Chiral recognition and efficient enantiopurification of l-lactic acid by diastereomeric crystallization

Abstract

The production of high-performance polylactic acid (PLA) with tailored thermomechanical properties is critically dependent on the enantiomeric purity of its L-lactic acid (L-LA) precursor. Current industrial processes often yield low-grade L-LA streams (around 80% ee) due to racemization during lactide formation, leading to substantial material loss and limiting the widespread adoption of high-stereoregularity PLA. Herein, we report on a highly efficient and industrially viable diastereomeric crystallization strategy for the upgrading of L-LA. Our method leverages the selective formation of crystalline salts between L-LA and specific chiral aromatic amines. Systematic screening identified (R)-1-phenylpropylamine ((R)-1-PA) and (R)-1-phenylethylamine ((R)-1-PEA) as superior resolving agents, enabling the crystallization of L-LA in acetonitrile (MeCN) with exceptional enantiomeric excess (ee ≥ 99% and ≥ 97%, respectively) and high yields (70% and 68%). Single-crystal X-ray diffraction (SCXRD) reveals pronounced structural divergence among the corresponding diastereomeric salts, including distinct hydrogen-bonding networks and π–π stacking arrangements. Combined thermochemical analysis, phase-equilibrium studies, and molecular simulations demonstrate that chiral recognition arises from the cooperative interplay of electrostatic complementarity, directional hydrogen bonding, and multivalent aromatic interactions. Leveraging these insights, we establish an integrated reaction-crystallization-distillation process that upgrades low-grade L-LA to high-purity feedstock with efficient recovery and recycling of both solvent and resolving agent. This work presents an industrially viable crystallization-based purification strategy, offering a practical solution for enhancing the stereoregularity, performance, and industrial applicability of PLA, thereby addressing a key bottleneck in the sustainable polymer industry.

Keywords: Polylactic acid; L-lactic acid; Chiral recognition; Diastereomeric crystallization; Aromatic amine.