C(ALPHA)-PROTON TRANSFER FROM 2-(1-HYDROXYBENZYL)OXYTHIAMIN - THE UNIT BRONSTED SLOPE OVERESTIMATES THE AMOUNT OF BOND FORMATION TO THE BASE CATALYST IN THE TRANSITION-STATE

Rate constants for C(alpha)-hydron transfer from racemic 2-(1-hydroxyb enzyl)oxythiamin (HBOT) in oxygen-containing (cacodylate, phosphate, o r alcohol) and primary amine buffers are reported. Thermodynamically u nfavorable C(alpha)-H transfer from HBOT (pK(a) 15 +/- 1) shows genera l-base catalysis with a Bronsted beta value of greater than or equal t o 0.95, which suggests rate-limiting diffusional separation of the con jugate buffer acid from the C(alpha)-carbanion/enamine. The calculated rate constant for the reverse protonation of the C(alpha)-carbanion/e namine by buffer acids, k(BH) = 10(4+/-1) M(-1) s(-1), is independent of pK(a)(BH) with alpha less than or equal to 0.05, but is far below t he diffusion-controlled limit. The primary kinetic isotope effects for cacodylate catalysis, k(H)/k(T) = 1.8 +/- 0.1 and k(H)/k(D) = 1.5 +/- 0.1 in H2O, obey the Swain-Schaad relation and require incomplete pro ton transfer in the rate-limiting transition state. These results are consistent with the suggestion that a value of alpha(d) approximate to -0.2 for desolvation of the buffer acid offsets alpha = 0.2 for proto nation to give alpha(obsd) = 0 for some carbanions. General-base catal ysis is detectable because there is a 10(2.9)-fold negative deviation from the Bronsted correlation for hydroxide ion.