Prediction of Rate Constants for Cyanohydrin Formation Using Equilibrium Constants and Distortion Energies

Rate constants for cyanohydrin formation in aqueous solution can be predicted, with no use of kinetics information, by the application of a simple model requiring only equilibrium constants and distortion energies for the species involved in the reaction. The detailed model for cyanohydrin formation involves two reaction coordinates: C−C bond formation, which would lead to a cyanohydrin with an orthogonal geometry, and conversion of the carbonyl center from sp2 to sp3. Allowance must be made for the necessary desolvation of cyanide ion before C−C bond formation begins and for the initial partial desolvation of the newly formed cyanohydrin anion. The energies of the “corner intermediates” can be calculated, and then the rest of the surface can be deduced using an assumed interpolation formula. With distortion energies derived from semiempirical or ab initio molecular orbital calculations and overall energy changes based on experimental equilibrium constants, and with the assumption of a quadratic dependence of energy on reaction coordinates, the literature data for rate constants for cyanohydrin formation in solution can be matched for a representative selection of compounds spanning the reactivity range which has been studied.