title: Studies on quinazolines. 11. Intramolecular imidate-amide rearrangement of 2-substituted 4-(omega-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.
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan, Republic of China.
authors.forename: Grace Shiahuy
authors.initials: GS
authors.lastname: Chen
authors.forename: Shivaramayya
authors.initials: S
authors.lastname: Kalchar
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Kuo
authors.forename: Chih-Shiang
authors.initials: CS
authors.lastname: Chang
authors.forename: Cyril O
authors.initials: CO
authors.lastname: Usifoh
authors.forename: Ji-Wang
authors.initials: JW
authors.lastname: Chern
mesh_terms: D000478:Alkylation; D020650:Combinatorial Chemistry Techniques; D007202:Indicators and Reagents; D009584:Nitrogen / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D011799:Quinazolines / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature
chemical_list: D007202:Indicators and Reagents; D011799:Quinazolines; D009584:Nitrogen; D010100:Oxygen