Editing Chloroform

{{Short description|CHCl3, historical anaesthetic and common solvent}}{{other uses}}{{Use dmy dates|date=April 2023}}
{{Expand Turkish|Kloroform|date=September 2024|fa=yes}}
{{Chembox
|Verifiedimages = changed
|Watchedfields = changed
|verifiedrevid = 407464807
|ImageFileL1_Ref = {{chemboximage|correct|??}}
|ImageFileL1 = Chloroform_displayed.svg
|ImageClassL1 = skin-invert
|ImageFileR1 = Chloroform-3D-balls.png
|ImageFile2 = Chloroform_by_Danny_S._-_002.JPG
|ImageName2 = Chloroform in its liquid state shown in a test tube
|ImageSize2 = 100px
|PIN = Trichloromethane
|OtherNames = {{ubl|''Chloroformium''|Freon 20|Methane trichloride|Methyl trichloride|Methenyl trichloride|Methenyl chloride|Refrigerant-20|terchloride/perchloride of formyle<ref>Gregory, William, A Handbook of Organic Chemistry (Third edition corrected and much extended), 1852, page 177</ref><ref>Daniel Pereira Gardner, Medicinal Chemistry for the Use of Students and the Profession: Being a Manual of the Science, with Its Applications to Toxicology, Physiology, Therapeutics, Hygiene, Etc (1848), page 271</ref> ''(archaic)''|''Trichloretum Formylicum'' ([[Latin]])}}
|Section1 = {{Chembox Identifiers
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = 7V31YC746X
| Abbreviations = R-20, TCM
|InChIKey = HEDRZPFGACZZDS-UHFFFAOYAG
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 44618
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/CHCl3/c2-1(3)4/h1H
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = HEDRZPFGACZZDS-UHFFFAOYSA-N
|CASNo = 67-66-3
|CASNo_Ref = {{cascite|correct|CAS}}
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 5977
|EINECS = 200-663-8
|PubChem = 6212
| UNNumber =  1888
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 35255
|KEGG_Ref = {{keggcite|correct|kegg}}
|KEGG = C13827
|SMILES = ClC(Cl)Cl
|InChI = 1/CHCl3/c2-1(3)4/h1H
|RTECS = FS9100000
}}
|Section2 = {{Chembox Properties
|C=1|H=1|Cl=3
|Appearance = Highly refractive colorless liquid
|Odor = Sweet, minty, pleasant
|Density = 1.564 g/cm<sup>3</sup> (−20&nbsp;°C)<br /> 1.489 g/cm<sup>3</sup> (25&nbsp;°C)<br /> 1.394 g/cm<sup>3</sup> (60&nbsp;°C)
|MeltingPtC = −63.5
|BoilingPtC = 61.15
|BoilingPt_notes = <br /> decomposes at 450&nbsp;°C
|VaporPressure = 0.62 kPa (−40&nbsp;°C)<br /> 7.89 kPa (0&nbsp;°C)<br /> 25.9 kPa (25&nbsp;°C)<br /> 313 kPa (100&nbsp;°C)<br /> 2.26 MPa (200&nbsp;°C)
|Solubility = 10.62 g/L (0&nbsp;°C)<br /> 8.09 g/L (20&nbsp;°C)<br /> 7.32 g/L (60&nbsp;°C)
|SolubleOther = Soluble in [[benzene]]<br /> Miscible in [[diethyl ether]], [[oil]]s, [[ligroin]], [[ethanol|alcohol]], [[carbon tetrachloride|CCl<sub>4</sub>]], [[carbon disulfide|CS<sub>2</sub>]]
|Solubility1 = ≥ 100 g/L (19&nbsp;°C)
|Solvent1 = acetone
|Solubility2 = ≥ 100 g/L (19&nbsp;°C)
|Solvent2 = dimethyl sulfoxide
|RefractIndex = 1.4459 (20&nbsp;°C)
|LambdaMax = 250 nm, 260 nm, 280 nm
|Viscosity = 0.563 cP (20&nbsp;°C)
