The effect of intramolecular interactions on hydrogen bond acidity

Abstract

DFT calculations on a range of molecules containing intramolecular hydrogen bonds are reported, with a view to establishing how intramolecular hydrogen bonding affects their intermolecular interactions. It is shown that properties such as the energy of the intramolecular H-bond are unrelated to the ability to form external H-bonds. Conversely, several properties of complexes with a reference base correlate well with an experimental scale of H-bond acidity, and accurate predictive models are determined. A more detailed study, using electrostatic and overlap properties of complexes with a reference base, is used to predict the location, as well as strength, of hydrogen bond acidity. The effects of intramolecular hydrogen bonding on acidity can be seen not just on O–H and N–H, where acidity is greatly reduced, but also on certain C–H groups, which in some cases become the primary source of acidity.