Intramolecular general acid catalysis in the halogenation of ketones

Abstract

Measurements have been made of the rate of iodination in aqueous solution of 2-oxobicyclo[2.2.2]octane-1-carboxlic acid and its methyl ester. These reactions are of zero order with respect to iodine, the measured velocities representing the rate of ionization or enolization. In self-buffered or acid solutions the observed rate can be represented by v=k_H[RCO₂H][H⁺]+k₁[RCO₂^–][H⁺]+k₃[RCO₂H][RCO₂^–]. k₁ Is ca. 200 times greater than the corresponding rate constant for the methyl ester, which we attribute either to intramolecular general acid catalysis, or to electrostatic stabilization of the transition state for the normal acid-catalysed mechanism of enolization. k₃ Is probably attributable to bifunctional catalysis, since the rate of the iodination of the ionized form of the keto-acid, catalysed by acetic acid, is at least 16 times greater than for the corresponding methyl ester. Kinetic measurements on the halogenation of several other keto-carboxylic acids are also reported.