Chloroform
82933
225803448
2008-07-15T14:01:35Z
Russoc4
292538
[[WP:UNDO|Undid]] revision 225801461 by [[Special:Contributions/58.69.51.248|58.69.51.248]] ([[User talk:58.69.51.248|talk]]): redundant and of poor quality english.
{{Chembox new
| ImageFileL1 = Chloroform displayed.svg
| ImageSizeL1 =
| ImageFileR1 = Chloroform 3D.svg
| ImageSizeR1 =
| IUPACName = Trichloromethane
| OtherNames = Chloroform, Formyl trichloride, Methane trichloride, Methyl trichloride, Methenyl trichloride, TCM, Freon 20, R-20, UN 1888
| Section1 = {{Chembox Identifiers
| CASNo = 67-66-3
| EINECS = 200-663-8
| PubChem = 6212
| ChEBI = 35255
| KEGG = C13827
| SMILES = C(Cl)(Cl)Cl
| InChI = 1/CHCl3/c2-1(3)4/h1H
| RTECS = FS9100000
}}
| Section2 = {{Chembox Properties
| Formula = CHCl<sub>3</sub>
| MolarMass = 119.38 g/mol
| Appearance = Colorless liquid
| Density = 1.48 g/cm³, liquid
| MeltingPt = -63.5 °C
| BoilingPt = 61.2 °C
| Solubility = 0.8 g/100 ml at 20 °C
}}
| Section3 = {{Chembox Structure
| CrystalStruct =
| Coordination =
| MolShape = Tetrahedral
}}
| Section7 = {{Chembox Hazards
| MainHazards = Harmful ('''Xn'''), Irritant ('''Xi'''),
[[Carcinogen|Carc. Cat. 2B]]
| NFPA-H = 2
| NFPA-F =
| NFPA-R =
| NFPA-O =
| RPhrases = {{R22}}, {{R38}}, {{R40}}, {{R48/20/22}}
| SPhrases = {{S2}}, {{S36/37}}
| FlashPt = Non-flammable
| Autoignition =
| PEL = 50 ppm (240 mg/m<sup>3</sup>) (OSHA)
}}
}}
'''Chloroform''', also known as '''trichloromethane''' and '''methyl trichloride''', is a [[chemical compound]] with [[chemical formula|formula]] [[Carbon|C]][[Hydrogen|H]][[Chlorine|Cl]]<sub>3</sub>. It does not undergo [[combustion]] in air, although it will burn when mixed with more flammable substances. It is a member of a group of compounds known as [[trihalomethane]]s. Chloroform has myriad of uses as a [[reagent]] and a [[solvent]]. It is also considered an environmental hazard.
== History ==
Chloroform was discovered in July 1831 by the American physician [[Samuel Guthrie (U.S. physician)|Samuel Guthrie]] ,<ref>{{cite journal
| author = [[Samuel Guthrie (U.S. physician)|Samuel Guthrie]]
| title = .
| journal = Am. J. Sci. and Arts
| volume = 21
| issue =
| pages = 64
| year = 1832
| doi = }}</ref> and independently a few months later by the French [[chemist]] [[Eugène Soubeiran]]<ref>{{cite journal
| author = [[Eugène Soubeiran]]
| title = .
| journal = Ann. Chim.
