Chiral NMR discrimination of piperidines and piperazines using (18-crown-6)-2,3,11,12-tetracarboxylic acid

Enantiomeric discrimination is observed in the (1)H and (13)C NMR spectra of piperidines and piperazines in the presence of (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. The amines are protonated by the carboxylic acid groups of the crown ether to produce the corresponding ammonium and carboxylate ions. Association of the ammonium ion with the crown ether likely involves two hydrogen bonds with the crown ether oxygen atoms and an ion pair with the carboxylate anion. Methyl, hydroxymethyl, phenyl, carboxyl, pyridyl, and cyclohexyl substituent groups alpha to the nitrogen atom do not inhibit binding of the ammonium ion to the crown ether. The NMR spectra of piperidines with the stereogenic center alpha or beta to the nitrogen atom exhibit substantial enantiomeric discrimination. Dibasic substrates such as the piperizines are likely converted to their diprotonated form in the presence of the crown ether, and both nitrogen atoms appear to associate with the crown ether moiety.