ACIDITY AND TAUTOMERISM OF BETA-KETO-ESTERS AND AMIDES IN AQUEOUS-SOLUTION

The pH-rate profiles for the keto-enol tautomerization of 17 beta-keto esters and amides (RCOCH2COX: R = methyl; phenyl; 2-, 3-, and 4-pyridyl; 3(and 4)-(N-methylpyridinio); X = OCH3, OC2H5, NH2, or N(CH3)2) have been measured by stopped-flow spectrophotometry in aqueous solution (ionic strength 0.1, 25-degrees-C) over the range pH = 2-12. Analysis of these profiles gives the microscopic rate constants for ketonization and enolization of each of these species in these aqueous solutions. Analysis of the pH dependence of the buffer catalysis for the general-acid-catalyzed protonation of these enolate conjugate bases allowed the evaluation of pK(a)E for the deprotonation of each enol species. In combination with pK(a)eq, these data in turn allow the calculation of the acidities of the keto tautomers (pK(a)K) and the equilibrium constants for enolization (K(E) = [enol]/[keto]). In all cases, both the keto and enol tautomers of the amides are more acidic than the corresponding ester derivatives. The equilibrium enol/keto ratios (K(E)) were found to decrease in the order: 2-pyridyl > 4-pyridyl > 3-pyridyl > 4-(N-methylpyridinio) > 3-(N-methylpyridinio) > methyl almost-equal-to phenyl for both beta-keto esters and amides. A simple linear correlation between pK(a)E and pK(a)K was observed for these series of beta-keto esters and amides. Bronsted plots of second-order rate constants for deprotonation of the keto tautomer as a function of keto tautomer acidity were found to be linear, with a values in the range 0.37-0.54 for hydroxide ion, acetate ion, and several amine bases. However, the ''water-catalyzed'' reaction is unusual with Bronsted alpha = -0.17. This alpha value is only readily explicable in terms of a combined general acid + general base catalysis involving two water molecules for the equilibration of the keto tautomer and the neutral enol species.