Exposing the Origins of Irreproducibility in Fluorine NMR Spectroscopy

Abstract

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 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 F spectra correctly.

An Experimental Acidity Scale for Intramolecularly Stabilized Silyl Lewis Acids

“…The 19 F{ 1 H} NMR spectraw ere collected at room temperature in CD 2 Cl 2 ,a nd were calibrated against the signal of the p-fluorine atoms of the [B(C 6 F 5 ) 4 ] À anion (d 19 F = À163.44), which was referenced against fluorobenzene [d 19 F(C 6 H 5 F) = À113.78]. [22] In this series of intramolecularly stabilized silyl cations,t he two NMR parameters varied from d 19 F = À102.1 and 1 J(CF) = 257.1 Hz for the telluryl-substituted nitrilium ion 10 d to d 19 F = À86.6 and 1 J(CF) = 272.8 Hz for the unsubstituted silyl cation 6 (Figure 6a,b). The valuesf or the tellurium compound 10 d are close to those measured for the free FBN, which indicates for cation 2d the strongesti nteraction between the donor group and the silicon center.F or the other extreme, the bromo-substituted species 10 e,t he parameters are close to those for cation 5.H ence, bromo-substi-tuted silyl cation 2e is the strongest Lewis acid in this series, whereas the tellurium compound 2d is the weakest.…”

Dynamic host–guest behavior in halogen-bonded two-dimensional molecular networks investigated by scanning tunneling microscopy at the solid/liquid interface

“…The PhCF 3 signal at À62.61 ppm (ref. 36) was used as the internal standard for 19 F NMR measurements. Matrix-assisted laser desorption/ ionization high-resolution mass spectrometry (MALDI-HRMS) was conducted on a JMS-S3000 spiralTOF mass spectrometer (JEOL, Tokyo, Japan).…”

Regioselektive oxidative Arylierung von Fluorophenolen

“…I‐1 (PIDA) wurde in dieser Reaktion als Oxidationsmittel eingesetzt und das 19 F‐NMR‐Spektrum nach Reaktionsstart alle 30 Minuten gemessen. Die rasche Erscheinung vom charakteristischen Quartett bei einer Verschiebung von δ = +49 ppm (q, 3 J F‐H =7 Hz), kalibriert mit Benzotrifluorid (−63 ppm), entspricht der Bildung von Acetylfluorid (AcF, siehe Hintergrundinformationen) . Dies gibt einen Hinweis auf die Rolle und das Schicksal der Fluoridabgangsgruppe.…”