Organofluorine chemistry describes the
chemistry
Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that covers the Chemical element, elements that make up matter to the chemical compound, compounds made of atoms, molecules and ions ...
of the organofluorines,
organic compounds
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The s ...
that contain the
carbon–fluorine bond
The carbon–fluorine bond is a polar covalent bond between carbon and fluorine that is a component of all organofluorine compounds. It is one of the strongest single bonds in chemistry (after the B–F single bond, Si–F single bond, and H–F s ...
. Organofluorine compounds find diverse applications ranging from
oil
An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturated ...
and
water repellents to
pharmaceuticals
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
, refrigerants, and
reagent
In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
s in
catalysis
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
. In addition to these applications, some organofluorine compounds are
pollutant
A pollutant or novel entity is a substance or energy introduced into the environment that has undesired effects, or adversely affects the usefulness of a resource. These can be both naturally forming (i.e. minerals or extracted compounds like oi ...
s because of their contributions to
ozone depletion
Ozone depletion consists of two related events observed since the late 1970s: a steady lowering of about four percent in the total amount of ozone in Earth's atmosphere, and a much larger springtime decrease in stratospheric ozone (the ozone l ...
,
global warming
In common usage, climate change describes global warming—the ongoing increase in global average temperature—and its effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes to E ...
,
bioaccumulation
Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance at a rate faster than that at which the substance is lost or eliminated ...
, and
toxicity
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...
. The area of organofluorine chemistry often requires special techniques associated with the handling of fluorinating agents.
The carbon–fluorine bond
Fluorine has several distinctive differences from all other substituents encountered in organic molecules. As a result, the physical and chemical properties of organofluorines can be distinctive in comparison to other
organohalogens
Halocarbon compounds are chemicals in which one or more carbon atoms are linked by covalent bonds with one or more halogen atoms (fluorine, chlorine, bromine or iodine – ) resulting in the formation of organofluorine compounds, organochlorin ...
.
# The
carbon–fluorine bond
The carbon–fluorine bond is a polar covalent bond between carbon and fluorine that is a component of all organofluorine compounds. It is one of the strongest single bonds in chemistry (after the B–F single bond, Si–F single bond, and H–F s ...
is one of the strongest in organic chemistry (an average bond energy around 480 kJ/mol
[Kirsch, Peer ''Modern fluoroorganic chemistry: synthesis, reactivity, applications''. Wiley-VCH, 2004.]). This is significantly stronger than the bonds of carbon with other halogens (an average bond energy of e.g. C-Cl bond is around 320 kJ/mol
) and is one of the reasons why fluoroorganic compounds have high thermal and chemical stability.
# The
carbon–fluorine bond
The carbon–fluorine bond is a polar covalent bond between carbon and fluorine that is a component of all organofluorine compounds. It is one of the strongest single bonds in chemistry (after the B–F single bond, Si–F single bond, and H–F s ...
is relatively short (around 1.4 Å
).
# The
Van der Waals radius
The van der Waals radius, ''r'', of an atom is the radius of an imaginary hard sphere representing the distance of closest approach for another atom.
It is named after Johannes Diderik van der Waals, winner of the 1910 Nobel Prize in Physics, ...
of the fluorine substituent is only 1.47 Å,
which is shorter than in any other substituent and is close to that of hydrogen (1.2 Å). This, together with the short bond length, is the reason why there is no steric strain in polyfluorinated compounds. This is another reason for their high thermal stability. In addition, the fluorine substituents in polyfluorinated compounds efficiently shield the carbon skeleton from possible attacking reagents. This is another reason for the high chemical stability of polyfluorinated compounds.
# Fluorine has the highest
electronegativity
Electronegativity, symbolized as , is the tendency for an atom of a given chemical element to attract shared electrons (or electron density) when forming a chemical bond. An atom's electronegativity is affected by both its atomic number and the d ...
of all elements: 3.98.
This causes the high
dipole moment of C-F bond (1.41 D
).
# Fluorine has the lowest polarizability of all atoms: 0.56
10
−24 cm
3.
This causes very weak
dispersion forces
London dispersion forces (LDF, also known as dispersion forces, London forces, instantaneous dipole–induced dipole forces, fluctuating induced dipole bonds or loosely as van der Waals forces) are a type of intermolecular force acting between at ...
between polyfluorinated molecules and is the reason for the often-observed boiling point reduction on fluorination as well as for the simultaneous
hydrophobicity
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, th ...
and
lipophobicity Lipophobicity, also sometimes called lipophobia (from the Greek λιποφοβία from λίπος ''lipos'' "fat" and φόβος ''phobos'' "fear"), is a chemical property of chemical compounds which means "fat rejection", literally "fear of fat". ...
of polyfluorinated compounds whereas other perhalogenated compounds are more
lipophilic
Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipop ...
.
In comparison to aryl chlorides and bromides, aryl fluorides form
Grignard reagent
A Grignard reagent or Grignard compound is a chemical compound with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromide ...
s only reluctantly. On the other hand, aryl fluorides, e.g. fluoro
aniline
Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine
In organic chemistry, an aromatic amine is an organic compound consisting of an aroma ...
s and fluoro
phenol
Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it req ...
s, often undergo nucleophilic substitution efficiently.
Types of organofluorine compounds
Fluorocarbons
Formally,
fluorocarbon
Fluorocarbons are chemical compounds with carbon-fluorine bonds. Compounds that contain many C-F bonds often has distinctive properties, e.g., enhanced stability, volatility, and hydrophobicity. Fluorocarbons and their derivatives are commerci ...
s only contain carbon and fluorine. Sometimes they are called perfluorocarbons. They can be gases, liquids, waxes, or solids, depending upon their molecular weight. The simplest fluorocarbon is the gas tetrafluoromethane (CF
4). Liquids include perfluorooctane and perfluorodecalin. While fluorocarbons with single bonds are stable, unsaturated fluorocarbons are more reactive, especially those with triple bonds.
Fluorocarbon
Fluorocarbons are chemical compounds with carbon-fluorine bonds. Compounds that contain many C-F bonds often has distinctive properties, e.g., enhanced stability, volatility, and hydrophobicity. Fluorocarbons and their derivatives are commerci ...
s are more chemically and thermally stable than hydrocarbons, reflecting the relative inertness of the C-F bond. They are also relatively
lipophobic Lipophobicity, also sometimes called lipophobia (from the Greek λιποφοβία from λίπος ''lipos'' "fat" and φόβος ''phobos'' "fear"), is a chemical property of chemical compounds which means " fat rejection", literally "fear of fat". ...
. Because of the reduced intermolecular
van der Waals interactions, fluorocarbon-based compounds are sometimes used as lubricants or are highly volatile. Fluorocarbon liquids have medical applications as oxygen carriers.
