstituted propargylic alcohols with thioamides to yield di- and trisubstituted thiazoles. The reaction was optimized in terms of solvent (only dioxane afforded a clearly lower yield, 29% vs. 90% in dichloroethane) and acid catalyst, of which PTSA was superior. The reaction scope was quite well studied and the product yields were mostly good or excellent. The use of tertiary alcohols seems to be a requirement as secondary ­alcohols afforded the acyclic N-propargyl thio­amides (see structure in parentheses). Additio-nally, when both R^¹ and R^² are alkyl groups, ­starting materials were recovered and an acid-sensitive propargylic ketone (R^³ = COC≡CPh) ­underwent decomposition under the reaction conditions. A mechanism was proposed based on similar metal-catalyzed cyclizations, albeit without proof.