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

随着人们需要在一种越来越可持续的物质中产生新材料，催化对化学工业的重要性仍在增加。目前，催化剂的设计和优化采用了在反应结束时单独使用的多种技术，这往往会导致较长的开发时间。核磁共振技术因其使用方便、信息量大、内在定量等特点，在化学开发过程中得到了广泛的应用。最近，已经开发了流动核磁共振系统，与将静态溶液放置在光谱仪中相反，溶液可以通过磁体流动。这已被证明在没有反应体系扰动的情况下，快速提供了传统核磁共振方法无法获得的数据。在成功地对有机和均相过渡金属催化反应进行Flow核磁共振后，将继续对更复杂的有机分子、过渡金属络合物和其他多核络合物进行反应监测。在此基础上，将研究系统基本知识的扩展，包括流动条件的影响，以确保取得有意义的结果。还将探索这项技术的实用性，将Flow核磁共振扩展到其他类型的反应，这些反应特别繁琐，难以用传统技术如光化学和电化学进行监测。Flow核磁共振已经表明，它有助于了解催化剂的激活/失活机理，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展过程中通用。随着在开发的早期阶段对催化循环的了解的加深，有可能在学术界和工业研发的许多部门加快化学开发。由于不需要使用多种繁琐的技术来表征，从而缩短了时间框架，使用FlowNMR有可能节省时间和金钱。虽然广泛的化合物是核磁共振活性的，但设计补充技术将是有利的，可以与流动核磁共振结合来实现全面的反应监测。为此，我们将研究开发FlowEPR的可能性，以实时检测、表征和量化顺磁物种，否则仅用Flow核磁共振就无法检测到这些顺磁物种。最终，我们将与我们的工业合作伙伴阿斯利康一起探索使用从Flow核磁共振和/或FlowEPR获得的实时反应进度数据的可能性，通过适当的算法对连续流动系统进行自我调节和自我优化。

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.