Flow chemistry offers important benefits over batch chemistry in terms of reproducibility, scalability and safety of the process. This is especially true for photochemical reactions.[1] The better control over reaction conditions and illumination also improves reaction rate and selectivity. The growing use of flow chemistry in both research laboratories and fine chemical industries brings new opportunities for analytical chemistry.[2] While the analysis of batch reaction output is usually performed off line, after work-up and sample preparation, the output of flow reactions is particularly suitable for an analysis on the fly. Particularly enabling is the coupling with in-line monitoring through flow NMR.[3] It offers quantitative and structural information in a non-invasive fashion that does not perturb the system and its composition, allowing to observe also sensitive species.
Here we describe the potentiality of the operando monitoring of flow photochemical reactions with 1D and ultrafast (UF) 2D NMR spectroscopy at high field. The output of the flow reactor is directly flown through a high-field NMR spectrometer thanks to a commercial flowtube. This set-up can provide detailed structural and quantitative information on the reaction mixture in real-time. The direct analysis of reaction mixtures requires the capability to distinguish among rather similar chemical species, and 1D 1H experiments can result in overcrowded spectra that are strongly affected by signal overlap. In this work, we show how UF 2D NMR experiments make it possible to address overlap problems while keeping a short experiment duration. This is illustrated with the monitoring of a photoactivated thiol-ene reaction, as a function of the residence time in the flow reactor. 1H 1D and UF 2D COSY experiments are used, and we find that the COSY cross-peaks provide reliable conversion information and kinetic rate constants. The in-line NMR detection approach and the short analysis duration open many perspectives for the monitoring and optimization of flow photochemical reactions.
[1] C. Sambiagio, T. Noël, TRECHEM 2020, 2, 92–106.
[2] M. Rodriguez-Zubiri, F.-X. Felpin, Org. Process Res. Dev. 2022, 26, 1766–1793.
[3] P. Giraudeau, F.-X. Felpin, React. Chem. Eng. 2018, 3, 399–413.