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

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=kBr[ketone] and the following correlation with the keto-enol equilibrium constant: log kBr=0.3pKE+C1, 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 kBr=−0.6pKE+C2, indicating higher reactivity of substrates with higher enolization constant (KE). 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.