Organofluorine

Some important organofluorine compounds
A: fluoromethane
B: isoflurane
C: a CFC
D: an HFC
E: triflic acid
F: Teflon
G: PFOS
H: fluorouracil
I: Prozac

Organofluorine compounds are organic chemical compounds that contain carbon and fluorine bonded in the polarized and remarkably strong carbon–fluorine bond. Organofluorine compounds are diverse, they can be fluorocarbons, perfluorinated, or biologically synthesized mono-fluorinated compounds, among other possibilities. These compounds have a wide range of function and can serve as refrigerants, pharmaceuticals, agrichemicals, surfactants, ozone depletors, poisons, or pollutants.

Bond

C–F partial charges

Main article: Carbon–fluorine bond

The carbon–fluorine bond is referred to as the strongest in organic chemistry 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 fluorocarbons, fluorocarbon derivatives, fluorinated pharmaceuticals and agrichemicals, or mono-fluorinated biologically synthesized compounds, among others. Fluorocarbons are compounds that contain only carbon and fluorine,^[1] while other molecules that contain many carbon–fluorine bonds are commonly referred to as fluorocarbons.^[2] Pharmaceuticals and agrichemicals commonly contain only one fluorine or a trifluoromethyl group.^[2] However, some are more highly fluorinated, such as hexaflumuron, which has six fluorines, in large part to a tetrafluoroethoxy functional group. All known biologically synthesized organofluorines contain only one carbon–fluorine bond.^[3]

Fluorocarbons

Main article: Fluorocarbon

Fluorocarbons are molecules that only contain carbon and fluorine. They can be gases, liquids, waxes, or solids, depending upon their molecular weight. The simplest fluorocarbon is the gas tetrafluoromethane (CF₄). Liquids include perfluorooctane and perfluorodecalin. The fluoropolymer polytetrafluoroethylene (PTFE/Teflon) is a solid. While fluorocarbons with single bonds are stable, unsaturated fluorocarbons are more reactive, especially those with triple bonds.

Perfluorinated compounds

Main article: Perfluorinated compounds

Perfluorinated compounds are fluorocarbon derivatives, as they are closely structurally related to fluorocarbons. However, they also possess new atoms such as nitrogen, iodine, or ionic groups, such as perfluorinated carboxylic acids.

Alkyl fluorides

Alkyl monofluorides can be obtained from alcohols and Olah reagent or another fluorinating agents.

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 Florida chemistry professor William R. Dolbier Jr.^[4] 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.^[5] While both uracil 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 in water is vinegar.

Biological role

Biologically synthesized organofluorines have been found in microorganisms and plants, but not animals.^[3] The most common example is fluoroacetate, which occurs as a plant defence against herbivores in at least 40 plants in Australia, Brazil and Africa.^[6] Other biologically synthesized organofluorines include ω-fluoro fatty acids, fluoroacetone, and 2-fluorocitrate which are all believed to be biosynthesized in biochemical pathways from the intermediate fluoroacetaldehyde.^[3] Adenosyl-fluoride synthase is an enzyme capable of biologically synthesizing the carbon–fluorine bond.^[7] Man made carbon–fluorine bonds are commonly found in pharmaceuticals and agrichemicals because it adds stability to the carbon framework; also, the relatively small size of fluorine is convenient as fluorine acts as an approximate bioisostere of the hydroxyl group.^[8] 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.^[4] An estimated 20% of pharmaceuticals, and 30–40% of agrichemicals are organofluorines, including several of the top drugs.^[4] Examples include 5-fluorouracil, fluoxetine (Prozac), paroxetine (Paxil), ciprofloxacin (Cipro), mefloquine, and fluconazole.

Environmental and health issues

Abiotic processes can also result in organofluorines considered as "problem molecules." Fluorocarbon based CFCs and tetrafluoromethane have been reported in igneous and metamorphic rock.^[3] However, environmental and health issues still face many organofluorines. Because of the strength of the carbon–fluorine bond, many synthetic fluorocarbons and fluorcarbon-based compounds are persistent in the environment. Others, such as CFCs, participate in ozone depletion. Fluoroalkanes, commonly referred to as perfluorocarbons, are potent greenhouse gases. The fluorosurfactants PFOS and PFOA, and other related chemicals, are persistent global contaminants. PFOS is a persistent organic pollutant and may be harming the health of wildlife; the potential health effects of PFOA to humans are under investigation by the C8 Science Panel.

See also

• Organochlorine compounds
• Organobromine compounds
• Organoiodine compounds

References

1. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006–) "fluorocarbons".
2. ^ ^{a b} Lemal, David M. (2004). "Perspective on Fluorocarbon Chemistry". The Journal of Organic Chemistry 69 (1): 1–11. doi:10.1021/jo0302556. PMID 14703372. 
3. ^ ^{a b c d} Murphy, Cormac D.; Schaffrath, Christoph; O'Hagan, David (2003). "Fluorinated natural products: The biosynthesis of fluoroacetate and 4-fluorothreonine in Streptomyces cattleya". Chemosphere 52 (2): 455–61. doi:10.1016/S0045-6535(03)00191-7. PMID 12738270. 
4. ^ ^{a b c} Thayer, Ann M. (5 June 2006). "Fabulous Fluorine". Chemical & Engineering News 84 (23): 15–24. http://pubs.acs.org/cen/coverstory/84/8423cover1.html. Retrieved 17 January 2009. 
5. ^ Hagmann, William K. (2008). "The Many Roles for Fluorine in Medicinal Chemistry". Journal of Medicinal Chemistry 51 (15): 4359–69. doi:10.1021/jm800219f. PMID 18570365. 
6. ^ Proudfoot, Alex T; Bradberry, Sally M; Vale, J Allister (2006). "Sodium Fluoroacetate Poisoning". Toxicological Reviews 25 (4): 213–9. doi:10.2165/00139709-200625040-00002. PMID 17288493. 
7. ^ O'Hagan, David; Schaffrath, Christoph; Cobb, Steven L.; Hamilton, John T. G.; Murphy, Cormac D. (2002). "Biochemistry: Biosynthesis of an organofluorine molecule". Nature 416 (6878): 279. doi:10.1038/416279a. PMID 11907567. 
8. ^ Halocarbon: "Fluorine 101" Technical Archives. Accessed November 8, 2008.

External links

• Chemical Personality of Fluorinated Organics or Why Chemical Architecture Matters