1H 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 1H NMR spectroscopy with chiral Eu(lll) 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 nonequivalency In the 1H NMR spectrum. Optimum complexing conditions corresponded to concentrations of substrate and Eu(hfc)3 of 0.1 M each in CDCI3. In this matter, the enantiomeric ester-methyl protons and α-methyl protons yielded well-resolved resonance signals of utility in the measurement of enantiomeric compositions. Recovery studies demonstrated that the proposed method Is quantitative.