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Exposing the Origins of Irreproducibility in Fluorine NMR Spectroscopy
Author(s) -
Rosenau Carl Philipp,
Jelier Benson J.,
Gossert Alvar D.,
Togni Antonio
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201802620
Subject(s) - heteronuclear molecule , chemical shift , chemistry , nuclear magnetic resonance spectroscopy , fluorine 19 nmr , fluorine , spectroscopy , characterization (materials science) , analytical chemistry (journal) , nmr spectra database , calibration , spectral line , computational chemistry , nanotechnology , organic chemistry , materials science , physics , quantum mechanics , astronomy
Fluorine chemistry has taken a pivotal role in chemical reaction discovery, drug development, and chemical biology. NMR spectroscopy, arguably the most important technique for the characterization of fluorinated compounds, is rife with highly inconsistent referencing of fluorine NMR chemical shifts, producing deviations larger than 1 ppm. Herein, we provide unprecedented evidence that both spectrometer design and the current unified scale system underpinning the calibration of heteronuclear NMR spectra have unintentionally led to widespread variation in the standardization of 19 F NMR spectral data. We demonstrate that internal referencing provides the most robust, practical, and reproducible method whereby chemical shifts can be consistently measured and confirmed between institutions to less than 30 ppb deviation. Finally, we provide a comprehensive table of appropriately calibrated chemical shifts of reference compounds that will serve to calibrate 19 F spectra correctly.