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The use of capillary microreactors for enantioselective liquid-liquid extraction (ELLE) was successfully demonstrated using a model system consisting of a buffered aqueous amino acid derivative (3,5-dinitrobenzoyl-(R,S)-leucine) solution (phosphate buffer, pH 6.58) and a chiral cinchona alkaloid (CA) host in an organic solvent. It was shown that 1-octanol is a suitable replacement for the commonly used chlorinated solvents like 1,2-dichloroethane. Experiments were conducted in a capillary microreactor set-up (0.8 mm internal diameter) operated in the slug flow regime at 294 K (residence times between 12 and 900 s, 1 : 1 flow ratio of the aqueous to organic phases, 1 mM of host and 1 mM of amino acid derivative). The enantiomeric excess (ee) was shown to be a function of the solvent and residence time and varied between 37% and 49% in 1,2-DCE and 28 and 46% in 1-octanol in the organic phase. The ee values in the organic phase at shorter residence times were higher than the independently determined equilibrium ee values (41% in 1,2-DCE and 31% in 1-octanol at a host concentration of 1 mM). This is an unprecedented observation with large implications for ELLE, as it implies that operation in the kinetic regime may lead to improved enantioseparation performance

Proof of concept for continuous enantioselective liquid–liquid extraction in capillary microreactors using 1-octanol as a sustainable solvent