Direct crystallization resolution of chiral compounds assisted by chiral ionic liquids through conformational matching

Stereoselective recognition using “tailor-made” chiral ionic liquids (CILs) is an effective approach to obtaining enantiopure compounds through crystallization resolution. In this study, CILs were used as additives to stereoselectively inhibit the nucleation and growth of unwanted enantiomers via a conformational matching mechanism. Interestingly, a cosolvency phenomenon was found in the threonine-CILs-ethanol solvent system. Based on this, an enhanced stereoselective crystallization resolution strategy that combines ultrasound and cosolvency was proposed. The goal of this strategy was to improve the crystallization yield and enantiomeric purity. The results showed that the crystallization resolution yield of the cosolvency system was 33.43%, higher than that of the pure water system (13.56%). More importantly, the introduction of ultrasonic enhancement further increased the crystallization resolution yield to 39.45%. This work will facilitate the exploration of the unlimited potential of utilizing the cosolvency phenomenon and ultrasonic enhancement for crystallization resolution.