Fine structures in vibrational circular dichroism spectra of chiral molecules with rotatable hydroxyl groups and their application in the analysis of local intermolecular interactions

Abstract

The effect of hydroxyl group on vibrational circular dichroism is addressed. (−)-Menthol is investigated as a representative chiral molecule which has been widely used as a chiral starting material. Free rotation of the hydroxyl group in (−)-menthol allows it to exist in various conformations in solution. The variety of conformations inevitably affects local intermolecular interactions and the resultant efficiency of asymmetric syntheses. However, the precise relationship between the conformations and intermolecular interactions arising from rotation of the hydroxyl group has remained an unsolved issue despite the molecule’s importance. Here, the conformations and interactions are investigated using vibrational circular dichroism (VCD). VCD is quite sensitive to slight differences in the conformation of chiral molecules and their local environment. We examined various conformers in (−)-menthol and compared the VCD spectrum with that of (−)-menthone. It revealed the rotation of the polar hydroxyl group sensitively affects the VCD activity, resulting in the emergence of various patterns in the corresponding VCD spectra, especially in the wavenumber regions at around 1064cm−1 and 1254cm−1. Among these regions, the latter one is further investigated to examine the feasibility of applying the sensitive response to the analysis on the local intermolecular environment. It includes solute–solvent interactions via hydroxyl groups, which is important for biomacromolecule structural stability and efficient stereoselective syntheses. As a consequence, distinctive fine structures in the VCD spectra, including an unpredicted band, are observed when varying temperature and concentration. Their possible assignment is also discussed.