Synthesis, NMR and crystallographic studies of 2-substituted dihydroquinazolinones derived from (S)-phenylethylamine

• Published in: Molecules (Basel, Switzerland) Switzerland), 2007-02, Vol.12 (2), p.173-182
• Main Authors: Escalante, Jaime, Ortíz-Nava, Claudia, Flores, Patricia, Priego, Jaime M, García-Martínez, Cirilo
• Format: Article
• Language: English
• Subjects: Chiral dihydroquinazolinones; configurational analysis; Crystallography, X-Ray; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Molecular Structure; NMR method; Phenethylamines - chemistry; Quinazolinones - chemical synthesis; Quinazolinones - chemistry; π-stacking interactions
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/12020173

2,3-Dihydro-3-[(S)-1-phenethyl]quinazolinone and some new 2-substituted derivatives bearing isopropyl, o-nitrophenyl and p-nitrophenyl groups were prepared in 40-90% yield by amidation of isatoic anhydride with (S)-phenylethylamine, followed by condensation with triethyl orthoformate, isopropylaldehyde, o-nitro- and p-nitro-benzaldehyde, respectively. The two 2-subtituted dihydroquinazolinones obtained either by using isopropylaldehyde, o-nitro- or p-nitrobenzaldehyde, were separated and purified before their NMR spectra in CDCl3 solutions were recorded. The detection of the low energy conformation of O=C-N-phenethyl segment in solution allowed the correlation of the NMR data with the configuration of newly stereogenic carbon C-2; thus, one diastereomer was labeled SS while the other was RS. Configurations determined by the NMR method were corroborated by X-ray diffraction analysis. X-ray structures of each diastereomeric series showed characteristic conformational types: a propeller-like for the SS and a hairpin for the RS series. Interatomic distances of the hairpin conformation suggest the existence of intramolecular face-to-face interactions between two aromatic rings.