NMR Studies of Drugs. Application of Achiral and Chiral Lanthanide Shift Reagents to α-Ethyl-α-Phenylsuccinimide

Abstract

The 60 MHz ¹H NMR spectra of 3-ethyl-3-phenylpyrrolidine-2,5-dione, 1, were studied in CDCl₃ at 28° using the achiral lanthanide shift reagent (LSR) tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium(III), Eu(FOD)₃ 2, for spectral simplification, and the chiral LSR, tris[3-heptafluoropropylhydroxymethylene)-(+)-camphorato]-europium(III), Eu(HFC)₃ 3, to induce enantiomeric shift differences (δδδ) for several nuclei. A non-racemic sample of 1 was treated with 3 to determine the sense of magnetic nonequivalence of selected nuclei. Significant δδδ is seen for the signals of the methyl and aryl ortho protons. Modest δδδ can also be seen for the NH signal and for one of the H-4 protons, although LSR-induced broadening for the two latter signals is severe. The (-) enantiomer appeared to exhibit an upfield sense of magnetic nonequivalence (3:1 molar ratio ca. 0.15—0.35) for the methyl signal but a downfield sense for H_ortho (3:1 ratio ca. 0.6).

Key Words:

• 3-Ethyl-3-phenylpyrrolidine-2,5-dione
• Optical Purity
• Europium
• Stereoisomer
• Enantiomer
• Anticonvulsant
• LSR
• NMR
• Analysis