Chiral stationary phase based on chitosan Schiff base derivatives for enantioseparation

Abstract

Chitosan derivatives play an important role in the field of enantioseparation due to their favorable chiral recognition properties. However, the preparation of chitosan derivatives with good chiral separation properties and organic solvent tolerance still needs further exploration. Herein, we report the synthesis of two types of chitosan Schiff bases via condensation reactions between chitosan and halogenated benzaldehydes, and subsequently modified with methyl-substituted phenylcarbamates, resulting in four chitosan-3,6-bis(phenylcarbamate)-2-Schiff base derivatives with high substitution degree. Thereafter, four chiral stationary phases were prepared by coating the chitosan derivatives onto aminopropyl silica gel and assessed for their enantioseparation performance using 20 chiral compounds via high-performance liquid chromatography. Findings show that the best chiral stationary phase recognizes 19 chiral compounds and provides a baseline separation of 10 chiral compounds, including a pharmaceutical intermediate ethyl mandelate (maximum resolution: 4.18) and aromatic amide-type chiral drugs. Based on the strong interaction of molecular forces in the structure of chitosan-3,6-bis(phenylcarbamate)-2-Schiff base derivatives, the chiral stationary phases based on chitosan Schiff base derivatives are tolerant to ethyl acetate and acetone. Furthermore, electronic circular dichroism analysis revealed that substituents at the C2, C3, and C6 positions significantly influenced the secondary structure of chitosan derivatives, and thus correlating with their enantioselectivity.