Process Analytical Technology (PAT) Approaches for Continuous Flow Chemistry

监测、控制和维护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一直是批量进行的，但最近的趋势是走向连续流动化学，因为它更安全和更高的合成效率。最近，过程分析技术(PAT)已经被开发，以允许在现场和实时地执行过程监控。这一策略提供了更多的详细信息，因为数据是在反应条件下获得的。通过对反应过程中形成的中间体的研究，可以观察到反应中的所有物种，提供机理上的见解。优势进一步体现在实时查看系统的能力上。这允许在反应过程中检测到杂质，允许通过最大限度地减少杂质的形成来确定最佳反应条件。新的PAT和自我优化算法的结合将带来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。本项目的目的是将流动化学与PAT技术相结合，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相结合，以减少使用稳态和时间分辨光谱学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，涉及一系列元素过程，跨越从皮秒到许多秒的非常广泛的时间范围。在这些时间尺度上应用PAT的能力将导致一种非常强大的优化工具。因此，我们计划应用时间分辨光谱对光氧化还原和其他反应中涉及的瞬时物种进行过程监控，以提供机理洞察，从而促进反应优化和放大。

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.