The structure of organofluorine compounds can be distinctive. As shown below, perfluorinated aliphatic compounds tend to segregate from hydrocarbons. This "like dissolves like effect" is related to the usefulness of fluorous phases and the use of
PFOA
Perfluorooctanoic acid (PFOA; conjugate base perfluorooctanoate; also known colloquially as C8, for its 8 carbon chain structure) is a perfluorinated carboxylic acid produced and used worldwide as an industrial surfactant in chemical processes a ...
in processing of fluoropolymers. In contrast to the aliphatic derivatives, perfluoroaromatic derivatives tend to form mixed phases with nonfluorinated aromatic compounds, resulting from donor-acceptor interactions between the pi-systems.
Fluoropolymers
Polymeric organofluorine compounds are numerous and commercially significant. They range from fully fluorinated species, e.g.
PTFE
Polytetrafluoroethylene (PTFE) is a synthetic fluoropolymer of tetrafluoroethylene that has numerous applications. It is one of the best-known and widely applied PFAS. The commonly known brand name of PTFE-based composition is Teflon by Chemour ...
to partially fluorinated, e.g.
polyvinylidene fluoride
Polyvinylidene fluoride or polyvinylidene difluoride (PVDF) is a highly non-reactive thermoplastic fluoropolymer produced by the polymerization of vinylidene difluoride.
PVDF is a specialty plastic used in applications requiring the highest pur ...
(
2CF2">H2CF2sub>n) and
polychlorotrifluoroethylene
Polychlorotrifluoroethylene (PCTFE or PTFCE) is a thermoplastic chlorofluoropolymer with the molecular formula , where ''n'' is the number of monomer units in the polymer molecule. It is similar to polytetrafluoroethene (PTFE), except that it is a ...
(
2">FClCF2sub>n). The fluoropolymer polytetrafluoroethylene (PTFE/Teflon) is a solid.
Hydrofluorocarbons
Hydrofluorocarbons (HFCs), organic compounds that contain fluorine and hydrogen atoms, are the most common type of organofluorine compounds. They are commonly used in
air conditioning
Air conditioning, often abbreviated as A/C or AC, is the process of removing heat from an enclosed space to achieve a more comfortable interior environment (sometimes referred to as 'comfort cooling') and in some cases also strictly controlling ...
and as
refrigerants
A refrigerant is a working fluid used in the refrigeration cycle of air conditioning systems and heat pumps where in most cases they undergo a repeated phase transition from a liquid to a gas and back again. Refrigerants are heavily regulated due ...
[
] in place of the older
chlorofluorocarbon
Chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are fully or partly halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F), produced as volatile derivatives of methane, ethane, and prop ...
s such as
R-12 and hydrochlorofluorocarbons such as
R-21. They do not harm the ozone layer as much as the compounds they replace; however, they do contribute to
global warming
In common usage, climate change describes global warming—the ongoing increase in global average temperature—and its effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes to E ...
. Their atmospheric concentrations and contribution to
anthropogenic greenhouse gas emissions are rapidly increasing, causing international concern about their
radiative forcing
Radiative forcing (or climate forcing) is the change in energy flux in the atmosphere caused by natural or anthropogenic factors of climate change as measured by watts / metre2. It is a scientific concept used to quantify and compare the external ...
.
Fluorocarbons with few C-F
bonds behave similarly to the parent hydrocarbons, but their reactivity can be altered significantly. For example, both
uracil
Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by ...
and
5-fluorouracil
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancrea ...
are colourless, high-melting crystalline solids, but the latter is a potent anti-cancer drug. The use of the C-F bond in pharmaceuticals is predicated on this altered reactivity.
[G. Siegemund, W. Schwertfeger, A. Feiring, B. Smart, F. Behr, H. Vogel, B. McKusick "Fluorine Compounds, Organic" in "Ullmann's Encyclopedia of Industrial Chemistry" 2005, Wiley-VCH, Weinheim. ] Several drugs and
agrochemical
An agrochemical or agrichemical, a contraction of ''agricultural chemical'', is a chemical product used in industrial agriculture. Agrichemical refers to biocides ( pesticides including insecticides, herbicides, fungicides and nematicides) an ...
s contain only one fluorine center or one
trifluoromethyl
The trifluoromethyl group is a functional group that has the formula -CF3. The naming of is group is derived from the methyl group (which has the formula -CH3), by replacing each hydrogen atom by a fluorine atom. Some common examples are trifluorom ...
group.
Unlike other greenhouse gases in the
Paris Agreement
The Paris Agreement (french: Accord de Paris), often referred to as the Paris Accords or the Paris Climate Accords, is an international treaty on climate change. Adopted in 2015, the agreement covers climate change mitigation, Climate change a ...
, hydrofluorocarbons have other international negotiations.
In September 2016, the so-called New York Declaration urged a global reduction in the use of HFCs.
On 15 October 2016, due to these chemicals contribution to
climate change
In common usage, climate change describes global warming—the ongoing increase in global average temperature—and its effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes to E ...
, negotiators from 197 nations meeting at the summit of the
United Nations Environment Programme
The United Nations Environment Programme (UNEP) is responsible for coordinating responses to environmental issues within the United Nations system. It was established by Maurice Strong, its first director, after the United Nations Conference on th ...
in Kigali, Rwanda reached a legally-binding accord to phase out hydrofluorocarbons (HFCs) in an amendment to the
Montreal Protocol
The Montreal Protocol is an international treaty designed to protect the ozone layer by phasing out the production of numerous substances that are responsible for ozone depletion
Ozone depletion consists of two related events observed sinc ...
.
Fluorocarbenes
As indicated throughout this article, fluorine-substituents lead to reactivity that differs strongly from classical organic chemistry. The premier example is
difluorocarbene
Difluorocarbene is the chemical compound with formula CF2. It has a short half-life, 0.5 and 20 ms, in solution and in the gas phase, respectively.Douglas A Jean Osteraas "Difluorocarbene Modification of Polymer and Fiber Surfaces," ''Journal ...
, CF
2, which is a
singlet whereas
carbene
In organic chemistry, a carbene is a molecule containing a neutral carbon atom with a valence of two and two unshared valence electrons. The general formula is or where the R represents substituents or hydrogen atoms.
The term "carbene" ma ...
(CH
2) has a
triplet ground state. This difference is significant because difluorocarbene is a precursor to
tetrafluoroethylene
Tetrafluoroethylene (TFE) is a fluorocarbon with the chemical formula C2 F4. It is the simplest perfluorinated alkene. This gaseous species is used primarily in the industrial preparation of fluoropolymers.
Properties
Tetrafluoroethylene is a ...
.
