Expeditious and environmentally benign synthesis of imidazo[4,5,1-ij]quinolines via sequential Povarov reaction/reductive cyclization

Abstract

In this contribution, a novel, simple, diastereoselective and environmentally benign two-step diversity-oriented synthesis of imidazo[4,5,1-ij]quinolines is described for the first time. The synthesis of the target compounds involves a deep eutectic solvent-mediated one-pot Povarov reaction leading to the obtention of 8-nitrotetrahydroquinolines, followed by a microwave-assisted reductive cyclocondensation employing different aromatic and aliphatic aldehydes. The target compounds were obtained in up to 70% overall yield starting from commercially available o-nitroanilines, natural phenylpropanoids (trans-anethole and trans-isoeugenol) and aromatic or aliphatic aldehydes. The eutectic solvent employed in the first step was reused in four runs without observing a drastic decrease in catalytic activity, and sodium dithionite showed to be an efficient and green reducing agent for the second step. This methodology provides significant advantages in terms of synthetic and green chemistry such as mild reaction conditions, short reaction time, energy-efficiency, simple work-up procedure, low cost, scalability and utilization of renewable substrates and a reusable solvent.