High-resolution Online NMR Spectroscopy for Reaction and Process Monitoring

Modern reaction and separation technology in the chemical industry is highly optimized, and advanced process analytics is crucial for understanding and monitoring complex process behavior. This work discusses the use of NMR spectroscopy for process-engineering applications—especially reaction and process monitoring—and provides the necessary methodological foundations. Such applications require non-destructive acquisition of high-resolution spectra, often at elevated pressure and temperature, enabling both quantitative composition analysis of complex reacting mixtures and identification of side products. A central focus is online NMR, which has been reported only sporadically in the literature despite its strong potential; the work shows that continuous online coupling can now be implemented using commercially available components, supported by decreasing instrument and operating costs and the growing feasibility of compact, lower-field magnets. Key practical challenges arise because deuterated solvents and classical sample preparation are often impossible in technical environments, so highly concentrated mixtures must be measured directly; the resulting methodological implications are investigated and addressed through experimental strategies. The work develops and validates approaches for quantitative online ^1H and ^13C NMR of technical mixtures without sample preparation, designs dedicated apparatus for studying reaction equilibria and kinetics over wide pressure/temperature ranges, and integrates NMR spectrometers via flow cells in a minimally invasive manner. Measurement and evaluation strategies for quantitative parameters are established, and the accessible pressure/temperature window and time resolution are expanded through peripheral equipment and probe-head modifications. As a core example, binary and ternary mixtures of formaldehyde, water, and methanol are studied, where formaldehyde is largely bound in poly(oxymethylene) glycols and hemiformals, strongly affecting thermodynamics and thermal separations. Demonstrations include online NMR coupling to a thin-film evaporator and to a stirred reactor for process monitoring. Further applications show suitability for analyzing complex reaction networks, gas solubilities, and trace product formation under demanding technical conditions, including CO₂ absorption in aqueous amines up to 30 bar, esterification kinetics with comparison to GC analytics, and reactions in ionic liquids. High-pressure fluid-mixture studies are also presented, such as hydrogen-bond equilibria of methanol in supercritical CO₂, providing experimental data for validating molecular simulation models. Finally, the work outlines NMR-based determination of physicochemical properties (e.g., diffusion coefficients) and reports, for the first time, the use of NMR in Taylor-dispersion measurements with experimental validation.