Esters of Mandelic Acid as a Basis for Chiral Eutectic Solvents: An Investigation of Physical Properties and Enantioselectivity

Deep eutectic solvents (DES) are mixtures of two or more components with a large depression in the freezing point due to strong intermolecular interactions such as hydrogen bonding. If one or more of the components are chiral, the DES is a chiral solvent that can be used in chirality-dependent applications, such as asymmetric catalysis or chiral separations. In this study, esters of mandelic acid were utilized as hydrogen bond donors (HBD) in the formation of 16 chiral DES with a variety of hydrogen bond acceptors. A common chiral HBD, (R/S) ethyl mandelate, is prepared in ionic DES with tetraalkylammonium (alkyl = ethyl, propyl, and butyl) chlorides, and tetrabutylammonium bromide and nonionic DES with thymol and 1,8-cineole. The density, viscosity, conductivity, and Kamlet-Taft parameters are measured and compared for each of the 16 chiral DES. The enantioselectivity of the ionic DES is measured by measuring the circularly polarized luminescence induced when a racemic mixture of lanthanide complexes is dissolved in the chiral DES. The thermodynamics show that the chiral DES with tetrabutylammonium bromide are most effective as enantioselective solvents. This correlates with the Kamlet-Taft measurements that show the bromide DES are the most effective hydrogen bond donors. Molecular dynamics (MD) simulations were performed for a subset of the DES to understand the molecular level interactions. MD results are analyzed to compare specific hydrogen bonding interactions in ionic and nonionic ethyl mandelate DES.