Process Analytical Technology (PAT) Approaches for Continuous Flow Chemistry

监测、控制和保持过程化学质量的能力是所有化学工业的关键。虽然历史上化学过程已经在批量中预防性地进行，但最近的趋势已经转向连续流化学，因为其合成更安全和更高的效率。 最近，过程分析技术（PAT）已经被开发以允许在现场和真实的时间中执行过程监测。该策略提供了更大量的详细信息，因为数据是在反应条件下获得的。通过研究反应过程中形成的中间体，可以观察到反应中的所有物质，提供机理见解。好处还体现在能够真实的查看系统。这允许在反应期间检测杂质，允许通过最小化杂质形成来鉴定最佳反应条件。 新的PAT和自优化算法的结合将导致更快的优化和更可持续的过程;具有更短的反应时间，更高质量的产品，以及更少的废物产生。本项目的目的是将联合收割机流动化学与PAT技术相结合，以提高化学合成的效率。我们将使用几种不同的PAT方法，并将这些方法与自我优化联合收割机相结合，以减少使用稳态和时间分辨光谱进行工艺开发所需的时间。许多有机反应，特别是光化学反应，涉及一系列基本过程，时间跨度从皮秒到许多秒。在这些时间尺度上应用PAT的能力将成为一种非常强大的优化工具。因此，我们计划将时间分辨光谱应用于光氧化还原和其他反应中所涉及的瞬态物质的过程监测，以提供机理见解，从而促进反应优化和规模扩大。

The ability to monitor, control and maintain the quality in process chemistry, is key to all chemical industry. Whilst historically chemical processes have been performed prevently in batch, recent trends have moved towards continuous flow chemistry, due to its safer and higher efficiency for synthesis. Recently, Process Analytical Technology (PAT) has been developed to allow for process monitoring to be performed both in-situ and in real time. This strategy offers a greater amount of detailed information, as the data is acquired under reaction conditions. All species within the reaction can be observed, providing mechanistic insights, via the study of intermediates formed in the process. Benefits are further seen in the ability to view a system in real time. This allows for impurities to be detected during the reaction, allowing for optimal reaction conditions to be identified by minimising impurity formation. The combination of new PAT and self-optimisation algorithms will lead to faster optimisation and more sustainable processes; featuring shorter reaction times, higher quality products, as well as less waste being produced. The aim of this project is to combine flow chemistry with PAT techniques, to increase the efficiency of chemical synthesis. We will use several different PAT approaches, and combine these with self-optimisation, to reduce the time needed for process development using steady state and time-resolved spectroscopy. Many organic reactions, particularly photochemical ones, involve a sequence of elemental processes spanning a very wide range of timescales from picoseconds up to many seconds. The ability to apply PAT across these timescales would lead to a very powerful means of optimisation tool. Thus, we plan to apply Time Resolved spectroscopies for process monitoring of the transient species involved in photoredox and other reactions to give mechanistic insight, thereby facilitating reaction optimisation and scale up.