The Mechanism of Hemiacetal Decomposition. Substituent Effect in Breakdown of Substituted Benzaldehyde Ethyl Hemiacetals

Article abstract of DOI:10.1021/ja00406a036

A series of substituted benzaldehyde ethyl hemiacetals has been generated from the corresponding substituted benzaldehyde ethyl salicyl acetals.Rate constants have been determined for decomposition of the hemiacetals in H2O at 30 deg C.From the magnitude of the rate constants it is clear that in hydrolysis of the corresponding diethyl acetals formation of an oxocarbonium ions is the rate-determining step at all pH values.The pH-log K_obsd profiles for hemiacetal breakdown have slopes of -1.0, 0, and 1.0, indicating hydronium ion, water and OH^- catalysis, respectively.The Hammet ρ value for hydronium ion catalysis is -1.9 in contrast to the value of -3.25 for hydrolysis of substituted benzaldehyde diethyl acetals.The Hammet plots for these compounds cross at ? = -0.5.Thus, hemiacetal breakdown will only be rate determining with strongly electron-donating substituents in the phenyl group.The D2O solvent isotope effect k_D/k_H is 1.7 for hydronium ion catalyzed hemiacetal breakdown.Changing the solvent from H2O to 50percent dioxane-H2O (v/v) reduces the rate of hydronium ion catalyzed hydrolysis of the diethyl acetals by a factor of 30, whereas the effect is only twofold with the corresponding hemiacetal.Thus, it is probable that the hemiacetal reaction involves proton transfer and charge dispersal in the transition state.The pH-independent hemiacetal decomposition has a ρ value of +0.35 and a D2O solvent isotope effect (k_H2O/K_D2O) of 2.0, thus indicating that a proton transfer is taking place either internally or through solvent molecules to the leaving group.In contrast to the large difference in rate constants in the hydronium ion catalyted reaction for benzaldehyde ethyl hemiacetal and formaldehyde ethyl hemiacetal (>10³), the benzaldehyde derivative decomposes less than eightfold faster in the pH-independent reaction.There is very likely considerable proton transfer from the hemiacetal -OH group in the transition state of the pH-independent reaction of the benzaldehyde ethyl hemiacetals, whereas less proton transfer from that group is required in the hydronium ion catalyzed reaction.