Conformational analyses of 2,3-dihydroxypropanoic acid as a function of solvent and ionization state as determined by NMR spectroscopy

Abstract

Vicinal ^1H-^1H coupling constants were used to determine the conformational preferences of 2,3-dihydroxypropanoic acid (1) (DL-glyceric acid) in various solvents and its different carboxyl ionization states. The stereospecific assignments of J_(12) and J_(13) were confirmed through the point-group substitution of the C-3 hydrogen with deuterium, yielding rac-(2SR,3RS)-[3^(-2)H]-1, and the observation of only J_(13) in the ^1H NMR spectra. While hydrogen bonding and steric strain may be expected to drive the conformational equilibrium, their role is overshadowed by a profound gauche effect between the vicinal hydroxyl groups that mimics other substituted ethanes, such as 1,2-ethanediol and 1,2-difluoroethane. At low pH, the conformational equilibrium is heavily weighted toward the gauche-hydroxyl rotamers with a range of 81% in DMSO-d_6 to 92% in tert-butyl alcohol-d_(10). At high pH, the equilibrium exhibits a larger dependence upon the polarity and solvating capability of the medium, although the gauche effect still dominates in D_2O, 1,4-dioxane-d_8, methanol-d_4, and ethanol-d_6 (96, 89, 85, and 83% gauche-hydroxyls respectively). The observed preference for the gauche-hydroxyl rotamers is believed to stem primarily from hyperconjugative σC-H → σ^*C-OH interactions.