Extractive resolution of racemic phenylalanine and preparation of optically pure product by chiral magnetic ionic liquid aqueous two-phase system

Abstract

In this report, chiral magnetic ionic liquid aqueous two-phase system was developed for the first time. Three novel chiral magnetic ionic liquids ([C2-4MIM-Tempo][L-Pro]) were synthesized and successfully used to construct aqueous two-phase system with inorganic salts (K2HPO4, K2CO3, K3PO4, Na2SO4, Na2CO3) for the extractive resolution of racemic phenylalanine. This novel system combined the advantages of organic solvent free, magnetic phase separation and rapid extraction together in an enantiomer resolution process for the first time. Phase behaviors and various influencing factors on resolution performance were systematically studied and optimized. The optimal extractive resolution conditions are: 1.4 g added water, 450 mg [C4MIM-Tempo][L-Pro], 100 mg Cu(OAc)2, 20 mg DL-Phe, 0.85 g K2HPO4, pH of added water as 7, system temperature as 298.15 K. Based on this, a novel preparation method of highly optically pure L-phenylalanine and D-phenylalanine was developed and achieved a satisfactory performance even in gram-scale. The e.e. value of L-phenylalanine in chiral MIL-rich phase reached 94.3% and the e.e. value of D-phenylalanine in salt-rich phase could reach 98.1%. Moreover, chiral magnetic ionic liquid could be recycled for at least 6 times with consistently good resolution ability. Hopefully, this green and recyclable resolution approach is showing great potential in industry.