A novel access to 4-trifluoromethyl-1,3-thiazole derivatives via an intermediate thiocarbonyl ylide

A Lewis acid catalyzed reaction of trifluoroacetyldiazomethane (CF3COCHN2) with thiourea occurs in boiling THF solution in the presence of BF3·OEt2 yielding 2-amino-4-trifluoromethyl-1,3-thiazole in a fair yield. Analogous reactions with aromatic thioamides, performed in the presence of a mesylchloride/triethylamine mixture as a dehydrating agent led to the corresponding 2-aryl-4-trifluoromethyl-1,3-thiazoles. Aromatic thioamides also react with CF3COCHN2 under MW irradiation, and after 2 min, the corresponding 1,3-thiazoles were obtained in fair yields. The obtained fluorinated 2-amino-1,3-thiazole was used for the reactions with selected N-alkylating and N-acylating reagents to give trifluoromethylated analogues of commonly known pharmaceuticals with 1,3-thiazole structures (Fanetizole and Lotifazole).