A nuclear magnetic resonance and theoretical investigation of the effect of charge and solvation on the conformations of 1,2-disubstituted ethanes

Abstract

The conformational energies of a number of 1,2-disubstituted ethanes (CH₂X·CH₂Y) have been obtained by ab initio and MNDO calculations (i.e. for the vapour phase) and by ¹H n.m.r. spectroscopy (for aqueous solutions). There is generally good agreement between theory and experiment for the neutral molecules. The 2-halogenoethylamines (X = F or Cl, Y = NH₂), 3-chloropropionic acid (X = Cl, Y = CO₂H), and succinic acid (X = Y = CO₂H) all favour the gauche conformer, whereas ethylenediamine (X = Y = NH₂) has no conformational preference.

For the charged molecules, although theory correctly predicts the direction of the conformer energy changes on ionisation of the amino and carboxy groups, it vastly overrates the extent of these changes. The most extreme case is β-alanine zwitterion (X =⁺NH₃, Y = CO₂^–), which is predicted to be wholly in the gauche form (by 10–30 kcal mol^–1), yet which shows no conformational preference in aqueous solution (ΔE_g–t– 0.1 kcal mol^–1).

These results suggest that in carrying out molecular mechanics calculations on molecules containing charged groups exposed to aqueous solution, the dominant effect of the solvent in ‘neutralising’ the electrostatic interactions of the charged species must always be considered.