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The reaction is conducted in the presence of a catalytic amount of [[antimony pentafluoride]]. Chlorodifluoromethane is then converted into tetrafluoroethylene, the main precursor to [[Teflon]]. Before the [[Montreal Protocol]], chlorodifluoromethane (designated as R-22) was also a popular refrigerant.
The reaction is conducted in the presence of a catalytic amount of [[antimony pentafluoride]]. Chlorodifluoromethane is then converted into tetrafluoroethylene, the main precursor to [[Teflon]]. Before the [[Montreal Protocol]], chlorodifluoromethane (designated as R-22) was also a popular refrigerant.


===As a solvent===
===Solvent===
Worldwide, chloroform is also used in pesticide formulations, as a solvent for fats, oils, rubber, alkaloids, waxes, gutta-percha, and resins, as a cleansing agent, grain fumigant, in fire extinguishers, and in the rubber industry.<ref name="cicad" /><ref name="pth">{{citation | editor=Jerrold B. Leikin | editor2=Frank P. Paloucek | contribution=Chloroform | title=Poisoning and Toxicology Handbook | edition=4th | publisher=Informa | year=2008 | page=774}}</ref> CDCl<sub>3</sub> is a common solvent used in [[NMR spectroscopy]].
Chloroform is a common [[solvent]] in the laboratory because it is relatively unreactive, miscible with most organic liquids, not flammable and conveniently volatile.<ref>Perrin, D. D. and Armarego, W. L. F. (2009) ''Purification of Laboratory Chemicals'', Pergamon Press: Oxford, ISBN 1856175677.</ref> Chloroform is used as a solvent in the [[pharmaceutical]] industry and for producing [[dye]]s and [[pesticide]]s. Chloroform is an effective solvent for [[alkaloid]]s in their base form and thus plant material is commonly extracted with chloroform for pharmaceutical processing. For example, it is used in commerce to extract [[morphine]] from [[poppy|poppies]] and [[scopolamine]] from ''[[Datura]]'' plants.
It can be used to bond pieces of [[Poly(methyl methacrylate)|acrylic glass]] (also known under the trade names Perspex and Plexiglas).
A solvent of phenol, chloroform, and isoamyl alcohol in a 25:24:1 ratio is used to dissolve non-nucleic acid biomolecules in DNA and RNA extractions.
Chloroform containing [[deuterium]] (heavy hydrogen), [[CDCl3|CDCl<sub>3</sub>]], is a common solvent used in [[NMR spectroscopy]].
Chloroform exhibits some chemical interaction with polypropylene. Longer term (multi-hour) storage of chloroform in polypropylene containers is not advised.<ref>[http://www.borealisgroup.com/pdf/chemical-resistance/chemtab_PP.pdf "Chemical Resistance of Polypropylene"]. borealisgroup.com. 11 July 2001.</ref>


===Reagent===
===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. (2001) "Chloroform" in ''Encyclopedia of Reagents for Organic Synthesis'', 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 affects 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. In the [[Kharasch addition]] chloroform forms the CHCl<sub>2</sub> free radical in addition to alkenes.
As a [[reagent]], chloroform serves as a source of the dichlorocarbene CCl<sub>2</sub> group.<ref>Srebnik, M.; Laloë, E. (2001) "Chloroform" in ''Encyclopedia of Reagents for Organic Synthesis'', 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 affects 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. In the [[Kharasch addition]] chloroform forms the CHCl<sub>2</sub> free radical in addition to alkenes.


The most important reaction of chloroform is that with [[hydrogen fluoride]] in the presence of antimony pentahalides to give [[monochlorodifluoromethane]] ([[CFC 22]]), a precursor in the production of polytetrafluoroethylene ([[Teflon]]).<ref name="Ullmann" />
===As an anesthetic===