|pKa = 15.7 (20&nbsp;°C)
|HenryConstant = 3.67 L·atm/mol (24&nbsp;°C)
|ThermalConductivity = 0.13 W/(m·K) (20&nbsp;°C)
|MagSus = −59.30·10<sup>−6</sup> cm<sup>3</sup>/mol
}}
|Section3 = {{Chembox Structure
|MolShape = Tetrahedral
|Dipole = 1.15 D
}}
|Section4 = {{Chembox Thermochemistry
|HeatCapacity = 114.25 J/(mol·K)
|Entropy = 202.9 J/(mol·K)
|DeltaHf = −134.3 kJ/mol
|DeltaGf = −71.1 kJ/mol
|DeltaHc = 473.21 kJ/mol
}}
|Section6 = {{Chembox Pharmacology
|ATCCode_prefix = N01
|ATCCode_suffix = AB02
}}
|Section7 = {{Chembox Hazards
|ExternalSDS = [https://www.merckmillipore.com/Web-IE-Site/en_US/-/EUR/ShowDocument-File?ProductSKU=MDA_CHEM-107024&DocumentType=MSD&DocumentId=107024_SDS_GB_EN.PDF&DocumentUID=370414&Language=EN&Country=GB&Origin=PDP&Display=inline]
|Hazards_ref = <ref name= PubChem>{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/6212#section=Safety-and-Hazards|title=PubChem: Safety and Hazards – GHS Classification|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine|access-date=17 August 2018|archive-date=17 August 2018|archive-url=https://web.archive.org/web/20180817125017/https://pubchem.ncbi.nlm.nih.gov/compound/6212#section=Safety-and-Hazards|url-status=live}}</ref>
|MainHazards = Decomposes into [[phosgene]] and [[hydrogen chloride]] in presence of heat – likely carcinogenic – [[reproductive toxicity]] – hepatotoxic<ref name=PGCH/><ref name=":1">Toxicity on [https://pubchem.ncbi.nlm.nih.gov/compound/6212#section=Toxicity <nowiki>PubChem</nowiki>] {{Webarchive|url=https://web.archive.org/web/20180817125017/https://pubchem.ncbi.nlm.nih.gov/compound/6212#section=Toxicity |date=17 August 2018 }}</ref>
|GHSPictograms = {{GHS06}} {{GHS08}} {{GHS corrosion}} 
|GHSSignalWord = Danger
|HPhrases = {{H-phrases|302|315|319|331|336|351|361d|372}}
|PPhrases = {{P-phrases|201|202|260|264|270|271|280|281|301+330+331|310|302+352|304+340|311|305+351+338|308+313|314|332+313|337+313|362|403+233|235|405|501}}
|NFPA-H = 2
|NFPA-F = 0
|NFPA-R = 1
|FlashPt = Nonflammable
|PEL = 50 ppm (240 mg/m<sup>3</sup>)<ref name=PGCH>{{PGCH|0127}}</ref>
|IDLH = 500 ppm<ref name=PGCH/>{{cln|reason=What is "ppm"??? Is it a mass/mass fraction, volume/volume fraction, mole/mole fraction, mass/volume fraction, and who knows what else??? Using ambiguous units like "ppm" without unambiguous explanation what that unit stands for irritates readers who are not experts in this field, and the readers have no power to read the writer's mind!|date=June 2023}}
|REL = Ca ST 2 ppm (9.78 mg/m<sup>3</sup>) [60-minute]<ref name=PGCH/>
|LD50 = 704 mg/kg (mouse, dermal)<ref>{{cite book |title=Sax's Dangerous Properties of Industrial Materials |edition=12th |year=2012 |last=Lewis |first=Richard J. |publisher=Wiley |isbn=978-0-470-62325-1}}</ref>
|LC50 = 47,702 mg/m<sup>3</sup> (rat, 4 hr)<ref>{{cite web|url=https://www.epa.gov/sites/default/files/2016-09/documents/chloroform.pdf |title=Chloroform |date=September 2016 |website=Environmental Protection Agency |access-date=19 February 2024}}</ref>
