Integrating Flow Chemistry With Electrospray Ionization Mass Spectrometry

Flow chemistry is a transformative method that facilitates the exploration of chemical reactivity and enables process automation. In this context of high-throughput experimentation, analysing reaction outputs often constitutes a bottleneck. The direct integration of flow chemistry with electrospray ionization mass spectrometry (ESI-MS) is emerging as a method for the real-time monitoring of reaction mixtures in flow conditions, paving the way for reaction optimization and mechanistic investigations. As shown in selected examples, flow chemistry coupled to ESI-MS facilitates the detection and characterization of reaction intermediates and allows for tracking reaction dynamics under continuously changing conditions. Furthermore, establishing direct feedback between the flow setup and the analytical instrument enables the autonomous optimization of experimental conditions based on the real-time MS readout. Altogether, MS approaches hold the potential to streamline the development of complex synthetic pathways in flow.