Technical Notes Anal. Chem. 1995, 67,4437-4439
6A,6B=~-Cyclodextrin-Hexasiloxane Copolymers: Enantiomeric Separations by a /?-Cyclodextrin-ContainingRotoxane Copolymer Jerald S. Bradshaw,*it Zhen Chem,t Guoliang Yi,t Bryant E. RossHer,t~il Abdul Malilt,* Dongjin Pyo,e Hao Yun,t Delbert R. Blaclqt 8. Scott Zimmennan,t Milton L. Lee,*it Weida Tong,l and Valerian T. D%o& Department of Chemistty and Biochemistty, Brigham Young University, Provo, Utah 84602, and Departments of Chemistry, University of South Florida, Tampa, Florida 33620, Kangweon National University, Chuncheon 200-701, Korea, and University of Missouri-St. Louis, St. Louis, Missouri 63 121-4499
GA,6B-Bis-O-[p-(allyloxy)phenyllper-O-methyl-B-cyclodextrin, prepared from /?-cyclodextrin(CD) by a five-step process, has two isomeric forms. Form A has the two A p-(allyl0xy)phenylsubstituents directed away fromthe CD cavity, while form B is a rotoxane with one p-(alIyloxy)phenyl group in the CD cavity. CD-hexasiloxane copolymers were prepared by treating each form with ,, .., ... ..,...,.. ~- 1,1,3,3,5,5,7,7,9,9,11,11 -dodecamethylhexasiloxane (with Si-H functions on each end) using a platinum catalyst These copolymericstationary phases were coated on fused silica capillary columns and found to separate enantiomeric solutes in gas chromatography (GC). The copolymer prepared from form A separated both enantiomeric hydrocarbons and polar solutes. Rotomne co. . . . .. . . .. polymer prepared from form B separated only polar Figure I. I H NMR spectra of the two isomers of GA,GB-bis[(allyloxy)solutes. Since form B copolymer is a rotoxme with the phenyl]-substitutedP-cyclodextrin. (A) I H NMR spectrum of the isomer benzene part of the copolymer in the cavity,these results with both (allyloxy)phenyl groups outside the CD cavity (2A). (e) I H show that an open CD cavity is necessary for interaction NMR spectrum of the isomer with one (allyloxy)phenyl group in the and enantiomeric resolution of nonpolar hydrocarbons; CD cavity (28). however, polar solutes interact effectivelywith the polar CD rim or exterior surface.
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Chiral stationary phases (CSPs) are important for the determination of enantiomeric compositions of drugs and other fine organic compounds.'-* 0-Derivatized cyclodextrins (CD) have been used as CSPs in capillary gas chromatography (GC) and supercritical fluid chromatography (SFC) to separate enantiomeric s0lutes.5-~ Initially, the derivatized CD was mixed with polysi+
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loxanes to make a stationary p h a ~ e . ~More - ~ recently, alkene substituted CDs have been chemically bonded to the polysiloxane backbone by a hydrosilylation r e a ~ t i o n . ~We ' ~ have used two methods to prepare CD phases that have defined structures. First, permethylated CDs containing one alkene substituent have been hydrosilylated onto a polysiloxane of known composition and molecular weight.lOJ1These phases provide superior separations
Brigham Young University.
* University of South Florida.
