Direct Liquid Chromatographic Separation of Enantiomers of Phthalides, Phthalimidines and Related Compounds on Chiral Stationary Phases
The enantiomers of a diverse series of 3-arylphthalides are separable by high performance liquid chromatography on chiral stationary phases (CSPs) derived from the N-3,5-dinitrobenzamides of (S)-leucine or (R)-phenylglycine covalently bonded to aminopropyl silanized silica. A chiral recognition model for the separation of phthalide enantiomers has been formulated based on the observed chromatographic behavior of these phthalides. Assignment of elution orders based on the a priori model proposed are consistent with those ultimately determined by independent chemical and spectroscopic means. A phthalide structurally optimized to maximize the chromatographic separability of its enantiomers on the aforementioned CSPs is incorporated into a phthalide-based CSP which has proven to be effective for the separation of enantiomers of numerous analytes. The chromatographic behavior of a variety of 3-arylphthalimidines and their corresponding ureide derivatives on the amino acid CSPs, as well as a novel procedure for C-3 alkylation without N-2 alkylation of these phthalimidines via conversion to the ureide derivatives, is described. Alkylation of certain enantiomerically pure ureides affords enantiomerically enriched products owing to the self-immolative transfer of chirality from central to axial, back to central chirality. Factors affecting this process are discussed.
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign