NMR investigations of weak molecular interactions, with special focus on hydrogen bonding involving organic fluorine

Abstract

Over the years a number of articles have been published from our laboratory establishing the presence of inter- and intra- molecular hydrogen bonding involving organic fluorine, in a large number of synthesized molecules, viz. derivatives of imides, benzanilides, benzamides, hydrazides and diphenyloxamides. The two and three centred hydrogen bonds occurring in all the investigated molecules have ben unequivocally established by extensive utility of one and two-dimensional NMR experiments, viz. 15N-1H HSQC, 19F-1H HOESY and DOSY, temperature perturbation, solvent dilution studies, etc. In particular the measurement of coupling between 1H and 19F, where there is hydrogen bond mediated polarization transfer between the NMR active spins, has been of prime importance. Furthermore, the physical parameter dependent changes in the chemical shifts of NH protons and the magnitude of 1JNH have proven invaluable in understanding not only the existence of hydrogen bond involving organic fluorine but also whether it is predominantly covalent bond mediated or electrostatic. The DFT based theoretical calculations, such as, NCI, QTAIM, MD simulations and NBO analysis, provided confirmatory evidence for the NMR experimental findings. This article provides an overview of the voluminous amount of work carried out mainly in our laboratory. The article starts with a brief introduction to weak molecular interactions, available NMR methods and the theoretical calculations, before embarking on the detailed discussion on the results derived on number of synthesized molecules containing organic fluorine.