Fluorine-19 NMR

Fluorine-19 nuclear magnetic resonance spectroscopy (fluorine NMR or 19F NMR) is an analytical technique used to detect and identify fluorine-containing compounds. 19F is an important nucleus for NMR spectroscopy because of its receptivity and large chemical shift dispersion, which is greater than that for proton nuclear magnetic resonance spectroscopy. Fluorine-19 nuclear magnetic resonance spectroscopy (fluorine NMR or 19F NMR) is an analytical technique used to detect and identify fluorine-containing compounds. 19F is an important nucleus for NMR spectroscopy because of its receptivity and large chemical shift dispersion, which is greater than that for proton nuclear magnetic resonance spectroscopy. 19F has a nuclear spin (I) of ½ and a high magnetogyric ratio. Consequently, this isotope is highly responsive to NMR measurements. Furthermore, 19F comprises 100% of naturally occurring fluorine. The only other highly sensitive spin ½ NMR-active nuclei that are monoisotopic (or nearly so) are 1H and 31P. Indeed, the 19F nucleus is the third most receptive NMR nucleus, after the 3H nucleus and 1H nucleus. The 19F NMR chemical shifts span a range of ca. 800 ppm. For organofluorine compounds the range is narrower, being ca. -50 to -70 ppm (for CF3 groups) to -200 to -220 ppm (for CH2F groups). The very wide spectral range can cause problems in recording spectra, such as poor data resolution and inaccurate integration. It is also possible to record decoupled 19F{1H} and 1H{19F} spectra and multiple bond correlations 19F-13C HMBC and through space HOESY spectra. 19F NMR chemical shifts in the literature vary strongly, commonly by over 1 ppm, even within the same solvent. Although the reference compound for 19F NMR spectroscopy, neat CFCl3 (0 ppm), has been used since the 1950s, clear instructions on how to measure and deploy it in routine measurements were not present until recently. An investigation of the factors influencing the chemical shift in fluorine NMR spectroscopy revealed the solvent to have the largest effect (Δδ = ±2 ppm or more). A solvent-specific reference table with 5 internal reference compounds has been prepared (CFCl3, C6H5F, PhCF3, C6F6 and CF3CO2H) to allow reproducible referencing with an accuracy of Δδ = ±30 ppb. As the chemical shift of CFCl3 is also affected by the solvent, care must be taken when using dissolved CFCl3 as reference compound with regards to the chemical shift of neat CFCl3 (0 ppm). Example of chemical shifts determined against neat CFCl3: For a complete list the reference compounds chemical shifts in 11 deuterated solvents the reader is referred to the cited literature. A concise list of appropriately referenced chemical shifts of over 240 fluorinated chemicals has also been recently provided, which can be acquired free of charge in the supplementory information. 19F NMR chemical shifts are more difficult to predict, reflecting contributions from excited states. In contrast, 1H NMR shifts are dominated by the diamagnetic term.1H NMR. Data presented in this section are referenced to CFCl3 as the standard (i.e. δCFCl_3 = 0). For vinylic fluorine substituents, the following formula allows for estimation of 19F chemical shfits: