“Fluorocarbons”
-Alex J. Roche
A Graduate Level Advanced Organic Course
Rutgers, The State University of New Jersey
56:160:519
Office: Sci 311
Labs: Sci 309, 328F, 304A
[email protected]
Tel: (856) 225-6166
Fax: (856) 225-6506
http://crab.rutgers.edu/~alroche/
“Fluorine leaves nobody indifferent; it inflames emotions be that affections or aversions.
As a substituent, it is rarely boring, always good for a surprise, but often completely
unpredictable” – Manfred Schlosser, 1998.
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Fluorocarbons
Fluorocarbons are organic compounds that contain fluorine, and they are (almost
always) synthetic or man made compounds.
Compounds bearing a C-F bond do not occur in nature (almost true).
Thus the replacement of a C-H bond with a C-F bond gives rise to a potentially vast man
made organic chemistry.
Adds an entirely synthetic extra dimension to Organic Chemistry.
Fluorocarbons can Provide:
New Chemistry
Unique Chemistry (Special Effects)
New materials
New Applications
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Organofluorine Chemists (should) Aim to:
-Develop the Organic Chemistry of compounds that contain Fluorine
-Encourage application by collaboration with industry
-Integrate the subject on a mechanistic basis with modern organic
chemistry (get to a level of understanding so F is predictably unique)
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History
Hydrogen Fluoride was first reported by Scheele in 1771.
The first reported synthesis of an organofluorine compound was in 1836, when Dumas
and Peligot reported the synthesis of fluoromethane.
It was in 1886 that Henri Moissan prepared and isolated molecular elemental fluorine
gas (F2).
Moissan in 1890 erroneously reported the isolation of carbon tetrafluoride as a product
of the reaction of fluorine and carbon.
It was the Belgian chemist Swarts’ work between 1890 and 1938 on simple aliphatic
fluorocarbons which is widely considered as establishing the foundations of
organofluorine chemistry.
In the 1930’s, Midgley and Henne extended Swarts’ exchange reaction methods and this
promoted the introduction of CFC’s (chlorofluorocarbons) as refrigerants.
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History cont
The chemistry of perfluorinated (fully fluorinated) organic compounds began in 1926
when Lebeau and Damiens synthesized carbon Tetrafluoride.
This compound was fully characterized in 1930 by the above workers, and also by Ruff
and Kleim in the same year.
Pre-1930, household refrigerators used methyl chloride and ammonia as their coolant. In
the 1930’s, it was discovered that dichlorodifluoromethane was a safe, stable gas
whose liquefied state had low compressibility, and importantly, was not flammable.
Dupont and General Motors were the pioneers of the application of CFCs as
refrigerants. Later CFC’s would find diverse applications as inert gases, blowing
agents, cleaning agents and chemical reagents (monomers).
Another important event in the growth of fluorine chemistry was the Second World
War.The development of the atomic bomb meant extensive research into Uranium.
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The desired isotope of Uranium was 235U.
The best way to separate the different isotopes of Uranium is gaseous diffusion
separation (lighter ones travel faster).
The best compound for this was UF6.
The enriched UF6 is converted to the oxide which is used as the fuel for nuclear power.
Interest in UF6 spawned two major areas of development for fluorine chemistry:
One was the ability to handle F2 gas effectively, since UF6 is made by fluorination of
UF4, which itself is made by fluorination with elemental fluorine.
Secondly, UF6 is extremely reactive, and in order to safely handle this material,
unreactive materials needed to be created.
The Manhattan Project during WWII successfully developed a family of fluorine
containing compounds which could be used for UF6 handling and equipment.
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Such early materials form the basis of the current fluorochemical and fluoropolymer
material industries.
Starting in the 1970’s, concern over the detrimental environmental effects of
accumulating CFC emissions into the atmosphere, led to the formation of The
Montreal Protocol on Substances That Deplete the Ozone Layer, which is phasing
out the production and use of ozone depleting CFC’s.
The search for CFC replacements like HCFC’s and HFC’s are thus a current hot
research area.
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-Fluorine Chemistry Statistics
Bruce E. Smart in Chemical Reviews, 1996:
“ Scientific and commercial interests in fluorine chemistry burgeoned after 1980,
largely fueled by the need to replace industrial chlorofluorocarbons and the
rapidly growing practical opportunities for organofluorine compounds in crop
protection, medicine and diverse materials applications.
Although fluorine is much less abstruse now than when I entered the field a
generation ago, it remains a specialized topic and most chemists are
unfamiliar, or at least uncomfortable, with the synthesis and behavior of
organofluorine compounds”.
Fluorine Chemistry is a relatively new and growing area of chemistry.
In 1990, Wilkinson and Seebach determined that 6.2% of all compounds
registered in chemical abstracts contained at least one C-F bond.
