169. A comparison of non‐uniform sampling and model‐based analysis of NMR spectra for reaction monitoring

Ellen Steimers, Yevgen Matviychuk, Anne Friebel, Kerstin Münnemann, Erik von Harbou and Daniel J. Holland; Magnetic Resonance in Chemistry; (2020); DOI: 10.1002/mrc.5095

NMR spectroscopy is widely used for applications in the field of reaction and process monitoring. When complex reaction mixtures are studied, NMR spectra often suffer from low resolution and overlapping peaks, which places high demands on the method used to acquire or to analyze the NMR spectra. This work presents two NMR methods that help overcome these challenges, 2D non‐uniform sampling (NUS) and a recently proposed model‐based fitting approach for the analysis of 1D NMR spectra. We use the reaction of glycerol with acetic acid as it produces five reaction products that are all chemically similar, and hence challenging to distinguish. The reaction was measured on a high‐field 400 MHz NMR spectrometer with a 2D NUS‐HSQC and a conventional 1D 1H NMR sequence. We show that comparable results can be obtained using both 2D and 1D methods, if the 2D volume integrals of the 2D NUS‐HSQC NMR spectra are calibrated. Further, we monitor the same reaction on a 43 MHz benchtop NMR spectrometer and analyse the acquired 1D 1H NMR spectra with the model‐based approach and with partial least‐square regression (PLS‐R), both trained using a single, calibrated data set. Both methods achieve results that are in good quantitative agreement with the high field data. However, the model‐based method was found to be less sensitive to the training data set used than PLS‐R, and hence was more robust when the reaction conditions differed from that of the training data.