===Anesthetic===
[[File:Chickamauga 2009, Chloroform.jpg|thumb|left|Antique bottles of chloroform]]
[[File:Chickamauga 2009, Chloroform.jpg|thumb|left|Antique bottles of chloroform]]
Chloroform was once a widely used [[anesthesia|anesthetic]]. Its vapor depresses the [[central nervous system]] of a patient, allowing a doctor to perform various otherwise painful procedures. On 4 November 1847, the Scottish [[obstetrics|obstetrician]] [[James Young Simpson]] discovered the anaethestic qualities of chloroform when he and his friends were experimenting with different substances on themselves in search of a replacement for [[Diethyl ether|ether]] as a [[general anaesthesia|general anesthetic]]. He was so astounded by the success of his own trial that the next morning he hired a chemist and within the next few days was administering it to his patients during [[childbirth]].<ref name="Gordon2002">{{cite book|last=Gordon|first=H. Laing|title=Sir James Young Simpson and Chloroform (1811–1870)|url=http://books.google.com/books?id=pYer05UwKBYC&pg=PA106|accessdate=11 November 2011|date=November 2002|publisher=The Minerva Group, Inc.|isbn=978-1-4102-0291-8|pages=106–109}}</ref> The use of chloroform during [[surgery]] expanded rapidly thereafter in Europe. In the 1850s, chloroform was used during the birth of Queen Victoria's last two children.<ref>[http://www.ph.ucla.edu/epi/snow/victoria.html Anesthesia and Queen Victoria]. Ph.ucla.edu. Retrieved on 2012-08-13.</ref> In the United States, chloroform began to replace 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 sniffing death syndrome"|sudden sniffer's death]]". Some people used chloroform as a recreational drug or to attempt suicide.<ref>{{cite journal|author=Martin, William|title=A Case of Chloroform Poisoning; Recovery|journal=Br Med J|date=3 July 1886|volume=2|issue=1331|pages=16–17|pmc=2257365|doi=10.1136/bmj.2.1331.16-a|pmid=20751619}}</ref> One possible mechanism of action for chloroform is that it increases movement of potassium ions through certain types of [[potassium channels]] in [[nerve cells]].<ref>{{Cite journal|last1 = Patel|first1 = Amanda J.|last2 = Honoré|first2 = Eric|last3 = Lesage|first3 = Florian|last4 = Fink|first4 = Michel|last5 = Romey|first5 = Georges|last6 = Lazdunski|first6 = Michel|publication-date =|date = May 1999|title = Inhalational anesthetics activate two-pore-domain background K+ channels|journal = Nature Neuroscience|volume = 2|pages = 422–426|doi = 10.1038/8084|pmid = 10321245|issue = 5}}</ref> Chloroform could also be mixed with other anaesthetic agents such as ether to make C.E. mixture, or ether and [[Ethanol|alcohol]] to make [[A.C.E. mixture]].
Chloroform was once a widely used [[anesthesia|anesthetic]]. On 4 November 1847, the Scottish [[obstetrics|obstetrician]] [[James Young Simpson]] discovered the anaethestic qualities of chloroform.<ref name="Gordon2002">{{cite book|last=Gordon|first=H. Laing|title=Sir James Young Simpson and Chloroform (1811–1870)|url=http://books.google.com/books?id=pYer05UwKBYC&pg=PA106|accessdate=11 November 2011|date=November 2002|publisher=The Minerva Group, Inc.