NMR Studies of Drugs. Applications of Achiral and Chiral Wthanide Shift Reagents to Bupropion

Abstract

The ¹H NMR spectra of racemic samples of the antidepressant drug, bupropion, 1, have been studied in CDCl₃ solution at 60 and 200 MHz with the achiral lanthanide shift reagent (LSR), tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium (III), 2, and the chiral reagent, tris[3-(heptafluoropropylhydroxymethylene)-d-camphorato]europium(III), 3. Both LSR produced substantial lanthanide induced shifts consistent with ¹H assignments, but the bound complexes of 1 with 2 versus 3 may not be isostructural. With 3, substantial enantiomeric shift differences were observed for the t-butyl, CH ₃CH, NCH, and the aryl H-2 and H-6 signals, which should permit potential direct determination of enantiomeric excess.

Key Words:

• NMR Shift Reagents
• Enantiomer
• Optical Purity
• Eu(FOD)₃
• Eu(HFC)₃
• Chiral
• Bupropion
• Analysis
• 1-(3-Chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone