Enantioselective membrane extraction

Fig. 5-12. Separation of d,1-leucine in hollow-fiber membrane extraction using a Al- -dodecyl-l-hydrox-yproline solution in octanol as the enantioselective extraction liquid. The modules used were 32 cm long and contained 96 Celgard X-20 polypropylene fibers [57].

In the classical set-up of bulk liquid membranes, the membrane phase is a well-mixed bulk phase instead of an immobilized phase within a pore or film. The principle comprises enantioselective extraction from the feed phase to the carrier phase, and subsequently the carrier releases the enantiomer into the receiving phase. As formation and dissociation of the chiral complex occur at different locations, suitable conditions for absorption and desorption can be established. In order to allow for effective mass transport between the different liquid phases involved, hollow fiber... 

Nonselective membranes can assist enantioselective processes, providing essential nonchiral separation characteristics and thus making a chiral separation based on enantioselectivity outside the membrane technically and economically feasible. For this purpose several configurations can be applied (i) liquid-liquid extraction based on hollow-fiber membrane fractionation (ii) liquid- membrane fractionation and (iii) micellar-enhanced ultrafiltration (MEUF). 

As described above, the application of classical liquid- liquid extractions often results in extreme flow ratios. To avoid this, a completely symmetrical system has been developed at Akzo Nobel in the early 1990s [64, 65]. In this system, a supported liquid-membrane separates two miscible chiral liquids containing opposite chiral selectors (Fig. 5-13). When the two liquids flow countercurrently, any desired degree of separation can be achieved. As a result of the system being symmetrical, the racemic mixture to be separated must be added in the middle. Due to the fact that enantioselectivity usually is more pronounced in a nonaqueous environment, organic liquids are used as the chiral liquids and the membrane liquid is aqueous. In this case the chiral selector molecules are lipophilic in order to avoid transport across the liquid membrane. 

It turned out that for all the polymeric amphiphiles of the (EO) -(PO)m-(EO) type there was an increase in enantioselectivity compared with the reaction without amphiphile. Moreover, the ratio of the length of the (PO) block compared with the (EO) block seemed to determine enantioselectivity and activity and not the cmc (critical micelle concentration). A (PO) block length of 56 units works best with different length of the (EO)n block in this type of hydrogenation [30]. for the work-up of the experiments, G. Oehme et al. used the extraction method, but initial experiments failed and the catalyst could not be recycled that way. To solve this problem the authors applied a membrane reactor in combination with the amphiphile (EO)37-(PO)5g-(EO)37 (Tab. 6.1, entry 9) [31]. By doing so, the poly-mer/Rh-catalyst was retained and could be reused several times without loss of activity and enantioselectivity by more than 99%. 

It is significant that the reaction mixture was worked up by removal of the unreacted ester by hexane extraction and concentration of the aqueous layer to obtain the desired (i )-amino acid. The process has a high throughput and was easy to handle on a large scale. However, because of the nature of a batch process, the enzyme catalyst could not be effectively recovered, adding significantly to the cost of the product. In the further scale up to 100-kg quantity productions, the resolution process was performed using Sepracor s membrane bioreactor module. The enzyme was immobilized by entrapment into the interlayer of the hollow-fiber membrane. Water and the substrate amino ester as a neat oil or hexane solution were circulated on each side of the membrane. The ester was hydrolyzed enantioselectively by the enzyme at the membrane interface, and the chiral acid product... 

Pickering, P. J., Chaudhuri, J. B. (1997). Enantioselective extraction of (D)-phenylalanine from racemic (D/L)-phenylalanine using chiral emulsion liquid membranes. Journal of Membrane Technology 127 115-130. 

Polyurea membranes have been produced in the reaction between L-Lysine ethyl ester dihydrochloride with 1,4-phenylene diisocyanate, followed by dissolving the polymer in DMAc/LiCl (5%) and obtaining the membrane by evaporation of the solvent [56]. By the addition to the membrane synthesis mixture of N-a membrane-benzyloxycarbonyl-D-glutamic acid (ZD-Glu) or N-a-benzyloxycarbonyl-L-glutamic acid (ZL-Glu), and extraction of these imprint molecules using a solution of ethanol in water, a molecularly imprinted membrane is obtained, which has an affinity for Z-D-Glu or Z-L Glu. The material thus obtained was used for enantioselective electrodialysis, the imprinted molecule being retained in the membrane, and transport being allowed only for the other enantiomer. 

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