
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
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic f ...
because of its
receptivity
Receptivity, or receptive agency, is a practical capacity and source of normativity, which, according to the philosopher Nikolas Kompridis, has both ontological and ethical dimensions, and refers to a mode of listening and "normative response" t ...
and large
chemical shift
In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of ...
dispersion, which is greater than that for
proton nuclear magnetic resonance
Proton nuclear magnetic resonance (proton NMR, hydrogen-1 NMR, or 1H NMR) is the application of nuclear magnetic resonance in NMR spectroscopy with respect to hydrogen-1 Atomic nucleus, nuclei within the molecules of a substance, in order to deter ...
spectroscopy.
Operational details
19F has a
nuclear spin
Nuclear may refer to:
Physics
Relating to the nucleus of the atom:
* Nuclear engineering
* Nuclear physics
* Nuclear power
* Nuclear reactor
* Nuclear weapon
* Nuclear medicine
*Radiation therapy
*Nuclear warfare
Mathematics
* Nuclear space
* ...
(I) of and a high
gyromagnetic ratio
In physics, the gyromagnetic ratio (also sometimes known as the magnetogyric ratio in other disciplines) of a particle or system is the ratio of its magnetic moment to its angular momentum, and it is often denoted by the symbol , gamma. Its SI u ...
. Consequently, this
isotope
Isotopes are distinct nuclear species (or ''nuclides'') of the same chemical element. They have the same atomic number (number of protons in their Atomic nucleus, nuclei) and position in the periodic table (and hence belong to the same chemica ...
is highly responsive to NMR measurements. Furthermore,
19F comprises 100% of naturally occurring fluorine. The only other highly sensitive spin 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 about 800 ppm. For ''organo''fluorine compounds the range is narrower, being about −50 to −70 ppm (for CF
3 groups) to −200 to −220 ppm (for CH
2F 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 and
1H spectra and multiple bond correlations
19F-
13C HMBC and through space HOESY spectra.
Chemical shifts
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 CFCl
3 is also affected by the solvent, care must be taken when using dissolved CFCl
3 as reference compound with regards to the chemical shift of neat CFCl
3 (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.
Chemical shift prediction
19F NMR chemical shifts are more difficult to predict than
1H NMR shifts. Specifically,
19F NMR shifts are strongly affected by contributions from electronic excited states whereas
1H NMR shifts are dominated by diamagnetic contributions.
Fluoromethyl compounds
Fluoroalkenes
For vinylic fluorine substituents, the following formula allows estimation of
19F chemical shfits:
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
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
19F-
19F coupling constants are generally larger than
1H-
1H coupling constants. Long range
19F-
19F coupling, (
2J,
3J,
4J or even
5J) are commonly observed. Generally, the longer range the coupling, the smaller the value.
[Dolbier, W. R. (2009) An Overview of Fluorine NMR, in Guide to Fluorine NMR for Organic Chemists, John Wiley & Sons, Inc., Hoboken, NJ, USA. .] 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 fluorines usually have a J-value of 250-300 Hz.
There are many good references for coupling constant values.
The citations are included below.
Magnetic resonance imaging
19F can be used as an alternative to
1H for
magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
(MRI). The sensitivity issues can be mitigated by using soft
nanoparticle
A nanoparticle or ultrafine particle is a particle of matter 1 to 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 100 nm in only two directions. At ...
s. Application include pH-, temperature-, enzyme-, metal ion- and redox responsive-
contrast agent
A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radiop ...
s. They can also be used for long-term cell labelling.
Notes
References
{{NMR by isotope
Nuclear magnetic resonance
Fluorine