A Review of Inline Infrared and Nuclear Magnetic Resonance Applications in Flow Chemistry

Abstract

As a safe and efficient synthesis technique, flow chemistry has recently gained attention in the pharmaceutical, materials, and environmental protection industries. However, researchers always face challenges in handling samples and selecting sufficiently flexible analytical techniques. Generally, real-time process analysis is crucial for monitoring reactions. The combination of flow chemistry with real-time process analysis can be beneficial for studying reaction kinetics and thermodynamics, monitoring, and control of the chemical synthesis processes, reaction optimization of macro and microreactors, and qualitative and quantitative analyses of compounds. Thus far, studies investigating the combination of flow chemistry with inline monitoring have included ultraviolet–infrared spectroscopy, Raman spectroscopy, gas chromatography, mass spectrometry, liquid chromatography, nuclear magnetic resonance (NMR) spectroscopy, and other automated conventional or unconventional methods. This review sheds light on applying inline infrared and inline NMR spectroscopies in flow chemistry.

The role of PAT in the development of telescoped continuous flow processes

“…This review will discuss the role of PAT in enabling telescoping of continuous flow processes; an operation where a number of reactions are performed consecutively in the same linear stream. 19 There have been many extensive reviews over the last number of years detailing the incorporation of PAT into manufacturing processes for the synthesis of active pharmaceutical ingredients (APIs), 20–25 to facilitate in-line purification and work-up techniques, 26 in advancing quality and sustainability, 27 and in the development of self-optimising processes in continuous flow. 28,29 Some reviews have focussed on certain aspects of the technologies such as in situ sensors for flow reactors 30 and also challenges and advantages associated with the use of PAT in both industry and academic settings.…”