Fluorination of 2,4-diphenylthiazoles with the N-F reagent Accufluor®

ORGN 509

Chad E. Stephens, cstephe7@aug.edu, Department of Chemistry and Physics, Augusta State University, Augusta, GA 30904 and Timmeda Campbell, Department of Chemistry, Georgia State University, Atlanta, GA 30303.
A series of 2,4-diphenylthiazoles derivatives were prepared by the Hantzsch synthesis and their reactivity with various electrophilic N-F fluorinating reagents was studied. Reaction with Accufluor® in refluxing acetonitrile gave partial, yet selective, conversion to the 5-fluorothiazole. Reaction with Selectfluor® also gave partial conversion to the 5-fluorothiazole, but, in addition, also gave a small amount of the 5-chlorothiazole. The identity of this chlorinated byproduct was confirmed by GC, HRMS and independent synthesis using N-chlorosuccinimide as chlorinating agent. Using Accufluor® as fluorinating agent, the various 5-fluoro-2,4-diphenylthiazoles were obtained in 9-44% yield following column chromatography to remove residual starting material. Products were characterized by 1H, 13C and 19F NMR, as well as IR, MS, and combustion analysis. This appears to represent the first report on the direct electrophilic fluorination of thiazoles. This also appears to be the first report on the formation of a chlorinated byproduct arising from the use of Selectfluor®.