Convenient one-pot formation of highly functionalized 5-halothiazoles

Attempts to synthesize substituted thiazole N-oxides by treatment of 1,3-thiazoles with mCPBA(1,2) did not afford the expected products. Spectral analyses proved that corresponding 5-bromothiazoles were formed instead in very good yields. This can be explained by the fact that the starting compounds were, in fact, obtained as hydrobromide salts. Oxidative bromination mediated by mCPBA then occurred in the 5-position of the thiazole ring. Highly functionalized 5-bromo-2-amino-1,3-thiazoles bearing various substituents in the 4-position and on the 2-nitrogen could be easily prepared by this rapid and efficient one-pot method, using simple starting materials and mild conditions while avoiding the use of metal catalysts or hazardous reagents like elemental bromine. A number of oxidants, solvents and reaction conditions were next studied. The synthesis scope was successfully extended to 5-chlorothiazoles. Attempts were undertaken to further elaborate the 5-halothiazoles to pharmacologically interesting compounds.1. Campeau, L.-C. et al; J. Am. Chem. Soc. 2009, 131, 3291-3306. 2. Campeau, L.-C. et al; J. Am. Chem. Soc. 2008, 130, 3276-3277. This work is supported by the Belgian Fonds National pour la Recherche Scientifique (FNRS) and the Walloon Region (BioWin project CANTOL: Convention n° 5678).