|LCLo = {{ubl|20,000 ppm (guinea pig, 2 hr)|7,056 ppm (cat, 4 hr)|25,000 ppm (human, 5 min)}}<ref name=IDLH>{{IDLH|67663|Chloroform}}</ref>{{cln|reason=What is "ppm"??? Is it a mass/mass fraction, volume/volume fraction, mole/mole fraction, mass/volume fraction, and who knows what else??? Using ambiguous units like "ppm" without unambiguous explanation what that unit stands for irritates readers who are not experts in this field, and the readers have no power to read the writer's mind!|date=June 2023}}
}}
|Section9 = {{Chembox Related
|OtherFunction_label = chloromethanes
|OtherCompounds = {{ubl|[[Deuterated chloroform]] {{chem2|CDCl3}}|[[Chloromethane]] {{chem2|CH3Cl}}|[[Dichloromethane]] {{chem2|CH2Cl2}}|[[Tetrachloromethane]] {{chem2|CCl4}}|[[Fluoroform]] {{chem2|CHF3}}|[[Bromoform]] {{chem2|CHBr3}}|[[Iodoform]] {{chem2|CHI3}}|[[Chlorodifluoromethane]] {{chem2|CHF2Cl}}|[[Dichlorofluoromethane]] {{chem2|CHFCl2}}|[[Bromodichloromethane]] {{chem2|CHCl2Br}}|[[Dibromochloromethane]] {{chem2|CHClBr2}}|[[Bromodifluoromethane]] {{chem2|CHF2Br}}|[[Dibromofluoromethane]] {{chem2|CHFBr2}}}}
}}
}}
'''Chloroform''',<ref name=iupac2013>{{cite book | title = Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry|The Royal Society of Chemistry]] | date = 2014 | location = Cambridge | page = 661 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4 | quote = The retained names 'bromoform' for HCBr<sub>3</sub>, 'chloroform' for HCCl<sub>3</sub>, and 'iodoform' for HCI<sub>3</sub> are acceptable in general nomenclature. Preferred IUPAC names are substitutive names.| chapter = Front Matter }}</ref> or '''trichloromethane''' (often abbreviated as '''TCM'''), is an [[organochloride]] with the [[chemical formula|formula]] {{chem2|CHCl3|auto=1}} and a common [[solvent]]. It is a [[Volatility (chemistry)|volatile]], colorless, sweet-smelling, dense liquid produced on a large scale as a precursor to [[refrigerant]]s and [[PTFE]].<ref name="Ullmann"> {{Ullmann|last=Rossberg|first=M.|display-authors=etal|title=Chlorinated Hydrocarbons|doi=10.1002/14356007.a06_233.pub2}}</ref> Chloroform was once used as an [[inhalational anesthetic]] between the 19th century and the first half of the 20th century.<ref>{{cite web |url=http://www.history.com/topics/ether-and-chloroform |title=Ether and Chloroform |access-date=2018-04-24 |url-status=live |archive-url=https://web.archive.org/web/20180324191303/https://www.history.com/topics/ether-and-chloroform |archive-date=24 March 2018}}</ref><ref>{{Cite book | doi=10.1002/3527600418.mb6766e0014|chapter = Chloroform [MAK Value Documentation, 2000] |title = The MAK-Collection for Occupational Health and Safety = 20–58|year = 2012|isbn = 978-3-527-60041-0}}</ref> It is miscible with many solvents but it is only very slightly soluble in water (only 8 g/L at 20°C).

