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Fluorine-19 nuclear magnetic resonance (fluorine NMR or 19F NMR) is an analytical technique used to identify fluorine-containing compounds. 19F is one of the most important nuclei for NMR spectroscopy and is 100% naturally abundant. 19F NMR benefits from having a larger range of possible chemical shifts than proton nuclear magnetic resonance (1H NMR); as a result, peak overlap is quite rare. Subsequently, minor changes to the chemical environment of a fluorine atom results in a much more dramatic change in chemical shift when compared to 1H NMR. For this reason, 19F NMR based experiments are frequently used to study ligand binding events to proteins. This increased sensitivity to chemical change has led to the widespread use of 19F NMR in analyzing various other biological processes as well.

Operational details
19F has a nuclear spin of ½ and a high magnetogyric ratio, which means that this isotope is highly responsive to NMR measurements. Furthermore, 19F comprises 100% of naturally occurring fluorine. The only other highly sensitive NMR-active nuclei spin ½ that are monoisotopic (or nearly so) are 1H and 31P.

Because of its favorable nuclear properties and high abundance, 19F NMR measurements are very fast, comparable with 1H NMR spectroscopy. Indeed, the 19F nucleus is the third most receptive NMR nucleus, after the 3H nucleus and 1H nucleus.

The 19F NMR chemical shift range is very wide, ranging from ca. 550 to -250 ppm. The very wide spectral range can cause problems in recording spectra, such as poor data resolution and inaccurate integration.

The reference compound for 19F is CFCl3, although in the past a number of other compounds have been used, including CF3COOH (-76 ppm w.r.t. CFCl3) and C6F6 (-163 ppm w.r.t CFCl3). 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.

Chemical Shifts
19F NMR and 1H NMR were developed contemporaneously due to the fact that 19F NMR is about 0.83 times as sensitive compared to 1H NMR. (see Chemical Shifts) However, unlike 1H NMR, the 19F chemical shifts are much more difficult to predict, potentially due to the fact that paramagnetic shielding is the dominating force that affects the chemical shifts for 19F nuclei, compared to the diamagnetic shielding that affects the shifts in 1H NMR. Regardless, this section serves to give a brief overview of trends observed in different, fluorinated compounds. All data presented in this section are relative to CFCl3 as the standard (i.e. δCFCl_3 = 0).

Tri-, Di-, and Mono-Fluoromethyl Compounds
Below are some representative data for fluoromethyl compounds:

Fluoroalkenes
When determining the 19F chemical shifts of vinylic fluorine atoms, there is a formula that allows for reasonable estimation based on the stereochemistry of the olefin in-question. The shift of 19F in a vinylic fluroalkene can be calculated as such:$$\delta_{C=CF}~(ppm)=-133.9+Z_{cis}+Z_{trans}+Z_{gem}+S_{cis/trans}+S_{cis/gem}+S_{trans/gem}$$where Z is the statistical substituent chemical shift (SSCS) for the substituent in the listed position, and S is the interaction factor. Some representative values for use in this equation are provided in the table below:

Fluorobenzenes
When determining the 19F chemical shifts of aromatic fluorine atoms, specifically phenyl fluorides, there is another equation that allows for an approximation. Adopted from "Structure Determination of Organic Compounds," this equation is:$$\delta_F~(ppm)=-113.9+\Sigma Z_{ortho}+\Sigma Z_{meta}+\Sigma Z_{para}$$where Z is the SSCS value for a substituent in a given position relative to the fluorine atom. Some representative values for use in this equation are provided in the table below: The data shown above are only representative of some trends and molecules. Other sources and data tables can be consulted for a more comprehensive list of trends in 19F chemical shifts. Something to note is that, historically, most literature sources switched the convention of using negatives. Therefore, be wary of the sign of values reported in other sources.

Spin-Spin Coupling
Fluorine-19 has high detection sensitivity, comparable to proton NMR. Spin-spin coupling gives one information about the immediate molecular environment of a fluorine atom. These are transmitted through chemical bonds and are displayed through the multiplet structure of peaks. Fluorine NMR coupling constants are different than what one would expect in a 1H NMR. They coupling constants are generally larger in fluorine NMR. It is possible, and fairly common, to see long range coupling in fluorine NMR (2J, 3J or 4J of even 5J). Generally, the longer range the coupling, the smaller the value. Hydrogen couples with fluorine, which is very typical to see in 19F spectrum. With a geminal hydrogen, the coupling constants can be as large as 50 Hz. Other nuclei can couple with fluorine, however, this can be prevented by running decoupled experiments. It is common to run fluorine NMRs with both carbon and proton decoupled. Fluorine atoms can also couple with each other. Between fluorine atoms, homonuclear coupling constants are much larger than with hydrogen atoms. Geminal flourines usually have a J-value of 250-300 Hz. There are many good references for coupling constant values. The citations are included below.

Applications
Most commonly 19F NMR spectroscopy is used to analyze the structure of organofluorine compounds. Representative targets of this method are the many pharmaceuticals that contain C-F bonds. The technique is also used to analyze fluoride salts.