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.
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.
Chen
Grace Shiahuy
GS
School of Pharmacy, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan, Republic of China.
Kalchar
Shivaramayya
S
Kuo
Chun-Wei
CW
Chang
Chih-Shiang
CS
Usifoh
Cyril O
CO
Chern
Ji-Wang
JW
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
D007202:Indicators and Reagents; D011799:Quinazolines; D009584:Nitrogen; D010100:Oxygen