Non‐Covalent Interactions in Molecular Systems: Thermodynamic Evaluation of the Hydrogen‐Bond Strength in Amino‐Ethers and Amino‐Alcohols

The intramolecular hydrogen bond (intra‐HB) is one of the best‐known examples of non‐covalent interactions in molecules. Among the different types of intramolecular hydrogen bonding, the NH⋅⋅⋅O hydrogen bond in amino‐alcohols and amino‐ethers is one of the weakest. In contrast to the strong OH⋅⋅⋅N intramolecular hydrogen bond, the strength of the NH⋅⋅⋅O bond can hardly be measured with conventional spectroscopic methods, even for simple amino‐alcohols, since the band belonging to the NH⋅⋅⋅O conformer merges with the free OH band. In this work, we developed a combination of G4 calculations, and a method based on experimental vaporization enthalpies to determine the NH⋅⋅⋅O hydrogen bonding strength. The archetypal compounds for this study are 2‐amino‐1‐ethanol and 3‐amino‐1‐propanol as well as their respective methoxy analogs. Based on these molecules, different series were studied to investigate various factors influencing NH⋅⋅⋅O intra‐HB strength. In the first series, the influence of alkylation near the hydroxy or methoxy group and the amino group in sterically hindered aminoalcohols was examined. In the second series, the influence of alkylation of the amino‐group was investigated. In the third series, the effect of extending the alkyl chain between functional groups was studied. The strength of NH⋅⋅⋅O bond in three series of amino‐alcohols characterized by branching, mono‐alkylation of the amino group, or increased chain length between the functional groups, was evaluated by a combination of quantum chemistry and a method based on experimental vaporization enthalpies. It was observed that moderate tertiary branching at the H‐acceptor or at the H‐donor side has only a marginal effect on the NH⋅⋅⋅O hydrogen bond strength so that it remains in the range of −4 kJ⋅mol−1 to −6 kJ⋅mol−1.