|isbn=978-1-4102-0291-8|pages=106–109}}</ref> The use of chloroform during [[surgery]] expanded rapidly thereafter in Europe. In the 1850s, chloroform was used during the birth of Queen Victoria's last two children.<ref>[http://www.ph.ucla.edu/epi/snow/victoria.html Anesthesia and Queen Victoria]. Ph.ucla.edu. Retrieved on 2012-08-13.</ref> In the United States, chloroform began to replace 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 sniffing death syndrome"|sudden sniffer's death]]". Some people used chloroform as a recreational drug or to attempt suicide.<ref>{{cite journal|author=Martin, William|title=A Case of Chloroform Poisoning; Recovery|journal=Br Med J|date=3 July 1886|volume=2|issue=1331|pages=16–17|pmc=2257365|doi=10.1136/bmj.2.1331.16-a|pmid=20751619}}</ref> One possible mechanism of action for chloroform is that it increases movement of potassium ions through certain types of [[potassium channels]] in [[nerve cells]].<ref>{{Cite journal|last1 = Patel|first1 = Amanda J.|last2 = Honoré|first2 = Eric|last3 = Lesage|first3 = Florian|last4 = Fink|first4 = Michel|last5 = Romey|first5 = Georges|last6 = Lazdunski|first6 = Michel|publication-date =|date = May 1999|title = Inhalational anesthetics activate two-pore-domain background K+ channels|journal = Nature Neuroscience|volume = 2|pages = 422–426|doi = 10.1038/8084|pmid = 10321245|issue = 5}}</ref> Chloroform could also be mixed with other anaesthetic agents such as ether to make C.E. mixture, or ether and [[Ethanol|alcohol]] to make [[A.C.E. mixture]].
In 1848, Hannah Greener, a 15-year-old girl who was having an infected toenail removed, died after being given the anesthetic.<ref>{{cite journal|title=An Unexplained Death: Hannah Greener and Chloroform |author= Knight, Paul R. III and Bacon, Douglas R. | year=2002 |volume = 96 |issue = 5 |journal=Anesthesiology|doi=10.1097/00000542-200205000-00030|pages=1250–3|pmid=11981167}}</ref> A number of physically fit patients died after inhaling it. However, in 1848 [[John Snow (physician)|John Snow]] developed an inhaler that regulated the dosage and so successfully reduced the number of deaths.<ref>{{cite web|last1 = Snow|first1 = John|publication-date =|year = 1858|title = On Chloroform and Other Anaesthetics and Their Action and Administration| pages = 82–85|url=http://archive.org/stream/onchloroformothe1858snow#page/82/mode/2up/search/inhaler}}</ref>
In 1848, Hannah Greener, a 15-year-old girl who was having an infected toenail removed, died after being given the anesthetic.<ref>{{cite journal|title=An Unexplained Death: Hannah Greener and Chloroform |author= Knight, Paul R. III and Bacon, Douglas R. | year=2002 |volume = 96 |issue = 5 |journal=Anesthesiology|doi=10.1097/00000542-200205000-00030|pages=1250–3|pmid=11981167}}</ref> A number of physically fit patients died after inhaling it. However, in 1848 [[John Snow (physician)|John Snow]] developed an inhaler that regulated the dosage and so successfully reduced the number of deaths.<ref>{{cite web|last1 = Snow|first1 = John|publication-date =|year = 1858|title = On Chloroform and Other Anaesthetics and Their Action and Administration| pages = 82–85|url=http://archive.org/stream/onchloroformothe1858snow#page/82/mode/2up/search/inhaler}}</ref>


