A high-performance chiral selector derived from chitosan (p-methylbenzylurea) for efficient enantiomer separation

Abstract

N-Methoxycarbonyl chitosan was prepared by selectively modifying the amino group at the 2-position of chitosan with methyl chloroformate, which was further functionalized with p-methylbenzylamine to produce chitosan (p-methylbenzylurea). Then, the hydroxyl groups at the 3- and 6-positions of the glucose skeleton were modified with various phenyl isocyanates, affording a series of chitosan 3,6-bis(arylcarbamate)-2-(p-methylbenzylurea)s, which were characterized and proposed as chiral selectors for enantiomer separation. Nineteen racemates, most of which are drugs or intermediates for drugs, were selected as the model analytes to evaluate the enantioseparation performance. The structure-performance relationship of the chiral selectors was investigated in detail. It was found that the methyl-substituted chiral selectors possessed more preferable enantioseparation performance compared with the chloro-substituted ones, and the chiral selectors containing a methyl substituent at the 4-position of the benzene ring showed the best chiral recognition and separation ability with 17 racemates being recognized and 13 racemates being baseline separated. The prepared chiral separation materials derived from these chiral selectors exhibited favorable solvent tolerance towards ethyl acetate, acetone, chloroform and a low proportion of tetrahydrofuran in normal phase. To sum up, this work provided a useful reference for the design and preparation of high-performance chiral separation materials for efficient enantiomer separation.