(496c) Enantioselective Extraction in Process Intensified Columns

Living organisms interact with biologically active molecules. Most of the molecules in a metabolism are chiral, such as amino acids, nucleic acids and sugars, as well as composed basic molecules such as peptides, proteins, and polysaccharides. Enantiomers play a key role inside the metabolism of plants and animals. They are important for regulation of processes and for specific interactions inside the biogenesis. Thus, chiral molecules are essential for pharmaceuticals, agrochemicals, foods, aromas, and flavors. The production of pure enantiomers is therefore a necessary requirement.
Due to the same molecular structure, enantiomers have mostly the same physico-chemical properties, like boiling or melting point, solubility, optical spectra, and bonding length. This makes the separation of both molecules complex, and requires delicate separation techniques. Beside common preparative techniques, such as diastereomeric crystallization and chromatography, the enantioselective liquid-liquid extraction (ELLE) is a highly promising alternative to realize a continuous and flexible process that is easily scalable.
The separation is based on a selective complex formation between the enantiomers and a selector molecule, where typically the enantiomers are fed in one liquid phase, and the selector molecule is dissolved in a second liquid phase. In the past decades, a range of selector molecules were identified for various classes of racemates [1], so that nowadays the separation of a broad spectrum of enantiomers is possible. However, the selectivity of the separation is often rather poor, which makes the complete separation more complicated. Therefore, the economic and ecologically sustainable realization of ELLE implies a high selectivity of the selector molecules and high extraction efficiencies for the counter-current extraction process.
Often, the enantioselector molecules are delicate and very expensive, and processing ELLE is therefore preferentially done in compact, highly efficient equipment. We here report the use of miniaturized extraction columns and show that they offer a good solution for the enantioselective extraction in small scale applications. With different test systems, it was demonstrated that the extraction efficiency in these miniaturized columns is more than twice as in conventional miniplant extraction columns [2].
The fractional extraction of racemic mixtures is investigated theoretically and experimentally inside these extraction columns (H_ac=1.1 m) with aromatic acids and amino acids. It could be demonstrated that the enantioselective extraction of (R/S)-phenyl succinic acid (PSA) and dinitrobenzoyl-(R/S)-leucine (DNB-Leu) inside this columns is possible. The enantiomeric excess was measured up to 60 % for PSA (the system with a lower intrinsic selectivity), whereas the enantiomers of DNB-Leu could be separated with enantiomeric excesses of over 98%.

[1] Schuur, et al., Organic & Biomolecular Chemistry, 9, 36-51, 2011

[2] Holbach, et al., Chemical Engineering and Processing, 80, 21-28, 2014