Chiral Ionic Liquids for Enantioselective Liquid–Liquid Extraction of DL-3-Phenyllactic Acid: Synthesis, Characterization, and Mechanistic Insights

Abstract

In this work, a novel pair of chiral ionic liquids (CILs) based on cis- and trans-myrtanol was designed, synthesized, and applied in the enantioselective liquid–liquid extraction (LLE) of DL-3-phenyllactic acid (DL-3-PLA). DL-3-PLA, a naturally occurring broad-spectrum antimicrobial compound, exhibits distinct biological activities in its enantiomeric forms, making its separation of significant interest for pharmaceutical and food applications. The CILs were synthesized starting from (1S)-(−)-β-pinene via oxidative hydroboration, followed by subsequent functional group modifications, and were fully characterized using ¹H NMR, FTIR, DSC, and TGA. Optimization of the LLE parameters (0.10-M CILs in n-octanol, 0.10-M DL-3-PLA in water, pH 6.8, 298.15 K) yielded a single-stage enantiomeric excess (ee) of 15.68%. Using five consecutive extractions with the trans-CILs isomer, a cumulative ee of 95.18% was achieved. Quantum mechanical calculations, including electrostatic potential analysis, IGMH isosurface mapping, and binding energy evaluations, revealed that both the cis- and trans-CILs isomers exhibited strong chiral recognition toward D-3-PLA, with the trans-CILs isomer showing superior recognition performance compared to the cis-CILs isomer. These results underscore the potential of the designed CILs as effective chiral selectors for the DL-3-PLA separation and provide a promising strategy for practical applications in enantioselective separations.