Polarisation effects on the H-bond acceptor properties of secondary amides

Abstract

H-bonding interactions in networks are stabilised by cooperativity, but the relationship between the chemical structures of the interacting functional groups and the thermodynamic consequences is not well-understood. We have used compounds with an intramolecular H-bond between a pyridine H-bond acceptor and an amide NH group to quantify cooperative effects on the H-bond acceptor properties of the amide carbonyl group. ¹H NMR experiments in n-octane confirm the presence of the intramolecular H-bond and show that this interaction is intact in the 1 : 1 complex formed with perfluoro-tert-butanol (PFTB). UV-vis absorption titrations were used to measure the relationship between the association constant for formation of this complex and the H-bond acceptor properties of the pyridine involved in the intramolecular H-bond. Electron-donating substituents on the pyridine increase the strength of the intermolecular H-bond between PFTB and the amide. There is a linear relationship between the H-bond acceptor parameter β measured for the amide carbonyl group and the H-bond acceptor parameter for the pyridine. The cooperativity parameter κ determined from this relationship is 0.2, i.e. β for an amide carbonyl group is increased by one fifth of the value of β of an acceptor that interacts with the NH group. This result is reproduced by DFT calculations of H-bond parameters for the individual molecules in the gas phase, which implies that the observed cooperativity can be understood as polarisation of the electron density in the amide π-system in response to formation of a H-bond. The cooperativity parameter κ measured for the secondary amide H-bond donor and H-bond acceptor is identical, which implies that polarisation of an amide mediates the interaction between an external donor or acceptor in a reciprocal manner.