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A sample 19F NMR spectrum of a simple organic compound. Integrations are shown under each peak.

19F NMR spectrum of 1-bromo-3,4,5-trifluorobenzene. The expansion shows the spin-spin coupling pattern arising from the para-fluorine coupling to the 2 meta-fluorine and 2 ortho proton nuclei.

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. δ_{CFCl_3} = 0).

Tri-, Di-, and Mono-Fluoromethyl Compounds

Below are some representative data for fluoromethyl compounds:

¹⁹F Chemical Shifts of F₃C-R Groups

-R	δ (ppm)
H	-78
CH3	-62
CH2CH3	-70
CH2NH2	-72
CH2OH	-78
CH=CH2	-67
C=CH	-56
CF3	-89
CF2CF3	-83
F	-63
Cl	-29
Br	-18
I	-5
OH	-55
NH2	-49
SH	-32
C(=O)Ph	-58
C(=O)CF3	-85
C(=O)OH	-77
C(=O)F	-76
C(=O)OCH2CH3	-74

¹⁹F Chemical Shifts of F₂CH-R Groups

-R	δ (ppm)
H	-144
CH3	-110
CH2CH3	-120
CF3	-141
CF2CF3	-138
C(=O)OH	-127

¹⁹F Chemical Shifts of FH₂C-R Groups

-R	δ (ppm)
H	-268
CH3	-212
CH2CH3	-212
CH2OH	-226
CF3	-241
CF2CF3	-243
C(=O)OH	-229

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:

SSCS Values for Fluroalkene Substituents

Substituent R	Zcis	Ztrans	Zgem
-H	-7.4	-31.3	49.9
-CH3	-6.0	-43.0	9.5
-CH=CH2	---	---	47.7
-Ph	-15.7	-35.1	38.7
-CF3	-25.3	-40.7	54.3
-F	0	0	0
-Cl	-16.5	-29.4	---
-Br	-17.7	-40.0	---
-I	-21.3	-46.3	17.4
-OCH2CH3	-77.5	---	84.2

Interaction Factors for Fluroalkene Substituents

Substituent	Substituent	Scis/trans	Scis/gem	Strans/gem
-H	-H	-26.6	---	2.8
-H	-CF3	-21.3	---	---
-H	-CH3	---	11.4	---
-H	-OCH2CH3	-47.0	---	---
-H	-Ph	-4.8	---	5.2
-CF3	-H	-7.5	-10.6	12.5
-CF3	-CF3	-5.9	-5.3	-4.7
-CF3	-CH3	17.0	---	---
-CF3	-Ph	-15.6	---	-23.4
-CH3	-H	---	-12.2	---
-CH3	-CF3	---	-13.8	-8.9
-CH3	-Ph	---	-19.5	-19.5
-OCH2CH3	-H	-5.1	---	---
-Ph	-H	---	---	20.1
-Ph	-CF3	-23.2	---	---

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:

SSCS Values for Fluorobenzene Substituents

Substituent	Zortho	Zmeta	Zpara
-CH3	-3.9	-0.4	-3.6
-CH=CH2	-4.4	0.7	-0.6
-F	-23.2	2.0	-6.6
-Cl	-0.3	3.5	-0.7
-Br	7.6	3.5	0.1
-I	19.9	3.6	1.4
-OH	-23.5	0	-13.3
-OCH3	-18.9	-0.8	-9.0
-NH2	-22.9	-1.3	-17.4
-NO2	-5.6	3.8	9.6
-CN	6.9	4.1	10.1
-SH	10.0	0.9	-3.5
-CH(=O)	-7.4	2.1	10.3
-C(=O)CH3	2.5	1.8	7.6
-C(=O)OH	2.3	1.1	6.5
-C(=O)NH2	0.5	-0.8	3.4
-C(=O)OCH3	3.3	3.8	7.1
-C(=O)Cl	3.4	3.5	12.9

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.