Organofluorine
Encyclopedia
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
chemical compounds that contain carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
and fluorine
Fluorine
Fluorine is the chemical element with atomic number 9, represented by the symbol F. It is the lightest element of the halogen column of the periodic table and has a single stable isotope, fluorine-19. At standard pressure and temperature, fluorine is a pale yellow gas composed of diatomic...
bonded
Chemical bond
A chemical bond is an attraction between atoms that allows the formation of chemical substances that contain two or more atoms. The bond is caused by the electromagnetic force attraction between opposite charges, either between electrons and nuclei, or as the result of a dipole attraction...
in the polarized and remarkably strong carbon–fluorine bond
Carbon–fluorine bond
The carbon–fluorine bond is a bond between carbon and fluorine that is a component of all organofluorine compounds. It is the strongest single bond in organic chemistry—and relatively short—due to its partial ionic character. The bond also strengthens and shortens as more fluorines are...
. Organofluorine compounds are diverse, they can be fluorocarbon
Fluorocarbon
Fluorocarbons, sometimes referred to as perfluorocarbons or PFCs, are organofluorine compounds that contain only carbon and fluorine bonded together in strong carbon–fluorine bonds. Fluoroalkanes that contain only single bonds are more chemically and thermally stable than alkanes...
s, perfluorinated, or biologically synthesized mono-fluorinated compounds, among other possibilities. These compounds have a wide range of function and can serve as refrigerants, pharmaceuticals
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
, agrichemical
Agrichemical
Agrochemical , a contraction of agricultural chemical, is a generic term for the various chemical products used in agriculture. In most cases, agrichemical refers to the broad range of pesticides, including insecticides, herbicides, and fungicides...
s, surfactant
Surfactant
Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...
s, ozone depletors, poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
s, or pollutants
Pollution
Pollution is the introduction of contaminants into a natural environment that causes instability, disorder, harm or discomfort to the ecosystem i.e. physical systems or living organisms. Pollution can take the form of chemical substances or energy, such as noise, heat or light...
.
Bond
The carbon–fluorine bond is referred to as the strongest in organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
because of stability added by its partial ionic character; it forms the strongest single bond to carbon. The ionic character is a result of the electronegativity of fluorine. It induces partial charges on the carbon and fluorine atoms, leading to electrostatic attraction, making the bond short and strong.
Compounds
Organofluorine compounds that have the carbon–fluorine bond are diverse in their types. They can be fluorocarbonFluorocarbon
Fluorocarbons, sometimes referred to as perfluorocarbons or PFCs, are organofluorine compounds that contain only carbon and fluorine bonded together in strong carbon–fluorine bonds. Fluoroalkanes that contain only single bonds are more chemically and thermally stable than alkanes...
s, fluorocarbon derivatives, fluorinated pharmaceuticals and agrichemicals, or mono-fluorinated biologically synthesized compounds, among others. Fluorocarbons are compounds that contain only carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
and fluorine
Fluorine
Fluorine is the chemical element with atomic number 9, represented by the symbol F. It is the lightest element of the halogen column of the periodic table and has a single stable isotope, fluorine-19. At standard pressure and temperature, fluorine is a pale yellow gas composed of diatomic...
, 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
Trifluoromethyl
Trifluoromethyl is a functional group in organofluorines that has the formula -CF3. The naming of is group is derived from the methyl group , by replacing each hydrogen atom by a fluorine atom. The trifluomethyl group has a significant electronegativity that is often described as being...
group. However, some are more highly fluorinated, such as hexaflumuron, which has six fluorines, in large part to a tetra
Tetra (disambiguation)
Tetra is a numerical prefix that refers to four. It may also refer to:* Tetra, a South American freshwater fish in the family Characidae* Tetra Company, a supplier of aquarium equipment and fish food...
fluoroethoxy functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
. All known biologically synthesized organofluorines contain only one carbon–fluorine bond.
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 tetrafluoromethaneTetrafluoromethane
Tetrafluoromethane, also known as carbon tetrafluoride, is the simplest fluorocarbon . It has a very high bond strength due to the nature of the carbon–fluorine bond. It can also be classified as a haloalkane or halomethane...
(CF4). Liquids include perfluorooctane
Perfluorooctane
Perfluorooctane, also known as octadecafluorooctane, is a fluorocarbon liquid—a perfluorinated derivative of the hydrocarbon octane. Under the name PF5080 it is sold by 3M as part of their Fluorinert range of heat transfer fluids. It can be a good substitute for insulating oil in high...
and perfluorodecalin
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 dissolve gases....
. The fluoropolymer
Fluoropolymer
A fluoropolymer is a fluorocarbon based polymer with multiple strong carbon–fluorine bonds. It is characterized by a high resistance to solvents, acids, and bases.-History:Fluoropolymers were accidentally discovered in 1938 by Dr. Roy J...
polytetrafluoroethylene
Polytetrafluoroethylene
Polytetrafluoroethylene is a synthetic fluoropolymer of tetrafluoroethylene that finds numerous applications. PTFE is most well known by the DuPont brand name Teflon....
