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-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-nitrobenzaldehyde, 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 CDCl 3 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. Molecules 2007, 12 174

Structural optimization of a retrograde trafficking inhibitor that protects cells from infections by human polyoma- and papillomaviruses

“…In two cases, chiral α-methylbenzylamines (compounds 28-29 ) were used to generate the amide moieties with the hopes of achieving stereochemical induction at the DHQZ aminal stereocenter. 17 The DHQZ-forming reactions of substrates prepared from chiral α-methylbenzylamines yielded configurationally stable products as single diastereomers. The compounds with chiral α-methylbenzylamide groups were more than four-fold less active than the compound with the unsubstituted benzylamide (compound 17 ).…”

Synthesis, Resolution and Absolute Configuration of 2,3-Dihydro-2-<i>Tert</i>-Butyl-3-<i>N</i>-Benzylquinazolin-4-One: A Possible Chiral Auxiliary for Synthesis of <i>β</i>-Amino Cyclohexancarboxylic Acid

“…Our research was focused in the preparation of starting material following the methodology previously reported by our group [11]- [13] in which a reaction between isatoic anhydride and benzylamine in ethyl acetate at 40˚C results in the corresponding aminobenzamide 10 with 90% yield. Next, cyclocondensation of 10 with pivalaldehyde in dichloromethane and p-toluenesulfonic acid monohydrate gives (±)-2,3,dihydro-4(1H)-quinazolinone rac-11 at 86% yield (Scheme 3).…”

“…Optical rotations were determined in a Perkin-Elmer 241 polarimeter at the sodium D-line. 1 H NMR spectra: Varian Oxford 400 MHz, 13 C NMR spectra: Varian Oxford 100 MHz. Chemical shifts (δ) in ppm downfield from the integral TMS reference; the coupling constants (J) in Hz.…”

“…A suspension of isatoic anhydride (10.0 g, 62 mmol) was treated with 1.0 equiv of benzylamine (6.7 mL, 62 mmol) in ethyl acetate according to published procedures [11]- [13]. The reaction mixture was warmed to 40˚C during 1 h. The solution was then concentrated under reduced pressure.…”

Benzodiazepine‐induced photosensitivity reactions: A compilation of cases from literature review with Naranjo causality assessment

“…1 Despite its frequent use, benzodiazepines may not be a well-known cause of photosensitivity due to its low incidence (<1%) and tertiary resources do not consistently list benzodiazepines as a potential cause of photosensitivity. 2,3 Cutaneous photosensitivity reactions occur when drugs, taken systemically or applied topically, increase sensitivity to ultraviolet (UV) rays from the sun and other light sources. 4 Usually, the reaction is initiated by biochemical changes in the patient's tissue subsequent to an exogenous substance absorbing sunlight.…”