Chiral discrimination of aliphatic amines and amino alcohols using NMR spectroscopy

Abstract

Two methods are compared for analyzing the enantiomeric purity of aliphatic amines and amino alcohols using NMR spectroscopy. The first employs (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating agent in methanol-d(4) . The second involves a derivatization scheme in which the amine is reacted with naphtho[2,3-c]furan-1,3-dione to form the corresponding amide. The naphthyl amide is then mixed with a chiral calix[4]resorcinarene in deuterium oxide. The crown ether only produces sufficient enantiomeric discrimination to determine enantiomeric purity for three of the nine substrates studied. The system with the naphthyl amide and a calix[4]resorcinarene produces enantiomeric discrimination of sufficient magnitude to determine enantiomeric purity for all nine substrates. The H1 and H4 resonances of the naphthyl ring are especially suitable to monitor for enantiomeric discrimination. The order of the (R)- and (S)-enantiomers of the H1 and H4 resonances exhibit specific trends for aliphatic amines and amino alcohols that correlate with the absolute configuration.