=== Criminal use ===
=== Criminal use ===
Chloroform has been reputed to be used by criminals to knock out, daze or even murder their victims. Joseph Harris was charged with using chloroform in 1894 to rob people.<ref>{{Cite news|url=http://news.google.com/newspapers?id=Ec1VAAAAIBAJ&sjid=sEANAAAAIBAJ&pg=2904,2720400&dq=chloroform+knockout&hl=en|title=Knock-out and Chloroform|publisher=The Philadelphia record|date=9 February 1894|accessdate=31 March 2011}}</ref> In 1901, chloroform was also implicated in the murder the American businessman [[William Marsh Rice]], the namesake of the institution now known as [[Rice University]]. Chloroform was also deemed to be a factor in the alleged murder of a woman in 1991 when she was asphyxiated while she was sleeping.<ref>{{cite web|url=http://news.google.com/newspapers?id=I91HAAAAIBAJ&sjid=4f8MAAAAIBAJ&pg=2367,1007950&dq=chloroform+knockout&hl=en|title=Chloroform case retrial underway|date=7 July 1993|accessdate=31 March 2011|publisher=Record-Journal}}</ref> In a 2007 plea bargain a man confessed to using stun guns and chloroform to sexually assault minors.<ref>{{cite web|url=http://www.usatoday.com/news/nation/2007-11-06-chloroform-rapes_N.htm|title=Man admits to raping friends' daughters|date=6 November 2007|accessdate=31 March 2011|publisher=USA Today}}</ref> Use of chloroform as an [[incapacitating agent]] has become widely recognized, bordering on [[cliché]]d, due to the popularity of [[crime fiction]] authors having criminals use chloroform-soaked rags to render victims unconscious. However, it is nearly impossible to incapacitate someone using chloroform.<ref name="Issue 7 pages 685">J. P. Payne The criminal use of chloroform Anaesthesia Volume 53, Issue 7, pages 685–690, July 1998</ref> It takes at least 5 minutes of inhaling an item soaked in chloroform to render a person unconscious. Most criminal cases involving chloroform also involve another drug being co-administered, such as [[alcohol]] or diazepam, or the victim being found to have been complicit in its administration. After a person has lost consciousness due to chloroform inhalation, a continuous volume must be administered and the chin must be supported in order to keep the tongue from obstructing the airway, a difficult procedure even for an anesthesiologist. In 1865 as a direct result of the criminal reputation chloroform had gained, the medical journal Lancet offered a "permanent scientific reputation" to anyone who could demonstrate "instantaneous insensibility" using chloroform,<ref>Medical Annotation. Chloroform amongst Thieves. Lancet 1865; 2: 490 – 1.</ref> and no such demonstration has been forthcoming.<ref name="Issue 7 pages 685"/>
Chloroform has been reputed to be used by criminals to knock out, daze or even murder their victims. Joseph Harris was charged with using chloroform in 1894 to rob people.<ref>{{Cite news|url=http://news.google.com/newspapers?id=Ec1VAAAAIBAJ&sjid=sEANAAAAIBAJ&pg=2904,2720400&dq=chloroform+knockout&hl=en|title=Knock-out and Chloroform|publisher=The Philadelphia record|date=9 February 1894|accessdate=31 March 2011}}</ref> In 1901, chloroform was also implicated in the murder the American businessman [[William Marsh Rice]], the namesake of the institution now known as [[Rice University]]. Chloroform was also deemed to be a factor in the alleged murder of a woman in 1991 when she was asphyxiated while she was sleeping.<ref>{{cite web|url=http://news.google.com/newspapers?id=I91HAAAAIBAJ&sjid=4f8MAAAAIBAJ&pg=2367,1007950&dq=chloroform+knockout&hl=en|title=Chloroform case retrial underway|date=7 July 1993|accessdate=31 March 2011|publisher=Record-Journal}}</ref> In a 2007 plea bargain a man confessed to using stun guns and chloroform to sexually assault minors.<ref>{{cite web|url=http://www.usatoday.com/news/nation/2007-11-06-chloroform-rapes_N.htm|title=Man admits to raping friends' daughters|date=6 November 2007|accessdate=31 March 2011|publisher=USA Today}}</ref> Use of chloroform as an [[incapacitating agent]] has become widely recognized, bordering on [[cliché]]d, due to the popularity of [[crime fiction]] authors having criminals use chloroform-soaked rags to render victims unconscious. However, it is nearly impossible to incapacitate someone using chloroform.<ref name="Issue 7 pages 685">J. P. Payne The criminal use of chloroform Anaesthesia Volume 53, Issue 7, pages 685–690, July 1998</ref> It takes at least 5 minutes of inhaling an item soaked in chloroform to render a person unconscious. Most criminal cases involving chloroform also involve another drug being co-administered, such as [[alcohol]] or diazepam, or the victim being found to have been complicit in its administration. After a person has lost consciousness due to chloroform inhalation, a continuous volume must be administered and the chin must be supported in order to keep the tongue from obstructing the airway, a difficult procedure even for an anesthesiologist. In 1865 as a direct result of the criminal reputation chloroform had gained, the medical journal Lancet offered a "permanent scientific reputation" to anyone who could demonstrate "instantaneous insensibility" using chloroform,<ref>Medical Annotation. Chloroform amongst Thieves. Lancet 1865; 2: 490 – 1.</ref> and no such demonstration has been forthcoming.<ref name="Issue 7 pages 685"/>

