Halogenation of ketones with N-halosuccinimides under solvent-free reaction conditions

Abstract

Several aryl substituted ketones, cyclic ketones, 1,3-diketones and a β-ketoamide were halogenated with N-halosuccinimides under solvent-free reaction conditions (SFRC) at various temperatures (20–80 °C), whereas less enolized ketones required the presence of an acid catalyst ( p-toluenesulfonic acid, PTSA). Bromination of substituted acetophenones obeys first order kinetics v= k Br[ketone] and the following correlation with the keto–enol equilibrium constant: log k Br=0.3p K E+ C 1, less enolized substrates being more reactive; the moderate positive charge developed in the rate determining step was confirmed by the Hammett correlation ( ρ=−0.5). On the other hand, in cyclic ketones an opposite relation was observed: log k Br=−0.6p K E+ C 2, indicating higher reactivity of substrates with higher enolization constant ( K E). The important role of the nature of the solvent (MeCN, MeOH) in preorganization of the ketone–NBS–PTSA mixture prior to SFRC bromination was found.