1H NMR Spectral Simplification with Achiral and Chiral Lanthanide Shift Reagents. Mexiletine

Abstract

Abstract The 60 MHz 1H NMR spectra of mexiletine, 1-(2,6-dimethylphenoxy)-2-propanamine, 1, have been studied at 28° in CDCl3 solution with the achiral reagent, tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium(III), 2, Eu(FOD)3, and the chiral reagents tris[3-(trifluoromethylhydroxymethylene)-d-camphorato]europium(III), 3, Eu(FACAM)3, and tris[3-(heptafluoropropylhydroxymethylene)-d-camphorato]europium(III), 4, Eu(HFC)3. Substantial lanthanide-induced shifts were seen for the proton signals of 1 with each reagent. Appreciable enantiomeric shift differences were seen for both methyl signals and for each of the CH2CH proton signals using 3 and 4 that should permit direct determinations of enantiomeric excess for samples of 1. A predominant conformation for 1 is suggested based on observed splittings of the CH2 proton signals and their relative lanthanide-induced shifts.