Enantioseparation of aldols by high-performance liquid chromatography on polysaccharide-based chiral stationary phases that bear chlorinated substituents

Abstract

Two families of aldols, obtained from the condensation of aromatic aldehydes with cyclohexanone or acetone (ten examples in each group), were analyzed by high-performance liquid chromatography in normal phase elution mode on three polysaccharide-based chiral stationary phases of the Lux series, namely, Lux Cellulose-2, Lux Cellulose-4 and Lux Amylose-2, which share the common feature of chlorinated substituents in the chiral selectors. Following simple optimization steps, the enantioseparation of all aldols derived from cyclohexanone was achieved and the highest values of separation factor (α, 1.32 < α < 2.20) and resolution (Rs , 4.5 < Rs <17.2) were observed on Lux Cellulose-2, with the only exception of the 4-nitro-substituted derivative that was better resolved on Lux Cellulose-4. On the contrary, Lux Amylose-2 was the best choice for aldols derived from acetone and only specific analytes in this group were resolved on the cellulose-based supports. A variable-temperature study of selected compounds allowed us to determine thermodynamic parameters of the enantioseparation process, which was enthalpy-controlled in all the cases except one.

Keywords: Aldols; Enantioseparation; High-performance liquid chromatography; Polysaccharide-based selectors.