Perfluorinated compounds
Perfluorinated compounds are fluorocarbon derivatives, as they are closely structurally related to fluorocarbons. However, they also possess new atoms such as
nitrogen
Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
,
iodine
Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...
, or ionic groups, such as
perfluorinated carboxylic acid
Perfluoroalkyl carboxylic acids (PFCAs), or perfluorocarboxylic acids are compounds of the formula CnF(2n+1)CO2H that belong to the class of per- and polyfluoroalkyl substances. The simplest example is trifluoroacetic acid. These compounds are o ...
s.
Methods for preparation of C–F bonds
Organofluorine compounds
Organofluorine chemistry describes the chemistry of the organofluorines, organic compounds that contain the carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from oil and water repellents to pharmaceuticals, ref ...
are prepared by numerous routes, depending on the degree and regiochemistry of fluorination sought and the nature of the precursors. The direct fluorination of hydrocarbons with F
2, often diluted with N
2, is useful for highly fluorinated compounds:
: + → +
Such reactions however are often unselective and require care because hydrocarbons can uncontrollably "burn" in , analogous to the
combustion
Combustion, or burning, is a high-temperature exothermic redox chemical reaction between a fuel (the reductant) and an oxidant, usually atmospheric oxygen, that produces oxidized, often gaseous products, in a mixture termed as smoke. Combusti ...
of hydrocarbon in . For this reason, alternative fluorination methodologies have been developed. Generally, such methods are classified into two classes.
Electrophilic fluorination
Electrophilic fluorination rely on sources of "F
+". Often such reagents feature N-F bonds, for example
F-TEDA-BF4. Asymmetric fluorination, whereby only one of two possible enantiomeric products are generated from a prochiral substrate, rely on electrophilic fluorination reagents. Illustrative of this approach is the preparation of a precursor to anti-inflammatory agents:
:
Electrosynthetic methods
A specialized but important method of electrophilic fluorination involves
electrosynthesis
Electrosynthesis in chemistry is the synthesis of chemical compounds in an electrochemical cell. Compared to ordinary redox reaction, electrosynthesis sometimes offers improved selectivity and yields. Electrosynthesis is actively studied as a scien ...
. The method is mainly used to perfluorinate, i.e. replace all C–H bonds by C–F bonds. The hydrocarbon is dissolved or suspended in liquid HF, and the mixture is
electrolyzed at 5–6
V using Ni
anodes
An anode is an electrode of a polarized electrical device through which conventional current enters the device. This contrasts with a cathode, an electrode of the device through which conventional current leaves the device. A common mnemonic is ...
.
The method was first demonstrated with the preparation of perfluoropyridine () from
pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a d ...
(). Several variations of this technique have been described, including the use of molten
potassium bifluoride
Potassium bifluoride is the inorganic compound with the formula . This colourless salt consists of the potassium cation () and the bifluoride anion (). The salt is used as an etchant for glass. Sodium bifluoride is related and is also of commercia ...
or organic
solvents
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for p ...
.
Nucleophilic fluorination
The major alternative to electrophilic fluorination is, naturally, nucleophilic fluorination using reagents that are sources of "F
−," for
Nucleophilic displacement
In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...
typically of chloride and bromide.
Metathesis reactions employing
alkali metal
The alkali metals consist of the chemical elements lithium (Li), sodium (Na), potassium (K),The symbols Na and K for sodium and potassium are derived from their Latin names, ''natrium'' and ''kalium''; these are still the origins of the names ...
fluorides are the simplest. For aliphatic compounds this is sometimes called the
Finkelstein reaction
The Finkelstein reaction named after the German chemist Hans Finkelstein, is an SN2 reaction (Substitution Nucleophilic Bimolecular reaction) that involves the exchange of one halogen atom for another. It is an equilibrium reaction, but the reac ...
, while for aromatic compounds it is known as the
Halex process
In chemistry, the Halex process is used to convert aromatic chlorides to the corresponding aromatic fluorides. The process entails ''Hal''ide ''ex''change, hence the name. The reaction conditions call for hot (150-250 °C) solution of the aryl ch ...
.
: + → + (M = Na, K, Cs)
Alkyl monofluorides can be obtained from alcohols and
Olah reagent The Olah reagent is a nucleophilic fluorinating agent. It consists of a mixture of 70% hydrogen fluoride and 30% pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, wit ...
(pyridinium fluoride) or another fluoridating agents.
The decomposition of aryldiazonium tetrafluoroborates in the
Sandmeyer or
Schiemann reaction Schiemann is a surname. Notable people with the surname include:
* Elisabeth Schiemann (1881–1972), German geneticist, crop researcher and resistance fighter in the Third Reich
* Konrad Schiemann, PC (born 1937), British barrister and judge
*Paul ...
s exploit
fluoroborate
Tetrafluoroborate is the anion . This tetrahedral species is isoelectronic with tetrafluoroberyllate (), tetrafluoromethane (CF4), and tetrafluoroammonium () and is valence isoelectronic with many stable and important species including the perchl ...
s as F
− sources.
: → + +
Although
hydrogen fluoride
Hydrogen fluoride (fluorane) is an inorganic compound with the chemical formula . This colorless gas or liquid is the principal industrial source of fluorine, often as an aqueous solution called hydrofluoric acid. It is an important feedstock i ...
may appear to be an unlikely nucleophile, it is the most common source of fluoride in the synthesis of organofluorine compounds. Such reactions are often catalysed by metal fluorides such as chromium trifluoride.
1,1,1,2-Tetrafluoroethane
1,1,1,2-Tetrafluoroethane (also known as norflurane (INN), R-134a, Freon 134a, Forane 134a, Genetron 134a, Green Gas, Florasol 134a, Suva 134a, or HFC-134a) is a hydrofluorocarbon (HFC) and haloalkane refrigerant with thermodynamic properties s ...
, a replacement for CFC's, is prepared industrially using this approach:
:
Cl2C=CClH + 4 HF → F
3CCFH
2 + 3 HCl
Notice that this transformation entails two reaction types, metathesis (replacement of Cl
− by F
−) and hydrofluorination of an
alkene
In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond.
Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
.
Deoxofluorination
Deoxofluorination agents effect the replacement
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
and
carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...
groups with one and two fluorides, respectively. One such reagent, useful for fluoride for oxide exchange in carbonyl compounds, is
sulfur tetrafluoride
Sulfur tetrafluoride is the chemical compound with the formula S F4. It is a colorless corrosive gas that releases dangerous HF upon exposure to water or moisture. Despite these unwelcome characteristics, this compound is a useful reagent for t ...
:
:RCO
2H + SF
4 → RCF
3 +
SO2 + HF
Alternates to SF
4 include the
diethylaminosulfur trifluoride
Diethylaminosulfur trifluoride (DAST) is the organosulfur compound with the formula Et2NSF3. This liquid is a fluorinating reagent used for the synthesis of organofluorine compounds. The compound is colourless; older samples assume an orange colou ...
