Preparation and application of an (S)-naproxen chiral stationary phase

A chiral stationary phase (CSP) for the liquid chromatographic separation of enantiomers was prepared by immobilizing the 3,5-dimethylanidide derivative of (S)-naproxen on silica gel through the 6-methoxy-2-naphthyl functionality of (S)-naproxen. The enantioselectivities exerted by this π-basic CSP for resolving π-acidic racemates were generally greater than those on the previously reported CSPs prepared by immobilizing an alkylamide of (S)-naproxen on silica gel through the alkylamide functionality. Based on the chromatographic resolution trends, two chiral recognition mechanisms are proposed. One mechanism applied for the resolution of N-(3,5-dinitrobenzoyl)-α-amino esters is proposed to utilize the 6-alkoxy-2-naphthyl group of the CSP as a π-basic interaction site for enantioselective π-π complexation with the 3,5-dinitrobenzoyl group of the analyte and the other mechanism is proposed to utilize the 3,5-dimethylanilide group of the CSP in resolving N-(3,5-dinitrobenzoyl)-α-arylalkylamines.