Experimental and computational thermochemistry: how strong is the intramolecular hydrogen bond in alkyl 2-hydroxybenzoates (salicylates)

Abstract

Hydrogen bonding (HB) is a fascinating phenomenon that exhibits unusual properties in organic and biomolecules. The qualitative manifestation of hydrogen bonds is known in numerous chemical processes. However, quantifying HB strength is a challenging task, especially in the case of intra-molecular hydrogen bonds. It is qualitatively well established that the alkyl 2-hydroxybenzoates have strong intra-HB. The thermochemical methods suitable for the determination of intra-HB strength were the focus of this study. The experimental gas phase formation enthalpies for alkyl 2-hydroxybenzoates (including methyl, ethyl, n-propyl and n-butyl) at 298.15 K were derived from a combination of vapour pressure measurements and high-precision combustion calorimetry and validated by the quantum chemical methods G3MP2 and G4. The intra-HB strength in methyl 2-hydroxybenzoate was determined from the evaluated gas-phase enthalpies of formation by comparing the energies of cis- and trans- conformers, by well-balanced reactions, the “para–ortho” method and the “HB and Out” method. All these methods give a common level of intra-molecular hydrogen bond strength of −43 kJ mol⁻¹. The intra-HB strength was found to be independent of the chain length of the alkyl 2-hydroxybenzoates.