C(α)-proton transfer from 2-(1-hydroxybenzyl)oxythiamin: The unit brønsted slope overestimates the amount of bond formation to the base catalyst in the transition state

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

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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 Brønsted 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 αd ≈ -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 102.9-fold negative deviation from the Brønsted correlation for hydroxide ion.

Original languageEnglish (US)
Pages (from-to)7094-7097
Number of pages4
JournalJournal of the American Chemical Society
Volume116
Issue number16
StatePublished - Aug 10 1994

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Oxythiamine
Proton transfer
Catalysis
Protons
Buffers
Protonation
Cacodylic Acid
Catalysts
Acids
Rate constants
Isotopes
Amines
Phosphates
Alcohols
Kinetics
Oxygen
Ions

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

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title = "C(α)-proton transfer from 2-(1-hydroxybenzyl)oxythiamin: The unit br{\o}nsted slope overestimates the amount of bond formation to the base catalyst in the transition state",
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{\o}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 αd ≈ -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 102.9-fold negative deviation from the Br{\o}nsted correlation for hydroxide ion.",
author = "Washabaugh, {Michael W.} and James Stivers and Hickey, {Karen A.}",
year = "1994",
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TY - JOUR

T1 - C(α)-proton transfer from 2-(1-hydroxybenzyl)oxythiamin

T2 - The unit brønsted slope overestimates the amount of bond formation to the base catalyst in the transition state

AU - Washabaugh, Michael W.

AU - Stivers, James

AU - Hickey, Karen A.

PY - 1994/8/10

Y1 - 1994/8/10

N2 - 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 Brønsted 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 αd ≈ -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 102.9-fold negative deviation from the Brønsted correlation for hydroxide ion.

AB - 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 Brønsted 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 αd ≈ -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 102.9-fold negative deviation from the Brønsted correlation for hydroxide ion.

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