| volume = 48
| issue =
| pages = 131
| year = 1831
| doi = }}</ref> and [[Justus von Liebig]]<ref>{{cite journal
| author = [[Justus Liebig]]
| title = Ueber die Verbindungen, welche durch die Einwirkung des Chlors auf Alkohol, Aether, ölbildendes Gas und Essiggeist entstehen
| journal = [[Annalen der Pharmacie]]
| volume = 1
| issue = 2
| pages = 182–230
| year = 1832
| doi = 10.1002/jlac.18320010203 }}</ref> in Germany, all of them using variations of the [[haloform reaction]]. Soubeiran produced chloroform through the action of chlorine [[Bleach (chemical)|bleach]] powder (calcium hypochlorite) on [[acetone]] (2-propanone) as well as [[ethanol]]. Chloroform was named and chemically characterised in 1834 by [[Jean-Baptiste Dumas]].<ref>{{cite journal
| author = [[Jean-Baptiste Dumas]]
| title = Untersuchung über die Wirkung des Chlors auf den Alkohol
| journal = [[Annalen der Pharmacie]]
| volume = 107
| issue = 41
| pages = 650–656
| year = 1834
| doi = 10.1002/andp.18341074103 }}</ref>
In 1847, the [[Edinburgh]] [[obstetrics|obstetrician]] [[James Simpson (doctor)|James Young Simpson]] first used chloroform for [[general anaesthesia|general anesthesia]] during [[childbirth]]. The use of chloroform during [[surgery]] expanded rapidly thereafter in Europe. In the United States, chloroform began to replace [[Diethyl ether|ether]] as an anesthetic at the beginning of the 20th century; however, it was quickly abandoned in favor of ether upon discovery of its toxicity, especially its tendency to cause fatal [[cardiac arrhythmia]] analogous to what is now termed "[[solvent abuse|sudden sniffer's death]]". [[Diethyl ether|Ether]] is still the preferred anesthetic in some [[developing nation]]s due to its high [[therapeutic index]] (~1.5-2.2) <ref> Calderone, F.A. ''J. Pharmacology Experimental Therapeutics'', '''1935''', ''55(1)'', 24-39, http://jpet.aspetjournals.org/cgi/reprint/55/1/24.pdf</ref> and low price. [[Trichloroethylene]], a halogenated [[aliphatic hydrocarbon]] related to chloroform, was proposed as a safer alternative, though it too was later found to be [[carcinogen]]ic.
== Production ==
Industrially, chloroform is produced by heating a mixture of [[chlorine]] and either [[methyl chloride|chloromethane]] or [[methane]].{{Fact|date=December 2007}} At 400-500 °C, a [[free radical halogenation]] occurs, converting the [[methane]] or [[methyl chloride|chloromethane]] to progressively more chlorinated compounds.
:CH<sub>4</sub> + Cl<sub>2</sub> → CH<sub>3</sub>Cl + [[hydrogen chloride|HCl]]
:CH<sub>3</sub>Cl + Cl<sub>2</sub> → [[Dichloromethane|CH<sub>2</sub>Cl<sub>2</sub>]] + HCl
:CH<sub>2</sub>Cl<sub>2</sub> + Cl<sub>2</sub> → CHCl<sub>3</sub> + HCl
Chloroform undergoes further chlorination to give [[carbon tetrachloride|CCl<sub>4</sub>]]:
:CHCl<sub>3</sub> + Cl<sub>2</sub> → CCl<sub>4</sub> + HCl
The output of this process is a mixture of the four chloromethanes: chloromethane, dichloromethane, chloroform (trichloromethane), and carbon tetrachloride, which are then separated by [[distillation]].{{Fact|date=December 2007}}
Chloroform was first produced industrially by the reaction of [[acetone]] (or [[ethanol]]) with [[sodium hypochlorite]] or [[calcium hypochlorite]], known as the [[haloform reaction]].{{Fact|date=December 2007}} The chloroform can be removed from the attendant [[acetate]] salts (or [[formate]] salts if ethanol is the starting material) by distillation. This reaction is still used for the production of [[bromoform]] and [[iodoform]]. {{Fact|date=December 2007}} The haloform process is obsolete for the production of ordinary chloroform. It is, however, used to produce deuterated material industrially.{{Fact|date=December 2007}} Deuterochloroform may be prepared by the reaction of sodium deuteroxide with [[chloral hydrate]],{{Fact|date=December 2007}} or from ordinary chloroform.<ref>[http://patents.ic.gc.ca/cipo/cpd/en/patent/1085423/summary.html Canadian Patent 1085423]</ref>
===Inadvertent synthesis of chloroform===
The haloform reaction can also occur inadvertently in domestic settings. Sodium hypochlorite solution ([[chlorine bleach]]) mixed with common household liquids such as [[acetone]], [[methyl ethyl ketone]], [[ethanol]], or [[isopropyl alcohol]] may produce some chloroform, in addition to other compounds such as chloroacetone, or dichloroacetone.