===As a working fluid in a heat engine===
At least one experimental [[heat engine]] has been constructed using chloroform as a [[working fluid]] in place of [[steam]]; similar experiments had been conducted using [[diethyl ether|ether]] as a low-boiling-point working fluid, but its highly flammable nature caused difficulties, so chloroform was tried as a non-flammable alternative. Such experiments were apparently inspired by the misconception that a fluid with a lower boiling point than [[water]], being easier to vaporise, would allow the construction of a more efficient engine; in fact the reverse is the case,<ref name="carnot">{{cite web|url=http://www.douglas-self.com/MUSEUM/POWER/thermo/thermo.htm#ce|title=Carnot efficiency|work=douglas-self.com|accessdate=2012-09-24}}</ref> but this was not widely appreciated in the days when [[thermodynamics]] was a young science. Grandiose claims for the efficiency of this engine were reported in [[Scientific American]] in 1848, along with an editorial comment casting grave doubts on them; it appears that the development of the invention did not proceed further.<ref name="engines">{{cite web|url=http://www.douglas-self.com/MUSEUM/POWER/ether/ether.htm|title=Ether and Chloroform Engines|accessdate=2012-09-24}}</ref>


==Safety==
==Safety==

Revision as of 19:34, 8 September 2014

Chloroform
Chloroform in its liquid state shown in a test tube
Names
IUPAC name
Trichloromethane
Other names
Trichloromethane; Formyl trichloride; Methane trichloride; Methyl trichloride; Methenyl trichloride; TCM; Freon 20; Refrigerant-20; R-20; UN 1888
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.603 Edit this at Wikidata
EC Number
  • 200-663-8
KEGG
RTECS number
  • FS9100000
UNII
  • InChI=1S/CHCl3/c2-1(3)4/h1H checkY
    Key: HEDRZPFGACZZDS-UHFFFAOYSA-N checkY
  • InChI=1/CHCl3/c2-1(3)4/h1H
    Key: HEDRZPFGACZZDS-UHFFFAOYAG
  • ClC(Cl)Cl
Properties
CHCl3
Molar mass 119.37 g·mol−1
Appearance Colorless liquid
Odor Heavy, ethereal odor
Density 1.564 g/cm3 (-20 °C)
1.489 g/cm3 (25 °C)
1.394 g/cm3 (60 °C)
Melting point −63.5 °C (−82.3 °F; 209.7 K)
Boiling point 61.15 °C (142.07 °F; 334.30 K)
1.062 g/100 mL (0 °C)
0.809 g/100 mL (20 °C)
0.732 g/100 mL (60 °C)
Solubility Soluble in benzene
Miscible in diethyl ether, oils, ligroin, alcohol, CCl4, CS2
Solubility in acetone ≥ 10 g/100 mL (19 °C)
Solubility in dimethyl sulfoxide ≥ 10 g/100 mL (19 °C)
Vapor pressure 0.62 kPa (-40 °C)
7.89 kPa (0 °C)
25.9 kPa (25 °C)
313 kPa (100 °C)
2.26 MPa (200 °C)
3.67 L·atm/mol (24 °C)
Acidity (pKa) 15.7 (20 °C)
Thermal conductivity 0.13 W/m·K (20 °C)
1.4459 (20 °C)
Viscosity 0.563 cP (20 °C)
Structure
Tetrahedral
1.15 D
Thermochemistry
114.25 J/mol·K
202.9 J/mol·K
-134.3 kJ/mol
-71.1 kJ/mol
473.21 kJ/mol
Hazards
GHS labelling:
GHS07: Exclamation markGHS08: Health hazard
Warning
H302, H315, H319, H332, H336, H351, H361, H373
P261, P281, P305+P351+P338
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 0: Will not burn. E.g. waterInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
0
0
Flash point Non-flammable
Lethal dose or concentration (LD, LC):
1250 mg/kg (rats, oral)
NIOSH (US health exposure limits):
PEL (Permissible)
 50 ppm (240 mg/m3) (OSHA)
Supplementary data page
Chloroform (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes.[1] The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered hazardous. Several million tons are produced annually as a precursor to PTFE and refrigerants, but its use for refrigerants is being phased out.[1]

Natural occurrence

The total global flux of chloroform through the environment is approximately 660 000 tonnes per year, and about 90 % of emissions are natural in origin. Many kinds of seaweed produce chloroform, and fungi are believed to produce chloroform in soil. The other main chloroform releases to the environment occur as a result of using chlorine-based chemicals for bleaching and disinfection at pulp and paper mills and water treatment plants.[2]

Chloroform volatilizes readily from soil and surface water and undergoes degradation in air to produce phosgene, dichloromethane, formyl chloride, carbon monoxide, carbon dioxide, and hydrogen chloride. Its halflife in air ranges from 55 to 620 days. Biodegradation in water and soil is slow. Chloroform does not bioaccumulate to any significant extent in aquatic organisms.[2]

History

Trichloromethane was synthesized independently by two groups in 1831: Liebig carried out the alkaline cleavage of chloral, whereas Soubeirain obtained the compound by the action of chlorine bleach on both ethanol and acetone. In 1835, Dumas prepared the substance by the alkaline cleavage of trichloroacetic acid. Regnault prepared trichloromethane by chlorination of monochloromethane. By the 1850s, chloroform was being produced on a commercial basis by using the Liebig procedure, which retained its importance until the 1960s. Today, trichloromethane — along with dichloromethane — is prepared exclusively and on a massive scale by the chlorination of methane and/or monochloromethane.[1]

