Correlation between the pK and nuclear shielding of α-hydrogen of ketones.

The α-H acidity is an important chemical property of ketones that has attracted much research interest. Theoretical prediction of pK for ketone α-H is significant. In this work, we theoretically studied the nuclear shielding of various α-Hs in a set of ketones and that of the corresponding enolic hydroxyl Hs in tautomeric enol forms. It has been demonstrated through linear regression analyses that the pK values of these ketones correlate with both sets of the calculated nuclear shielding values. The correlation coefficient R of the linear correlation relationship is 0.90. The present work has provided a new approach to computationally evaluating the acidity of α-Hs in ketones, enabling us to semi-empirically predict the ketone α-H acidity from the calculated nuclear shielding values. Graphical AbstractExperimental pK values in DMSO vs predicted pK values calculated from H nuclear shielding for the hydroxyl hydrogens in the enol forms and for the α-Hs in the keto forms. The surrounding solvent effects were modelled by keto/enol-DMSO clusters and SMD solvent models.