Kangweon National University. University of Missouri-St. Louis. 'I Deceased, February 5, 1995. This paper is dedicated to his memory. (1) Chem. Eng. News 1992,70 (Sept 28), 58. (2) Stinson, S. C. Chem. Eng. News 1994,72 (Sept 19), 38. (3) Pirkle, W. H.; Pochapsky, J. C. Adu. Chromafogr. 1987,27, 73. (4) Allenmark, S. Chromatographic enantioseparation: methods and application, 2nd ed.; Ellis Horwood New York, 1993. (5) Schurig, V.; Novotny, H.-P.]. Chromafogr. 1988,441, 155. (6) Blum, W.; Aickholz, R J. High Resolut. Chromafogr. 1990,13, 515. 5
0003-2700/95/0367-4437$9.00/0 Q 1995 American Chemical Society
(7) Mosandl, A; Rettinger, IC;Fischer, IC;Schubert, V.; Schmarr, H. G.; Maas, B. J. High Resolut. Chromatogr. 1990,13, 382. (8) Fischer, P.; Aickholz, R; Juza,M.; Krimmer, S. Angew. Chem., Int. Ed. Engl. 1990,29, 427. (9) Schurig, V.; Schmalzing,V.; Muhleck, U.; Jung, M.; Schleimer, M.; Mussche, P.; Duvekot, C.; Buyten, J. C.J High Resolut. Chromatog. 1990,13, 713. (10) Yi, G.-L.; Bradshaw, J. S.; Rossiter, B. E.; Malik, A; Li, W.-B.; Petersson, P.; Markides, IC E.; Lee, M. L. 1.0%. Chem. 1993,58, 4844. (11) Yi, G.-L.; Bradshaw, J. S.; Rossiter, B. E.; Malik, A; Li, W.-B.; Yun., H.; Lee, M. L.J. Chromafogr. 1994, 673, 219.
Analytical Chemistry, Vol. 67, No. 23, December 1, 1995 4437
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Figure 2. 6A,6B-~Cyclodextrin-hexasiloxanecopolymer stationary phases.
Most researchers believe that chiral recognition by cyclodex-
trin (CD) requires the formation of an inclusion complex.15J6
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of chiral solutes in capillary GC and SFC.12 Second, we have prepared dialkene-substituted permethylated CDs where the alkene substituents are located in 6A and 6c or 6A and 6" positions on the CD macroring. These dialkene-substituted CDs were hydrosilylated with a hexasiloxane containing an Si-H unit on each end to form CD-hexasiloxane copolymeric stationary phases.13J4 These phases, likewise, provide excellent resolution of enantiomeric organic solutes.12
However, no studies to date have reported results obtained with phases in which the CD cavity was blocked. We have now prepared a CD phase with a benzenecontaining chain passing through the CD cavity. Although this new phase does not resolve chiral hydrocarbon solutes, it does resolve chiral polar compounds which can interact with the polar ether groups on the cavity exterior. New GA,GB-b-CD-hexasiloxane copolymers were prepared by fist preparing the GA,GB-bis-O[P-(allyloxy)phenyl]-substitutedper0-methyl-PCD as shown in Scheme 1. Heptakis(2,Mi-@methyl)b-CD ( l ) I 3 was treated with 2,4diiethoxy-l,5benzenedisulfonyl dichloride, followed by sodium P(ally1oxy)phenoxideto give two p-(ally1oxy)phenyl-substituted K D s (2A,B) in low yields.l7 These materials exhibited very different physical and spectral properties. 2A melted at 202 "Cand gave the partial 'H NMR spectrum shown in Figure 1A. 2B melted at 144 "C and gave the partial 'H NMR spectrum shown in F i e 1B. It is clear from the 'H NMR spectra in Figure 1 that these isomers have very different structures. In particular, the spectra differ in the 6.6-6.9 ppm region, attributable to the aromatic hydrogen atoms, and at 4.364.46 ppm, attributable to the allyl protons. In the latter case, 2A causes one doublet at 4.44 ppm, indicating that the allyl protons are the same, and 2B causes two equal sets of doublets at 4.36 and 4.44 ppm, showing that the two sets of allyl protons are in different environments. The lH NMR spectrum for 2A is much the same as those for the 6A,6c- and sA,P-bis-O-lp-(allyloxy)phenyl]-substituted-P-CDs, which have the two j-(ally1oxy)phenyl substituents directed away from the CD ~avity.'~"~ The 'H NMR spectrum of 2B is similar to that of other CDs containing aromatic host molecules in the CD cavity.18-zoThese data strongly suggest (15) Armstrong, D.W.; Ward, T.J.; Armstrong, R D.; Beesley, T. E. Science
(12) Malik, A;Yun, H.; Yi, G.; Bradshaw, J. S.; Rossiter, B. E.; Markides, K E.; Lee, M. L. J. Microcolumn. Sep. 1995,7, 91. (13) Yi, G.-L.; Bradshaw, J. S.; Rossiter, B. E.; Reese, S. L;Petenson, P.; Markides, K E.; Lee, M. L. j . Org. Chem. 1993,58, 2561. (14) X, G.-L.; Bradshaw, J. S.; Rossiter, B. E.; Malik, A; Yun, H.; Lee, M. L. j. Heterocycl. Chem. 1995,32, 621.
