Online Monitoring of Isomeric Reaction Intermediates

Ephemeral intermediates often hold the key to a more detailed understanding of chemical reaction pathways. Online methods to unambiguously identify the structure of such molecular entities, in particular in the presence of multiple isomers, are scarce. This paper presents a methodology that allows real-time monitoring of isomeric solution-phase reaction intermediates of continuous-flow reactions by coupling a microfluidic chip-reactor to a cryogenic ion trap triple mass spectrometer. The technique combines the excellent reaction control associated with microfluidic chips with the unique specificity and sensitivity of infrared photodissociation (IRPD) spectroscopy, which allows for an unambiguous structural assignment of gaseous ions based on their IR fingerprint. It represents a valuable extension to the instrumentation for online-analysis of reactive intermediates and proves particularly valuable whenever the sensitivity of NMR is not sufficient. After a brief description of the experimental approach, illustrative examples are provided to highlight the application of the chip-IRPD setup for mechanistic studies, particularly for stereoselective processes. The article concludes with an outlook on future challenges and perspectives.

Automated summary

This paper introduces a methodology for real-time monitoring isomeric solution-phase reaction intermediates, combining the excellent reaction control of microfluidic chips with the unique specificity and sensitivity of infrared photodissociation spectroscopy. The technique is valuable for mechanistic studies, particularly for stereoselective processes.