H-1-NMR SPECTROSCOPIC METHOD WITH CHIRAL EU(III) SHIFT-REAGENT FOR THE DETERMINATION OF THE ENANTIOMERIC COMPOSITION OF NAPROXEN

A simple method based on the use of H-1 NMR spectroscopy with chiral Eu(III) shift reagent is described for the determination of (S)-(+)- and (R)-(-)-naproxen In the presence of each other. To enhance the coordinating affinity of the substrate for the lanthanide ion, the sample was first derivatized to a mixture of methyl esters, which in the presence of Eu(hfc)3 formed short-lived diastereomeric complexes with sufficient non-equivalency in the H-1 NMR spectrum. Optimum complexing conditions corresponded to concentrations of substrate and Eu(hfc)3 of 0.1 M each in CDCl3. In this matter, the enantiomeric ester-methyl protons and alpha-methyl protons yielded well-resolved resonance signals of utility in the measurement of enantiomeric compositions. Recovery studies demonstrated that the proposed method is quantitative.