NMR Studies of Drugs. Use of Lanthanide Shift Reagents in Polar Solvent with Thalidomide

Abstract

The 200.1 MHz ¹H NMR spectra of thalidomide, 1, have been studied in CD₃CN solution at ambient temperatures with the achiral shift reagent, 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)-(+)-camphorato]europium (III), 3.

The use of sufficiently high LSR:1 molar ratios served to compensate for competitive binding of LSR by the polar solvent, and permitted substantial lanthanide-induced shifts to be observed with 2 or 3. With 3, significant enantiomeric shift differences were produced for the methine NCH multiplets of each enantiomer to be fully separated from one another, offering the potential for direct determination of enantiomeric excess of 1.

Key Words:

• NMR shift reagents
• Europium
• Eu (FOD)₃
• Eu (HFC)₃
• Stereoisomers
• Optical purity
• Enantiomeric excess
• Chiral
• Analysis
• Chelation
• 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3 (2H)-dione