== Uses ==
The major use of chloroform today is in the production of the refrigerant [[Chlorodifluoromethane|R-22]], commonly used in the air conditioning business. However, as the [[Montreal Protocol]] takes effect, this use can be expected to decline as R-22 is replaced by refrigerants that are less liable to result in [[ozone depletion]]. In addition, it is used under research conditions to anesthetize mosquitoes for experiments, most frequently for the study of malaria. In film and television, it is sometimes used in a fictional manner to knock out an unsuspecting victim, leaving no trace.
====Anesthetic====
Chloroform was developed in the mid-1800s and was mainly used as an anesthetic. Inhaling chloroform vapors depressed the [[central nervous system]] of a patient, causing dizziness, fatigue and unconsciousness, allowing a doctor to perform simple surgery or other painful operations.
The precise mechanism by which chloroform produces anesthesia is not
certain<ref>http://www.anes.upmc.edu/anesnews/volume/2003winter_spring/articles/focus.html</ref>. This is due, in part, to the fact that the mechanism of anesthesia itself is uncertain.
There are two main theories of how drugs produce anesthesia. The Meyer
Overton theory states that anesthetics dissolve in cellular membranes,
causing structural distortion of the membranes. The distortion may
reduce the conduction of a nerve impulse along a nerve cell. This theory
is based on the observation that the potency of most anesthetic drugs is
correlated with their solubility in oil. As an alternative to the Meyer
Overton theory, it has been proposed that anesthetics interact with
specific proteins. Examples of proteins that may be altered by binding
of an anesthetic are neurotransmitter receptors and ion channels.
Anesthetics may change the conformation (structure) of the protein.
Other theories include actions at the interface between proteins and
lipids.
One possible mechanism of action for chloroform is that it increases
movement of potassium ions through certain types of potassium channels in
nerve cells. A paper by Patel et al. published in Nature Neuroscience
(May 1999, Volume 2, Number 5, pp. 422-426) shows that chloroform
activates potassium channels. This can lead to hyperpolarization of
membranes. Hyperpolarization of a nerve cell membrane makes it less
excitable. When this occurs presynaptically, it will decrease the
release of neurotransmitters. When this effect occurs postsynaptically,
it reduces the response to a neurotransimitter.
In general, most anesthetics enhance inhibitory neurotransmission in the
brain. Many of them do this by increasing the actions of the primary
inhibitory neurotransmitter in the brain, gamma-aminobutyric (GABA).
Chloroform may also act by increasing GABA neurotansmission.
====As a solvent====
Chloroform is a common solvent because it is relatively unreactive, miscible with most organic liquids, and conveniently volatile. Small amounts of chloroform are used as a [[solvent]] in the [[pharmaceutical]] industry and for producing [[dye]]s and [[pesticide]]s. Chloroform is an effective solvent for alkaloids in their base form and thus plant material is commonly extracted with chloroform for pharmaceutical processing. For example, it is commercially used to extract [[morphine]] from [[poppy|poppies]], [[scopolamine]] from ''[[Datura]]'' plants. Chloroform containing [[deuterium]] (heavy hydrogen), [[CDCl3|CDCl<sub>3</sub>]], is a common solvent used in [[NMR spectroscopy]]. It can be used to bond pieces of [[polymethyl methacrylate|acrylic glass]] (which is also known under the trade name 'Perspex').