(DAST, NEt
2SF
3) and
bis(2-methoxyethyl)aminosulfur trifluoride (deoxo-fluor). These organic reagents are easier to handle and more selective:
:
From fluorinated building blocks
Many organofluorine compounds are generated from reagents that deliver perfluoroalkyl and perfluoroaryl groups. (Trifluoromethyl)trimethylsilane, CF
3Si(CH
3)
3, is used as a source of the
trifluoromethyl
The trifluoromethyl group is a functional group that has the formula -CF3. The naming of is group is derived from the methyl group (which has the formula -CH3), by replacing each hydrogen atom by a fluorine atom. Some common examples are trifluorom ...
group, for example. Among the available fluorinated building blocks are CF
3X (X = Br, I), C
6F
5Br, and C
3F
7I. These species form
Grignard reagents
A Grignard reagent or Grignard compound is a chemical compound with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromide . ...
that then can be treated with a variety of
electrophile
In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carries ...
s. The development of fluorous technologies (see below, under solvents) is leading to the development of reagents for the introduction of "fluorous tails".
A special but significant application of the fluorinated building block approach is the synthesis of
tetrafluoroethylene
Tetrafluoroethylene (TFE) is a fluorocarbon with the chemical formula C2 F4. It is the simplest perfluorinated alkene. This gaseous species is used primarily in the industrial preparation of fluoropolymers.
Properties
Tetrafluoroethylene is a ...
, which is produced on a large-scale industrially via the intermediacy of difluorocarbene. The process begins with the thermal (600-800 °C) dehydrochlorination of
chlorodifluoromethane
Chlorodifluoromethane or difluoromonochloromethane is a hydrochlorofluorocarbon (HCFC). This colorless gas is better known as HCFC-22, or R-22, or . It was commonly used as a propellant and refrigerant. These applications were phased out under ...
:
[
:CHClF2 → CF2 + HCl
:2 CF2 → C2F4
Sodium fluorodichloroacetate (CAS# 2837-90-3) is used to generate chlorofluorocarbene, for cyclopropanations.
]
18F-Delivery methods
The usefulness of fluorine-containing radiopharmaceutical
Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which is ...
s in 18F-positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
has motivated the development of new methods for forming C–F bonds. Because of the short half-life of 18F, these syntheses must be highly efficient, rapid, and easy. Illustrative of the methods is the preparation of fluoride-modified glucose by displacement of a triflate
In organic chemistry, triflate (systematic name: trifluoromethanesulfonate), is a functional group with the formula and structure . The triflate group is often represented by , as opposed to −Tf, which is the triflyl group, . For example, ' ...
by a labeled fluoride nucleophile:
:
Biological role
Biologically synthesized organofluorines have been found in microorganisms and plants, but not animals.[Murphy CD, Schaffrath C, O'Hagan D.]
"Fluorinated natural products: the biosynthesis of fluoroacetate and 4-fluorothreonine in ''Streptomyces cattleya''"
Chemosphere. 2003 Jul;52(2):455-61. The most common example is fluoroacetate, which occurs as a plant defence against herbivores
Plant defense against herbivory or host-plant resistance (HPR) describes a range of adaptations evolved by plants which improve their survival and reproduction by reducing the impact of herbivores. Plants can sense being touched, and they can ...
in at least 40 plants in Australia, Brazil and Africa. Other biologically synthesized organofluorines include ω-fluoro fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
s, fluoroacetone
Fluoroacetone is an organofluorine compound with the chemical formula . In contrast to trifluoroacetone, the compound has one fluorine atom. Under normal conditions, the substance is a colorless liquid. Fluoroacetone is also a highly toxic and fl ...
, 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
An agrochemical or agrichemical, a contraction of ''agricultural chemical'', is a chemical product used in industrial agriculture. Agrichemical refers to biocides ( pesticides including insecticides, herbicides, fungicides and nematicides) an ...
because it adds stability to the carbon framework; also, the relatively small size of fluorine is convenient as fluorine acts as an approximate bioisostere
In medicinal chemistry, bioisosteres are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to another chemical compound. In drug design, the purpose of exchanging one bi ...
of the hydrogen. 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
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancrea ...
, fluoxetine
Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...
(Prozac), paroxetine
Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder ...
(Paxil), ciprofloxacin
Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infec ...
(Cipro), mefloquine
Mefloquine, sold under the brand name Lariam among others, is a medication used to prevent or treat malaria. When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure. It ...
, and fluconazole
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent ...
.
Applications
Organofluorine chemistry impacts many areas of everyday life and technology. The C-F bond is found in pharmaceutical
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
s, agrichemicals, fluoropolymers
A fluoropolymer is a fluorocarbon-based polymer with multiple carbon–fluorine bonds. It is characterized by a high resistance to solvents, acids, and bases. The best known fluoropolymer is polytetrafluoroethylene under the brand name "Teflon," ...
, refrigerants
A refrigerant is a working fluid used in the refrigeration cycle of air conditioning systems and heat pumps where in most cases they undergo a repeated phase transition from a liquid to a gas and back again. Refrigerants are heavily regulated due ...
, surfactants
Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsion#Emulsifiers , ...
, anesthetics
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
, oil-repellents, catalysis
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
, and water-repellents, among others.
Pharmaceuticals and agrochemicals
The carbon-fluorine bond is commonly found in pharmaceuticals and agrochemicals because it is generally metabolically stable and fluorine acts as a bioisostere
In medicinal chemistry, bioisosteres are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to another chemical compound. In drug design, the purpose of exchanging one bi ...
of the hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic, an ...
atom. An estimated 1/5 of pharmaceuticals contain fluorine, including several of the top drugs. Examples include 5-fluorouracil
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancrea ...
, flunitrazepam
Flunitrazepam, also known as Rohypnol among other names, is a benzodiazepine used to treat severe insomnia and assist with anesthesia. As with other hypnotics, flunitrazepam has been advised to be prescribed only for short-term use or by those ...
(Rohypnol), fluoxetine
Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...
(Prozac), paroxetine
Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder ...
(Paxil), ciprofloxacin
Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infec ...
(Cipro), mefloquine
Mefloquine, sold under the brand name Lariam among others, is a medication used to prevent or treat malaria. When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure. It ...
, and fluconazole
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent ...
. Fluorine-substituted ethers
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...
are volatile anesthetic
An inhalational anesthetic is a chemical compound possessing general anesthetic properties that can be delivered via inhalation. They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vapori ...
s, including the commercial products methoxyflurane
Methoxyflurane, sold under the brand name Penthrox among others, is an inhaled medication primarily used to reduce pain following trauma. It may also be used for short episodes of pain as a result of medical procedures. Onset of pain relief is ...