==Structure and name==
The molecule adopts a [[tetrahedral molecular geometry]] with C<sub>3v</sub> [[symmetry group|symmetry]].<ref>{{Cite web |title=Illustrated Glossary of Organic Chemistry - Chloroform |url=http://www.chem.ucla.edu/~harding/IGOC/C/chloroform.html |access-date=2022-12-29 |website=www.chem.ucla.edu}}</ref> The chloroform molecule can be viewed as a [[methane]] molecule with three hydrogen atoms replaced with three chlorine atoms, leaving a single hydrogen atom.

The name "chloroform" is a [[portmanteau]] of ''terchloride'' (tertiary chloride, a trichloride) and ''formyle'', an obsolete name for the [[methylylidene]] radical (CH) derived from [[formic acid]].{{citation needed|date=February 2025}}

==Natural occurrence ==
Many kinds of [[seaweed]] produce chloroform, and [[fungi]] are believed to produce chloroform in soil.<ref>{{cite journal | last1 = Cappelletti | first1 = M. | year = 2012 | title = Microbial degradation of chloroform | journal = Applied Microbiology and Biotechnology | volume = 96 | issue = 6| pages = 1395–409 | doi = 10.1007/s00253-012-4494-1| pmid = 23093177 | s2cid = 12429523 }}</ref> Abiotic processes are also believed to contribute to natural chloroform productions in soils, although the mechanism is still unclear.<ref>{{cite journal | last1 = Jiao | first1 = Yi |display-authors=etal | year = 2018 | title = Halocarbon Emissions from a Degraded Forested Wetland in Coastal South Carolina Impacted by Sea Level Rise | journal = ACS Earth and Space Chemistry | volume = 2 | issue = 10 | pages = 955–967 | doi = 10.1021/acsearthspacechem.8b00044 | bibcode = 2018ESC.....2..955J | s2cid = 134649348 }}</ref>

Chloroform is a volatile organic compound.<ref>{{cite web | url=http://aqt-vru.com/emissions/complete-list-of-vocs/ | title=Complete list of VOC's }}</ref>