Production

In industry, chloroform is produced by heating a mixture of chlorine and either chloromethane or methane.[1] At 400–500 °C, a free radical halogenation occurs, converting these precursors to progressively more chlorinated compounds:

CH4 + Cl2 → CH3Cl + HCl
CH3Cl + Cl2 → CH2Cl2 + HCl
CH2Cl2 + Cl2 → CHCl3 + HCl

Chloroform undergoes further chlorination to yield carbon tetrachloride (CCl4):

CHCl3 + Cl2 → CCl4 + HCl

The output of this process is a mixture of the four chloromethanes (chloromethane, dichloromethane, chloroform, and carbon tetrachloride), which can then be separated by distillation.[1]

Deuterochloroform

Main article: Deuterated chloroform

Deuterated chloroform is an isotopologue of chloroform with a single deuterium atom. CDCl3 is a common solvent used in NMR Spectroscopy. Deuterochloroform is produced by the haloform reaction[citation needed], the reaction of acetone (or ethanol) with sodium hypochlorite or calcium hypochlorite.[1] The haloform process is now obsolete for the production of ordinary chloroform. Deuterochloroform can also be prepared by the reaction of sodium deuteroxide with chloral hydrate,[citation needed] or from ordinary chloroform.[3]

Inadvertent formation of chloroform

The haloform reaction can also occur inadvertently in domestic settings. Bleaching with hypochlorite generates halogenated compounds in side reactions; chloroform is the main byproduct.[4] Sodium hypochlorite solution (chlorine bleach) mixed with common household liquids such as acetone, butanone, ethanol, or isopropyl alcohol can 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 chlorodifluoromethane, a major precursor to tetrafluoroethylene:

CHCl3 + 2 HF → CHClF2 + 2 HCl

The reaction is conducted in the presence of a catalytic amount of antimony pentafluoride. Chlorodifluoromethane is then converted into tetrafluoroethylene, the main precursor to Teflon. Before the Montreal Protocol, chlorodifluoromethane (designated as R-22) was also a popular refrigerant.

Solvent

Worldwide, chloroform is also used in pesticide formulations, as a solvent for fats, oils, rubber, alkaloids, waxes, gutta-percha, and resins, as a cleansing agent, grain fumigant, in fire extinguishers, and in the rubber industry.[2][5] CDCl3 is a common solvent used in NMR spectroscopy.

Reagent

As a reagent, chloroform serves as a source of the dichlorocarbene CCl2 group.[6] It reacts with aqueous sodium hydroxide usually in the presence of a phase transfer catalyst to produce dichlorocarbene, CCl2.[7][8] This reagent affects ortho-formylation of activated aromatic rings such as phenols, producing aryl aldehydes in a reaction known as the Reimer-Tiemann reaction. Alternatively the carbene can be trapped by an alkene to form a cyclopropane derivative. In the Kharasch addition chloroform forms the CHCl2 free radical in addition to alkenes.

The most important reaction of chloroform is that with hydrogen fluoride in the presence of antimony pentahalides to give monochlorodifluoromethane (CFC 22), a precursor in the production of polytetrafluoroethylene (Teflon).[1]

Anesthetic

Antique bottles of chloroform

Chloroform was once a widely used anesthetic. On 4 November 1847, the Scottish obstetrician James Young Simpson discovered the anaethestic qualities of chloroform.[9] The use of chloroform during surgery expanded rapidly thereafter in Europe. In the 1850s, chloroform was used during the birth of Queen Victoria's last two children.[10] In the United States, chloroform began to replace 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 "sudden sniffer's death". Some people used chloroform as a recreational drug or to attempt suicide.[11] One possible mechanism of action for chloroform is that it increases movement of potassium ions through certain types of potassium channels in nerve cells.[12] Chloroform could also be mixed with other anaesthetic agents such as ether to make C.E. mixture, or ether and alcohol to make A.C.E. mixture. In 1848, Hannah Greener, a 15-year-old girl who was having an infected toenail removed, died after being given the anesthetic.[13] A number of physically fit patients died after inhaling it. However, in 1848 John Snow developed an inhaler that regulated the dosage and so successfully reduced the number of deaths.[14]

