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

Abstract

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 ε-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.

A guide to direct mechanocatalysis

“…2 Mechanochemistry is accordingly gaining substantial attention with the growing needs for greener approaches in synthetic chemistry. MC is applied in a variety of chemical disciplines with examples ranging from cocrystals, 3 metal-organic frameworks, 4 molecular rearrangement, [5][6][7] materials chemistry, 8 polymer chemistry, 9 porous materials, 10 organic chemistry, 11 biochemistry, 12 pharmaceuticals, 13 API (active pharmaceutical ingredient) 14,15 to energy storage materials. 16 One of the key subjects in the context of green chemistry and one of the major breakthroughs in chemistry in general is catalysis.…”

Mechanochemically Assisted Synthesis of Hexaazatriphenylenehexacarbonitrile

“…Within this contribution, we present a facile, cheap, time-resource-, and energy-efficient alternative based on mechanochemistry. 19 − 28 Compared to the traditional wet-chemical approach, the reaction mixture requires no external heating. The activation energy is provided by the colliding milling balls inside ball mills, and the reactions run in the absence of solvents within minutes.…”

Mechanochemical Organocatalysis: Do High Enantioselectivities Contradict What We Might Expect?

“…This type of reactor technology is very effective at homogenizing reactions mixtures (mixing) and inputting energy in the form of heat and pressure to reaction centres. All of this can be largely achieved in the absence of solvent, and thus the reactor environment of a ball mill is receiving increasing interest in recent times [32–60] …”