Rate constants for C (α)-hydron transfer from racemic 2-(1-hydroxybenzyl)oxythiamin (HBOT) in oxygen-containing (cacodylate, phosphate, or alcohol) and primary amine buffers are reported. Thermodynamically unfavorable C(α)-H transfer from HBOT (pKa = 15 ± 1) shows general-base catalysis with a Br⊘nsted β value of ≧0.95, which suggests rate-limiting diffusional separation of the conjugate buffer acid from the C(α)-carbanion/enamine. The calculated rate constant for the reverse protonation of the C(α)-carbanion/enamine by buffer acids, kbh = 104±1 M-1 s-1, is independent of pKaBH with α ≦ 0.05, but is far below the diffusion-controlled limit. The primary kinetic isotope effects for cacodylate catalysis, kH/kT = 1-8 ± 0.1 and kH/kD = 1.5 ± 0.1 in H2O, obey the Swain-Schaad relation and require incomplete proton transfer in the rate-limiting transition state. These results are consistent with the suggestion that a value of ad α≈ -0.2 for desolvation of the buffer acid offsets α = 0.2 for protonation to give αobsd = 0 for some carbanions. General-base catalysis is detectable because there is a 1029-fold negative deviation from the Br⊘nsted correlation for hydroxide ion.
ASJC Scopus subject areas
- Colloid and Surface Chemistry