Enantioseparation and Chiral Recognition Mechanism of Two Novel Organic Phosphonate Derivatives on Chiral Stationary Phases

Abstract

Direct enantiomeric resolution of two synthesized organic phosphonate derivatives [(2‐Chloro‐phenylamino)‐(2‐hydroxy‐phenyl)‐methyl]‐phosphonic acid diethyl ester (compound 1) and [(2‐Chloro‐phenyl)‐(4‐fluoro‐phenylamino)‐methyl]‐phosphonic acid diethyl ester (compound 2) has been achieved using hexane as the mobile phase with various alcohols as modifiers. The influence of the mobile phase composition and solute structure on the chiral separation was studied. It was found that compound 1 achieved good separation on (S,S)‐Whelk‐O1, cellulose tris(3,5‐dimethylphenylcarbamate) (CDMPC) and cellulose trisphenylcarbamate (CTPC) chiral stationary phases, while compound 2 could be separated on (R,R)‐3,5‐dinitrobenzoyl‐1,2‐diphenylethane‐1,2‐diamine((R,R)‐DNB‐DPEDA) and CDMPC chiral stationary phases. Interestingly, on cellulose derivative chiral stationary phases (CSPs), acidic additive was necessary for enantioseparation of compounds 1 and 2. The chiral recognition mechanism of (S,S)‐Whelk‐O1, (R,R)‐DNB‐DPEDA and cellulose derivative CSPs was explored. On (S,S)‐Whelk‐O1‐CSP, hydrogen‐bonding interactions play an important role in chiral recognition. On (R,R)‐DNB‐DPEDA‐CSP, the dipole‐dipole interactions and π‐π stacking are important to chiral discrimination. On (S,S)‐Whelk‐O1‐CSP and (R,R)‐DNB‐DPEDA‐CSP, a correlation is concluded between elution order and absolute configuration of the analytes. On cellulose CSPs, the inclusion and fitness of solute shape in the chiral cavity significantly contributed to the enantioseparation of solutes. Furthermore, as for the enantioseparation of compound 1, the hydrogen‐bonding interactions play an important role on CTPC, but play a minor role on CDMPC.

Keywords:

• Organic phosphonate derivatives
• chiral recognition mechanism
• (S,S)‐Whelk‐O1
• (R,R)‐DNB‐DPEDA
• CDMPC
• CTPC

We are grateful to Prof. Dr. Kinkel at the Georg‐Simon‐Ohm University of Applied Science (Nürnberg, Germany) for providing (S,S)‐Whelk‐O 1 chiral column and (R,R)‐DNB‐DPEDA chiral column. We also thank the Zhejiang Chemical Industry Research Institute for donating the solutes.