Preparation Of Chiral Stationary Phases And Application In Enantiomeric Separation By High Performance Liquid Chromatography

In order to develop Pirkle Type chiral stationary phases (CSPs) of High-Performance Liquid Chromatography(HPLC), eight kinds of amino acid derivatives including chiral amines of (R-(+)-2-methyl-1 -(p-chlorobenphyl)-1 -propanamine andS-(-)-2-2-methyl-1-(p-chlorobenphyl)-l-propanamine) covalated chiral stationary phases have been designed and synthesized, and their application in resolution of enantiomers by HPLC was studied. This eight kinds of novel chiral stationary phases were Ile-VII,-Ile-VII; Leu-VII,Leu-VII; Val-VII, -Val-VII, -XIand IX. The Ile-VII and -Ile-VII CSPs were derivatives of L-isoleucine prepared by covalently bonding to R-(+)amine or S-(-)-amine; The Leu-VII and-Leu-VII CSPs were derivatives of L-leucine prepared by covalently bonding to R-(+)amine or S-(-)-amine; The Val-W and -Val-VII CSPs were derivatives of L-valine prepared by covalently bonding to R-(+)amine or S-(-)-amine; The -XI and IX were derivatives of S-(-)-amime and R-(+)amine directly bonding to aminopropylated mesopore spherical silica gel.These CSPs have been successfully applied to resolve the enantiomers of N-benzoyl-DL-amino acid-methylesters(i.e. DL-leucine, DL-alaline) and DL-acetylphenyalaline-methylester. After comparing the resolution results on those eight of CSPs, it can be concluded that enantioselectivity depend mainly on the interactions of the enantiomers with the chiral selectors of hydrogen bonding and interactions.The cellulose derivative CDMPC of cellulose tris(3,5-dimethylphenylcarbamate) was synthesized under heterogeneous conditions using microcrystalline cellulose (MC). The CDMPC was dissolved in solution and coated on aminopropylated mesopore spherical silica gel by evaporation to prepare the chiral stationary phases for high-performance liquid chromatography.HPLC on a CDMPC column has enabled excellent separation of the enantiomers of sixteen racemic compounds using 2-propanol and hexane as mobile phase, among which the pesticides of ethoxyfen-ethyl, flamprop-methyl, tebuconazole and four impurities, twe impurities of triadimefon arising from its synthesis, twe impurities of metalaxyl, nissorun, 2-(l-hydroxyethyl)-l H-benzimidazole were resolved for the first time. No derivatization of the compounds was required. The results obtained suggest that chiral resolution on CDMPC occurred because the chiral 'grooves' on the CSP provide the chiral environment for enantiomers. Temporary partial inclusion complexes are formed between enantiomers and the CSP, and the stability of these complexes is affected by hydrogen bonding and n-n interactions between the enantiomers and the CSP. Resolution of enantiomers depends on a combination of the steric fit in the chiral grooves of the CSP and the effect of the other interactions.