Comparison of HPLC and NMR characterization of the stereogenic properties of cyclotriphosphazene derivatives containing two equivalent centres of chirality: Cis (meso) and trans (racemic) isomers

Abstract

The di-spiro derivatives of the reaction of gem-disubstituted cyclotriphosphazenes, N3P3Cl4X2 (X=Ph, PhS, PhNH, PhO) with 3-amino-1-propanol are expected to exist as cis and trans geometric isomers and exist as meso and racemic, respectively. The geometric isomers were separated by column chromatography on silica gel and analyzed by elemental analysis, mass spectrometry, and 31P and 1H NMR spectroscopies. The stereogenic properties of all the compounds (trans, 2a–5a) and (cis, 2b–5b) were investigated by 31P NMR spectroscopy on the addition of a chiral solvating agent (CSA), (S)-(+)-2,2,2-trifluoro-1-(9′-anthryl)ethanol; one example of a derivative with the trans configuration (compound 5a, X=PhO) has been found where the 31P NMR/CSA method does not lead to the expected separation of the signals of enantiomers, even up to a molar ratio of CSA:compound of 50:1. On the other hand, chiral HPLC methods have been developed in order to characterize the trans (2a–5a) and cis (2b–5b) forms of the cyclotriphosphazene derivatives and give good separation of enantiomers for the trans disubstituted compounds (2a–5a). It is found that chiral HPLC is more reliable than the 31P NMR/CSA method for characterising the stereogenic properties of the cis and trans isomers of di-spiro 3-amino-1-propanoxy cyclophosphazene derivatives.