Characterization of Transition-States by Isotopic Mapping and Structure Reactivity Coefficients - Solvent and Secondary Deuterium-Isotope Effects for the Base-Catalyzed Breakdown of Acetaldehyde Hemiacetals

by Coleman, C. A.; Murray, C. J.

Rate constants and structure-reactivity coefficients for the breakdown of acetaldehyde and acetaldehyde-d4 hemiacetals were determined in water and deuterium oxide by trapping the acetaldehyde formed with alpha-effect nucleophiles. General-base catalysis by substituted acetate and cacodylate ion catalysts represents equilibrium ionization of the hemiacetal CL3CL(OL)OR (L = H or D) to form the hemiacetal anion, CL3CL(O-)OR followed by rate-determining general-acid catalysis of the cleavage of the hemiacetal anion to form acetaldehyde and ROL. Solvent isotope effects for the catalytically active proton k(p)BH/k(p)BD = 0.9-2.5 do not change significantly with changes in the pK of the catalyst or the leaving group alcohol. The increase in the secondary alpha,beta-deuterium isotope effects k-alpha-beta-H/k-alpha-beta-D = 1.21-1.30 with decreases in the pK of the leaving group alcohol can be described by the interaction coefficient p(yy') = partial-derivative p(n)/- partial-derivative pK(lg) = -0.069. The increase in Bronsted-beta = 0.48-0.72 with decreases in the pK of the leaving group alcohol in water can be described by the interaction coefficient p(xy') = partial-derivative-beta/ - partial-derivative pK(lg) = 0.090 and in D2O by p(xy') = 0.078. The interaction coefficients and the observation of both solvent and secondary deuterium isotope effects are consistent with a coupling between proton transfer to the leaving group oxygen and changes in hybridization about the central carbon in the transition state for cleavage of the hemiacetal anion. The results are discussed in the context of proposals for stable hydrogen-bonded protons in concerted acid- and base-catalyzed reactions in water.

Journal of the American Chemical Society
Start Page
1520-5126; 0002-7863