Membranes chiral separation using

Novel chiral. separations using enzymes and chiral surfactants as carriers have been realized using facilitated transport membranes. Japanese workers have reported the synthesis of a novel norbornadiene polymeric membrane with optically active pendent groups that show enantio.selectivity, which has shown promi.se in the. separation of propronalol. 

Chiral separation using MIPs can also be achieved by bubble fractionation [63] and with MIP membranes [64-68], MIP particles selective for an amino acid derivative were used as collectors for enantiomeric enrichment by bubble fractionation. The method is envisaged to be a potentially powerful approach to process-scale separations [63]. 

Wang PC, Gao J, and Lee CS. High-resolution chiral separation using microfluidics-based membrane chromatography. J. Chromatogr. A 2002 942 115-122. 

Liquid membranes can be constituted by liquid chiral selectors used directly [170] or by solutions of the chiral molecules in polar or apolar solvents. This later possibility can also be an advantage since it allows the modulation of the separation con-... 

Another possibility of constructing a chiral membrane system is to prepare a solution of the chiral selector which is retained between two porous membranes, acting as an enantioselective liquid carrier for the transport of one of the enantiomers from the feed solution of the racemate to the receiving side (Fig. 1-5). This system is often referred to as membrane-assisted separation. The selector should not be soluble in the solvent used for the elution of the enantiomers, whose transport is driven by a gradient in concentration or pH between the feed and receiving phases. As a drawback common to all these systems, it should be mentioned that the transport of one enantiomer usually decreases when the enantiomer ratio in the permeate diminishes. Nevertheless, this can be overcome by designing a system where two opposite selectors are used to transport the two enantiomers of a racemic solution simultaneously, as it was already applied in W-tube experiments [171]. 

For the separation of racemic mixtures, two basic types of membrane processes can be distinguished a direct separation using an enantioselective membrane, or separation in which a nonselective membrane assists an enantioselective process [5]. The most direct method is to apply enantioselective membranes, thus allowing selective transport of one of the enantiomers of a racemic mixture. These membranes can either be a dense polymer or a liquid. In the latter case, the membrane liquid can be chiral, or may contain a chiral additive (carrier). Nonselective membranes can also... 

In this chapter we will provide an overview of the application of membrane separations for chiral resolutions. As we will focus on physical separations, the use of membranes in kinetic (bio)resolutions will not be discussed. This chapter is intended to provide an impression, though not exhaustive, of the status of the development of membrane processes for chiral separations. The different options will be discussed on the basis of their applicability on a large scale. 

Possible applications of MIP membranes are in the field of sensor systems and separation technology. With respect to MIP membrane-based sensors, selective ligand binding to the membrane or selective permeation through the membrane can be used for the generation of a specific signal. Practical chiral separation by MIP membranes still faces reproducibility problems in the preparation methods, as well as mass transfer limitations inside the membrane. To overcome mass transfer limitations, MIP nanoparticles embedded in liquid membranes could be an alternative approach to develop chiral membrane separation by molecular imprinting [44]. 

Membranes offer a format for interaction of an analyte with a stationary phase alternative to the familiar column. For certain kinds of separations, particularly preparative separations involving strong adsorption, the membrane format is extremely useful. A 5 x 4 mm hollow-fiber membrane layered with the protein bovine serum albumin was used for the chiral separation of the amino acid tryptophan, with a separation factor of up to 6.6.62 Diethey-laminoethyl-derivatized membrane disks were used for high-speed ion exchange separations of oligonucleotides.63 Sulfonated membranes were used for peptide separations, and reversed-phase separations of peptides, steroids, and aromatic hydrocarbons were accomplished on C18-derivatized membranes. 

Several attempts to perform enantioselective separations using membranes of a chiral mobile carrier have been reported and have been extensively discussed in a recent review [185]. Various chiral carriers, mainly crown ethers, were used for this purpose but poor enantioselectivity was usually obtained and no preparative application has been described. 

It can be concluded that stereoselective (and particularly enantioselective) separation can proceed by the simple apphcation of a chiral organic phase or in most cases by incorporation of carriers in the membrane phase. Sometimes, their structure is very complex and these molecules can act as real receptors for the enantiomers. Different types of transport mechanisms are involved in the separation and the most popular one is cotransport. This is a result of the fact that most frequently used carriers are based on crown ethers structure. The stereoselectivities by apphcation of carrier-mediated SLM separation are very different and depend on the structure of the guest and host molecules. The magnitudes of the stereoselectivity are in most cases moderate but similar to other membrane-based separation techniques for stereoisomers. 

Catalytically active supported ionic liquid membranes were used for propylene/propane vapor mixture separation. In this case, the ionic Hquid was immobilized in the pores of an asymmetric ceramic support, displaying sufficient permeability, good selectivity, and long-term stabUity [51]. Porous inorganic membranes were also used as a support for chiral-selective liquid membranes. For this purpose, porous tubular ceramic membranes were impregnated with 3-cyclodextrin polymer. Such SLMs were used for separation of enantiomers of racemic pharmaceutical chlorthahdone [52]. 

The use of LLC-based membrane systems is still in its infancy. Promising early results indicate that research in this field will be expanded. The applications outlined here are just a few where functional LLC materials might be implemented. More challenging separation materials, such as water desalination membranes, selective proton-conducting membranes for fuel cells, catalytic membranes, chromatography, and chiral separation media are perhaps future candidates for new LLC membrane materials. 

Polymeric membranes also show potential for application in the area of chiral catalysis. Here metallocomplexes find use as homogeneous catalysts, since they show high activity and enantioselectivity. They are expensive, however, and their presence in the final product is undesirable they must be, therefore, separated after the reaction ends. Attempts have been made to immobilize these catalysts on various supports. Immobilization is a laborious process, however, and often the catalyst activity decreases upon immobilization. An alternative would be a hybrid process, which combines the homogeneous catalytic reactor with a nanofiltration membrane system. Smet et al. [2.98] have presented an example of such an application. They studied the hydrogenation of dimethyl itaconate with Ru-BINAP as a homogeneous chiral catalyst. The nanofiltration membrane helps separate the reaction products from the catalyst. Two different configurations can be utilized, one in which the membrane is inserted in the reactor itself, and another in which the membrane is extraneous to the reactor. Ru-BINAP is known to be an excellent hydrogenation catalyst... 

M. Nakamura, S. Kiyohara, K. Saito, K. Sugita and T. Sugo, Chiral Separation of DL-Tryptophan Using Porous Membranes Containing Multilayered Bovine Serum Albumin Crosslinked with Glutaraldehyde, J. Chromatogr. A, 822 (1998) 53. 

The importance to use optically pure isomers as pharmaceuticals, food additives, agrochemicals, (etc) is becoming more and more evident. The classical resolution still accounts for a large part of chiral production, however the asymmetric synthesis and the use of chiral separation system one becoming increasingly popular. The enantioseletive hydrolytic resolution of racemic epoxides was performed in the ZSM-5/MCM-41 membrane system containing chiral salen complexes. The chiral salen complexes immobilized on the membrane showed a very high enantioselectivity in the hydrolysis of epichlorohydrine, epoxybutane, styrene oxide and 1,2-epoxyhexane. 

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