, enflurane
Enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether) is a halogenated ether. Developed by Ross Terrell in 1963, it was first used clinically in 1966. It was increasingly used for inhalational anesthesia during the 1970s and 1980s but is ...
, isoflurane
Isoflurane, sold under the brand name Forane among others, is a general anesthetic. It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia rather than isoflurane, due to airway irritation w ...
, sevoflurane
Sevoflurane, sold under the brand name Sevorane, among others, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflura ...
and desflurane
Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether) is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane, and isoflurane, it is a racemic mixture of (''R'') and (''S'') optical i ...
. Fluorocarbon anesthetics reduce the hazard of flammability with diethyl ether
Diethyl ether, or simply ether, is an organic compound in the ether class with the formula , sometimes abbreviated as (see Pseudoelement symbols). It is a colourless, highly volatile, sweet-smelling ("ethereal odour"), extremely flammable liq ...
and cyclopropane
Cyclopropane is the cycloalkane with the molecular formula (CH2)3, consisting of three methylene groups (CH2) linked to each other to form a ring. The small size of the ring creates substantial ring strain in the structure. Cyclopropane itself ...
. Perfluorinated alkanes are used as blood substitute
A blood substitute (also called artificial blood or blood surrogate) is a substance used to mimic and fulfill some functions of biological blood. It aims to provide an alternative to blood transfusion, which is transferring blood or blood-based ...
s.
Inhaler propellant
Fluorocarbons are also used as a propellant for metered-dose inhaler
A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the lungs, in the form of a short burst of aerosolized medicine that is usually self-administered by the patient via inhalation. It is the most commonly used ...
s used to administer some asthma medications. The current generation of propellant consists of hydrofluoroalkanes (HFA), which have replaced CFC-propellant-based inhalers. CFC inhalers were banned as part of the Montreal Protocol
The Montreal Protocol is an international treaty designed to protect the ozone layer by phasing out the production of numerous substances that are responsible for ozone depletion
Ozone depletion consists of two related events observed sinc ...
because of environmental concerns with the ozone layer. HFA propellant inhalers like FloVent and ProAir ( Salbutamol
Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing rel ...
) have no generic versions available as of October 2014.
Fluorosurfactants
Fluorosurfactants, which have a polyfluorinated "tail" and a hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are no ...
"head", serve as surfactants
Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsion#Emulsifiers , ...
because they concentrate at the liquid-air interface due to their lipophobicity Lipophobicity, also sometimes called lipophobia (from the Greek λιποφοβία from λίπος ''lipos'' "fat" and φόβος ''phobos'' "fear"), is a chemical property of chemical compounds which means "fat rejection", literally "fear of fat". ...
. Fluorosurfactants have low surface energies and dramatically lower surface tension. The fluorosurfactants perfluorooctanesulfonic acid
Perfluorooctanesulfonic acid (PFOS) (conjugate base perfluorooctanesulfonate) is a chemical compound having an eight-carbon fluorocarbon chain and a sulfonic acid functional group and thus a perfluorosulfonic acid. It is an anthropogenic (man-ma ...
(PFOS) and perfluorooctanoic acid
Perfluorooctanoic acid (PFOA; conjugate base perfluorooctanoate; also known colloquially as C8, for its 8 carbon chain structure) is a perfluorinated carboxylic acid produced and used worldwide as an industrial surfactant in chemical processes an ...
(PFOA) are two of the most studied because of their ubiquity, toxicity, and long residence times in humans and wildlife.
Solvents
Fluorinated compounds often display distinct solubility properties. Dichlorodifluoromethane
Dichlorodifluoromethane (R-12) is a colorless gas usually sold under the brand name Freon-12, and a chlorofluorocarbon halomethane (CFC) used as a refrigerant and aerosol spray propellant. Complying with the Montreal Protocol, its manufacture was ...
and chlorodifluoromethane
Chlorodifluoromethane or difluoromonochloromethane is a hydrochlorofluorocarbon (HCFC). This colorless gas is better known as HCFC-22, or R-22, or . It was commonly used as a propellant and refrigerant. These applications were phased out under ...
were at one time widely used refrigerants. CFCs have potent ozone depletion
Ozone depletion consists of two related events observed since the late 1970s: a steady lowering of about four percent in the total amount of ozone in Earth's atmosphere, and a much larger springtime decrease in stratospheric ozone (the ozone l ...
potential due to the homolytic cleavage of the carbon-chlorine bonds; their use is largely prohibited by the Montreal Protocol
The Montreal Protocol is an international treaty designed to protect the ozone layer by phasing out the production of numerous substances that are responsible for ozone depletion
Ozone depletion consists of two related events observed sinc ...
. Hydrofluorocarbons
Hydrofluorocarbons (HFCs) are man-made organic compounds that contain fluorine and hydrogen atoms, and are the most common type of organofluorine compounds. Most are gases at room temperature and pressure. They are frequently used in air conditi ...
(HFCs), such as tetrafluoroethane
1,1,1,2-Tetrafluoroethane (also known as norflurane (INN), R-134a, Freon 134a, Forane 134a, Genetron 134a, Green Gas, Florasol 134a, Suva 134a, or HFC-134a) is a hydrofluorocarbon (HFC) and haloalkane refrigerant with thermodynamic properties si ...
, serve as CFC replacements because they do not catalyze ozone depletion. Oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
exhibits a high solubility in perfluorocarbon compounds, reflecting on their lipophilicity. Perfluorodecalin
Perfluorodecalin () is a fluorocarbon, a derivative of decalin in which all of the hydrogen atoms are replaced by fluorine atoms. It is chemically and biologically inert and stable up to 400 °C. Several applications make use of its ability to di ...
has been demonstrated as a blood substitute
A blood substitute (also called artificial blood or blood surrogate) is a substance used to mimic and fulfill some functions of biological blood. It aims to provide an alternative to blood transfusion, which is transferring blood or blood-based ...
transporting oxygen to the lungs.
The solvent 1,1,1,2-tetrafluoroethane
1,1,1,2-Tetrafluoroethane (also known as norflurane (INN), R-134a, Freon 134a, Forane 134a, Genetron 134a, Green Gas, Florasol 134a, Suva 134a, or HFC-134a) is a hydrofluorocarbon (HFC) and haloalkane refrigerant with thermodynamic properties s ...
has been used for extraction of natural products
A natural product is a natural Chemical compound, compound or chemical substance, substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural product ...
such as taxol
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cance ...
, evening primrose oil
''Oenothera biennis'', the common evening-primrose, is a species of flowering plant in the family Onagraceae, native to eastern and central North America, from Newfoundland west to Alberta, southeast to Florida, and southwest to Texas, and widely ...
