SEPARATION OF ENANTIOMERS BY CHIRALLY MODIFIED MEMBRANES

Transcription

1 XXIII ARS SEPARATORIA Toruń, Poland SEPARATION OF ENANTIOMERS BY CHIRALLY MODIFIED MEMBRANES Izabela KOTER Nicolaus Copernicus University, Faculty of Chemistry, 7 Gagarin St., Torun, Poland Abstract The use of various membrane techniques for enantiomer separation was discussed. Enantioselective transport of some amino acids and other model compounds in chirally modified membranes was investigated. The chiral selectors (cinchonidine, methyl-β-cyclodextrin) were immobilized in mesoporous ceramic membranes and polymer flat membranes. The influence of some factors as membrane pore size, immobilization type etc. on enantioselective permeation of enantiomers through the chiral membranes was studied. 1. INTRODUCTION The preparation of chiral compounds is an important area of contemporary synthetic organic chemistry. In spite of the advances in asymmetric synthesis of pure enantiomers, the resolution of racemates is still the most important industrial approach to the synthesis of enantiomerically pure compounds. Among the methods of enantiomer separation are diastereomer crystallization, high performance liquid chromatography (HPLC) using chiral stationary phase and kinetic resolution. An alternative is the use of synthetic enantioselective membranes to transport selectively a desired enantiomer from the racemic mixture. The advantages of membrane techniques over traditional methods are their ease of use, low-energy consumption, large processing capacity, continuous operation mode, etc. The membranes used for chiral separation can be liquid, including supported liquid membranes, or solid. The liquid membranes [1-3] containing enantiomer recognizing carriers such as chiral crown ether or cyclodextrins show highly enantioselective permeability but usually low durability because of losses of the liquid and carriers. This greatly limits their applications to a large extent. Solid membrane is more stable and therefore a durable enantiomer separation process is possible. Solid membranes for enantioselective processes can be categorized into several types:

2 42 XXIII ARS SEPARATORIA Toruń, Poland 2008 a) chiral polymer membranes, obtained by polymerization of chiral monomers (e.g. chirally derived polysulfone [4,5], chiral polysaccharides, e.g. chitosan, polyglutamates, etc. [6-8]), b) membranes with immobilized chiral selectors, such as cyclodextrins, chiral ligands or proteins, e.g. BSA, incorporated into nonchiral membranes [9-11] c) molecularly imprinted polymer membranes [12]. A molecularly imprinted polymer (MIP) is a synthetic polymer possessing selective molecular recognition properties because of recognition sites within the polymer matrix that are complementary to the analyte molecule in the shape and positioning of functional groups. d) Polymer membranes with immobilized chiral catalysts, mostly enzymes, have been used widely for kinetic resolution of enantiomers [e.g ]. A kinetic resolution is defined as a process where the two enantiomers of a racemate are transformed into products at different rates. The ideal enantioselective membrane should combine good transport rate with high selectivity. However, it is well known, that usually higher transport rates imply low selectivities and vice versa. It is important therefore to find a good compromise to optimize the separation process. A variety of chiral selectors have been employed in enantioselective membrane separation including tartaric acid derivatives, chiral crown ethers, cyclodextrins, quinine-type compounds, hydroxyproline derivatives etc. The chiral selector can be immobilized on membrane covalently or just by entrapping it during membrane formation. The first method needs additional immobilization procedure, but it gives more stable membrane avoid the loss of the selector during the process. In this work, a few examples of enantioselective membrane separations by chiral selectors immobilized in solid membranes has been discussed. 2. PREPARATION AND CHARACTERISTICS OF CHIRALLY MODIFIED MEMBRANES 2.1. PREPARATION OF A CINCHONIDINE IMMOBILIZED MEMBRANE Application of optically pure alkaloids as resolving agents is a very useful method of racemic resolution. These alkaloids react with racemic acids to form diastereomeric salts of differing solubility. (-)-Cinchonidine is also an alkaloid used frequently in catalytic asymmetric hydrogenations as a chiral metal surface modifier. It has been applied as a chiral carrier in separation of amino acids in liquid membrane system [1]. The anchorage of

3 XXIII ARS SEPARATORIA Toruń, Poland cinchonidine to an inorganic suport such as silica can be used to allow its application in continuous processes. Scheme 1. Scheme of (-)-cinchonidine molecule. The commercial ceramic UF disc membrane was modified by depositing a thin layer of silica of define pore size. Mesoporous silica of pore diameter Å was obtained by sol-gel method with nonionic surfactants of varying length of alkyl chain. The chiral selector was then immobilized covalently on the inner surface of the pores using triethoxychlorosilane. Membranes of varying pore sizes and ammount of the chiral selector immobilized were thus obtained. The membranes were used in enantioseparation of phenylalanine. Fig.1. Immobilization of a functionalized cinchonidine in the pores of a ceramic membrane.

