Synthesis of dihydroquinazolines from 2-aminobenzylamine: N3-aryl derivatives with electron-withdrawing groups

NADIA GRUBER; JIMENA E. DÍAZ; LILIANA R. ORELLI

BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY

BEILSTEIN-INSTITUT

Año: 2018 vol. 14 p. 2510 - 2519

1860-5397

Sequential N-functionalization of 2-aminobenzylamine (2-ABA) followed by cyclodehydration allowed for a straighforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing EWGs. The sequence involves an initial SNAr displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2-ABA led to the monosubstitution product using equimolar amounts of both reagents. The individual steps were optimized achieving good to excellent overall yields of the desired heterocycles, avoiding additional protection and deprotection steps. A mechanistic interpretation for the cyclodehydration reaction promoted by trimethylsilyl polyphosphate (PPSE) is also advanced on the basis of literature data and our experimental observations