HCl-mediated cascade cyclocondensation of oxygenated arylacetic acids with arylaldehydes: one-pot synthesis of 1-arylisoquinolines

Abstract

In this paper, a concise, open-vessel synthesis of 1-arylisoquinolines is described via HCl-mediated intermolecular cyclocondensation of oxygenated arylacetic acids with arylaldehydes in the presence of NH₂OH and alcoholic solvents under mild and one-pot reaction conditions. A plausible mechanism is proposed and discussed herein. In the overall reaction process, only water was generated as the byproduct. Various environmentally friendly reaction conditions are investigated for convenient transformation via the (4C + 1C + 1N) annulation. This protocol provides a highly effective ring closure via the formations of one carbon–carbon (C–C) bond, two carbon–nitrogen (C–N) bonds and one carbon–oxygen (C–O) bond.