NMR-STUDIES OF DRUGS - APPLICATIONS OF A CHIRAL LANTHANIDE SHIFT-REAGENT TO METHOXAMINE IN CHLOROFORM-D OR ACETONITRILE-D(3)

The H-1 NMR spectra of racemic (erythro) methoxamine free base, 1, alpha-(1-aminoethyl)-2,5-dimethoxybenzenemethanol, have been studied at or near ambient temperatures in CDCl3 or CD3CN with the added chiral lanthinide shift reagent (LSR), tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium(III), 2. Spectrometers operating at 60, 200 and 300 MHz were employed; some COSY spectra were acquired to support assignments. Enantiomeric shift differences (DELTADELTAdelta) were observed for several nuclei of with added 2 in either CDCl3 or CD3CN and an ''anomalous'' (upfield) shift was seen for the NCH signal. A high degree of signal broadening was seen for runs with either solvent, and surprising similarity was found for the slopes in plots of chemical shift versus (2]/[1] molar ratios for the different nuclei of 1 whether the hydrogen bond donor solvent (CDCl3) or the hydrogen bond acceptor solvent (CD3CN) was used. Together with the anomalous shift noted above, these results are interpreted as consistent with strong bidentate chelation of 2 by 1.