Continuous enantiomeric separation using water-oil-water segmented flow system

Abstract

The multiphase segmented flow, which consisted of the material, extraction, and recovery phases, was applied to the chiral separation. The use of simultaneous extraction and back-extraction with multiple phases aims to prevent the accumulation of target material in the extraction phase by efficiently removing it in the recovery phase, thereby enabling extraction performance beyond the equilibrium. This study demonstrated the chiral separation of an aqueous racemic amino acid derivative (3,5-dinitrobenzoyl-(R,S)-leucine) with a cinchona alkaloid chiral host. A droplet manipulation system comprising PFA manifolds and valves was utilized to alternately form an acidic material phase slug and a basic recovery phase slug in a 1-octanol oil phase containing the chiral host. Two aqueous phases were collected separately using valves controlled by an optical sensor signal. The manipulation system achieved stable operation across various conditions, including flow rate, residence time, and slug lengths. The enantiomeric excess, which represents the purity of the chirality, could be increased to 50 % through 200 s extraction in a one-step operation.