C(α)-Proton Transfer from 2-(1-Hydroxybenzyl)oxythiamin: The Unit Br⊘nsted Slope Overestimates the Amount of Bond Formation to the Base Catalyst in the Transition State

Michael W. Washabaugh, James T. Stivers, Karen A. Hickey

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7094-7097
Number of pages4
JournalJournal of the American Chemical Society
Volume116
Issue number16
DOIs
StatePublished - Aug 1 1994

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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