Multi-nuclear operando FlowNMR investigations of catalytic amine formation reactions

在这个项目中，我将应用Bath的动态反应监测设备的Operando光谱功能，以获得对一系列均相催化的胺形成反应(包括亚胺还原、还原胺化、借氢胺化和C-N交叉偶联反应)机理的新见解。方法将是将产物形成动力学(通过RPKA方法在反应过程中进行分析)与在相同条件下获得的催化剂形态分布相关联。这将提供对激活和抑制/失活途径的新见解，以及关于休眠非周期物种的信息。根据CSCT可持续发展的精神，这将有望导致合理开发改进的方案(包括易于操作、促进下游分离、过程质量强度、能源需求、成本和毒性等方面)和在活性、选择性、生产率或稳定性方面效率更高的催化剂。根据CSCT的精神，这些研究有望为均相催化胺形成反应开发更可持续的方案。最后，我们希望在适当的机理洞察的基础上开发新的转化。我们的目标是，在核磁共振专家John Lowe博士和Catherine Lyall的帮助下，开发高效的协议，使多核流动核磁共振谱能够对催化反应进行定量实时监控。这可能包括硬件修改(适应管材、过滤器、反应器、泵、流管尖端等)，这取决于温度、压力、粘度和相行为等条件。以及由感兴趣的反应中间体的浓度和寿命决定的一维和二维脉冲序列的优化。此外，还将使用扩散(剂量)和动态(EXSY，CEST)核磁共振方法，以及与补充技术(如UV-Vis和IR/Raman光谱)的整合和交叉校准，以及根据需要采样HPLC和MS。此外，我们希望开发自动数据分析和量化(如果需要的话，跨多种技术)的方法，以及使用图形方法(VTNA)进行反应过程动力学分析。此外，我们设想，并将在适当的情况下，利用实时分析和自动化数据解释，并使用算法调节过程参数，以建立一个完全自主的均匀分散自我优化系统。大部分实验工作将在

In this project I will apply the operando spectroscopic capabilities of Bath's Dynamic Reaction Monitoring Facility togain new insights into the mechanisms of a range of homogeneously catalysed amine formation reactions (includingimine reduction, reductive amination, hydrogen-borrowing amination, and C-N cross coupling reactions).The approach will be to correlate product formation kinetics (analysed over the course of the reaction via RPKAmethods) with catalyst speciation profiles acquired under the same conditions. This will give new insights intoactivation and inhibition/deactivation pathways as well as information on dormant off-cycle species. In line with theCSCT ethos of sustainability, this will hopefully lead to the rational development of improved protocols (includingaspects of ease of operation, facilitated downstream separations, process-mass-intensity, energy demand, cost andtoxicity) and catalysts with increased efficiency in terms of activity, selectivity, productivity or stability. In line with theethos of the CSCT, these studies will hopefully lead to the development of more sustainable protocols forhomogeneously catalysed amine formation reactions. Lastly, we would like to develop novel transformations basedupon the mechanistic insights where appropriate.Our aim, with the help of NMR specialist's Dr John Lowe and Catherine Lyall, is to develop efficient protocols thatenable the quantitative real-time monitoring of catalytic reactions by multi-nuclear FlowNMR spectroscopy.Depending on conditions like temperature, pressure, viscosity and phase behaviour this may include hardwaremodifications (adaption of tubing materials, filters, reactors, pumps, flow-tube tips etc.) as well as optimisation of oneand two-dimensional pulse sequences as dictated by concentrations and lifetimes of reaction intermediates ofinterest. Furthermore, diffusional (DOSY) and dynamic (EXSY, CEST) NMR methods will be used as well asintegration and cross-calib ration with complementary techniques such as UV-vis and IR/Raman spectroscopies andsampling HPLC and MS as required.In addition, we hope to develop methods for automated data analysis and quantification (across multiple techniques ifrequired) as well as reaction progress kinetic analysis using graphical methods (VTNA). Further, we envision, and willpursue if appropriate, the use of use of real-time analysis and automated data interpretation with regulation ofprocess parameters using algorithms to establish a fully autonomous self-optimising system for homogeneouscatalysisMost of the experimental work will be conducted at the