Simultaneous ¹⁹F-¹H medium resolution NMR spectroscopy for online reaction monitoring

Medium resolution nuclear magnetic resonance (MR-NMR) spectroscopy is currently a fast developing field, which has an enormous potential to become an important analytical tool for reaction monitoring, in hyphenated techniques, and for systematic investigations of complex mixtures. The recent developments of innovative MR-NMR spectrometers are therefore remarkable due to their possible applications in quality control, education, and process monitoring. MR-NMR spectroscopy can beneficially be applied for fast, non-invasive, and volume integrating analyses under rough environmental conditions. Within this study, a simple 1/16″ fluorinated ethylene propylene (FEP) tube with an ID of 0.04″ (1.02mm) was used as a flow cell in combination with a 5mm glass Dewar tube inserted into a benchtop MR-NMR spectrometer with a ¹H Larmor frequency of 43.32MHz and 40.68MHz for ¹⁹F. For the first time, quasi-simultaneous proton and fluorine NMR spectra were recorded with a series of alternating ¹⁹F and ¹H single scan spectra along the reaction time coordinate of a homogeneously catalysed esterification model reaction containing fluorinated compounds. The results were compared to quantitative NMR spectra from a hyphenated 500MHz online NMR instrument for validation. Automation of handling, pre-processing, and analysis of NMR data becomes increasingly important for process monitoring applications of online NMR spectroscopy and for its technical and practical acceptance. Thus, NMR spectra were automatically baseline corrected and phased using the minimum entropy method. Data analysis schemes were designed such that they are based on simple direct integration or first principle line fitting, with the aim that the analysis directly revealed molar concentrations from the spectra. Finally, the performance of 1/16″ FEP tube set-up with an ID of 1.02mm was characterised regarding the limit of detection (LOQ (¹H)=0.335molL^-1 and LOQ (¹⁹F)=0.130molL^-1 for trifluoroethanol in D₂O (single scan)) and maximum quantitative flow rates up to 0.3mLmin^-1. Thus, a series of single scan ¹⁹F and ¹H NMR spectra acquired with this simple set-up already presents a valuable basis for quantitative reaction monitoring.