4438 Analytical Chemistry, Vol. 67,No. 23,December 7, 7995
1986,232,1132. (16) Kobor, F.; Angermund, K; %homburg, G. j . High Resolut. Chromatogr, 1993,16,299. (17) Satisfactory spectral and elemental analyses were obtained for all new p-CD derivatives. (18) Inoue, Y.; Kuan, F.-H.; Chujo, R Bull. Chem. Soc. Jpn. 1987,60, 2539.
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Figure 3. Separation of enantiomers on a 15 m fused silica capillary column coated with copolymer 4A (see Figure 2): column temperature, 80 "C;helium carrier gas, P = 0.5 bar; FID detector. (A) a-Pinene, (B) limonene, (C) 2,4-pentanediol,and (D) 2-phenyl-1cyclohexanol.
that one of the (ally1oxy)phenyl substituents of 2B is in the cyclodextrin cavity. When either 2A or 2B was treated with methyl iodide and base, a mixture of pennethylated 3A (mp 100 "C) and 3B (mp 95 "C) was is01ated.I~The 'H NMR spectra for 3 4 B were similar to those of 2A,B, respectively. It is instructive to note that all four compounds are stable at high temperatures and that pure 2A or pure 2B isomerizes to a mixture of 2A,B when heated in base solution, but 3 4 B do not. A molecular modeling study of these systems suggested that, when deprotonated, one of the P(ally1oxy)phenyl-substituted glucose units of the 2 4 B could rotate about its glycosidic oxygen atoms. This would cause 2A,B to convert to the other isomer. When the molecules are not deprotonated, this rotation seems less likely because of internal hydrogen bonding in the CD molecule. Also, steric hindrance by the &@methyl groups makes this rotation less favorable in permethylated 3 4 B . Bisakenes 3 4 B were treated with 1,1,3,3,5,5,7,7,9,9,11,11dodecamethylhexasiloxane(with Si-H functions on each end) and enough 1-octeneto control the molecular weight using a platinum catalyst as reported for similar systems13J4 to form copolymers 4A,B (Figure 2). The lH NMR spectra of these polymers showed that they were different and that 4B probably had a benzene ring ~
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(19) Takahashi, K.; Ohtsuka, Y.; Nakada, S.; Hattori, K. J Inclusion Phenom.
1991,IO, 63. (20) Ndou, T. T.; Mukundan, S., Jr.; Warner, I. M. J. Inclusion Phenom. 1993, 15, 9.
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in the CD cavity. To the best of our knowledge, this is the first rotoxane polymer where the CD is part of the polymer chain. These polymer materials were coated on fused silica capillaries (0.25 pm film thickness) and evaluated as stationary phases in GC. As shown in Figure 3, the stationary phase composed of copolymer 4 .4 readily separated enantiomers of chiral hydrocarbons a-pinene and limonene as well as chiral polar compounds 2,4pentanediol and 2-phenyl-l-cyclohexanol.Figure 4 shows that the phase composed of 4B, in which the CD cavity is blocked, does not separate the chiral hydrocarbons but does resolve the chiral polar enantiomers. These experiments demonstrate that enantiomer resolution can take place either in the CD cavity or on the polar groups outside the cavity, depending on the nature of the solutes. For the fist time, clear evidence is presented that separation of apolar hydrocarbon enantiomers requires inclusion complexation with the hydrophobic CD inner cavity, while polar compounds can be resolved by interaction with chiral sites on the exterior of the CD torroid.
Received for review June 21, 1995. Accepted September 15, 1995.@ AC9506286 e Abstract
published in Advance ACS Abstracts, November 1, 1995.
Analytical Chemistry, Vol. 67, No. 23, December 1, 1995
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