====As a [[reagent]] in organic synthesis====
As a reagent, chloroform serves as a source of the dichlorocarbene CCl<sub>2</sub> group.<ref>Srebnik, M.; Laloë, E. "Chloroform" Encyclopedia of Reagents for Organic Synthesis" 2001 John Wiley. {{doi|10.1002/047084289X.rc105}}</ref> It reacts with aqueous [[sodium hydroxide]] (usually in the presence of a [[phase transfer catalyst]]) to produce [[dichlorocarbene]], CCl<sub>2</sub>.<ref>{{OrgSynth | Vogel, E.; Klug, W.; Breuer. A. | title = <nowiki>1,6-Methano[10]annulene</nowiki> | collvol = 6 | collvolpages = 731 | year = 1988 | prep = cv6p0731}}</ref><ref>{{OrgSynth | author = Gokel, G. W.; Widera, R. P.; Weber, W. P. | title = Phase-Transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide | collvol = 6 | collvolpages = 232 | year = 1988 | prep = cv6p0232}}</ref> This reagent effects ortho-formylation of activated [[aromatic rings]] such as [[phenols]], producing aryl [[aldehyde]]s in a reaction known as the [[Reimer-Tiemann reaction]]. Alternatively the [[carbene]] can be trapped by an [[alkene]] to form a [[cyclopropane]] derivative.
== Safety ==
As might be expected for an [[general anaesthetic|anesthetic]], inhaling chloroform vapors depresses the [[central nervous system]]. It is [[IDLH|immediately dangerous to health and life]] at approximately 500 [[parts per million|ppm]] according to the [[National Institute for Occupational Safety and Health|United States National Institute for Occupational Safety and Health]]. Breathing about 900 ppm for a short time can cause dizziness, fatigue, and headache. Chronic chloroform exposure may cause damage to the [[liver]] (where chloroform is metabolized to [[phosgene]]) and to the [[kidney]]s, and some people develop sores when the skin is immersed in chloroform.
[[Animal study|Animal studies]] have shown that [[miscarriage]]s occur in [[rat]]s and [[mouse|mice]] that have breathed [[air]] containing 30 to 300 [[part per million|ppm]] of chloroform during [[pregnancy]] and also in rats that have ingested chloroform during pregnancy. [[Offspring]] of rats and mice that breathed chloroform during pregnancy have a higher incidence of [[birth defect]]s, and abnormal [[spermatozoon|sperm]] have been found in male mice that have breathed air containing 400 ppm chloroform for a few days. The effect of chloroform on [[reproduction]] in humans is unknown.
Chloroform once appeared in [[toothpaste]]s, [[cough syrup]]s, [[ointment]]s, and other [[pharmaceutical]]s, but it has been banned as a [[consumer product]] in the [[United States]] since [[1976]].<ref>{{cite web| title= The National Toxicology Program: Substance Profiles: Chloroform CAS No. 67-66-3| url=http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s038chlo.pdf| format=pdf| accessdate=2007-11-02}}</ref>
[[The National Toxicology Program]]'s eleventh report on carcinogens<ref>{{cite web| title= 11th Report on Carcinogens| url=http://ntp.niehs.nih.gov/ntp/roc/toc11.html| accessdate=2007-11-02}}</ref> implicates it as reasonably anticipated to be a human [[carcinogen]], a designation equivalent to [[International Agency for Research on Cancer]] class 2A. It has been most readily associated with [[hepatocellular carcinoma]].<ref>{{cite web| url=http://www.cdc.gov/Niosh/78127_9.html| title=Centers for Disease Control and Prevention: CURRENT INTELLIGENCE BULLETIN 9}}</ref><ref>{{cite web| title= National Toxicology Program: Report on the carcinogenesis bioassay of chloroform|url=http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/trChloroform.pdf}}</ref> Caution is mandated during its handling in order to minimize unnecessary exposure; safer alternatives, such as [[dichloromethane]], have resulted in a substantial reduction of its use as a solvent.
