Transition-metal-free reaction sequence on solid base: One-pot synthesis of quinoline derivatives catalyzed by Mg-Al hydrotalcite

Abstract

Quinoline derivatives are important intermediates in the production of pharmaceutical products. Recently, a modified Friedländer quinoline synthesis using stable 2-aminobenzyl alcohols and ketones over transition metal catalysts and inorganic bases have been investigated. In this study, we found that only simple Mg-Al hydrotalcite (HT) was active toward the modified Friedländer quinoline synthesis. Various HT samples were prepared by the co-precipitation method under several pH and Mg-Al ratio conditions. Mg-Al HT prepared at pH 11 exhibited the highest activity among the HT samples and other solid base catalysts. Kinetic and spectroscopic analyses revealed that quinoline formation occurs via base-catalyzed hydrogen transfer between 2-aminobenzyl alcohol and a ketone, followed by the cyclization of the corresponding aldehyde intermediate with a ketone. Mg-Al HT showed wide applicability toward the one-pot synthesis quinoline using various alcohols and ketones and afforded the corresponding products in high yield.