Comparison of Calibration Methods for the Monitoring of a Fluorobenzene Batch Reaction Using Low-Field ¹⁹F NMR, ¹H NMR, NIR, and Raman Spectrometries

Abstract

The suitability of different process spectrometry techniques has been assessed, in terms of calibration requirements, accuracy, and precision, for the at-line monitoring of the sulfonation of fluorobenzene. Partial least-squares (PLS) calibration was required to analyze the spectra obtained by NIR spectrometry and low-field (29.1 MHz) 1H NMR spectrometry. The low-field (27.4 MHz) 19F NMR spectra contained well-resolved signals for the three fluorine containing compounds and univariate calibration was adequate. The Raman spectra of two of the compounds exhibited fluorescence and so this technique was not considered suitable for monitoring the reaction. The accuracy of the results obtained using univariate analysis of the 19F NMR data and PLS analysis of NIR data were comparable (average % error of 3.5 and 2.9%, respectively, for concentrations >0.5 mol dm−3 and 11.3 and 11.1%, respectively, for <0.5 mol dm−3). The least accurate results were obtained using PLS analysis of low-field 1H NMR data, as the spectra of two of the components were too similar. For concentrations >0.05 mol dm−3, the most precise results were obtained with PLS analysis of NIR data (average RSD of 1.6%), although the precision of the results obtained using univariate analysis of 19F NMR data was still good (average RSD of 3.7%).

Consideration of some sampling problems in the on-line analysis of batch processes by low-field NMR spectrometry

“…40, 41 At-line 19 F NMR spectra have been obtained with the low-field NMR spectrometer described here. 29 On-line analysis by 19 F NMR spectrometry will be particularly advantageous for processes where the solvents used do not contain fluorine. 29…”

“…29 On-line analysis by 19 F NMR spectrometry will be particularly advantageous for processes where the solvents used do not contain fluorine. 29…”

Exploration of continuous‐flow benchtop NMR acquisition parameters and considerations for reaction monitoring

“…Along with flow cells, benchtop NMR instruments have emerged as especially versatile tools for rapid compound characterization and reaction monitoring [13][14][15][16][17][18][19]. These instruments are low-field, as they incorporate permanent rather than superconducting magnets, and typically generate magnetic fields under 2.35 T (100 MHz 1 H Larmor frequency).…”

Investigation of Hydrogenation of Toluene to Methylcyclohexane in a Trickle Bed Reactor by Low-Field Nuclear Magnetic Resonance Spectroscopy

“…Recently, investigations of the potential of low-field NMR systems with respect to on-line and in-line process control were published. [5][6][7][8][9][10][11] These systems are based on permanent magnet technology, exhibit a 1 H NMR frequency in the range of 2-65 MHz, and can be found especially in quality control in the food and chemical industries. However, these systems are in general not suited for performing 1 H spectroscopy.…”