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Rapid Chemical Reaction Monitoring by Digital Microfluidics‐NMR: Proof of Principle Towards an Automated Synthetic Discovery Platform
Author(s) -
Wu Bing,
Ecken Sebastian,
Swyer Ian,
Li Chunliang,
Jenne Amy,
Vincent Franck,
Schmidig Daniel,
Kuehn Till,
Beck Armin,
Busse Falko,
Stronks Henry,
Soong Ronald,
Wheeler Aaron R.,
Simpson André
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201910052
Subject(s) - chemistry , reagent , organic synthesis , microfluidics , nuclear magnetic resonance spectroscopy , chemical reaction , proton nmr , spectrometer , carbon 13 nmr , organic chemistry , nanotechnology , materials science , catalysis , physics , quantum mechanics
Microcoil nuclear magnetic resonance (NMR) has been interfaced with digital microfluidics (DMF) and is applied to monitor organic reactions in organic solvents as a proof of concept. DMF permits droplets to be moved and mixed inside the NMR spectrometer to initiate reactions while using sub‐microliter volumes of reagent, opening up the potential to follow the reactions of scarce or expensive reagents. By setting up the spectrometer shims on a reagent droplet, data acquisition can be started immediately upon droplet mixing and is only limited by the rate at which NMR data can be collected, allowing the monitoring of fast reactions. Here we report a cyclohexene carbonate hydrolysis in dimethylformamide and a Knoevenagel condensation in methanol/water. This is to our knowledge the first time rapid organic reactions in organic solvents have been monitored by high field DMF‐NMR. The study represents a key first step towards larger DMF‐NMR arrays that could in future serve as discovery platforms, where computer controlled DMF automates mixing/titration of chemical libraries and NMR is used to study the structures formed and kinetics in real time.