Electrophilic Fluorination of 2,5-Diphenylthiazole With Various N-F Reagents
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Abstract
In previous research, 2,4-diphenylthiazoles have been successfully fluorinated at the 5- position using the N-F reagent Accufluor. The current research involves fluorination of the 2,5- diphenylthiazole isomers, the formation of which was accomplished using the Heck reaction of thiazole with bromobenzene. Fluorination of these 2,5-diphenylthiazoles by electrophilic aromatic substitution using N-F reagents mainly took place at the C-4 position of the thiazole. In our initial fluorinations, a unique trifluorinated product, 4,4,5-trifluoro-4,5-dihydro-2,5- diphenylthiazole, also formed. As it was very difficult to separate the trifluorinated product from the monofluorinated product, other fluorinating conditions were pursued. Ultimately, we found that the use of the N-F reagent N-fluorobenzenesulfonimide (NFS) in bromobenzene near reflux gave the monofluorinated product with good selectivity (21.0% yield, 99.0% pure). In addition, we found that a reaction using no solvent, excess NFS, and that ran for only 45 minutes yielded trifluorinated product in a near-selective manner (36.9% yield, 93.5% pure). Unfortunately, these reactions were always incomplete, even with an excess amount of NFS, thus isolated yields were low. Nevertheless, this research has shown that monofluorination, as well as the unique trifluorination, can be selectively achieved. This research is significant because fluorinated heterocycles have favorable properties as pharmaceuticals, materials, and agricultural compounds.