Secondary Deuterium Isotope Effects for Enolization Reactions

Secondary α- and β-deuterium isotope effects for enolization reactions and equilibria have been determined by ab initio calculations, 1H NMR spectroscopy, and triton exchange kinetics. Kinetic and equilibrium α-deuterium isotope effects for hydroxide ion-catalyzed enolization of acetaldehyde calculated by ab initio methods are normal and depend on the orientation of the secondary hydrogen with respect to the carbonyl group. The computed transition state structure indicates a small degree of bond rehybridization at the transition state. Experimentally measured secondary isotope effects on the deuteroxide ion-catalyzed proton exchange of acetophenone are kH/kD = 1.08 ± 0.07 for α-CH3 exchange and kH/kD = 0.96 ± 0.08 for α-CH2D exchange. For α-CH2T exchange in water, the corresponding secondary isotope effect is kH/kD = 1.06 ± 0.02, assuming the rule of the geometric mean is valid. These effects are smaller than the calculated equilibrium isotope effect for formation of the enolate ion−water complex:  KH/KD = 1.11−1.22 at the MP2 level. The normal kinetic isotope effects are smaller than might be expected due to a loss in hyperconjugation of the out-of-plane C−H bond and a lag in structural reorganization that contributes to the intrinsic barrier for proton transfer from carbon. Ionization of protonated acetone gives rise to an inverse secondary isotope effect of 0.97/D for the C−L bond adjacent to the carbonyl group and is consistent with a loss in hyperconjugation upon formation of the neutral ketone.