NMR studies of chiral discrimination relevant to the enantioseparation of N-acylarylalkylamines by an (R)-phenylglycinol-derived chiral selector

Recently, it was reported that the chiral recognition ability of (R)-N-3,5-dinitrobenzoyl phenylglycinol derivative was examined as a new HPLC chiral stationary phase (CSP 1) for the resolution of racemic N-acylnaphthylalkylamines. However, the mechanism of chiral discrimination on the CSP remained elusive until now. In this study, a spectroscopic investigation of the chiral discrimination mechanism of CSP 1 was undertaken using mixtures of (R)-N-3,5-dinitrobenzoyl phenylglycinol-derived chiral selector (2) and each of the enantiomers of N-acylnaphthylalkylamines (3) by NMR study. First, the differences in free energy changes (AAG) upon diastereomeric complexation in solution between the complex of each isomer with chiral selector 2 by NMR titration were calculated. The values were then compared with those estimated by chiral HPLC. The chemical shift changes of each proton on the chiral selector and analytes were also checked and it was found that the chemical shift changes decreased continuously as the acyl group on analytes increased in length. This observation was consistent with the HPLC data. From these experimental results, the interaction mechanism of chiral discrimination between the chiral selector and the analytes is more precisely explained.