2. Fluorine-19 nuclear magnetic
resonance
Fluorine-19 nuclear magnetic resonance is
an analytical technique used to identify
fluorine-containing compounds. 19F is one of
the most important nuclei for NMR
spectroscopy
19F has a nuclear spin of 1/2 and a high
magnetogyric ratio, which means that this
isotope is highly responsive to NMR
measurements. Furthermore, 19F comprises
100% of naturally-occurring fluorine.
3. Because of its favorable nuclear
properties and high abundance, 19F
NMR measurements are very fast,
comparable with 1H NMR
spectroscopy.
The reference compound for 19F is
CFCl3.
Other reference standard are given
below.
6. Chemical Shift of fluorine-19
19F NMR spectra can be performed in a
way equal to 1H NMR. Chemical shifts of
organofluorine compounds using CFCl3
as standard range from 50 to -250 ppm, a
maximum range is as wide 900ppm, much
wider than proton NMR. Which ranges 10
to 20 ppm at best.
19F spectra is very much more sensitive to
the structural and environmental changes
of molecules.
9. Solvent effect on fluorine chemical shift
Isotopic effect on fluorine chemical shift
Steric de-shielding of Fluorine.
10. Solvent effect on fluorine chemical
shift
There will usually not be much variation
observed in fluorine chemical shifts for
the three most common solvents used for
obtaining NMR spectra, that is CDCl3,
DMSO-d6 and acetone-d6, as can be seen
in the data presented in table for spectra of
a series of typical fluorine containing
compounds in various solvents.
11. Table showing solvent effect on
chemical shift of fluorine
The variation in fluorine chemical shift for these
three solvents is not more than + or - 1ppm.Vast
majority of spectra are measured in CDCl3.
12. Isotopic effect on fluorine chemical
shift
Because fluorine is relatively sensitive to
environment and has such a larger range
of chemical shifts, considerable changes
in chemical shift can be observed when a
nearby atom is replaced by an isotope
For example replacement of C-12 by C-13
for the atom to which the fluorine is
attached , give rise to a quite measurable
shift, usually to lower frequency.
13. DEUTRIUM SUBSTION EFFECT
Shifts due to either alpha or beta deutrium
substitution is also quiet significant,
usually leading to well resolved signals
for the deutrated and undeutrated species,
which can be useful in charaterization of
deutrium labeled fluorinated compounds.
An example of alpha effect is shown in
Fig below
14. 19F NMR spectrum of 1,6-difluorohexane-1,1 –D2, demonstrating the deuterium isoptopic effect
on the fluorine chemical shift
F
H H
F
HH
15. STERIC DE-SHIELDING OF FLOURINE
Another significant and not infrequently encountered
impact on fluorine chemical shift is the deshielding
influence of alkyl or arlyl group attached with it
This deshielding occur only when there is direct
overlap of the van der Waals radii of alkyl group and
that of the fluorine , and the deshielding is thought to
be result of vander Waals forces of the alkyl group
restricting the motion of electrons on the fluorine and
thus making the fluorine nucleus respond to the
magnetic field as if the electron density were lowered.
The most common situation where this effect is seen is
in comparison of E and Z isomers of trifluromethyl or
difluoromethyl substituted alkenes,
16.
17. Coupling constant of fluorine
Fluorine like hydrogen gives
characteristic coupling constants
depending on the spacial displacement
and number of bonds between a coupling
partner atom.
In particular a long range coupling J5 is
observed in an olefinic system. As shown
in Fig.1.16
18.
19. FLUORINE-FLUORINE
COUPLING
Homonuclear coupling constants between fluorine atoms are
usually relatively large compared with those between
hydrogen atoms,
Coupling between germinal fluorines (2JF-F) also give a large
value of 250 to 300Hz
but varying greatly depending on environment of the
fluorines.
Three bond coupling 3JF-F in saturated aliphatic hydrocarbons
are usually 15-16Hz range.but F-F coupling constant usually
decreases as we increase the nuber of proximate fluorines or
other electronegative substients.
