Conformational effects on the enantioselective recognition of 4-(3,5-dinitrobenzamido)-1,2,3,4-tetrahydrophenanthrene derivatives by a Naproxen-derived chiral stationary phase

Abstract

4-(3,5-Dinitrobenzamido)-1,2,3,4-tetrahydrophenanthrene and derivatives having methyl groups in various positions on the tetrahydro ring were synthesized and resolved on an ( S)-Naproxen-derived chiral stationary phase. The difference in the Gibbs free energy, ΔΔ G, of the transient diastereomeric adsorbates was determined from the chromatographic data. The highest enantioselectivity was observed for cis-4-(3,5-dinitrobenzamido)-3-methyl-1,2,3,4-tetrahydrophenanthrene. Introducing methyl groups into other positions of the tetrahydrophenanthrene ring proved to be detrimental to enantioselectivity. Prior studies indicate that, in the 4-(3,5-dinitrobenzamido)-1,2,3,4-tetrahydrophenanthrene used in the Whelk-O chiral HPLC columns, the 3,5-dinitrobenzamide group occupies a pseudoaxial position, thus forming one wall of a binding cleft owing to its spatial relationship with the naphthyl portion of the selector. The effect of the methyl substituents on enantioselectivity is attributed to their ability to both influence the ‘psuedoaxiality’ of the dinitrobenzamido group and to their ability to sterically hinder the presentation of the ‘back face’ of this group to the Naproxen-derived selector.