Fluorination of Aromatic Derivatives with Fluoroxytrifluoromethane and Bis(fluoroxy)difluoromethane

Article abstract of DOI:10.1021/jo00223a030

Fluoroxytrifluoromethane (CF3OF) and bis(fluoroxy)difluoromethane CF2(OF)2 are formed by the reaction of F2 with CO and CO2, respectively, over a CsF catalyst in a continouous-stream process.Both reagents react with aromatic substrates by an electrophilic substitution mechanism to yield fluoro-substituted derivatives.Fluorobenzene is produced in good yield from benzene, and aniline derivatives afford monofluorination products.Acetanilide (1), N-phenylmethanesulfonamide (2), α,α,α-trifluoroacetanilide (3), and 1,1,1-trifluoro(N-phenyl)methanesulfonamide (4) react with either reagent to yield mixtures of o- and p-fluoro-substituted derivatives.Solvent effects and competitive rate experiments demonstrate a preference for ortho substitution, especially in aprotic, nonpolar solvents.With particular substrates, these fluorinating agents are of practical synthetic utility, e.g., 2-fluoro-4-(trifluoromethyl)aniline is produced in high yield by fluorinating the intermediate 4-(trifluoromethyl)acetanilide (6) with CF3OF.Activated substrates such as toluene, xylenes, anisole, and cresols give mixtures of products which reduce the synthetic utility of these reagents.Nitrobenzene is fairly unreactive toward CF3OF and gives low yields of substitution products.