Criminal use

Chloroform has been reputed to be used by criminals to knock out, daze or even murder their victims. Joseph Harris was charged with using chloroform in 1894 to rob people.[15] In 1901, chloroform was also implicated in the murder the American businessman William Marsh Rice, the namesake of the institution now known as Rice University. Chloroform was also deemed to be a factor in the alleged murder of a woman in 1991 when she was asphyxiated while she was sleeping.[16] In a 2007 plea bargain a man confessed to using stun guns and chloroform to sexually assault minors.[17] Use of chloroform as an incapacitating agent has become widely recognized, bordering on clichéd, due to the popularity of crime fiction authors having criminals use chloroform-soaked rags to render victims unconscious. However, it is nearly impossible to incapacitate someone using chloroform.[18] It takes at least 5 minutes of inhaling an item soaked in chloroform to render a person unconscious. Most criminal cases involving chloroform also involve another drug being co-administered, such as alcohol or diazepam, or the victim being found to have been complicit in its administration. After a person has lost consciousness due to chloroform inhalation, a continuous volume must be administered and the chin must be supported in order to keep the tongue from obstructing the airway, a difficult procedure even for an anesthesiologist. In 1865 as a direct result of the criminal reputation chloroform had gained, the medical journal Lancet offered a "permanent scientific reputation" to anyone who could demonstrate "instantaneous insensibility" using chloroform,[19] and no such demonstration has been forthcoming.[18]

Safety

A fatal oral dose of chloroform may be as small as 10 ml (14.8 g), with death due to respiratory or cardiac arrest.[20]

As might be expected for an anesthetic, chloroform vapors depress the central nervous system. It is immediately dangerous to life and health at approximately 500 ppm, according to the U.S. National Institute for Occupational Safety and Health. Breathing about 900 ppm for a short time can cause dizziness, fatigue, and headache. Chronic chloroform exposure can damage the liver (where chloroform is metabolized to phosgene) and the kidneys, and some people develop sores when the skin is immersed in chloroform.[citation needed]

Animal studies have shown that miscarriages occur in rats and mice that have breathed air containing 30 to 300 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 defects, and abnormal 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 disinfectants (under the Lysoform trade name, which also contained potassium hydroxide and alcohol), toothpastes, cough syrups, ointments, and other pharmaceuticals, but it has been banned as a consumer product in the US since 1976.[21] Cough syrups containing chloroform can still be legally purchased in pharmacies and supermarkets in the UK.

The US National Toxicology Program's twelfth report on carcinogens[22] implicates it as reasonably anticipated to be a human carcinogen, a designation equivalent to International Agency for Research on Cancer class 2A. The IARC itself classifies chloroform as possibly carcinogenic to humans, a Group 2B designation.[23] It has been most readily associated with hepatocellular carcinoma.[24][25] 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.

Conversion to phosgene

During prolonged storage in the presence of oxygen, chloroform converts slowly to phosgene, releasing HCl in the process. To prevent accidents, commercial chloroform is stabilized with ethanol or amylene, but samples that have been recovered or dried no longer contain any stabilizer. Amylene has been found ineffective, and the phosgene can affect analytes in samples, lipids, and nucleic acids dissolved in or extracted with chloroform.[26] Dissolved phosgene cannot be removed by distillation or carbon filters, but it is removed by calcium hydroxide or activated alumina.[27] Phosgene and HCl can be removed from chloroform by washing with saturated aqueous carbonate solutions, such as sodium bicarbonate. This procedure is simple and results in harmless products. Phosgene reacts with water to form carbon dioxide and HCl,[28] and the carbonate salt neutralizes the resulting acid.

Suspected samples can be tested for phosgene using filter paper (treated with 5% diphenylamine, 5% dimethylaminobenzaldehyde in alcohol, and then dried), which turns yellow in phosgene vapor. There are several colorimetric and fluorometric reagents for phosgene, and it can also be quantified with mass spectrometry.