, and vanillin
Vanillin is an organic compound with the molecular formula . It is a phenolic aldehyde. Its functional groups include aldehyde, hydroxyl, and ether. It is the primary component of the extract of the vanilla bean. Synthetic vanillin is now used ...
. 2,2,2-trifluoroethanol
2,2,2-Trifluoroethanol is the organic compound with the formula CF3CH2OH. Also known as TFE or trifluoroethyl alcohol, this colourless, water-miscible liquid has a smell reminiscent of ethanol. Due to the electronegativity of the trifluoromethy ...
is an oxidation-resistant polar solvent.
Organofluorine reagents
The development of organofluorine chemistry has contributed many reagents of value beyond organofluorine chemistry. Triflic acid
Triflic acid, the short name for trifluoromethanesulfonic acid, TFMS, TFSA, HOTf or TfOH, is a sulfonic acid with the chemical formula CF3SO3H. It is one of the strongest known acids. Triflic acid is mainly used in research as a catalyst for este ...
(CF3SO3H) and trifluoroacetic acid
Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It is a structural analogue of acetic acid with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with a ...
(CF3CO2H) are useful throughout organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
. Their strong acidity is attributed to the electronegativity
Electronegativity, symbolized as , is the tendency for an atom of a given chemical element to attract shared electrons (or electron density) when forming a chemical bond. An atom's electronegativity is affected by both its atomic number and the d ...
of the trifluoromethyl
The trifluoromethyl group is a functional group that has the formula -CF3. The naming of is group is derived from the methyl group (which has the formula -CH3), by replacing each hydrogen atom by a fluorine atom. Some common examples are trifluorom ...
group that stabilizes the negative charge. The triflate-group (the conjugate base of the triflic acid) is a good leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited t ...
in substitution reactions.
Fluorous phases
Of topical interest in the area of "Green Chemistry," highly fluorinated substituents, e.g. perfluorohexyl (C6F13) confer distinctive solubility properties to molecules, which facilitates purification of products in organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
. This area, described as "fluorous
Fluorous chemistry involves the use of perfluorinated compounds or perfluorinated substituents to facilitate recovery of a catalyst or reaction product. Perfluorinated groups impart unique physical properties including high solubility in perfluor ...
chemistry," exploits the concept of like-dissolves-like in the sense that fluorine-rich compounds dissolve preferentially in fluorine-rich solvents. Because of the relative inertness of the C-F bond, such fluorous phases are compatible with even harsh reagents. This theme has spawned techniques of "fluorous tagging'' and ''fluorous protection''. Illustrative of fluorous technology is the use of fluoroalkyl-substituted tin hydrides for reductions, the products being easily separated from the spent tin reagent by extraction using fluorinated solvents.
Hydrophobic fluorinated ionic liquid
An ionic liquid (IL) is a salt in the liquid state. In some contexts, the term has been restricted to salts whose melting point is below a specific temperature, such as . While ordinary liquids such as water and gasoline are predominantly made of ...
s, such as organic salts of bistriflimide
Bistriflimide, also known variously as bis(trifluoromethane)sulfonimide, bis(trifluoromethanesulfonyl)amide, bis(trifluoromethanesulfonyl)imidate (and variations thereof), informally and somewhat inaccurately as triflimide or triflimidate'','' or ...
or hexafluorophosphate
Hexafluorophosphate is an anion with chemical formula of . It is an octahedral species that imparts no color to its salts. is isoelectronic with sulfur hexafluoride, , and the hexafluorosilicate dianion, , and hexafluoroantimonate . In this anio ...
, can form phases that are insoluble in both water and organic solvents, producing multiphasic liquid A multiphasic liquid is a mixture consisting of more than two immiscible liquid phases. Biphasic mixtures consisting of two immiscible phases are very common and usually consist of an organic solvent and an aqueous phase ("oil and water").
Multip ...
s.
Organofluorine ligands in transition metal chemistry
Organofluorine ligands have long been featured in organometallic
Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and so ...
and coordination chemistry
A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...
. One advantage to F-containing ligands is the convenience of 19F NMR spectroscopy for monitoring reactions. The organofluorine compounds can serve as a "sigma-donor ligand," as illustrated by the titanium(III) derivative 5Me5)2Ti(FC6H5)">C5Me5)2Ti(FC6H5)Ph4. Most often, however, fluorocarbon substituents are used to enhance the Lewis acid
A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any sp ...
ity of metal centers. A premier example is " Eufod," a coordination complex of europium(III) that features a perfluoroheptyl modified acetylacetonate
Acetylacetone is an organic compound with the chemical formula . It is a colorless liquid, classified as a 1,3-diketone. It exists in equilibrium with a tautomer . These tautomers interconvert so rapidly under most conditions that they are tr ...
ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
. This and related species are useful in organic synthesis and as "shift reagents" in NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...
.
In an area where coordination chemistry and materials science overlap, the fluorination of organic ligands is used to tune the properties of component molecules. For example, the degree and regiochemistry of fluorination of metalated 2-phenylpyridine ligands in platinum(II) complexes significantly modifies the emission properties of the complexes.
The coordination chemistry of organofluorine ligands also embraces fluorous technologies. For example, triphenylphosphine
Triphenylphosphine (IUPAC name: triphenylphosphane) is a common organophosphorus compound with the formula P(C6H5)3 and often abbreviated to P Ph3 or Ph3P. It is widely used in the synthesis of organic and organometallic compounds. PPh3 exists a ...
has been modified by attachment of perfluoroalkyl substituents that confer solubility in perfluorohexane
Perfluorohexane (), or tetradecafluorohexane, is a fluorocarbon. It is a derivative of hexane in which all of the hydrogen atoms are replaced by fluorine atoms. It is used in one formulation of the electronic cooling liquid/insulator Fluorinert ...
as well as supercritical carbon dioxide
Supercritical carbon dioxide (s) is a fluid state of carbon dioxide where it is held at or above its critical temperature and critical pressure.
Carbon dioxide usually behaves as a gas in air at standard temperature and pressure (STP), or as ...
. As a specific example, [(C8F17C3H6-4-C6H4)3P.
C-F bond activation
An active area of organometallic chemistry encompasses the scission of C-F bonds by transition metal-based reagents. Both stoichiometric and catalytic reactions have been developed and are of interest from the perspectives of organic synthesis and remediation of xenochemicals. C-F bond activation has been classified as follows "(i) oxidative addition of fluorocarbon, (ii) M–C bond formation with HF elimination, (iii) M–C bond formation with fluorosilane elimination, (iv) hydrodefluorination of fluorocarbon with M–F bond formation, (v) nucleophilic attack on fluorocarbon, and (vi) defluorination of fluorocarbon". An illustrative metal-mediated C-F activation reaction is the defluorination of fluorohexane by a zirconium dihydride
In chemistry, a hydride is formally the anion of hydrogen( H−). The term is applied loosely. At one extreme, all compounds containing covalently bound H atoms are called hydrides: water (H2O) is a hydride of oxygen, ammonia is a hydride of ...
