Microwave-assisted continuous flow organic synthesis

微波辅助连续流有机合成

• 批准号: 338339-2006
• 负责人: Organ, Michael
• 金额: $ 17.3万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=481962
• 关键词: Microwave; assisted; continuous; flow; organic

The synthesis of new chemical entities is the backbone of discovery in the pharmaceutical, agrochemical, and materials sectors. In the business world, the race to be first to discover is essential in these societally-important areas; this will control the intellectual property (i.e., patent space) and the associated wealth from these efforts. As a result, chemists have strived to develop new reagents, catalysts, processes, and devices in order to make more compounds more quickly, and ideally more structurally diverse to feed into these important research areas. To meet this important demand, this proposal outlines the development of a conceptually new strategy for the simultaneous preparation of organic compounds both very rapidly, and in large numbers. Performing reactions in a flowed format, rather than statically in a conventional batch reaction set up allows for in-process alterations of reaction conditions, such as reaction optimization and in-line processing (analysis or purification) of the products. A potential drawback with flow is that reactions reside in the flow system for a shorter period of time than in a standard batch reactor. If a reaction is kinetically slow, the benefits of flow will be offset by the poor reaction conversion resulting in low yield and purification problems because the product mixture is contaminated with unreacted starting materials. Microwave irradiation is known to dramatically accelerate the rate of chemical transformations; combining microwave with flow will allow the realization of the full benefits of both techniques. Preliminary experiments have shown that reactions flowed through small diameter tubes (capillaries) while being irradiated actually show greater rate enhancement over larger diameter tubes and, we believe, offers the greatest hope for wide acceptance of flow synthesis. This proposal also proposes further advances by combing flow microwave with capillaries loaded with new supported reagents, catalysts, and scavengers through which the reactions flow to allow one-sequence synthesis and purification. Essentially, this amounts to the creation of an automated, multi-step chemical synthesis machine capable of running multiple reactions simultaneously through parallel capillaries.

新化学实体的合成是制药、农用化学品和材料领域发现的支柱。在商业世界中，首先发现的竞赛在这些社会重要领域是必不可少的;这将控制知识产权（即，专利空间）和相关的财富从这些努力。因此，化学家们一直在努力开发新的试剂、催化剂、工艺和设备，以便更快地制造更多的化合物，理想情况下，这些化合物的结构更加多样化，以满足这些重要研究领域的需要。为了满足这一重要需求，该提案概述了一个概念上的新战略的发展，同时制备有机化合物都非常迅速，大量。以流动形式进行反应，而不是在常规间歇反应设置中静态进行反应，允许反应条件的过程中改变，例如反应优化和产物的在线处理（分析或纯化）。流动的潜在缺点是反应在流动系统中停留的时间比在标准间歇式反应器中更短。如果反应在动力学上慢，流动的益处将被差的反应转化率抵消，导致低收率和纯化问题，因为产物混合物被未反应的起始材料污染。众所周知，微波辐射可以显著加快化学转化的速度;将微波与流动相结合将使这两种技术的全部好处得以实现。初步实验表明，反应流过小直径管（毛细管），而被照射实际上显示出更大的速率增强较大直径的管，我们相信，提供了最大的希望，广泛接受的流动合成。该提案还提出了通过将流动微波与装载有新的负载试剂、催化剂和清除剂的毛细管相结合的进一步进展，反应流动通过毛细管以允许单序列合成和纯化。从本质上讲，这相当于创建一个自动化的，多步骤的化学合成机器，能够通过并行毛细管同时运行多个反应。