==History==
Chloroform was synthesized independently by several investigators {{Circa|1831}}:
*Moldenhawer, a German pharmacist from [[Frankfurt an der Oder]], appears to have produced chloroform in 1830 by mixing [[chlorinated lime#Chlorine-based bleaches|chlorinated lime]] with [[ethanol]]; however, he mistook it for ''Chloräther'' (chloric ether, [[1,2-dichloroethane]]).<ref>{{cite journal|last=Moldenhawer|date=1830|url=https://books.google.com/books?id=a_E3AAAAMAAJ&pg=PA222|title=Verfahren den Spiritus von dem Fuselöl auf leichte Weise zu befreien|trans-title=Procedure for freeing ethanol of fusel oil in an easy way|journal=Magazin für Pharmacie|volume=8|issue=31|pages=222–227|access-date=6 May 2016|archive-date=29 July 2020|archive-url=https://web.archive.org/web/20200729120000/https://books.google.com/books?id=a_E3AAAAMAAJ&pg=PA222|url-status=live}}</ref><ref>{{cite journal|last1=Defalque|first1=Ray J.|last2=Wright|first2=A. J. |title=Was chloroform produced before 1831?|journal=Anesthesiology|volume=92|issue=1|pages=290–291|pmid=10638939|year=2000|doi=10.1097/00000542-200001000-00060|doi-access=free}}</ref>
*[[Samuel Guthrie (physician)|Samuel Guthrie]], a U.S. physician from [[Sackets Harbor, New York]], also appears to have produced chloroform in 1831 by reacting chlorinated lime with ethanol, and noted its [[Anesthetic|anaesthetic]] properties; however, he also believed that he had prepared chloric ether.<ref>{{cite journal|last=Guthrie|first=Samuel|year=1832|url=https://books.google.com/books?id=iuzRAAAAMAAJ&pg=PA64|title=New mode of preparing a spirituous solution of chloric ether|journal=The American Journal of Science and Arts|volume=21|pages=64–65 and 405–408|access-date=6 May 2016|archive-date=29 July 2020|archive-url=https://web.archive.org/web/20200729135541/https://books.google.com/books?id=iuzRAAAAMAAJ&pg=PA64|url-status=live}}</ref><ref>{{cite book|last=Guthrie|first=Ossian|date=1887|url=https://archive.org/details/39002011125375.med.yale.edu|page=[https://archive.org/details/39002011125375.med.yale.edu/page/n43 1]|title=Memoirs of Dr. Samuel Guthrie, and the History of the Discovery of Chloroform|location=Chicago|publisher=George K. Hazlitt & Co.}}</ref><ref>{{cite book|last=Stratmann|first=Linda|date=2003|title=Chloroform: The Quest for Oblivion|location=Stroud|publisher=Sutton Publishing|chapter-url=https://books.google.com/books?id=VvA7AwAAQBAJ&pg=PT30|chapter=Chapter 2|isbn=978-0-7524-9931-4|access-date=6 May 2016|archive-date=29 July 2020|archive-url=https://web.archive.org/web/20200729120316/https://books.google.com/books?id=VvA7AwAAQBAJ&pg=PT30|url-status=live}}</ref>
*[[Justus von Liebig]] carried out the [[Bond cleavage|alkaline cleavage]] of [[chloral]]. Liebig incorrectly states that the [[empirical formula]] of chloroform was {{chem2|C2Cl5}} and named it "''Chlorkohlenstoff''" ("carbon chloride").<ref>{{cite journal|last=Liebig|first=Justus von|url=https://babel.hathitrust.org/cgi/pt?id=uc1.a0002753747;view=1up;seq=462|doi=10.1002/andp.18310991111|title=Ueber die Zersetzung des Alkohols durch Chlor|journal=Annalen der Physik und Chemie|volume=99|issue=11|page=444|trans-title=On the decomposition of alcohol by chlorine|year=1831|bibcode=1831AnP....99..444L|access-date=6 May 2016|archive-date=10 May 2017|archive-url=https://web.archive.org/web/20170510154137/https://babel.hathitrust.org/cgi/pt?id=uc1.a0002753747;view=1up;seq=462|url-status=live}}</ref><ref>{{cite journal|last=Liebig |first=Justus von |url=https://babel.hathitrust.org/cgi/pt?id=wu.89048351662&view=1up&seq=861 |year=1832|title=Ueber die Verbindungen, welche durch die Einwirkung des Chlors auf Alkohol, Aether, ölbildendes Gas und Essiggeist entstehen|journal=Annalen der Physik und Chemie |volume=100 |issue=2 |pages=243–295 |trans-title=On the compounds which arise by the reaction of chlorine with alcohol [ethanol], ether [diethyl ether], oil-forming gas [ethylene], and spirit of vinegar [acetone] |doi=10.1002/andp.18321000206|bibcode=1832AnP...100..243L }}<br />On pages 259–265, Liebig describes ''Chlorkohlenstoff'' ("carbon chloride", chloroform), but on p. 264, Liebig incorrectly states that the [[empirical formula]] of chloroform is C<sub>2</sub>Cl<sub>5</sub>.</ref>
*[[Eugène Soubeiran]] obtained the compound by the action of [[chlorine bleach]] on both [[ethanol]] and [[acetone]].<ref>{{cite journal |last=Soubeiran |first=Eugène |date=1831 |url=https://babel.hathitrust.org/cgi/pt?id=ien.35556014127963;view=1up;seq=115 |title=Recherches sur quelques combinaisons du chlore |trans-title=Investigations into some compounds of chlorine |journal=Annales de Chimie et de Physique |series=Série 2 |volume=48 |pages=113–157 |access-date=6 May 2016 |archive-date=10 May 2017 |archive-url=https://web.archive.org/web/20170510154147/https://babel.hathitrust.org/cgi/pt?id=ien.35556014127963;view=1up;seq=115 |url-status=live }}
*Reprinted in {{cite journal |last=Soubeiran |first=Eugène |date=1831 |url=https://books.google.com/books?id=QP1BAAAAcAAJ&pg=PA657 |title=Recherches sur quelques combinaisons du chlore |trans-title=Investigations on some compounds of chlorine |journal=Journal de Pharmacie et des Sciences Accessoires |volume=17 |pages=657–672 |access-date=6 May 2016 |archive-date=29 July 2020 |archive-url=https://web.archive.org/web/20200729112744/https://books.google.com/books?id=QP1BAAAAcAAJ&pg=PA657 |url-status=live }}
*Reprinted in {{cite journal |last=Soubeiran |first=Eugène |date=1832 |url=https://books.google.com/books?id=aBZJAQAAMAAJ&pg=PA1 |title=Suite des recherches sur quelques combinaisons du chlore |trans-title=Continuation of investigations on some compounds of chlorine |journal=Journal de Pharmacie et des Sciences Accessoires |volume=18 |pages=1–24 |access-date=6 May 2016 |archive-date=29 July 2020 |archive-url=https://web.archive.org/web/20200729121309/https://books.google.com/books?id=aBZJAQAAMAAJ&pg=PA1 |url-status=live }}</ref>