References

  1. ^ a b c d e f g Rossberg, M. et al. “Chlorinated Hydrocarbons” in Ullmann’s Encyclopedia of Industrial Chemistry, 2006, Wiley-VCH, Weinheim. doi:10.1002/14356007.a06_233.pub2
  2. ^ a b c Chloroform (PDF), CICAD, vol. 58, World Health Organization, 2004
  3. ^ Koch, Hans A. Cholorofom Deuteration Process. Canadian Patent 1085423. Patents.ic.gc.ca. Issued: 1980-09-09. Retrieved on 2012-08-13.
  4. ^ Hans Ulrich Süss (2007), "Bleaching", Ullmann's Encyclopedia of Industrial Chemistry (7th ed.), Wiley, p. 5
  5. ^ Jerrold B. Leikin; Frank P. Paloucek, eds. (2008), "Chloroform", Poisoning and Toxicology Handbook (4th ed.), Informa, p. 774
  6. ^ Srebnik, M.; Laloë, E. (2001) "Chloroform" in Encyclopedia of Reagents for Organic Synthesis, Wiley, doi:10.1002/047084289X.rc105
  7. ^ "1,6-Methano[10]annulene". Organic Syntheses. 1988; Collected Volumes, vol. 6, p. 731.
  8. ^ Gokel, G. W.; Widera, R. P.; Weber, W. P. (1988). "Phase-Transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide". Organic Syntheses{{cite journal}}: CS1 maint: multiple names: authors list (link); Collected Volumes, vol. 6, p. 232.
  9. ^ Gordon, H. Laing (November 2002). Sir James Young Simpson and Chloroform (1811–1870). The Minerva Group, Inc. pp. 106–109. ISBN 978-1-4102-0291-8. Retrieved 11 November 2011.
  10. ^ Anesthesia and Queen Victoria. Ph.ucla.edu. Retrieved on 2012-08-13.
  11. ^ Martin, William (3 July 1886). "A Case of Chloroform Poisoning; Recovery". Br Med J. 2 (1331): 16–17. doi:10.1136/bmj.2.1331.16-a. PMC 2257365. PMID 20751619.
  12. ^ Patel, Amanda J.; Honoré, Eric; Lesage, Florian; Fink, Michel; Romey, Georges; Lazdunski, Michel (May 1999). "Inhalational anesthetics activate two-pore-domain background K+ channels". Nature Neuroscience. 2 (5): 422–426. doi:10.1038/8084. PMID 10321245.
  13. ^ Knight, Paul R. III and Bacon, Douglas R. (2002). "An Unexplained Death: Hannah Greener and Chloroform". Anesthesiology. 96 (5): 1250–3. doi:10.1097/00000542-200205000-00030. PMID 11981167.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Snow, John (1858). "On Chloroform and Other Anaesthetics and Their Action and Administration". pp. 82–85.
  15. ^ "Knock-out and Chloroform". The Philadelphia record. 9 February 1894. Retrieved 31 March 2011.
  16. ^ "Chloroform case retrial underway". Record-Journal. 7 July 1993. Retrieved 31 March 2011.
  17. ^ "Man admits to raping friends' daughters". USA Today. 6 November 2007. Retrieved 31 March 2011.
  18. ^ a b J. P. Payne The criminal use of chloroform Anaesthesia Volume 53, Issue 7, pages 685–690, July 1998
  19. ^ Medical Annotation. Chloroform amongst Thieves. Lancet 1865; 2: 490 – 1.
  20. ^ Chloroform, US Environmental Potection Agency
  21. ^ "The National Toxicology Program: Substance Profiles: Chloroform CAS No. 67-66-3" (PDF). Retrieved 21 May 2012.
  22. ^ "Substances Listed in the Twelfth Report on Carcinogens" (PDF). Retrieved 21 May 2012.
  23. ^ "International Agency for Research on Cancer (IARC) – Summaries & Evaluations: Chloroform". Retrieved 2 September 2010.
  24. ^ "Current Intelligence Bulletin 9: Chloroform (DDM)". Centers for Disease Control and Prevention cdc.gov.
  25. ^ "National Toxicology Program: Report on the carcinogenesis bioassay of chloroform" (PDF).
  26. ^ Turk, Eric (2 March 1998). "Phosgene from Chloroform". Chemical & Engineering News. 76 (9): 6. doi:10.1021/cen-v076n009.p006.
  27. ^ Cone, EJ; Buchwald, WF; Darwin, WD (1982). "Analytical controls in drug metabolic studies. II. Artifact formation during chloroform extraction of drugs and metabolites with amine substituents". Drug metabolism and disposition: the biological fate of chemicals. 10 (6): 561–7. PMID 6130900.
  28. ^ phosgene (chemical compound). Encyclopædia Britannica. Retrieved on 2013-08-16.

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