Secondary deuterium isotope effects for enolization reactions

by Alston, W. C.; Haley, K.; Kanski, R.; Murray, C. J.; Pranata, J.

Secondary alpha- and beta-deuterium isotope effects for enolization reactions and equilibria have been determined by ab initio calculations, H-1 NMR spectroscopy, and triton exchange kinetics. Kinetic and equilibrium alpha-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 stale 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 k(H)/k(D) = 1.08 +/- 0.07 for alpha-CH3 exchange and k(H)/k(D) = 0.96 +/- 0.08 for alpha-CH2D exchange. For alpha-CH2T exchange in water, the corresponding secondary isotope effect is k(H)/k(D) = 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: k(H)/k(D) = 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 lass in hyperconjugation upon formation of the neutral ketone.

Journal
Journal of the American Chemical Society
Volume
118
Issue
28
Year
1996
Start Page
6562-6569
URL
https://dx.doi.org/10.1021/ja942053k
ISBN/ISSN
1520-5126; 0002-7863
DOI
10.1021/ja942053k