Study On Synthesis And Chiral Recognition Ability Of Cellulose Phenylcarbamate Used As Chiral Stationary Phase

It is well know that a pair of optically pure enantiomers have exhibited quite different toxicological and pharmacological behaviors, bioactivities, etc. The separation or resolution of enantiomers have beome very import in many fields of sicence, for example intermediates, natural products, agrochemicals and drugs. In recent decades, the chromatographic techniques for the separation of enantiomers are developed extensively. The high-performance liquid chromatography (HPLC) method has become most advantageous for the research and development of chiral drugs, which is essential for analysizing the optical purity of enantiomers and preparing separation for a large scale. Among many chiral stationary phases (CSPs), the polysaccharide derivatives, such as the phenylcarbamayes of cellulose and amylose exhibit broad applicability to a wide range of compounds. In order to resolve the chiral compound better, more new CSPs have been attracting much attention.In order to widen the chiral recognition range of chiral compounds, three new cellulose phenylcarbamate derivatives, [6-(3,5-dichlorophenyl)-2,3-bisphenyl]carbamates (CSP-1), [6-(3,5-dichlorophenyl)-2,3-bis(4-methylphenyl)] carbamates (CSP-2) and [6-(3,5-dichlorophenyl)-2,3-bis(4-chlorophenyl)] carbamates (CSP-3) were synthesized and used as the chiral stationary phase for high-performance liquid chromatography (HPLC) after coating on aminopropyl silica gel. The synthesis involved the protection and deprotection of 6-position using triphenylmethyl chloride, which can predominantly react with 6-OH of cellulose. The chiral recognition ability of obtained derivatives was evaluated using 10 racemates and a hexane/2-propanol (90:10, v/v) mixture as the eluent. The result showed that most of racemates were better resolved on the new derivatives than on the typical homogeneously substituted phenylcarbamate derivatives, tris(3,5-dimethylphenylcarbamates), tris(3,5-dichlorophenylcarbamates), tris(phenylcarbamates), tris(4-methylphenylcarbamates) and tris(4- chlorophenylcarbamates), some of which are well known due to their high ability. Especially compound 7 not resolved on CDMPC could be seperated better on CSP-1, CSP-2 and CSP-3, and compound 3 not resolved on CTPC is able to obtain baseline separation (separation factorαis 1.38), andαvalue (1.95) of compound 2 on CSP-3 andαvalues of compound 4 on CSP-1 (2.06) and CSP-3 (1.81) are much higher than those on CDMPC and CDCPC. It indicates that the chiral recognition on the phenylcarbamate derivates is influenced by the electron-donating methyl group or electron-withdrawing halogen at r-position of the phenyl ring introduced at 2-,3-and 6-site.Because the coated CSPs can be sissolved or swelled by some organic solvents, such as THF, chloform, toluene, ethyl acetate, and acetone, which is sometimes essential for efficient analytical and preparative resolution of enantiomers, several immobilized polysaccharide-based CSPs have been prepared. In this study, the tri-(3,5-dichlorophenylcarbamates) of cellulose (CDCPC) bearing a small amount of 3-(triethoxysilyl) propyl residues (1.2%,1.7% and 3.0%) were synthesized by a simple process (one-pot method) and efficiently immobilized onto a silica gel through intermolecular polycondensation of the triethoxysilyl groups. The obtained chiral packing materials (CPMs) were evaluated by high-performance liquid chromatography with the polar solvents (THF and chloform) in the mobile phase, and compared with CDCPC. The results indicate that the new immobilized CSPs enhance the chiral separations, separation factor (chiral recognitions) for most of the racemates were immproved to different degrees. Even compound 3 can be resolved well on CSP-5 when using H/T (70/30) and H/T/I (90/10/1) as eluents, which couldn't be chiral recognized when the traditional mobile phase H/I (90/10) is used. The immobilized columns expand the kind of solvents which can be used as the eluent and have long life. We expect that the immobilized CSPs will become more popular and will replace the coated-type CSPs.In this study, we discovered a new method, exchange reaction, for obtaining the phenylcarbamates derivatives with different phenylcarbamate groups. Using the exchange reaction method, new phenylcarbamate derivatives containing 3,5-dichloropnenyl carbamate and 3,5-dimethylphenyl carbamate were synthesized, and their chiral recognition ability were studied used as CSPs. It is proved that the stability of cellulose derivatives, reaction time and reaction solvents can affect the reaction end and exchange degree of the exchange reaction. Because CDMPC has more stability than CDCPC, CDCPC is almost completely replaced by CDMPC when CDCPC reacts with DMPI, and the reaction end reaches at 13 h. Since the exchange reaction occurrs on the 6- site of cellulose first, the contents of two carbamate groups at 2-,3- and 6-positions can be controlled by changing reaction time. But only 3.0% CDCPC is changed by CDMPC when pyridine is used as solvent, and 24.6% CDCPC is substitute when DMSO is used as solvent and the reaction end occurrs at 44h. The result showed that the operation of exchange reaction is simple and convenient, and overcomeing the shortcomings of the waste of isocyanate and expensive the protection agents, various new derivatives with different carbamate groups at the three positions can be easily synthesized by changing the reaction conditions, and the cellulose derivatives obtained by exchange reaction can provide new chiral packing materials with interesting chiral recognition abilities.