4 44 XXIII ARS SEPARATORIA Toruń, Poland RESULTS The transport rate for both amino acid enantiomers through chiral activated membrane, and the membrane enantioselectivity were estimated. The typical results were depicted in Fig.2. Fig.2. Enantioselectivity of the permeated phenylalanine vs. time of the process at varying amino acid initial concentration. The effect of the active layer pore size at similar chiral selector loading per cm 2 of the active surface is shown in Table 1. Enantioselectivity of the membrane increases slightly with decreasing pore size and membrane permeability. It is understandable, as chiral membrane discriminate enantiomers through their interactions with the chiral selector attached to the pore wall. Small pores enable better contact between the solute and the chiral residue. Table 1. Enantioselectivity of membranes with immobilized cinchonidine for various pore sizes. Pore diameter Amount of immobilized [nm] CD [mg/m 2 ] α α a Calculated as a ratio of L and D-isomer fluxes, respectively.

5 XXIII ARS SEPARATORIA Toruń, Poland METHYL-β-CYCLODEXTRIN IMMOBILIZED MEMBRANES Cyclodextrins (CD) are cyclic oligosaccharides consisting of d-(+)- glucopyranose units, and have the ability to include various organic molecules in the central hydrophobic cavities. Currently, chiral separation is one of the most significant applications of cyclodextrins and their derivatives. Compared with other chiral selectors, cyclodextrins have a relatively lower cost, wider applicability and higher tolerance under various environments. Usually, the immobilization of cyclodextrin onto the solid membrane could be achieved by adding cyclodextrin into membrane casting solution, as well as by covalent binding between cyclodextrin and support. In the present work, both methods were applied. A polymer membrane with Met-β-CD was prepared by casting a polyamide solution containing ca. 2% (w/w) of methyl-β-cyclodextrin. As a result, an UF membrane with asymmetric structure was obtained. Methyl-β-cyclodextrin was also immobilized covalently in a silica layer of a ceramic flat membrane according to the procedure analogous as for cinchonidine. Selective properties of the Met-β-CD-modified membranes were studied in separation of 1-phenylethanol and its ester RESULTS The polymer membrane with Met-β-CD immobilized by simple entrapping exhibited enantioselectivity ca What is more important, selective properties of the membrane seemed to decrease with time (Fig.3). The reason of such a behaviour could be leaching of the chiral selector from the membrane during the process. The membrane with CD derivative immobilized covalently was more stable. After 5 runs enantioselectivity was practically the same and was higher than in the case of a Met-b-CD immobilized polymer membrane.

6 46 XXIII ARS SEPARATORIA Toruń, Poland 2008 Fig.3. Enantioselectivity of the separation of (R,S)-1-phenylethylpropionate in the Met-β-CD immobilized membranes. 3. CONCLUSIONS Immobilization of a chiral selector in a porous membrane is one of the methods to provide enantioselective transport of enantiomers through the membrane. Enantioselectivity of such a system depends on character of a selector, its loading density, method of immobilization, membrane pore size and its transport properties. REFERENCES [1] D. Stella, J.A. Calzado, A.M. Girelli, S. Canepari, R. Bucci, C. Palet, M. Valiente, J. Separation Sci. 2002, 25(4), 229. [2] P.J. Pickering, J.B. Chaudhuri, J. Chem. Eng. Sci, 1996, 52 (3), 377. [3] M. Bryjak, J. Kozlowski, P. Wieczorek, P. Kafarski, J. Membr. Sci. 1993, 85, 221. [4] T. Gumi, C. Minguillon, C. Palet, Polymer 2005, 46, [5] M. Yoshikawa,, K. Murakoshi, T. Kogita, K. Hanaoka, M.D. Guiver, G.P. Robertson, European Polym. J. 2006, 42, [6] C. Thoelen, M. De bruyn, E. Theunissen, Y. Kondo, I.F.J. Vankelecom,P. Grobet, M. Yoshikawa, P.A. Jacobs, J. Membr. Sci. 2001, 186, 153. [7] J.H. Kim, J.H. Kim, J. Jegal, K-H. Lee, J.Membr. Sci., 2003, 213 (1-2), [8] H. Swapnali, J. Membr. Sci. 310 (2008) 174. [9] S.E. Snyder, J.R. Carey, W.H. Pirkle, Tetrahedron 2005, 61, [10] Y. Xiao, T.-S. Chung, J. Membr. Sci. 2007, 290, 78. [11] Y. Matsuoka, N. Kanda, Y.M. Lee, A. Higuchi, J. Membr. Sci. 2006, 280, 116. [12] Z. Jiang, Y. Yu, H. Wu, J. Membr. Sci. 2006, 280, 876. [13] S.-D. Choi, G.-J. Kim, Catalysis Letters, 2004, 92, 35.. [14] D.R. Wu, S.M. Cramer, G. Belfort, Biotechnol. Bioeng. 1993, 41, 979. [15] J. Ceynowa, I. Koter, Sep. Sci. Technol. 2001, 36 (13), 2885.