Study On The Resolution And Chiral Discrimination Of Two Chlorine- Substituted Mandelic Acid

3-chloromandelic acid (3-ClMA) and 4-chloromandelic acid (4-ClMA) were resoloved by forming diastereometric salts using optical active (R)-N-(+)-benzyl-a-phenylethylamine ((R)-BPA) as resolving agent in this thesis. Follows were the details:First,3-ClMA was synthesized using phase transfer catalyzed reaction from 3-chlorobenzaldehyde as raw material by the method of dichlorocarbene, which producted from chloroform and concentrated NaOH solution. Method of response surface experiment was applied to optimize the affecting factors in this synthesis. The synthetic 3-ClMA was verified by 1H-NMR.Second, the enantiomers of 4-ClMA and 3-ClMA were base seperated on cyano column, using hydroxypropyl-beta-cyclodextrin(HP-(3-CD) as chiral mobile phase additive. So the method for determing the optical purity of entiomers of 4-ClMA and 3-ClMA was built, and their chromatographic conditions were also optimized.The thesis mainly was focused on the resolution of racemic 3-ClMA and 4-ClMA by optical (R)-BPA through forming diastereomeric salts. The absolute ethanol was considered the best fitting solvent in this procedure. The mole ratio of racemic chlorine-subtituted mandelic acid to (R)-BPA, the volume of absolute ethanol and the filting temperature were optimized by orthogonal experiment. To understand the mechanism of chiral discrimination, the properties of two less soluble salts, (R)-3-ClMA·(R)-BPA and (R)-4-ClMA-(R)-BPA were measured by DSC, XRD,1H-NMR and compared to the same property of two more soluble salts:(R)-3-ClMA·(S)-BPA and (R)-4-ClMA·(S)-BPA. The single crystals of four salts were cultivated and their structures were determined by X-ray four round instrument. The mechanism of chiral discrimination were closely investigated during the resolution based on the structure of single crystal for (R)-3-ClMA-(R)-BPA, (R)-3-ClMA·(S)-BPA and (R)-4-ClMA-(R)-BPA, (S)-4-ClMA-(R)-BPA, which existed in different kind between less soluble salt and more soluble salt. The halogen bond such as Cl……Cl or Cl/π were considered acting an important role in the resolution.