Design, preparation and performance of a phthalide-based chiral stationary phase

Abstract

A phthalide structurally optimized to maximize the chromatographic separability of its enantiomers on chiral stationary phases (CSPs) derived from the N-3,5-dinitrobenzamides of ( S)-leucine and ( R)-phenylglycine was prepared, preparatively resolved, and incorporated into a reciprocal phthalide-based CSP. This CSP, derived from 3-(4′,7′-dimethyl-1′-naphthyl)-3-(undec-10′-enyl) phthalide, has proven to be efficient for the separation of the enantiomers of numerous amino ester, amino amide, amino phosphonate, amino alcohol, amine, and alcohol 3,5-dinitrobenzoyl derivatives. Although not exhibiting the remarkably high degree of enantiomeric separation for some of the aforementioned analytes as some other reciprocal CSPs, the phthalide-based CSP is the most effective CSP to date for the separation of the enantiomers of secondary alcohols as their 3,5-dinitrobenzoates. Specific representative resolutions are presented for each of the aforementioned analyte classes. A study of the resolution of homologous series of α-phenylalkylamine and α-phenylalkanol derivatives is included.