In 1834, French chemist [[Jean-Baptiste Dumas]] determined chloroform's empirical formula and named it:<ref>{{cite journal|last=Dumas |first=J.-B. |date=1834 |title=Récherches rélative à l'action du chlore sur l'alcool |trans-title=Experiments regarding the action of chlorine on alcohol |journal=L'Institut, Journal Général des Sociétés et Travaux Scientifiques de la France et de l'Étranger |volume=2 |pages=106–108 and 112–115}}
*Reprinted in {{cite journal|url=https://babel.hathitrust.org/cgi/pt?id=umn.31951d00316736l;view=1up;seq=668|title=Untersuchung über die Wirkung des Chlors auf den Alkohol|journal=Annalen der Physik und Chemie|volume=107|issue=42|pages=657–673|trans-title=Investigation of the action of chlorine on alcohol|doi=10.1002/andp.18341074202|bibcode=1834AnP...107..657D|year=1834|last1=Dumas|first1=J.-B.|access-date=12 May 2016|archive-date=10 May 2017|archive-url=https://web.archive.org/web/20170510152609/https://babel.hathitrust.org/cgi/pt?id=umn.31951d00316736l;view=1up;seq=668|url-status=live}}<br />On p. 653, Dumas states chloroform's empirical formula:
::''"Es scheint mir also erweisen, dass die von mir analysirte Substance, … zur Formel hat: {{chem2|C2H2Cl6}}."'' (Thus it seems to me to show that the substance [that was] analyzed by me … has as [its empirical] formula: {{chem2|C2H2Cl6}}.) [Note: The coefficients of his empirical formula must be halved.]
:Dumas then notes that chloroform's simple [[empirical formula]] resembles that of [[formic acid]]. Furthermore, if chloroform is boiled with [[potassium hydroxide]], one of the products is [[potassium formate]]. On p. 654, Dumas names chloroform: 
::''"Diess hat mich veranlasst diese Substanz mit dem Namen 'Chloroform' zu belegen."'' (This caused me to bestow this substance with the name "chloroform" [i.e., formyl chloride or chloride of formic acid].)
*Reprinted in {{cite journal |doi=10.1002/jlac.18350160213 |url=https://babel.hathitrust.org/cgi/pt?id=uva.x002457902;view=1up;seq=542 |title=Ueber die Wirkung des Chlors auf den Alkohol |journal=Annalen der Pharmacie |volume=16 |issue=2 |pages=164–171 |trans-title=On the action of chlorine on alcohol |year=1835 |last1=Dumas |first1=J.-B. |access-date=12 May 2016 |archive-date=10 May 2017 |archive-url=https://web.archive.org/web/20170510152601/https://babel.hathitrust.org/cgi/pt?id=uva.x002457902;view=1up;seq=542 |url-status=live }}</ref> "''Es scheint mir also erweisen, dass die von mir analysirte Substanz, … zur Formel hat: C<sub>2</sub>H<sub>2</sub>Cl<sub>6</sub>.''" (Thus it seems to me to show that the substance I analyzed … has as [its empirical] formula: C<sub>2</sub>H<sub>2</sub>Cl<sub>6</sub>.). [Note: The coefficients of his empirical formula should be halved.] ... "''Diess hat mich veranlasst diese Substanz mit dem Namen 'Chloroform' zu belegen.''" (This had caused me to impose the name "chloroform" upon this substance [i.e., formyl chloride or chloride of formic acid].)

In 1835, Dumas prepared the substance by alkaline cleavage of [[trichloroacetic acid]]. 

