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

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.