Ethanol promoted titanocene Lewis acid catalyzed synthesis of quinazoline derivatives

Abstract

An efficient catalytic system involving in situ activation of kinetically inert titanocene dichloride with alcoholic solvent for the synthesis of quinazoline derivatives was developed. 1 mol% Cp₂TiCl₂ at 30 °C afforded 17 examples of quinazoline derivatives with yields of 95–98% in 7–12 minutes. Mechanistic experiments using in situ NMR and HRMS established that the coordination of ethanol to the titanocene moiety released the catalytic species [Cp₂Ti(OCH₂CH₃)₂].