Computational Study of the Acid Dissociation of Esters and Lactones. A Case Study of Diketene

A computational study of the aqueous pK a of some saturated and unsaturated cyclic and linear esters and ketones was carried out at the DFT-B3LYP 6-31++G(2df,2pd), CBS-Q, and G2 levels, with the integral equation formalism polarizable continuum model for solvation, using a proton exchange mechanism. The influence of unsaturation, position of the double bond, and cyclization were studied. The computational results show that (a) in all cases studied except that of diketene (4-methylene-2-oxetanone), the α-β unsaturated isomer is 20−30 kJ mol−1 lower in energy that the β-γ unsaturated one; (b) α-β unsaturation lowers the pK a of an ester ∼6 units, whereas β-γ unsaturation lowers it by ∼10 units, and cyclization lowers the pK a by ∼3 units. In order to check the predictive power of the methodology, the acid dissociation constant of diketene in water was measured via kinetic study of its base-catalyzed hydrolysis. The pK a value obtained (15.2 ± 0.3) is in keeping with the expected value for a β-γ unsaturated β-lactone. This low value also suggests that deprotonated diketene does not interconvert to a more stable, less acidic α-β unsaturated isomer, which is also consistent with computational results.