, an analogue of Schwartz's reagent
Schwartz's reagent is the common name for the organozirconium compound with the formula (C5H5)2ZrHCl, sometimes called zirconocene hydrochloride or zirconocene chloride hydride, and is named after Jeffrey Schwartz, a chemistry professor at Prince ...
:
:(C5Me5)2ZrH2 + 1-FC6H13 → (C5Me5)2ZrH(F) + C6H14
Fluorocarbon anions in Ziegler-Natta catalysis
Fluorine-containing compounds are often featured in noncoordinating or weakly coordinating anions. Both tetrakis(pentafluorophenyl)borate, B(C6F5)4−, and the related tetrakis orate">,5-bis(trifluoromethyl)phenylorate, are useful in Ziegler-Natta catalysis and related alkene polymerization methodologies. The fluorinated substituents render the anions weakly basic and enhance the solubility in weakly basic solvents, which are compatible with strong Lewis acids.
Materials science
Organofluorine compounds enjoy many niche applications in materials science. With a low coefficient of friction
Friction is the force resisting the relative motion of solid surfaces, fluid layers, and material elements sliding against each other. There are several types of friction:
*Dry friction is a force that opposes the relative lateral motion of ...
, fluid fluoropolymers are used as specialty lubricants. Fluorocarbon-based greases are used in demanding applications. Representative products include Fomblin and Krytox
Krytox is a registered trademark of The Chemours Company. It refers to a group of colourless synthetic lubricants (oils and greases) with a variety of applications. Invented by researchers at DuPont, Krytox oils are fluorocarbon ether polyme ...
, made by Solvay Solexis and DuPont
DuPont de Nemours, Inc., commonly shortened to DuPont, is an American multinational chemical company first formed in 1802 by French-American chemist and industrialist Éleuthère Irénée du Pont de Nemours. The company played a major role in ...
, respectively. Certain firearm lubricants such as "Tetra Gun" contain fluorocarbons. Capitalizing on their nonflammability, fluorocarbons are used in fire fighting foam. Organofluorine compounds are components of liquid crystal display
A liquid-crystal display (LCD) is a flat panel display, flat-panel display or other Electro-optic modulator, electronically modulated optical device that uses the light-modulating properties of liquid crystals combined with polarizers. Liqui ...
s. The polymeric analogue of triflic acid, nafion
Nafion is a brand name for a sulfonated tetrafluoroethylene based fluoropolymer-copolymer discovered in the late 1960s by Dr. Walther Grot of DuPont. Nafion is a brand of the Chemours company. It is the first of a class of synthetic polymers with ...
is a solid acid that is used as the membrane in most low temperature fuel cell
A fuel cell is an electrochemical cell that converts the chemical energy of a fuel (often hydrogen) and an oxidizing agent (often oxygen) into electricity through a pair of redox reactions. Fuel cells are different from most batteries in requ ...
s. The bifunctional monomer 4,4'-difluorobenzophenone is a precursor to PEEK
Polyether ether ketone (PEEK) is a colourless organic thermoplastic polymer in the polyaryletherketone (PAEK) family, used in engineering applications. The polymer was first developed in November 1978, later being introduced to the market by Vic ...
-class polymers.
Biosynthesis of organofluorine compounds
:
In contrast to the many naturally-occurring organic compounds containing the heavier halide
In chemistry, a halide (rarely halogenide) is a binary chemical compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative (or more electropositive) than the halogen, to make a fluor ...
s, chloride, bromide, and iodide, only a handful of biologically synthesized carbon-fluorine bonds are known. The most common natural organofluorine species is fluoroacetate
Fluoroacetate may refer to:
* Fluoroacetic acid
* Sodium fluoroacetate
Sodium fluoroacetate is an organofluorine chemical compound with the formula FCH2CO2Na. This colourless salt has a taste similar to that of sodium chloride and is used as a r ...
, a toxin found in a few species of plants. Others include fluorooleic acid, fluoroacetone
Fluoroacetone is an organofluorine compound with the chemical formula . In contrast to trifluoroacetone, the compound has one fluorine atom. Under normal conditions, the substance is a colorless liquid. Fluoroacetone is also a highly toxic and fl ...
, nucleocidin (4'-fuoro-5'-O-sulfamoyladenosine), fluorothreonine, and 2-fluorocitrate. Several of these species are probably biosynthesized from fluoroacetaldehyde
Fluoroacetaldehyde is a metabolic precursor of both fluoroacetate and 4-fluorothreonine in ''Streptomyces cattleya''.
References
{{reflist
Organofluorides
Aldehydes
Fluorine-containing natural products ...
. The enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
fluorinase
The fluorinase enzyme (, also known as adenosyl-fluoride synthase) catalyzes the reaction between fluoride ion and the co-factor '' S'' -adenosyl-L-methionine to generate L-methionine and 5'-fluoro-5'-deoxyadenosine, the first committed product ...
catalyzed the synthesis of 5'-deoxy-5'-fluoroadenosine (see scheme to right).
History
Organofluorine chemistry began in the 1800s with the development of organic chemistry. The first organofluorine compounds were prepared using antimony trifluoride
Antimony trifluoride is the inorganic compound with the formula SbF3. Sometimes called Swarts' reagent, is one of two principal fluorides of antimony, the other being SbF5. It appears as a white solid. As well as some industrial applications, ...
as the F− source. The nonflammability and nontoxicity of the chlorofluorocarbon
Chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are fully or partly halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F), produced as volatile derivatives of methane, ethane, and prop ...
s CCl3F and CCl2F2 attracted industrial attention in the 1920s. On April 6, 1938, Roy J. Plunkett
Roy J. Plunkett (June 26, 1910 – May 12, 1994) was an American chemist. He discovered polytetrafluoroethylene (PTFE), better known as Teflon, in 1938.
Personal life and education
Plunkett was born in New Carlisle, Ohio and attended Newton Hig ...
a young research chemist who worked at DuPont
DuPont de Nemours, Inc., commonly shortened to DuPont, is an American multinational chemical company first formed in 1802 by French-American chemist and industrialist Éleuthère Irénée du Pont de Nemours. The company played a major role in ...
's Jackson Laboratory in Deepwater, New Jersey
Deepwater is an unincorporated community located within Pennsville Township, in Salem County, New Jersey, United States.Lo ...
