The Triple Way: Combining Pot, Atom and Step Economy (PASE) for Greener Organic Synthesis

本项目旨在开发一种一锅、原子、步骤经济地合成高取代THPS和哌啶类化合物的方法。原子经济性是指所使用的每种试剂的每个原子都包含在所需的反应产物中。步骤经济是指在合成任何给定的目标分子时减少合成步骤(以及相关废物，如反应中使用的溶剂、加工和产品分离中使用的溶剂、产品纯化中使用的溶剂、层析纯化中使用的硅胶或相关物质、清洁设备和玻璃器皿产生的受污染的含水废物等)的努力。一锅反应将阶梯经济的概念推向了终极结论。这就是在一个锅里完成整个多步骤、多反应合成的能力。如果能够做到这一点，上述强调的浪费问题就会被消除。这些概念的应用体现了绿色化学十二原则中的原则1、2、5和8，并最终将导致理想合成，即一步、一锅、原子经济地从廉价的、可再生的起始材料构建目标分子，产率达到100%。在这个项目中，我们建议将我们在有机分子合成方面的专业知识与诺丁汉大学化学学院在绿色化学方面的一般专业知识相结合。该项目的目的是首次将原子和步骤经济相结合，用于合成中小型分子。首先，我们将该策略应用于四氢吡喃(THP)的合成。其次，我们将把这一策略应用于哌啶类化合物的合成。这些分子对制药、农化和生物技术工业具有相当重要的意义。这项工作既具有冒险性，又具有投机性，因此适合为EPSRC提供资金。然而，如果成功，它将导致更短、更清洁、更环保的合成路线到达这些重要的分子类别。我们要求电子资源中心拨款进行为期两年的原则证明研究的人力和消耗品

This project is aimed the development of a procedure for a one pot, atom and step economic synthesis of highly substituted THPs and piperidines. Atom economy, is the concept of every atom of each reagent being used is included in the desired product of the reaction. Step economy is the drive to reduce the number of synthetic steps (and hence the associated waste such as solvents used in the reaction, solvents used in work-up and product isolation, solvents used in product purification, silica gel or related substances used in chromatographic purification, contaminated aqueous waste generated from cleaning equipment and glassware, etc ) in the synthesis of any given target molecule. One pot reactions take the concept of step economy to its ultimate conclusion. That is the ability to complete an entire multi-step, multi-reaction synthesis in a single pot. If this can be achieved the problems of waste highlighted above would have been obviated. Application of these concepts embody Principles 1, 2, 5 and 8 of the Twelve Principles of Green Chemistry, and should ultimately lead to the `ideal synthesis', which is a one step, one pot, atom economic construction of a target molecule from cheap, renewable starting materials in a 100% yield.In this project we propose to combine our expertise in the synthesis of organic molecules with the general expertise in Green Chemistry in the School of Chemistry at the University of Nottingham. This project is aimed at combining atom and step economy for the first time for the synthesis of small and medium sized molecules. Firstly, we will apply this strategy to the synthesis of tetrahydropyrans (THP). Secondly, we will apply this strategy to the synthesis of piperidines. These molecules are of considerable importance to the pharmaceutical, agrochemical and biotech industries.This work is both adventurous and speculative making it appropriate for EPSRC funding. However, if successful it will lead to shorter, cleaner and greener synthetic routes to these important classes of molecules. We seek CRYSTAL/EPRRC funding for manpower and consumables to carry out a two year proof of principle study