1H NMR Spectral Simplification with Achiral and Chiral Lanthanide Shift Reagents. Tocainide. Method for Direct Optical Purity Determination and Observation of an “Anomalous” Shift

Abstract

Abstract The 60 MHz 1H NMR spectra of racemic tocainide, 1, have been studied in CDCL3 solution at 28° with the achiral shift reagent, tris(6,6,7,7,8,8,8-heptafluor-2,2-dimethyl-3,5-octanedionato)europiumIII), 2, and the chiral reagent, tris[3- (heptafluoropropylhydroxymethylene)-d-canphorato]- europium(III), 3. Substantial lanthanide induced shifts, Δδ, were served with both 2 and 3, A significant “anomalous” upfield shift for the CH signal of 1 was seen with added 2. The chiral reagent 3 led to appreciable emtiomeric shift differences for the CH3CH and amide NH signals. The potential for direct optical purity determinations of 1 using 3 was demonstrated for a non-racemic (“spiked”) sample of 1, based on the CH3 resonance. The sense of magnetic non-equivalence for these resonances was also determined.