The coupling costant 3JF-F of trans-vic-difluoroolefin is
larger than that of cis-olefin.
The largest 3JF-F are observed between trans-vinyl fluorines
where the coupling constant is larger than 35Hz
23. Other long range and through
space homonuclear and
hetronuclear couplings also
observed
24. HETRONUCLEAR COUPLING
H-F COUPLING
A typical coupling of organofluorine
compounds is observed in a geminal
coupling (2JH-F) with a geminal hydrogen
, being as large as 50Hz.
This coupling can also be observed by
proron NMR
25.
26.
27. HETRONUCLEAR COUPLING
F-C COUPLING
Coupling between fluorine and carbon is
also unique in 13C NMR 1JC-F ranges from
250 to 300 Hz
Generally coupling costants of 1JC-F,
2JC-F, 3JC-F, and 4JC-F are respectively,
16-370, 30-45, 5-25, and 1-5Hz.
This fact is reliable criterion for the
determination of fluoroolefin
configurations.
28.
29.
30. How to calculate the value of
J.
A typical example of a trifluromethy
ether is shown in Fig.1.17
A trifluromethyl carbon splits into a
quartet.
To obtained such well resolved
spectra, high concentration of sample
and long term accumulation is
necessary.
31.
32.
33. Spin System
Like proton we can also assign spin
system to compounds containing fluorine
on the bases of their chemical and
magnetic equivalence by using pople
notation
And by this way we can predict the type
of spectra that is that spectra is first order
or second order
34. Some Example of spin system of
fluorine containing compounds
38. VIRTUAL COUPLING
The term "virtual coupling" refers to an NMR
phenomenon in which apparently first-order
multiplets contain false coupling information.
In extreme cases, that are not actually coupled will
show splitting. More commonly, the magnitude of
coupling constants obtained by first-order analysis is
incorrect.
All virtual coupling effects arise when protons, well
isolated from other protons in chemical shift, are
coupled to a group of other protons which are strongly
coupled to each other. By strongly coupled we mean
that these protons are both close in chemical shift and
coupled to each other with J > Δν.
40. MULTIDIMENTIONAL F-19 NMR
In contrast to carbon and hydrogen 2D
NMR methods are not common for
fluorine-19.
Following are the some example of
compounds that can be identified through
multidimensional NMR.
41. Secondary alkyl Fluorides
Secondary alkylhalides exhibit a
downfield shieft of about +35 ppm from
their primary analogues , their fluorines
typically absorbs at about -183ppm and
such fluorines will also experience the
usual considerable shielding as a result of
branching.
Fluorine spectrum of typical secondry
fluoride, 2-fluropentane is shown in Fig
below
45. Tertiary Alkyl Fluorides
Tertiary alkyl fluorides exhibit an additional
downfield shift of about +25ppm, which is
also very sensitive to branching
The signal at -131ppm is split into 10 peaks
with a three bond H-F coupling constant of 21
Hz as shown below
47. COMPOUNDS OF FLUORINE
Elemental fluorine (F2) is the most reactive element.
Fluorine combines directly with all other elements,
except nitrogen and the lighter noble gases. It form
compounds of following type.
48. IONIC SALTS OF FLOURINE
A wide range of fluoride complexes may
be prepared from both metal (FeF6
3-,
RuF6
-, PtF6
2-, and SnF6
2-) and non-metal
(BF4
-, SiF6
2-, and PF6
-) fluorides.
While many fluorides are salts, when the
metal is in its higher oxidation states (e.g.,
OsF6 and WF6), the formation of an ionic
lattice with the appropriate cation (i.e.,
Os6+ and W6+ respectively) is
energetically unfavorable
49. COVALENT COMPOUNDS OF
FLUORINE
Organofluorine compounds that have the carbon–fluorine
bond are diverse in their types. They can be fluorocarbons,
fluorocarbon derivatives, fluorinated pharmaceuticals and
agrichemicals, or mono-fluorinated biologically synthesized
compounds, among others.
