(134f) Possibility of Separating Enantiomeric Compounds Continuously with Supercritical CO2 and Chiral Ionic Liquids

Continuous chiral separation processes are needed for practical-scale medical products. In separation processes for enantiomeric compounds, chiral selectivity, high purity and high throughout should be considered along with waste streams associated with the methods chosen. Ionic liquids, especially when combined with CO2 in its supercritical state, have been shown to be have some advantages over organic solvents from the viewpoint of environmental burden and their versatility in chemical processing due to the ease at which their chemical characteristics can be varied by changing the anion or cation constituent. The low volatility of ionic liquids and their lack of solubility in supercritical CO2 all enhance their appeal for use in chemical separations. Thus, the ionic liquid acts as the solvent phase for reaction or dissolution of the chemical compounds and the supercritical CO2 phase acts to extract the chemical compound that has lower affinity for the ionic liquid. Many products in the pharmaceutical industry involve the separation enantiomeric mixtures in which two basic methods exist (i) formation of a diastereomer and separation of the diastereomeric mixture by usual techniques and (ii) use of a chiral selector along with some type of phase contact system that is typically chromatography. In this work, we consider the possibility of using chiral ionic liquids as chiral selectors along with a supercritical CO2 phase. In the literature, chiral ionic liquids have been synthesized and studied, but frequently they have been found to lack chiral selectivity. On the other hand, with a CO2 phase, the chiral ionic liquid should exhibit different interactions with enantiomeric solutes and so partitioning in CO2 phase may be different between each the (R) and (S) forms. In the experiments, we use chiral ionic liquids, chiral solutes and supercritical CO2 to study the separation factors. First, properties of some ionic liquids and their characteristics with CO2 are reviewed and described. Then, a chromatographic method is used to evaluate the chiral selectivity of chiral ionic liquids. The chiral ionic liquid is used as the stationary phase in a packed column, and the CO2 was used as the mobile phase. Detection of solute was by UV/vis spectroscopy. The chiral ionic liquids studied were 1-ethyl-3-methylimidazolium-(S)-lactate [emim][(S)-lactate] and 1-butyl-3-methylimidazolium-(S)-lactate [bmim][(S)-lactate] and the racemic solutes used were 1-phenyl-1-propanol and 2-phenylpropionic acid. In some cases, only the (R)-enantiomer elutes, while in other cases, chiral selectivity can be achieved.