¹H NMR Spectral Simplification with Achiral and Chiral Lanthanide Shift Reagents. Ketazolam. Method for Direct Optical Purity Determination

Abstract

The 60 MHz ¹H NMR spectra of racemic ketazolam, 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 and the chiral reagent tris[3-(heptafluoropropylhydroxymethyl- ene)-d-camphoratoleuropium(III), 3. Dramatic differences in lanthanide-induced shifts,Δδ, were observed for the diastereotopic CH₂ protons with either added 2 or 1. Differences in these Δδ valuest as well as differences in lanthanide-induced line broadening and in enantiomeric shift differences (observed with 3) are interpreted in terms of a relatively rigid preferred conformation of 1. Assignments for the CH₂ protons are made. Direct optical purity determinations for samples of l should be possible by use of 3, based on resonances for either of the CH₂ protons or the allylic CH₃.

Key Words:

• Lanthanide
• Shift Reagents
• Enantiomers
• Optical Purity
• Chiral
• NMR
• Europium
• Ketazolam
• Conformation