Synthesis, NMR and Crystallographic Studies of 2-Substituted Dihydroquinazolinones Derived from (S)-Phenylethylamine

Abstract

2,3-Dihydro-3-[(S)-1-phenethyl]quinazolinone and some new 2-substitutedderivatives bearing isopropyl, o-nitrophenyl and p-nitrophenyl groups were prepared in40-90% yield by amidation of isatoic anhydride with (S)-phenylethylamine, followed bycondensation with triethyl orthoformate, isopropylaldehyde, o-nitro- and p-nitro-benzaldehyde, respectively. The two 2-subtituted dihydroquinazolinones obtained eitherby using isopropylaldehyde, o-nitro- or p-nitrobenzaldehyde, were separated and purifiedbefore their NMR spectra in CDCl3 solutions were recorded. The detection of the lowenergy conformation of O=C-N-phenethyl segment in solution allowed the correlation ofthe NMR data with the configuration of newly stereogenic carbon C-2; thus, onediastereomer was labeled SS while the other was RS. Configurations determined by theNMR method were corroborated by X-ray diffraction analysis. X-ray structures of eachdiastereomeric series showed characteristic conformational types: a propeller-like for theSS and a hairpin for the RS series. Interatomic distances of the hairpin conformationsuggest the existence of intramolecular face-to-face interactions between two aromaticrings.