Continuous Chiral Separation of Amino Acid Derivatives by Enantioselective Liquid−Liquid Extraction in Centrifugal Contactor Separators

Abstract

The continuous enantioselective liquid−liquid extraction of aqueous 3,5-dinitrobenzoyl-d,l-leucine (DNB-d,l-leu) by a cinchona alkaloid extractant (CA) in 1,2-dichloroethane using a centrifugal contact separator (CCS) was studied at 294 K. Typical concentrations were in the order of 1 mM for both DNB-d,l-leu and CA. The best results were found at a pH of 6, with 61% yield for DNB-l-leu and an enantiomeric excess of 34%. Back-extraction studies at different pH values showed that the host can be recovered efficiently in a single CCS, provided that pH > 9. Experimental studies indicate that the CCS behaves as an equilibrium extraction stage, even at total throughputs exceeding 50% of the equipment capacity (1.9 L min−1). A previously developed equilibrium stage extraction model was successfully applied to describe the data for both the extraction and the back-extraction experiments.

Resolution of Racemates and Enantioselective Analytics by Cinchona Alkaloids and Their Derivatives

“…Similar separation has been recently adapted for a continuous process using centrifugal contactor separator. Unfortunately, comparing the batch process much lower enantioselectivity (34% ee) was obtained [48].…”

Novel highly integrated biodiesel production technology in a centrifugal contactor separator device

“…for cleaning oils spills [28]), for extraction of fermentation broths [29] and several other extraction processes [30][31][32][33]. We recently demonstrated the use of the CCS for enantioselective extractions of amino acid derivatives [34] and reported process integration in the CCS by combining biphasic (bio)catalytic conversions with the separation of the catalyst and the reaction products in the device [35]. These examples clearly illustrate the potential of the CCS equipment for the combined reaction and separation for liquid-liquid systems.…”

Reaction kinetics in reactive extraction for chiral separation of α-cyclohexyl-mandelic acid enantiomers with hydroxypropyl-β-cyclodextrin

“…The demand for enantiopure compounds is growing rapidly (Schuur et al, 2008a, b). Especially in the fragrance, pharmaceutical, and food industries, a clear tendency towards the production of enantiopure compounds exists as both enantiomers often show different bioactivity in the human body (Wang et al, 2002;Tang et al, 2007a, b;Yokota et al, 2006;Gübitz and Schmid, 2008).…”

“…Therefore, there is a definite need for new more effective chiral separation methods. Liquid-liquid reactive extraction with a specified chiral extractant giving a higher distribution coefficient and enantioselectivity has been proposed as a promising technique for enantioselective separation of chiral compounds (Schuur et al, 2008a, b;Martínez-Aragó n et al, 2009;Steensma et al, 2007a, b). Development of fractional reactive extraction for chiral separations primarily asks for the identification of enantioselective extractants with sufficient enantioselectivity and capacity.…”