Automated flow and real-time analytics approach for screening functional group tolerance in heterogeneous catalytic reactions

Simon Kevin; Sagmeister Peter; Munday RachelLeslie KevinHone Christopher A.Kappe C. Oliver

摘要

Heterogeneous hydrogenation reactions are widely used in synthesis, and performing them using continuous flow technologies addresses many of the safety, scalability and sustainability issues. However, one of the main potential drawbacks is catalyst deactivation by substrate inhibition. The efficient and rapid evaluation of functional group/heterocycle tolerance of an heterogeneous hydrogenation reaction using an automated continuous flow and real-time analytics platform is achieved. The information obtained is important for benchmarking catalytic reactions, particularly in the preparation of complex molecules. The methodology is applied to an aromatic nitro group reduction using hydrogen gas and palladium on alumina (Pd/Al2O3) as a heterogeneous catalyst. The system utilizes catalytic static mixer (CSM) technology within a thermoregulated shell-and-tube reactor. The flow approach is configured to collect large datasets for a catalytic system with different additives (12 in total). The generation of data in real-time for complex reaction mixtures is a significant challenge. The flow setup integrates inline FT-IR and online UHPLC as orthogonal analytical methods for rapid data acquisition and for quantification of the main chemical species (substrate, product and all the additives). Thus, the change in the reaction outcome is assessed along with the stability of the additive to the reaction conditions. In particular, advanced data analysis models (partial least squares regression) were used to quantify the chemical species by FT-IR in real time. Our approach facilitates the generation of quantitative data early in development to understand the sensitivity of the reaction performance in the presence of different functional groups and heterocycles, greatly reducing experimental effort.

机译：异质氢化反应被广泛用于合成，并使用连续流动技术对其进行执行，以解决许多安全性，可伸缩性和可持续性问题。但是，主要潜在缺点之一是底物抑制作用催化剂失活。使用自动连续流和实时分析平台对功能组/异质氢化反应的功能组/杂环耐受性的有效和快速评估。获得的信息对于基准测试催化反应很重要，尤其是在复杂分子的制备方面。该方法用于使用氧气气体和钯（PD/AL2O3）作为异质催化剂的芳基硝基减少。该系统利用热管壳管反应器中的催化静态混合器（CSM）技术。该流量方法配置为收集具有不同添加剂的催化系统的大型数据集（总共12个）。实时生成复杂反应混合物是一个重大挑战。流程设置集成了内联FT-IR和在线UHPLC作为正交分析方法，用于快速数据获取和量化主要化学物种（底物，产品和所有添加剂）。因此，评估反应结果的变化以及添加剂对反应条件的稳定性。特别是，高级数据分析模型（部分最小二乘回归）用于实时通过FT-IR量化化学物种。我们的方法促进了开发早期的定量数据的产生，以了解在存在不同官能团和异环的存在下反应性能的敏感性，从而大大降低了实验努力。

Automated flow and real-time analytics approach for screening functional group tolerance in heterogeneous catalytic reactions

摘要

著录项

相似文献

相关主题

期刊订阅