"Click" analytics for "click" chemistry - A simple method for calibration-free evaluation of online NMR spectra
- 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 H-1 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 ally] 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 wereDriven 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 H-1 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 ally] 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 calibration free 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 degrees C. The obtained results were compared with direct integration of non-overlapping signals and showed good agreement with the implemented mass balance. (C) 2017 Elsevier Inc. All rights reserved.…
Verfasserangaben: | Aleksandra Michalik-Onichimowska, Simon Kern, Jens RiedelORCiD, Ulrich Panne, Rudibert King, Michael MaiwaldORCiD |
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DOI: | https://doi.org/10.1016/j.jmr.2017.02.018 |
ISSN: | 1090-7807 |
ISSN: | 1096-0856 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/28288418 |
Titel des übergeordneten Werks (Englisch): | Journal of magnetic resonance |
Verlag: | Elsevier |
Verlagsort: | San Diego |
Publikationstyp: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Jahr der Erstveröffentlichung: | 2017 |
Erscheinungsjahr: | 2017 |
Datum der Freischaltung: | 20.04.2020 |
Freies Schlagwort / Tag: | Automated data evaluation; NMR spectroscopy; Reaction monitoring; Thiol-ene click chemistry |
Band: | 277 |
Seitenanzahl: | 8 |
Erste Seite: | 154 |
Letzte Seite: | 161 |
Fördernde Institution: | Excellence Initiative of the German Research Foundation (DFG); European |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
Peer Review: | Referiert |