During prolonged storage hazardous amounts of [[phosgene]] can accumulate in the presence of [[oxygen]] and [[ultraviolet|ultraviolet light]]. To prevent accidents, commercial chloroform is stabilized with [[ethanol]] or [[pentene|amylene]], but samples that have been recovered or dried no longer contain any stabilizer and caution must be taken. Suspicious bottles should be tested for phosgene. Filter-paper strips, wetted with 5% diphenylamine, 5% dimethylaminobenzaldehyde, and then dried, turn yellow in phosgene vapor.
Commonly used in DNA extractions and generally in conjunction with phenol to form a biolayer with extraction buffer (tris etc). DNA will form in the supernatant while protein and non soluble cell materials will precipitate between the buffer chloroform layers.
==See also==
* [[Haloalkane]]
* [[Halomethane]]
* [[Chloromethane]]
* [[Dichloromethane]]
* [[Carbon tetrachloride]] (Tetrachloromethane)
* [[Fluoroform]]
* [[Bromoform]]
* [[Iodoform]]
==References==
{{reflist}}
== External links ==
* [http://www.chm.bris.ac.uk/motm/chloroform/chloroformv.htm Chloroform "The Molecular Lifesaver"] An article at Oxford University providing facts about chloroform.
* [http://www.inchem.org/documents/cicads/cicads/cicad58.htm Concise International Chemical Assessment Document 58]
* [http://www.general-anaesthesia.com/chloroform.html History of chloroform anesthesia]
* IARC Summaries & Evaluations: [http://www.inchem.org/documents/iarc/vol01/chloroform.html Vol. 1 (1972)], [http://www.inchem.org/documents/iarc/vol20/chloroform.html Vol. 20 (1979)], [http://www.inchem.org/documents/iarc/suppl7/chloroform.html Suppl. 7 (1987)], [http://www.inchem.org/documents/iarc/vol73/73-05.html Vol. 73 (1999)]
* {{ICSC|0027|00}}
* {{PGCH|0127}}
* [http://www.npi.gov.au/database/substance-info/profiles/23.html National Pollutant Inventory - Chloroform and trichloromethane]
* [http://webbook.nist.gov/cgi/cbook.cgi?ID=67-66-3&Units=SI&cTG=on&cTC=on&cTP=on NIST Standard Reference Database]
* [http://www.bbc.co.uk/radio4/science/thematerialworld_20050728.shtml Story on Chloroform] from BBC's [[The Material World]] (28 July 2005)
* [http://www.ncpoisoncenter.org/Consumers/Poisons_Inhalants.cfm Sudden Sniffer's Death Syndrome] article at Carolina Poison Center
{{General anesthetics}}
[[Category:Organochlorides]]
[[Category:Halomethanes]]
[[Category:Anesthetics]]
[[Category:Hazardous air pollutants]]
[[Category:IARC Group 2B carcinogens]]
[[Category:Halogenated solvents]]
[[bg:Хлороформ]]
[[ca:Cloroform]]
[[cs:Chloroform]]
[[da:Kloroform]]
[[de:Chloroform]]
[[es:Cloroformo]]
[[fr:Chloroforme]]
[[hi:क्लोरोफ़ॉर्म]]
[[hr:Kloroform]]
[[id:Kloroform]]
[[it:Cloroformio]]
[[he:כלורופורם]]
[[lv:Hloroforms]]
[[hu:Kloroform]]
[[nl:Chloroform]]
[[ja:クロロホルム]]
[[no:Kloroform]]
[[pl:Chloroform]]
[[pt:Clorofórmio]]
[[ro:Cloroform]]
[[ru:Хлороформ]]
[[sk:Trichlórmetán]]
[[fi:Kloroformi]]
[[sv:Kloroform]]
[[vi:Clorofom]]
[[tr:Kloroform]]
[[uk:Хлороформ]]
[[zh:氯仿]]