Synthesis Of Cellulose Derivatives As Chiral Stationary Phases (CSPs) For High-performance Liquid Chromatography (HPLC) Through Exchange Reaction

Chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC)has been considered as one of the most powerful tool for the analysis of enantiomercompositions as well the preparation of optical pure enantiomers due to its properties ofefficient and directive chiral separation. Among these CSPs for HPLC, the phenylcarbamates(PCs) derivatives of cellulose-based CSPs are continuously focused in the research field ofchiral separation because of their high chiral recognition ability and wide application. Thereare few reports published about the synthesis of the polysaccharides-based CSPs withdifferent substituents by the exchange reaction of the carbamates with correspondingisocyanates.In this paper, phenylcarbamate derivatives of cellulose containing two differentcarbamate groups whose contents could be controlled at2-,3-and6-positions of glucoseunits were synthesized by the exchange reaction of cellulose-tris(3,5-dichlorophenyl-carbamate)(CDCPC) with different phenyl-type isocyanates, and base on the research a newmethod was introduced to explore the effect of the substituents on the optical resolutioncapability of the cellulose derivative CSPs, moreover, this approach has important theoreticalresults and research value for the advantages of simplicity, save time and conserve resources.Firstly, some of the solvents and reagents that used in the experiment were purifiedthrough the method of vacuum distillation. To characterize the the experimental results, FT-IRand1H NMR spectra were measured, respectively. To prepare for the following experiments,CDCPC, CDMPC, CTPC, CTMPC and CTCPC were synthesized according to the traditionalmethod.Secondly, the thermostability of3,5-dichlorophenyl isocyanate (DCPI) and3,5-dimethyl-phenyl isocyanate (DMPI) in solvents (or no solvent) were estimated, and the effects on thestability of the isocyanates by substituents’electronegativity on the phenyl rings werecompared. The stability of CDCPC in different solvents was investigated, and the influence ofthe acidity or alkalinity of the solvents on the rate of dissociation of CDCPC was discussed.Then, the exchange reaction of CDCPC with phenyl-type isocyanates were studied, andthe influences of the reaction conditions such as the sorts of solvents, the content of catalyst(LiCl), the kind of substituents on the phenyl groups of the isocyanates were investigated. The results were indicated: the rate of the exchange reaction of CDCPC with DMPI increased asthe basicity of the solvents decreased, and the rate-determining step was the nucleophilicaddition reaction, moreover, the exchange reactivity at each position of glucose unit is muchdifferent, the reactivity of6-position is highest,2-position is lower, while3-position is theworst; Lithium chloride (LiCl) catalyzes the exchange reaction of CDCPC with DMPI in eachselected solvents, especially in the dehydrated Pyridine. As increased of the amount of LiCl,the rate of exchange reaction of CDCPC with DMPI was promoted in Pyridine/LiCl system;the electron-donating power of the substituents on the phenyl rings of the isocyanates greatlyinfluenced the rate of exchange reaction of CDCPC with phenyl-type isocyanates, the powerstronger, the rate faster.Finally, cellulose derivatives (from CSP-1to CSP-5) containing different content ofDMPCR group were synthesized by exchange reaction. The coated-type chiral stationaryphases for reversed-phase HPLC were prepared by coating the CDCPC、from CSP-1toCSP-5and CDMPC onto the surface of silica gel, then, the influence of the content ofDMPCR on the chiral separation ability was evaluated by ten typical racemates withacetonitrile/water (AcN/H2O,60/40, v/v) as mobile phases and the separation behavior ofracemates on CSP-2and CSP-3and their retention time was investigated according toincrease the content of AcN. The results showed that from CSP-1to CSP-5containingdifferent content DMPCR exhibit better chiral recognition abilities compared to CDCPC, andthe chiral recognition abilities of a variety of racemates changes regularly with the increase ofthe introduction content of DMPCR. The retention and separation behavior of racemates onCSP-2and CSP-3was greatly influenced by the content of AcN in mobile phases. Withpromoting the polarity of mobile phases, the retention time of racemates increased both onCSP-2and CSP-3and the separation factor () changed gradually.