Fluorocarbons are compounds that contain only carbon and
fluorine, while other molecules that contain many carbon–
fluorine bonds are commonly referred to as fluorocarbons.
Pharmaceuticals and agrichemicals commonly contain only
one fluorine or a trifluoromethyl group. However, some are
more highly fluorinated, such as hexaflumuron, which has six
fluorines, in large part to a tetrafluoroethoxy functional
group. All known biologically synthesized organofluorines
contain only one carbon–fluorine bond.
50. TYPES OF ORGANO FLUORINE
COMPOUNDS
Fluorocarbons
Fluorocarbons are molecules that only contain carbon and fluorine. They
can be gases, liquids, waxes, or solids, depending upon their molecular
weight. The simplest fluorocarbon is the gas tetrafluoromethane (CF4).
Liquids include perfluorooctane and perfluorodecalin. The fluoropolymer
polytetrafluoroethylene (PTFE/Teflon) is a solid. While fluorocarbons with
single bonds are stable, unsaturated fluorocarbons are more reactive,
especially those with triple bonds.
Perfluorinated compounds
Perfluorinated compounds are fluorocarbon derivatives, as they are
closely structurally related to fluorocarbons. However, they also possess
new atoms such as nitrogen, iodine, or ionic groups, such as perfluorinated
carboxylic acids.
Alkyl fluorides
Alkyl monofluorides can be obtained from alcohols and Olah reagent or
another fluorinating agents.
51. Biological role of organofluorine compounds
Biologically synthesized organofluorines have been found in microorganisms
and plants, but not animals.
The most common example is fluoroacetate, which occurs as a plant defence
against herbivores in at least 40 plants in Australia, Brazil and Africa. Other
biologically synthesized organofluorines include ω-fluoro fatty acids,
fluoroacetone, and 2-fluorocitrate which are all believed to be biosynthesized in
biochemical pathways from the intermediate fluoroacetaldehyde. Adenosyl-
fluoride synthase is an enzyme capable of biologically synthesizing the carbon–
fluorine bond. Man made carbon–fluorine bonds are commonly found in
pharmaceuticals and agrichemicals because it adds stability to the carbon
framework; also, the relatively small size of fluorine is convenient as fluorine
acts as an approximate bioisostere of the hydroxyl group. Introducing the
carbon–fluorine bond to organic compounds is the major challenge for
medicinal chemists using organofluorine chemistry, as the carbon–fluorine
bond increases the probability of having a successful drug by about a factor of
ten.An estimated 20% of pharmaceuticals, and 30–40% of agrichemicals are
organofluorines, including several of the top drugs.Examples include 5-
fluorouracil, fluoxetine (Prozac), paroxetine (Paxil), ciprofloxacin (Cipro),
mefloquine, and fluconazole.
52. Environmental and health issues
Abiotic processes can also result in organofluorines
considered as "problem molecules." Fluorocarbon
based CFCs and tetrafluoromethane have been
reported in igneous and metamorphic rock.
However, environmental and health issues still face
many organofluorines. Because of the strength of the
carbon–fluorine bond, many synthetic fluorocarbons
and fluorcarbon-based compounds are persistent in the
environment. Others, such as CFCs, participate in
ozone depletion. Fluoroalkanes, commonly referred to
as perfluorocarbons, are potent greenhouse gases. The
fluorosurfactants PFOS and PFOA, and other related
chemicals, are persistent global contaminants. PFOS is
a persistent organic pollutant and may be harming the
health of wildlife; the potential health effects of PFOA
to humans are under investigation by the C8 Science
Panel.
53. Refrences
Guide to Fluorine NMR for Organic
Chemists W. R. Dolbier
Organofluorine Compounds: Chemistry and
Applications by TAMEJIRO HIYAMA
www.Chem 605 - Structure Determination
Using Spectroscopic Methods
www.Instructor: Hans J. Reich
www.Wikipidea
Organic spectroscopy by William Camp