¹H NMR Spectral Simplification with Achiral and Chiral Lanthanide Shift Reagents. 2-Methyl-3-(2′-Hydroxymethylphenyl)-4(3H)-Quinazolinone, A Major Metabolite of Methaqualone

Abstract

The 60 MHz ¹H NMR spectra of 2-methyl-3-(2′-hydroxymethylphenyl)-4(3H)-quinazolinone, 1, a major metabolite of methaqualone, 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-(heptafluoropropylhydroxy-methylene)-d-camphorato]europium (III), 3, Lanthanide induced shifts, Δλ, are consistent with major LSR binding at the hydroxyl, and the diastereotopic hydrogens of the CH₂ are clearly anisochronous. Substantial Δλ values and spectral simplification are achieved with 2 or 3. Significant enantiomeric shift differences, ΔΔλ, are observed with 3 that should provide direct optical purity determinations of 1. Results are discused in terms of LSR binding sites and hindered rotations about selected bonds in 1.

Key Words:

• Europium
• Optical Purity
• Enantiomer
• Eu(FOD)₃
• Eu(HFC)₃
• Biaryl Hindered Rotation
• Analysis