Concentration-dependence of specific rotation of optically active glycerol analogues and structurally related compounds: The significance of intermolecular hydrogen bonding

Abstract

Specific rotation of optically active glycerol analogues, (S)-3-(benzyloxy)propane-1,2-diol [(S)-1], (S)-3-methoxypropane-1,2-diol [(S)-6] and (S)-3-phenoxypropane-1,2-diol [(S)-13], changed its sign from (+) to (–) with increasing concentration in CHCl3, whereas no significant concentration-dependent change was observed in MeOH. The 1H NMR spectrum of (S)-1 showed concentration-dependent changes of the chemical shift in CDCl3. Intermolecular interaction by OH⋯OH hydrogen bonds was suggested by single crystal X-ray crystallography of (S)-13. The concentration-dependent changes of specific rotation of (S)-1, (S)-6, and (S)-13 in CHCl3 can therefore be presumed to be due to self-assembly of these compounds via intermolecular hydrogen bonding at high concentration. The remarkable concentration-dependent changes in specific rotation were also observed to occur in the compounds with related chemical structures, such as (S)-3-hydroxy-4-methoxy-4-oxobutanoic acid [(S)-10], (S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid [Boc-L-Pro-OH, (S)-14], (R)-3-hydroxy-4,4-dimethylhydrofran-2(3H)-one [(R)-15], (R)-tetrahydrofuran-2-carboxylic acid [(R)-16], (S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid [Boc-L-Val-OH, (S)-17], (R)-oxiran-2-ylmethanol [(R)-18], and (4S)-4-isopropyloxazolidin-2-one [(S)-19]. The existence of intermolecular interaction by C=O⋯HO hydrogen bonds was suggested by single crystal X-ray crystallography of (S)-10, (S)-13, and (S)-14. Thus, this series of chiral compounds have multiple functional groups in appropriate positions that serve as hydrogen-bond donors and/or acceptors, resulting in significant concentration-dependent changes of specific rotation.