Multinuclear High-Resolution Flow NMR for In-Operando Investigation & Self-Optimisation of Chemical Reactions

催化对化学工业的重要性仍在增加，需要以越来越可持续的方式产生新材料。目前，催化剂的设计和优化是在反应结束时分别使用多种技术，这往往导致较长的开发时间。核磁共振（NMR）由于其易于使用、信息量大和固有的定量性质，在化学开发过程中被频繁使用。最近，FlowNMR系统已经开发出来，与放置在光谱仪中的静态溶液相反，溶液可以流过磁铁。这已被证明可以在不干扰反应系统的情况下快速提供传统核磁共振方法无法获得的数据。FlowNMR在有机和均相过渡金属催化反应中取得成功后，将继续对更复杂的有机分子、过渡金属配合物和其他多核配合物进行反应监测。有了这个，扩展系统的基本知识，包括流动条件的影响，将进行调查，以确保获得有意义的结果。对该技术的实用性的探索也将进行，将FlowNMR扩展到其他类型的反应，这些反应通过光化学和电化学等传统技术监测特别繁琐。FlowNMR已经被证明可以帮助理解催化剂的活化/失活机制，识别催化循环中的多种状态，并提供改进的动力学数据。目前还没有一种现成的技术可以在反应发育过程中普遍使用。随着对早期发展阶段催化循环的理解的提高，学术界和工业研发部门的许多化学品开发都有可能加快。不需要使用多种费力的表征技术，也不需要相应的更短的时间框架，使用FlowNMR可以节省时间和金钱。虽然很多化合物都具有核磁共振活性，但设计出与FlowNMR相结合的互补技术来实现全面的反应监测将是有利的。为此，我们将研究开发flowwepr的可能性，以实时检测，表征和量化顺磁物质，否则FlowNMR将无法单独检测到。巴斯新的反应监测设备将与实时质谱、紫外-可见光谱和高效液相色谱等其他技术相结合。最后，我们将与我们的工业合作伙伴阿斯利康（AstraZeneca）一起，探索利用FlowNMR和/或flowwepr获得的实时反应过程数据，使用适当的算法自我调节和自我优化连续流系统的可能性。

The importance of catalysis for the chemical industry is still increasing with the need to generate new materials in an increasingly sustainable matter. Catalysts are currently designed and optimised with multiple techniques used separately at the end of a reaction, which often leads to long development times. Nuclear Magnetic Resonance (NMR) is frequently used during the chemical development process due to its easy use, high information content and inherently quantitative nature. Recently, FlowNMR systems have been developed where, as opposed to a static solution being placed in a spectrometer, a solution can be flowed through the magnet. This has been shown to quickly provide data not achievable from traditional NMR methods with no perturbation of the reaction system. After success with FlowNMR for organic and homogenous transition metal catalysed reactions, continuation of reaction monitoring will take place for more complex organic molecules, transition metal complexes and other multinuclear complexes. With this, expansion of fundamental knowledge of the system, including the effect of flow conditions, will be investigated to ensure that meaningful results are achieved. Exploration of the usefulness of the technique will also take place, extending FlowNMR to other types of reactions which are particularly tedious to monitor by conventional techniques such as photochemistry and electrochemistry.FlowNMR has already shown to aid understanding of catalyst activation/de-activation mechanisms, identification of multiple states in the catalytic cycle alongside providing improved kinetic data. Currently there is not one readily available technique that can be used as universally during reaction development. With improved understanding of catalytic cycles in the early stages of development, there is potential to speed up chemical development across many sectors in both academia and industrial R&D. Without the need to use multiple laborious techniques for characterisation, and the consequential shorter time frames, there is potential to save both time and money with FlowNMR.Although a wide range of compounds are NMR active, it would be advantageous to devise complementary techniques that may be coupled with FlowNMR to achieve comprehensive reaction monitoring. For this purpose, we will look into the possibility of developing FlowEPR to detect, characterise and quantify paramagnetic species in real time that would otherwise go undetected by FlowNMR alone. This, and coupling with other techniques including real-time mass spectrometry, UV-vis spectroscopy and high-performance liquid chromatography will be pursued within Bath's new Reaction Monitoring Facility.Finally, together with our industrial partner AstraZeneca we will explore the possibility of using real-time reaction progress data derived from FlowNMR and/or FlowEPR to self-regulate and self-optimise continuous flow systems using appropriate algorithms.