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

合成化学对于生产现有产品和发现未来社会消费的产品都是至关重要的。我们必须继续制造具有新性能和改进性能的分子，以帮助满足全球对“更好”产品日益增长的需求。所有行业都是如此，包括制药、农用化学品、催化剂、纳米颗粒、聚合物、色素、食品添加剂、化妆品等等。然而，这些材料的发现和制造方式必须不断改进，以便人类能够对其地球栖息地负责，我们必须做更多的工作来解决人类生活质量的改善和对生态圈的责任之间的平衡。可持续性是改进化学加工技术和化学合成的关键驱动力。为了挑战现有的实践，必须进一步探索可大大改善可持续性指标的替代技术。对于大多数化学合成来说，一种传统的现有做法是使用溶剂作为进行化学反应的反应介质。这些溶剂是令人难以置信的浪费，因为它们被大量过量使用，通常在使用后焚烧（溶剂回收通常不允许FDA和cGMP流程）；此外，许多溶剂来自化石燃料资源。“机械化学”是一种在没有溶剂的情况下进行反应的方法，即在试剂之间以固态进行反应。进行“机械化学”的装置类似于机械杵和臼，通过快速摇动一个装有研磨球（滚珠轴承）的不锈钢罐，固体物质被磨在一起。关于有机分子的合成，它最近成为一种有用的技术。然而，工业界和学术界的采用相对缓慢。该项目旨在利用无溶剂机械化学技术为化学合成提供新的能力和概念，这些技术将引起工业界和学术界的极大兴趣。此外，该项目将提供如何使用设备的技术演示，并通过视频教程运行这些反应。此外，我们将探索使用连续固体磨削技术（称为连续螺杆挤压）在制造规模上扩大固态有机转化的可能性。具体来说，这个项目将展示有机合成和固态机械化学交叉领域的关键概念，提供：1)获得其他方法无法获得或拖延的分子。我们将通过进行溶剂限制反应（机械化学）来扩大产品的范围，大大减少催化反应过程的反应时间（与传统方法相比），以及使用未精制的地质样品进行催化。3)利用双螺杆挤压装置对固态有机合成反应进行规模化演示。

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.