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.