title: "Click" analytics for "click" chemistry - A simple method for calibration-free evaluation of online NMR spectra.
abstract: 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 of1H spectra with a time interval of 20s 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 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 3.9h-1at 25°C. The obtained results were compared with direct integration of non-overlapping signals and showed good agreement with the implemented mass balance.
authors.affiliation: Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstaetter-Str. 11, D-12489 Berlin, Germany; Physical Chemistry, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany; School of Analytical Sciences Adlershof, Humboldt-Universität zu Berlin, Zum Groβen Windkanal 6, 12489 Berlin, Germany.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Michalik-Onichimowska
authors.affiliation: Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstaetter-Str. 11, D-12489 Berlin, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Kern
authors.affiliation: Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstaetter-Str. 11, D-12489 Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Riedel
authors.affiliation: Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstaetter-Str. 11, D-12489 Berlin, Germany; Institut für Chemie, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany; School of Analytical Sciences Adlershof, Humboldt-Universität zu Berlin, Zum Groβen Windkanal 6, 12489 Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Panne
authors.affiliation: Department Measurement and Control, Institute of Process Engineering, Berlin University of Technology, Hardenbergstr. 36a, 10623 Berlin, Germany.
authors.forename: Rudibert
authors.initials: R
authors.lastname: King
authors.affiliation: Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstaetter-Str. 11, D-12489 Berlin, Germany. Electronic address: Michael.maiwald@bam.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Maiwald
keywords: Automated data evaluation; NMR spectroscopy; Reaction monitoring; Thiol–ene click chemistry