Enantioseparation of Organophosphonate Derivatives on Amylose Tris(3,5‐Dimethylphenylcarbamate) Chiral Stationary Phase by HPLC

Abstract

The enantiomers of fourteen O,O‐dialkyl‐2‐benzyl‐oxycarbonyl‐aminoaryl‐ methyl‐phosphonates are directly separated on tris(3,5‐dimethyl‐phenylcarbamate) amylose chiral stationary phases, known as Chiralcel AD. All of the selected compounds are baseline separated. The influence of the position and properties of substituents in benzene rings, the length and steric hindrance of alkoxyl groups of the phosphonate ester on the chiral separation are discussed. When the substituents are in the para‐position of the benzene ring, the separation factor is in the following order α p‐NO2 ≫ α p‐Cl > α p‐CH3 > α p‐H > α p‐OCH3 . When the same substituent is in a different position of the benzene ring, the order of the separation factor is α p‐Cl > α m‐Cl and α p‐NO2 ≫ α m‐NO2 . The values of the separation factor α of the enantiomers where R 1 substituent is a hydrogen (R 1 = H) are always smaller than those of the enantiomers with p‐Cl substituent, whether R 2 was Me, Et, Pr or i‐Pr. Compounds with different substituent R 2 and R 1 where the substituent is H or p‐Cl, the α values always show an order of αPr > αEt > αMe > α i‐Pr. The chiral discrimination in the amylose tris(3,5‐dimethyl‐phenylcarbamate) was based on π–π interaction and H‐bond interaction.