In 1842, [[Robert Mortimer Glover]] in London discovered the anaesthetic qualities of chloroform on laboratory animals.<ref name=pdf1>{{cite journal|pmid=15023112|url=http://www.ph.ucla.edu/epi/snow/anaesthesia59_394_400_2004.pdf|year=2004|last1=Defalque|first1=R. J.|title=The short, tragic life of Robert M. Glover|journal=Anaesthesia|volume=59|issue=4|pages=394–400|last2=Wright|first2=A. J.|doi=10.1111/j.1365-2044.2004.03671.x|s2cid=46428403|url-status=live|archive-url=https://web.archive.org/web/20160309080158/http://www.ph.ucla.edu/epi/snow/anaesthesia59_394_400_2004.pdf|archive-date=9 March 2016|doi-access=free}}</ref>

In 1847, Scottish obstetrician [[James Y. Simpson]] was the first to demonstrate the anaesthetic properties of chloroform (provided by local pharmacist [[William Flockhart]] of Duncan, Flockhart and company,<ref name="Gordon2002" />) in humans, and helped to popularize the drug for use in medicine.<ref name=eb>{{cite encyclopedia|title=Sir James Young Simpson|url=https://www.britannica.com/EBchecked/topic/545447/Sir-James-Young-Simpson-1st-Baronet|encyclopedia=Encyclopædia Britannica|access-date=23 August 2013|url-status=live|archive-url=https://web.archive.org/web/20130727130133/https://www.britannica.com/EBchecked/topic/545447/Sir-James-Young-Simpson-1st-Baronet|archive-date=27 July 2013}}</ref> 

By the 1850s, chloroform was being produced on a commercial basis. In Britain, about 750,000 doses a week were being produced by 1895,<ref>{{Cite journal|last=Worling|first=P.M.|date=1998|title=Duncan and Flockhart: the Story of Two Men and a Pharmacy|journal=Pharmaceutical Historian|volume=28|issue=2|pages=28–33|pmid=11620310}}</ref> using the Liebig procedure, which retained its importance until the 1960s. Today, chloroform – along with [[dichloromethane]] – is prepared exclusively and on a massive scale by the chlorination of methane and chloromethane.<ref name="Ullmann"/>

==Production==
Industrially, chloroform is produced by heating a mixture of [[chlorine]] and either [[methyl chloride]] ({{chem2|CH3Cl}}) or [[methane]] ({{chem2|CH4}}).<ref name=Ullmann/> At 400–500&nbsp;°C, [[free radical halogenation]] occurs, converting these precursors to progressively more chlorinated compounds:
:{{chem2|CH4 + [[Chlorine|Cl2]] → CH3Cl + [[Hydrogen chloride|HCl]]}}
:{{chem2|CH3Cl + Cl2 → [[Dichloromethane|CH2Cl2]] + HCl}}
:{{chem2|CH2Cl2 + Cl2 → CHCl3 + HCl}}

Chloroform undergoes further chlorination to yield [[carbon tetrachloride]] ({{chem2|CCl4}}):
:{{chem2|CHCl3 + Cl2 → CCl4 + HCl}}

The output of this process is a mixture of the four chloromethanes: [[chloromethane]], [[methylene chloride]] (dichloromethane), trichloromethane (chloroform), and tetrachloromethane (carbon tetrachloride). These can then be separated by [[distillation]].<ref name=Ullmann/>

Chloroform may also be produced on a small scale via the [[haloform reaction]] between [[acetone]] and [[sodium hypochlorite]]:
:{{chem2|3 NaOCl + (CH3)2CO → CHCl3 + 2 [[Sodium hydroxide|NaOH]] + [[Sodium acetate|CH3COONa]]}}

