Shaken not Stirred: Unleashing the Potential of Solvent-Free Mechanochemical Synthesis

Synthetic chemistry is vital for both the production of existing, and discovery of future products, consumed by society. We must continue to make molecules with new and improved properties to help fuel a growing global appetite for 'better' products. This is true across all industries, ranging from pharmaceuticals, agrochemicals, catalysts, nanoparticles, polymers, pigments, food additives, cosmetics and much more. However, the way in which these materials are discovered and manufactured must continually be improved so that the human population can be responsible for its planetary habitat, we must do more to address a balance between human quality of life improvements and responsibility for the ecosphere.
Sustainability is a key driver for the improvement of chemical processing techniques and chemical synthesis. In order to challenge existing practices, alternative, under-explored techniques that offer greatly improved sustainability metrics must be further explored. One such existing practice that is traditional for most chemical synthesis is the use of solvents as a reaction media for conducting chemical reactions. Such solvents are incredibly wasteful as they are used in vast excesses and typically incinerated after use (solvent recycling is not typically permitted for FDA and cGMP processes); furthermore, many solvents are derived from fossil fuel resources. 'Mechanochemistry' is a method by which reactions can be run in the absence of solvents, i.e between reagents in the solid state. The apparatus for conducting 'mechanochemistry' is akin to a mechanised pestle and mortar, in that the solid materials are ground together by rapidly shaking a stainless steel jar containing grinding balls (ball-bearings). With regard to synthesis of organic molecules, it has recently emerged as a useful technique. However adoption by industry and academia is relatively slow. This project aims to deliver new capabilities and concepts for chemical synthesis using solvent-free mechanochemistry techniques, those that will be of significant interest to industry and academia. Further, the project will deliver technical demonstrations of how to use the equipment and run such reactions through video tutorials. In addition we will explore the possibility to scale up solid-state organic transformations at the manufacturing scale using a continuous solid grinding technique, known as continuous screw-extrusion. Specifically this project will demonstrate key concepts at the intersection between organic synthesis and solid state mechanochemistry, providing, 1) access to molecules that are inaccessible or protracted by other methods. We will broaden the scope of products accessible by conducting solvent-limited reactions mechanochemically 2) greatly reduced reaction times for catalytic reaction processes (compared to conventional methods), as well as catalysis using unrefined geological samples. 3) demonstration of the scale up of organic synthesis reactions in the solid state using twin screw extrusion apparatus.

The aim of this proposal is to develop and demonstrate new concepts in the area of solvent free synthesis using mechanochemical grinding techniques. It is envisaged that by specifically targeting new reactivity; new opportunities for synthetically relevant catalysis and demonstrating the scale-up of solvent free synthesis reactions, awareness and adoption of the technique in both academia and industry will increase. This is a particularly attractive prospect for the synthesis of fine chemicals, pharmaceuticals and agrochemicals where currently for every kilogram of manufactured product there is 25-100 kg of waste to be incinerated, a large proportion of which is waste solvent (solvent recycling is not typically permitted for FDA and cGMP processes). The efficiencies are even worse at the discovery stage. This proposal looks to make an impact at both discovery and manufacturing stages by targeting proof-of-concept demonstrations at each scale level. Further to demonstrating the real power and potential of this method we also wish to prepare demonstration videos of how to set up such reactions so that those unfamiliar (most synthetic chemists) with the technology can have a visual tutorial which will reduce the barrier to adoption of the technique.