ACYL SUBSTITUENT EFFECTS ON THIOHEMIACETAL EQUILIBRIA

The equilibrium constants for thiohemiacetal formation between a series of aldehydes and two thiols (glutathione, pKa = 9.1, and p-nitrothlophenol, pka = 4.4) were measured. Thiohemiacetal formation and aldehyde hydration are equally sensitive to electron-withdrawing substituents on the aldehyde. The equilibrium constant for thiohemiacetal formation, Ks (where glutathione is the thiol), is related to the Taft polar substituent constant: log Ks = 1.65 σ* + 1.41, r = 0.986. The interval estimator of p* (at 90% confidence) is 1.47-1.83. Thiohemiacetal formation with p-nitrothiophenol is also correlated reasonably well with σ* by the same Taft equation obtained with glutathione. The relative stabilities of thiohemiacetals are independent of the basicity of the thiol. For all the aldehydes tested, however, the thiohemiacetal is stabilized over the aldehyde hydrate by 4.3 (±0.2) kcal/mol (25 °C). The p* value for formation of the thiohemiacetal anion is estimated to be 3.0. This provides a useful index for interpreting the p* value obtained for the rate of acyl transfers to thiolates in terms of the resemblance of the transition state to the anionic tetrahedral intermediate. © 1979, American Chemical Society. All rights reserved.