Figures from their data up to 1990 are shown on the next slide:
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Schofield produced figures for the last ten years concerning new C-F containing
compounds and publications.
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During 1989 - 1998 a total of 610,873 new C-F containing compounds were
registered with the Chemical Abstracts Service.
The figures for publications concerning C-F compounds are shown below:
(Typically around 30% of publications are patents).
(Typically around 30% of publications are patents).
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To put this into perspective with the rest of chemistry:
(The downward trend from 1994 is perhaps due to the massive increase in
numbers of compounds generated by combinatorial chemistry methods). 14
Fluorocarbons around us
Many fluoroorganic compounds are encountered on a daily basis.
This is generally not appreciated either by the general public and also (probably) by the
scientific community.
Consider an average morning:
You wake up and walk across your (Scotchguard protected) carpet to the kitchen
to have breakfast, take the milk out of your (CFC/HFC cooled) fridge, fry your
eggs on your (non-stick Teflon coated) frying pan, brush your teeth with
fluoride toothpaste, take your medication of choice (prozac / 5FU / efavirenz /
flurbiprofen), get dressed and grab your (Gore-Tex rain proof) coat, walk
across your (treflan / fusillade treated) lawn to your car which has a plastic
(surface fluorinated) petrol / gas tank....etc, etc
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Naturally Occurring Organofluorine compounds
To date (2000) there have been over 3,000 natural products characterized which contain
chlorine, bromine or iodine.
Currently there are 13 known to contain a carbon fluorine bond.
Most of these are tropical plant metabolites found in the southern hemisphere, and the
presence of such compounds makes the plants acutely toxic.
For example traces of fluoroacetic acid found in the plant, gifblaar (Dichapetalum
cymosum) in the South African veldt are believed to be responsible for numerous
cattle deaths from errant grazing.
It seems that nature (one of the best chemists around) does not seem to specialize in
fluorine chemistry.
This is not due to a lack of natural resources since Fluorine is the 13th most abundant
element in the earth’s crust. (Fluorspar – mainly CaF2)
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There is not really a very good explanation for this; the best offered so far are:
a) the fluoride ion is generally only available in insoluble mineral forms
b) no enzyme with fluorinating activity has been found yet. This is conjectured to be
related to the fact that fluoride ion is superbly solvated in aqueous media, and that
electrophilic or radical fluorination mechanisms are unlikely).
(So basically nature needs the fluoride ion needs to be a nucleophile in aqueous
solution, but generally the sources are insoluble, and even the soluble ones provide
a fluoride ion so well solvated it is a terrible nucleophile).
.....In 2002 Discovered in 2002
5’-fluoro-5’-deoxyadenosine synthase, trivially termed the “fluorinase”
O'Hagan D, Schaffrath C, Cobb SL, Hamilton JT, Murphy CD. Biochemistry:
biosynthesis of an organofluorine molecule.
Nature. 2002 Mar 21;416(6878):279.
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NEWS OF THE WEEK
BIOSYNTHESIS
March 25, 2002
Volume 80, Number 12
CENEAR 80 12 p. 11
ISSN 0009-2347[Previous Story] [Next Story]
First Fluorinase Enzyme Discovered
STEVE RITTER - Fluorine is the most chemically reactive of all the elements. The
flip side to that property is that fluorine forms extremely stable compounds.
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For example, even though fluorine is the most abundant halogen in Earth's crust,
most of the element is tied up in insoluble fluoride minerals. That means naturally
occurring organofluorine compounds are rare--only 12 have been discovered--and
how these compounds are biosynthesized is largely unknown.
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Chemistry professor David O'Hagan and graduate student Christoph Schaffrath of
the University of St. Andrews, in Scotland, and coworkers have now found a clue by
uncovering the first known fluorinase enzyme [Nature, 416, 279 (2002)].
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The researchers show that the fluorinase can catalyze carbon-fluorine bond
formation between an organic substrate and fluoride ion.
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They studied the enzymatic fluorination by incubating a protein extract from
Streptomyces cattleya with potassium fluoride and S-adenosylmethionine
(shown). The initial product is 5´-fluoro-5´-deoxyadenosine, which is further
converted by other enzymes to fluoroacetate, FCH2CO2–. Fluoroacetate, which
has been identified in more than 40 plant species, is the most ubiquitous of the
known natural organofluorine compounds.
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Although chemists have developed a number of synthetic strategies to prepare
organofluorine compounds, discovery of the fluorinase enzyme "opens up a new
biotechnological opportunity," O'Hagan says, and could have broad applications
in medicinal chemistry.
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Prof. David O’Hagan
University of St. Andrews
Research at Centre for
Biomolecular Sciences
Chairman of Royal Society of
Chemistry, Fluorine Subject
Group
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Poland 2004.
(Durham Connections)
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