Enantioseparation of mandelic acid compounds with Chiralpak AD-H and Chiralcel OJ-H chiral stationary phases

Abstract

Eight mandelic acid compounds were enantioseparated with amylose-based chiral stationary phase Chiralcel OJ-H and cellulose-based chiral stationary phase Chiralpak AD-H, in the normal-phase mode. It showed that Chiralcel OJ-H exhibited higher enantioseparation, and the eight mandelic acid compounds can be baseline separated in 36 min by Chiralcel OJ-H. Also, the substituents in the aromatic ring of mandelic acid compounds have great influence on the degree of difficulty in the resolution of mandelic acids. The negative inductive effect will reduce the retention time of the mandelic acid compounds on the stationary phase while the positive inductive effect will increase the retention time of the mandelic acid compounds. The steric hindrance effect of the substituents is the key factor influencing the success or failure of the resolution. The possible mechanism of chiral recognition is discussed by comparison and analysis of the differences in their structures. Many factors contribute to enantioseparation of the mandelic acids, including the hydrogen bonds, dipole-dipole interactions, pi-pi interactions and spatial adaptability between chiral stationary phases and the mandelic acids. Among them, the spatial adaptability plays a crucial role in the resolution of the mandelic acids. This study provides a reference for the enantiomeric purity determination and resolution of some practical optically active mandelic acid and its analogs.