Concise trichlorination of methyl ketones using sodium hypochlorite pentahydrate

We report a practical and efficient method for the synthesis of trichloromethyl ketones from the corresponding methyl ketones via a two-step sequence involving trifluoroacetylation followed by selective chlorination. The key chlorination step proceeds under mild, weakly acidic conditions using sodium hypochlorite pentahydrate, thus avoiding the use of hazardous chlorine gas or strong base. A wide range of aromatic and aliphatic methyl ketones was successfully converted into the corresponding trichloromethyl ketones in high yields. Mechanistic studies suggest that the reaction involves the formation of a 2,2-dichloro-1,3-diketone intermediate and subsequent cleavage of the trifluoroacetyl group. In contrast to previously reported base-mediated halogenation methods, the present protocol exhibits a high regioselectivity and operational simplicity under acidic conditions. This method provides a convenient alternative for the synthesis of trichloromethyl ketones from readily available substrates and is expected to be broadly applicable in organic synthesis and medicinal chemistry.