1H NMR and DFT studies of steric effects on intermolecular C–H···O hydrogen bonding in solution

Significant changes in 1H chemical shifts (Δδs) for Ha and Hb of l-2(S)-(1-imidazolyl)-3(S)-methylpentanol (IMP) from D2O to CDCl3 have been observed. Ha and Hb of IMP experience deshielding effects in D2O with respect to in CDCl3. In order to assess the effects on Δδs, comparisons of 1H chemical shifts (δs) with those for 2-(1-imidazolyl) ethanol (IE) and 1-methyl imidazole (MI) as well as density functional theory (DFT) calculations on IMP·nSol hydrogen-bonded models were performed. By analyzing the values for Δδ(IMP−MI) in both solvents and for structural parameters for IMP, it is indicative of that the main contribution to Δδs is most likely produced by an intermolecular C–H···O hydrogen bonding, which has been denoted as Δδ(C–H···O). The steric effects arising from the C2H5CH(CH3)–CH–CH2OH group of IMP favor interactions of IMP molecule with D2O molecules over CDCl3. Moreover, Δδ(C–H···O) is suggested to be rationalized by two effects: the electronic effects, Δδe(C–H···O), and the steric effects, Δδs(C–H···O). Experiments gave ΔδsIMP(C–H⋯O)exp for Ha and Hb of IMP 0.354 and 0.396 ppm, respectively. ΔδsIMP(C–H⋯O)cal for Ha and Hb of IMP are calculated to be 0.347 and 0.369 ppm, respectively, using the IMP·3Sol hydrogen-bonded models. The similarity of ΔδsIMP(C–H⋯O)exp to ΔδsIMP(C–H⋯O)cal encourages the use of IMP·3Sol hydrogen-bonded models as appropriate solution models for Δδs and the cause of Δδs attributing to an intermolecular C–H···O hydrogen bond produced by the steric effects of the C2H5CH(CH3)–CH–CH2OH group.