The Mechanochemical Beckmann Rearrangement: An Eco-efficient Cut-and-Paste Strategy to Design the Good Old Amide Bond

Discovered over a century ago, Beckmann rearrangement is still today fully compliant with all the green chemistry principles and consistent with the key aspects of sustainable development. Herein, we report on a sustainable mechanochemical procedure allowing the design of new amide frameworks via an eco-efficient cut-and-paste process of C-C and C-N bonds on the oxime backbone. We combined inexpensive and readily available reagents, such as p-tosyl imidazole (p-Ts-Im) and oxalic acid, to prepare smoothly and in good to high yields a library of structurally different amides, including value-added marketed compounds such as epsilon-caprolactam and the active pharmaceutical ingredient (API) paracetamol. This solvent-free mechanochemical procedure has also been optimized and successfully extended to several ketones serving as oxime precursors.

Automated summary

The Beckmann rearrangement, discovered over a century ago, remains compliant with green chemistry principles and sustainable development aspects. A sustainable mechanochemical procedure was developed to design new amide frameworks via a cut-and-paste process on the oxime backbone, utilizing inexpensive reagents to prepare various amides, including marketable compounds like epsilon-caprolactam and the API paracetamol, in good to high yields. This solvent-free procedure was also successfully extended to ketones serving as oxime precursors.