, accidentally discovered polytetrafluoroethylene
Polytetrafluoroethylene (PTFE) is a synthetic fluoropolymer of tetrafluoroethylene that has numerous applications. It is one of the best-known and widely applied PFAS. The commonly known brand name of PTFE-based composition is Teflon by Chemour ...
(PTFE). Subsequent major developments, especially in the US, benefited from expertise gained in the production of uranium hexafluoride.[
Starting in the late 1940s, a series of electrophilic fluorinating methodologies were introduced, beginning with CoF3. Electrochemical fluorination (" electrofluorination") was announced, which Joseph H. Simons had developed in the 1930s to generate highly stable perfluorinated materials compatible with ]uranium hexafluoride
Uranium hexafluoride (), (sometimes called "hex") is an inorganic compound with the formula UF6. Uranium hexafluoride is a volatile white solid that reacts with water, releasing corrosive hydrofluoric acid. The compound reacts mildly with alumin ...
.[ These new methodologies allowed the synthesis of C-F bonds without using elemental fluorine and without relying on metathetical methods.
In 1957, the anticancer activity of 5-fluorouracil was described. This report provided one of the first examples of rational design of drugs. This discovery sparked a surge of interest in fluorinated pharmaceuticals and agrichemicals. The discovery of the ]noble gas compound
In chemistry, noble gas compounds are chemical compounds that include an element from the noble gases, group 18 of the periodic table. Although the noble gases are generally unreactive elements, many such compounds have been observed, particular ...
s, e.g. XeF4, provided a host of new reagents starting in the early 1960s. In the 1970s, fluorodeoxyglucose
18F.html" ;"title="sup>18F">sup>18Fluorodeoxyglucose ( INN), or fluorodeoxyglucose F 18 (USAN and USP), also commonly called fluorodeoxyglucose and abbreviated 18F.html" ;"title="sup>18F">sup>18FDG, 2- 18F.html" ;"title="sup>18F">sup>18FDG or ...
was established as a useful reagent in 18F positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
. In Nobel Prize-winning work, CFC's were shown to contribute to the depletion of atmospheric ozone. This discovery alerted the world to the negative consequences of organofluorine compounds and motivated the development of new routes to organofluorine compounds. In 2002, the first C-F bond-forming enzyme, fluorinase
The fluorinase enzyme (, also known as adenosyl-fluoride synthase) catalyzes the reaction between fluoride ion and the co-factor '' S'' -adenosyl-L-methionine to generate L-methionine and 5'-fluoro-5'-deoxyadenosine, the first committed product ...
, was reported.
Environmental and health concerns
Only a few organofluorine compounds are acutely bioactive and highly toxic, such as fluoroacetate and perfluoroisobutene.
Some organofluorine compounds pose significant risks and dangers to health and the environment. CFCs and HCFCs (hydrochlorofluorocarbon
Chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are fully or partly halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F), produced as volatile derivatives of methane, ethane, and propan ...
) deplete the ozone layer and are potent greenhouse gases
A greenhouse gas (GHG or GhG) is a gas that absorbs and emits radiant energy within the thermal infrared range, causing the greenhouse effect. The primary greenhouse gases in Earth's atmosphere are water vapor (), carbon dioxide (), methane ...
. HFCs are potent greenhouse gases and are facing calls for stricter international regulation and phase out schedules as a fast-acting greenhouse emission abatement measure, as are perfluorocarbons
Fluorocarbons are chemical compounds with carbon-fluorine bonds. Compounds that contain many C-F bonds often has distinctive properties, e.g., enhanced stability, volatility, and hydrophobicity. Fluorocarbons and their derivatives are commerci ...
(PFCs), and sulphur hexafluoride (SF6).
Because of the compound's effect on climate, the G-20 major economies
The G20 or Group of Twenty is an Intergovernmental organization, intergovernmental forum comprising 19 countries and the European Union (EU). It works to address major issues related to the World economy, global economy, such as international f ...
agreed in 2013 to support initiatives to phase out use of HCFCs. They affirmed the roles of the Montreal Protocol
The Montreal Protocol is an international treaty designed to protect the ozone layer by phasing out the production of numerous substances that are responsible for ozone depletion
Ozone depletion consists of two related events observed sinc ...
and the United Nations Framework Convention on Climate Change
The United Nations Framework Convention on Climate Change (UNFCCC) established an international environmental treaty to combat "dangerous human interference with the climate system", in part by stabilizing greenhouse gas concentrations in th ...
in global HCFC accounting and reduction. The U.S. and China at the same time announced a bilateral agreement to similar effect.
Persistence and bioaccumulation
Because of the strength of the carbon–fluorine bond, many synthetic fluorocarbons and fluorocarbon-based compounds are persistent in the environment. Fluorosurfactants, such as PFOS
Perfluorooctanesulfonic acid (PFOS) (conjugate base perfluorooctanesulfonate) is a chemical compound having an eight-carbon fluorocarbon chain and a sulfonic acid functional group and thus a perfluorosulfonic acid. It is an anthropogenic (man ...
and PFOA
Perfluorooctanoic acid (PFOA; conjugate base perfluorooctanoate; also known colloquially as C8, for its 8 carbon chain structure) is a perfluorinated carboxylic acid produced and used worldwide as an industrial surfactant in chemical processes a ...
, are persistent global contaminants. Fluorocarbon based CFCs and tetrafluoromethane
Tetrafluoromethane, also known as carbon tetrafluoride or R-14, is the simplest perfluorocarbon ( C F4). As its IUPAC name indicates, tetrafluoromethane is the perfluorinated counterpart to the hydrocarbon methane. It can also be classified as a h ...
have been reported in igneous
Igneous rock (derived from the Latin word ''ignis'' meaning fire), or magmatic rock, is one of the three main rock types, the others being sedimentary and metamorphic. Igneous rock is formed through the cooling and solidification of magma or ...
and metamorphic rock
Metamorphic rocks arise from the transformation of existing rock to new types of rock in a process called metamorphism. The original rock (protolith) is subjected to temperatures greater than and, often, elevated pressure of or more, causin ...
. PFOS is a persistent organic pollutant
Persistent organic pollutants (POPs), sometimes known as "forever chemicals", are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. They are toxic chemicals that adversely ...
and may be harming the health of wildlife; the potential health effects of PFOA to humans are under investigation by the C8 Science Panel.
See also
* Hydrofluoroolefin
Hydrofluoroolefins (HFOs) are unsaturated organic compounds composed of hydrogen, fluorine and carbon. These organofluorine compound are of interest as refrigerants. Unlike traditional hydrofluorocarbons (HFCs) and chlorofluorocarbons (CFCs), whic ...
References
{{reflist, 30em
Organofluorides