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

Several aryl substituted ketones, cyclic ketones, 1,3-diketones and a beta-ketoamide were halogenated with N-halosuccinimides under solvent-free reaction conditions (SFRC) at various temperatures (20-80 degrees 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)=0.3pK(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 (rho=-0.5). On the other hand, in cyclic ketones an opposite relation was observed: log k(Br)=-0.6pK(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-BS-PTSA mixture prior to SFRC bromination was found. (c) 2008 Elsevier Ltd. All rights reserved.