Multi-nuclear operando FlowNMR investigations of catalytic amine formation reactions

催化胺形成反应的多核原位 FlowNMR 研究

• 批准号: 2436725
• 金额: --
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2436725
• 关键词: Multi; nuclear; operando; FlowNMR; investigations

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

在这个项目中，我将应用巴斯的动态反应监测设备的操作光谱能力来获得一系列均相催化胺形成反应的机理的新见解（包括亚胺还原，还原胺化，氢借用胺化，和C-N交叉偶联反应）。该方法将关联产物形成动力学（在反应过程中通过RPKA方法分析）与在相同条件下获得的催化剂形态分布。这将为激活和抑制/失活途径提供新的见解，以及休眠的关闭周期物种的信息。与CSCT的可持续性精神相一致，这将有望导致改进方案的合理开发（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）以及在活性、选择性、生产率或稳定性方面具有更高效率的催化剂。根据CSCT的精神，这些研究将有望为均相催化胺形成反应开发出更可持续的方案。最后，我们希望在适当的情况下开发基于机理见解的新转换。我们的目标是在NMR专家John Lowe博士和Catherine Lyall的帮助下，开发有效的协议，通过多核FlowNMR光谱学对催化反应进行定量实时监测。根据温度，压力，粘度和相行为，这可能包括硬件改造（管道材料、过滤器、反应器、泵、流量管尖端等的改造）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，将使用扩散（DOSY）和动态（EXSY，CEST）NMR方法，以及与补充技术（如UV-vis和IR/拉曼光谱）的集成和交叉校准，并根据需要进行采样HPLC和MS。此外，我们希望开发自动数据分析和定量（如需要，可跨多种技术）以及使用图形方法（VTNA）进行反应进程动力学分析的方法。此外，我们设想并将在适当的情况下继续使用实时分析和自动数据解释，并使用算法调节工艺参数，以建立一个完全自主的自优化系统，用于非线性散射分析。