39323 2017 eng 154 161 277 article Elsevier Inc. Oxford 1 -- -- -- Driven mostly by the search for chemical syntheses under biocompatible conditions, so called "click" chemistry rapidly became a growing field of research. The resulting simple one-pot reactions are so far only scarcely accompanied by an adequate optimization via comparably straightforward and robust analysis techniques possessing short set-up times. Here, we report on a fast and reliable calibration-free online NMR monitoring approach for technical mixtures. It combines a versatile fluidic system, continuous-flow measurement of 1H spectra with a time interval of 20 s per spectrum, and a robust, fully automated algorithm to interpret the obtained data. As a proof-of-concept, the thiol-ene coupling between N-boc cysteine methyl ester and allyl alcohol was conducted in a variety of non-deuterated solvents while its time-resolved behaviour was characterized with step tracer experiments. Overlapping signals in online spectra during thiol-ene coupling could be deconvoluted with a spectral model using indirect hard modeling and were subsequently converted to either molar ratios (using a calibrationfree approach) or absolute concentrations (using 1-point calibration). For various solvents the kinetic constant k for pseudo-first order reaction was estimated to be 3.9 h-1 at 25 °C. The obtained results were compared with direct integration of non-overlapping signals and showed good agreement with the implemented mass balance. Journal of Magnetic Resonance 10.1016/j.jmr.2017.02.018 http://www.sciencedirect.com/science/article/pii/S1090780717300575 urn:nbn:de:kobv:b43-393232 18.05.2017 Creative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International Aleksandra Michalik-Onichimowska Simon Kern Jens Riedel Ulrich Panne R. King Michael Maiwald eng uncontrolled Online NMR Spectroscopy eng uncontrolled Reaction Monitoring eng uncontrolled Automated Data Evaluation eng uncontrolled Thiol-ene click chemistry eng uncontrolled Click Chemistry eng uncontrolled Process Analytical Technology Analytische Chemie Verlagsliteratur Datei für die Öffentlichkeit verfügbar ("Open Access") Wissenschaftliche Artikel der BAM Bundesanstalt für Materialforschung und -prüfung (BAM) https://opus4.kobv.de/opus4-bam/files/39323/Manuskriptversion_Michalik-Onichimowska_and_Kern_et_al_Click_analytics_for_click_chemistry.pdf