Continuous Separation of α-Cyclohexyl-mandelic Acid Enantiomers by Enantioselective Liquid–Liquid Extraction in Centrifugal Contactor Separators: Experiments and Modeling

Abstract

Multistage enantioselective liquid–liquid extraction (ELLE) in centrifugal contactor separators was developed for separation of enantiomers. Performance of the process was evaluated by product purity (enantiomeric excess, ee) and yield (Y). Enantioselective liquid–liquid extraction of α-cyclohexyl-mandelic acid (α-CHMA) enantiomers with hydrophilic hydroxyphenyl-β-cyclodextrin as extractant (C) was performed in a countercurrent cascade of 10 centrifugal contactor separators (CCSs) at 278 K to investigate the influence of the operation variables including phase ratios and concentrations on extraction efficiency. On the basis of a single stage equilibrium model and the law of conservation of mass, a multistage equilibrium model of enantioselective liquid–liquid extraction was developed to investigate the influence of changes in the process parameters such as phase ratios and concentrations on extraction efficiency. The multistage model predicted the experimental data accurately and was applied to optimize the symmetrical separation of α-CHMA enantiomers. By modeling, the minimum number of stages for eeeq > 97% and eeeq > 99% was predicted as 42 and 48, respectively.

Enantioseparation of mandelic acid derivatives by high performance liquid chromatography with substituted β-cyclodextrin as chiral mobile phase additive and evaluation of inclusion complex formation

“…They generally show higher solubility in the aqueous solution and better enantiorecognition than native β-cyclodextrin for any class of enantiomers. In recent years many papers have been reported about their applications as chiral selector in various kinds of chiral separation methods, such as HPLC with chiral mobile phase additive [3-9], enantioselective liquid-liquid extraction [10,11], membrane separation [12], capillary electrophoresis [13,14], etc. In our previous studies, several aromatic carboxylic acids were enantioseparated by high speed countercurrent chromatography using HP-β-CD as a chiral selector in the two-phase solvent system, where strong chiral recognition was observed [15-18].…”

Process optimization of continuous liquid–liquid extraction in centrifugal contactor separators for separation of oxybutynin enantiomers

“…However, it is easier to obtain optimal extraction conditions by simulation and optimization. Recently, we reported on experiments and modeling on continuous separation of enantiomers by multistage ELLE in centrifugal contactor separators, and good agreements between the experimental results and the model predictions have been observed [35,36]. For an economically feasible process, it is necessary to obtain a high yield per unit time and product purity with minimum number of transfer units.…”

Studies on multistage enantioselective liquid–liquid extraction of amino-(4-nitro-phenyl)-acetic acid enantiomers using CuPF6{(S)-BINAP}: Experiments and modeling

“…In recent years, we have separated aromatic acid enantiomers by multistage centrifugal extraction successfully [29,38]. The extraction process was modeled based on homogeneous reaction mechanism and good agreements between the experimental results and the model predictions have been observed.…”