(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 nitrogenNitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
, iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
, or ionic groups, such as perfluorinated carboxylic acid
Perfluorinated carboxylic acid
Perfluorinated carboxylic acids , or perfluorocarboxylates are fully fluorinated organofluorine compounds—or perfluorinated compounds—with carboxylic acid or carboxylate functional groups. PFCAs are fluorocarbon derivatives...
s.
Alkyl fluorides
Alkyl monofluorides can be obtained from alcohols and Olah reagentOlah reagent
The Olah reagent is a nucleophilic fluorinating agent. It consists of a mixture of 70% hydrogen fluoride and 30% pyridine; alcohols react with this reagent to give alkyl fluorides:...
or another fluorinating agents.
Properties
Because of the varying degree of fluorination of organofluorine compounds, their properties are nearly impossible to compare as a group. "Every time you see a biologically active molecule that has fluorine in it, it could be in there for a different reason," says University of FloridaUniversity of Florida
The University of Florida is an American public land-grant, sea-grant, and space-grant research university located on a campus in Gainesville, Florida. The university traces its historical origins to 1853, and has operated continuously on its present Gainesville campus since September 1906...
chemistry professor William R. Dolbier Jr. By contrast, fluorocarbon based compounds are fluorinated for specific chemical, physical, and sometimes biological reasons, as they have properties that are very distinct from hydrocarbons. Organofluorines with only one carbon–fluorine bond can simply behave as a hydrocarbon. Therefore, the one salient point for all organofluorine compounds is that the carbon–fluorine bond can dramatically alter biological properties. While both uracil
Uracil
Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...
and 5-fluorouracil are colourless, high-melting crystalline solids, the organofluorine is a potent anti-cancer drug. Similarly, fluoroacetate is a potent natural poison while dilute acetate
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
in water is vinegar
Vinegar
Vinegar is a liquid substance consisting mainly of acetic acid and water, the acetic acid being produced through the fermentation of ethanol by acetic acid bacteria. Commercial vinegar is produced either by fast or slow fermentation processes. Slow methods generally are used with traditional...
.
Biological role
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 acidFatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s, fluoroacetone, and 2-fluorocitrate which are all believed to be biosynthesized in biochemical pathways from the intermediate fluoroacetaldehyde. Adenosyl-fluoride synthase
Adenosyl-fluoride synthase
In enzymology, an adenosyl-fluoride synthase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are S-adenosyl-L-methionine and fluoride, whereas its two products are 5'-deoxy-5'-fluoroadenosine and L-methionine....
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
Covalent radius of fluorine
The covalent radius of fluorine is a measure of the size of a fluorine atom; it is approximated at about 60 picometres.Since fluorine is a relatively small atom with a large electronegativity, its covalent radius is difficult to evaluate. The covalent radius is defined as half the bond lengths...
of fluorine is convenient as fluorine acts as an approximate bioisostere
Bioisostere
In medicinal chemistry, bioisosteres are substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to a chemical compound. In drug design, the purpose of exchanging one bioisostere for another is to enhance the desired biological or...
of the hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
group. Introducing the carbon–fluorine bond to organic compounds is the major challenge for medicinal chemists using organofluorine chemistry
Organofluorine chemistry
Organofluorine chemistry describes the chemistry of organofluorine compounds, organic compounds that contain the carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from oil- and water-repellents to pharmaceuticals, refrigerants and reagents in catalysis...
, 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
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
(Prozac), paroxetine
Paroxetine
Paroxetine is an SSRI antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline...
(Paxil), ciprofloxacin
Ciprofloxacin
Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...
(Cipro), mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
, and fluconazole
Fluconazole
Fluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. It is commonly marketed under the trade...
.
Environmental and health issues
Abiotic processes can also result in organofluorines considered as "problem molecules." Fluorocarbon based CFCs and tetrafluoromethaneTetrafluoromethane
Tetrafluoromethane, also known as carbon tetrafluoride, is the simplest fluorocarbon . It has a very high bond strength due to the nature of the carbon–fluorine bond. It can also be classified as a haloalkane or halomethane...
have been reported in igneous and metamorphic rock
Metamorphic rock
Metamorphic rock is the transformation of an existing rock type, the protolith, in a process called metamorphism, which means "change in form". The protolith is subjected to heat and pressure causing profound physical and/or chemical change...
. 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
Ozone depletion
Ozone depletion describes two distinct but related phenomena observed since the late 1970s: a steady decline of about 4% per decade in the total volume of ozone in Earth's stratosphere , and a much larger springtime decrease in stratospheric ozone over Earth's polar regions. The latter phenomenon...
. Fluoroalkanes, commonly referred to as perfluorocarbons, are potent greenhouse gases. The fluorosurfactant
Fluorosurfactant
Fluorosurfactants, or fluorinated surfactants, are synthetic organofluorine chemical compounds that have multiple fluorine atoms. They can be polyfluorinated or fluorocarbon-based . As surfactants, they are more effective at lowering the surface tension of water than comparable hydrocarbon...
s PFOS and PFOA, and other related chemicals, are persistent global contaminants. PFOS is a persistent organic pollutant
Persistent organic pollutant
thumb|right|275px|State parties to the Stockholm Convention on Persistent Organic PollutantsPersistent organic pollutants are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes...
and may be harming the health of wildlife; the potential health effects of PFOA to humans are under investigation by the C8 Science Panel.