Waste-minimized, solvent-free and continuous flow synthesis of α-ketoamides from aryl methyl ketones using recyclable CuBr2 catalyst, via bromo intermediate

Abstract

The α-ketoamide functional groups are abundant in a variety of drug molecules such as tacrolimus (immunosuppressant), boceprevir (antiviral), telaprevir (antiviral), and varespladib (anti-inflammatory). Molecular oxygen is an environmentally benign and cost-effective oxidant. The Solvent-free synthesis reduces environment pollution and cost of pharmaceuticals manufacturing. A new copper(II) bromide catalysed method for the synthesis of α-ketoamides from aryl ketones and amines, in presence of molecular oxygen, in a solvent-free condition is reported. This is the first copper(II)bromide-catalysed synthesis of α-ketoamides which proceeds via a bromo intermediate, in comparison to traditional copper(I)-catalysed reaction (enamine intermediate). The CuBr2 catalyst was recovered and successfully recycled. The reaction was performed in a continuous flow reactor to reduce the time of reaction (residence time: 20min).