Equilibrium Studies of Water and Thiol Addition to Ketones: Substituent and Solvent Effects for Methyl Ketones


Equilibrium constants for addition of water and 3-mercaptopropanoic acid to RCOCH3 (R = H, CH3, CH2OCH3, CH2F, CHCl2, COO, COOH, COOCH3, COCH3) were determined in D20 at 34 C Water addition was sensitive to electronic effects but not steric effects (log Kd2O = 1.61 σ* + 0.07Es - 4.55, r = 0.996, n = 7) whereas thiol addition was sensitive to both factors (log KrSD = 1.55σ* + 0.49Es - 2.14, r = 0.996, n = 7), the steric effect being ascribed to the R group in RSD. For D20 addition to fluoroacetone δH = -5.0 kcal mol-1 and δS = -29 cal mol-1 deg-1; values for thiol addition were δH = -7.7 kcal mol-1 and δS = -27 cal mol-1 deg-1. For fluoroacetone KH2O/KD2O = 0.85 ± 0.15 and KRsH/KRsD = 0.52 ± 0.10. Thiol addition was 2- to 9-fold less favorable in dioxane and 7- to 90-fold less favorable in benzene than in water whereas water addition was slightly moee favorable in dioxane than in water. The potential biological importance of thiol addition to ketones is considered. © 1983, American Chemical Society. All rights reserved.

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Journal of the American Chemical Society