Role of intramolecular hydrogen bonds and electron withdrawing groups in the acidity of aldimines and ketimines: a density functional theory study

Abstract

The role of intramolecular hydrogen bonds and the presence of electron withdrawing groups in the acidity of secondary aldimines and secondary ketimines is investigated by means of density functional theory simulations. We have found that the presence of an intramolecular hydrogen bond can increase the acidity up to ~ 20 kJ mol −1 with respect to structural isomers not showing it. In general, the excess of negative charge in the deprotonated species is hosted by the electron withdrawing group, thus stabilizing the anion and increasing the acidity. Among the studied structures, secondary ketimines, bearing a phenyl group, have shown to present the highest acidity and are therefore potential candidates that would be used for different Michael and nucleophilic additions in the synthesis of important pharmaceutical and natural products