Studies on Quinazolines. 11. Intramolecular Imidate-Amide Rearrangement of 2-Substituted 4-(ω-Chloroalkoxy)quinazoline Derivatives. 1,3 -O → N Shift of Chloroalkyl Groups via Cyclic 1,3-Azaoxonium Intermediates

Abstract

The omega-chloroalkylation of 2-substituted quinazolin-4(3H)-one derivatives 1 and 2 with Br-(CH(2))(n)-Cl (n = 2-4) and the intramolecular imidate-amide rearrangement of the alkylated products are described. At room temperature, the 2-phenyl substituent promoted O-alkylation, whereas the less steric 2-benzyl group led to a higher ratio of N-alkylation. The investigation of the O-alkylated products, 4-omega-chloroalkoxyquinazolines, revealed that the migration of omega-chloroethyl and omega-chloropropyl groups from oxygen to nitrogen should be intramolecular via five- and six-membered cyclic 1,3-azaoxonium intermediates, respectively. Competition between rearrangement and nucleophilic substitution results in the formation of 7a,b and 8a,b from the nucleophilic substitution of 4a,b and 6a,b, respectively.

Ab initio and density functional theory studies on vibrational spectra of 3-{[(4-methoxyphenyl)methylene]amino}-2-phenylquinazolin-4(3H)-one

“…Quinazolines are also used for the extraction and analytical determination of metal ions. The intramolecular imidate-amide rearrangement of 2-substituted 4-(chloroalkoxy)quinazoline derivatives have been reported by Chen et al [15]. Sawunyama and Bailey [16] have reported the quantum mechanical study of the competitive hydration between protonated quinazoline and Li + , Na + and Ca 2+ ions.…”

Vibrational spectra and computational study of 3-amino-2-phenyl quinazolin-4(3H)-one

“…The three dimensional quantitative structure activity relation (QSAR) studies for one large set of quinazoline type epidermal growth factor receptor (EGF-R) inhibitors were conducted using two types of molecular field analysis techniques: comparative molecular field analysis and comparative molecular similarity indices analysis [39]. A number of reports have shown that a broad class of 4-anilinoquinazolines are potent and highly selective inhibitors of EGF-R phosphorylation [4,5,42,40,41]. Chen et al [42] reported the intramolecular imidateamide rearrangement of 2-substituted 4-(chloroalkoxy)quinazoline derivatives.…”

“…A number of reports have shown that a broad class of 4-anilinoquinazolines are potent and highly selective inhibitors of EGF-R phosphorylation [4,5,42,40,41]. Chen et al [42] reported the intramolecular imidateamide rearrangement of 2-substituted 4-(chloroalkoxy)quinazoline derivatives. Quantum mechanical study of the competitive hydration between protonated quinazoline and Li + , Na + and Ca 2+ ions are reported by Sawunyama et al [43].…”

Synthesis of Novel Quinazolin-4-one Derivatives Bearing Benzo[c]-chromen-6-one and Their Anti-tumor and Antimicrobial Activities

“…由于路线一无法得到 7-醛基-3,4-苯并香豆素 11 1.2 化合物 3a～3e 和 3b'～3e'的合成 以邻氨基苯甲酰胺(18)和 5-醛基-3,4-苯并香豆素 (13)为原料, 在二甲基亚砜(DMSO)中 [12,13] , 一步简便合 [14,15] 8 Hz, 1H, Ar-H), 7.70 (d,J＝7.8 Hz,2H,7.61～7.66 (m,3H,7.57 (d,J＝6.6 Hz,1H,7.32 (d,J＝ 7.8 Hz,1H,; 13 C NMR (150 MHz, DMSO-d 6 ) δ: 161. 6,159.9,154.3,151.0,148.7,135.0,134.7,133.2,132.2,130.1,130.1,129.5,127.6,127.4,127.2,126.0,125.0,121.6,121.4,119.2,116.2;MS (ESI) 162.0,160.3,155.3,151.9,147.3,135.2,135.0,133.3,132.1,131.3,130.2,129.7,128.0,127.9,127.1,124.3,122.3,…”