===Deuterochloroform===
{{Main|Deuterated chloroform}}
[[Deuterated chloroform]] is an [[isotopologue]] of chloroform with a single [[deuterium]] atom. {{chem2|CDCl3}} is a common solvent used in [[NMR spectroscopy]]. Deuterochloroform is produced by the reaction of [[hexachloroacetone]] with [[heavy water]].<ref>{{cite journal |last1=Paulsen |first1=P. J. |last2=Cooke |first2=W. D. |title=Preparation of Deuterated Solvents for Nuclear Magnetic Resonance Spectrometry. |journal=Analytical Chemistry |date=1 September 1963 |volume=35 |issue=10 |page=1560 |doi=10.1021/ac60203a072}}</ref> The haloform process is now obsolete for production of ordinary chloroform. Deuterochloroform can also be prepared by reacting [[sodium deuteroxide]] with [[chloral hydrate]].<ref>{{cite journal|doi=10.1021/ja01314a058|title=Chloroform-d (Deuteriochloroform)1|journal=Journal of the American Chemical Society|volume=57|issue=11|pages=2236–2237|year=1935|last1=Breuer|first1=F. W.}}</ref><ref>{{cite journal|doi=10.1021/jo01030a526|title=A Convenient Preparation of Chloroform-d1|journal=The Journal of Organic Chemistry|volume=29|issue=7|pages=2045–2046|year=1964|last1=Kluger|first1=Ronald}}</ref>

===Inadvertent formation 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]] can produce some chloroform, in addition to other compounds, such as [[chloroacetone]] or [[dichloroacetone]].{{citation needed|date=November 2020}}

==Uses==
In terms of scale, the most important reaction of chloroform is with [[hydrogen fluoride]] to give [[monochlorodifluoromethane]] (HCFC-22), a precursor in the production of polytetrafluoroethylene ([[Teflon]]) and other fluoropolymers:<ref name="Ullmann" />
:{{chem2|CHCl3 + 2 HF → CHClF2 + 2 HCl}}
The reaction is conducted in the presence of a [[Catalysis|catalytic]] amount of [[Antimony trifluoride#Applications|mixed antimony halides]]. Chlorodifluoromethane is then converted to [[tetrafluoroethylene]], the main precursor of [[Teflon]].<ref>{{Cite web|title=Chlorodifluoromethane {{!}} chemical compound|url=https://www.britannica.com/science/chlorodifluoromethane|access-date=2021-09-08|website=Encyclopedia Britannica|language=en|archive-date=17 July 2021|archive-url=https://web.archive.org/web/20210717174046/https://www.britannica.com/science/chlorodifluoromethane|url-status=live}}</ref>

===Solvent===
The [[hydrogen]] attached to [[carbon]] in chloroform participates in hydrogen bonding,<ref>{{cite journal|last1=Wiley |first1=G. R. |last2=Miller |first2=S. I. |doi=10.1021/ja00765a001|title=Thermodynamic parameters for hydrogen bonding of chloroform with Lewis bases in cyclohexane. Proton magnetic resonance study|year=1972|journal=Journal of the American Chemical Society|volume=94|issue=10|pages=3287–3293}}</ref><ref>{{cite journal|pmid=18855462|year=2008|last1=Kwak|first1=K.|last2=Rosenfeld|first2=D. E.|last3=Chung|first3=J. K.|last4=Fayer|first4=M. D.|title=Solute-solvent complex switching dynamics of chloroform between acetone and dimethylsulfoxide-two-dimensional IR chemical exchange spectroscopy|volume=112|issue=44|pages=13906–13915|doi=10.1021/jp806035w|pmc=2646412|journal=The Journal of Physical Chemistry B}}</ref> making it a good solvent for many materials. 

Worldwide, chloroform is also used in pesticide formulations, as a [[solvent]] for [[lipids]], [[rubber]], [[alkaloid]]s, [[wax]]es, [[gutta-percha]], and [[resin]]s, as a cleaning agent, as a grain [[fumigant]], in [[fire extinguishers]], and in the rubber industry.<ref name="cicad">{{citation | title=Chloroform | series=[[CICAD]] | volume=58 | publisher=[[World Health Organization]] | year=2004 | url=https://www.who.int/ipcs/publications/cicad/en/cicad58.pdf | url-status=live | archive-url=https://web.archive.org/web/20200731202031/https://www.who.int/ipcs/publications/cicad/en/cicad58.pdf | archive-date=31 July 2020}}</ref><ref name="pth">{{cite encyclopedia| editor1-last=Leikin |editor1-first=Jerrold B. | editor2-last=Paloucek |editor2-first=Frank P. | title=Chloroform | encyclopedia=Poisoning and Toxicology Handbook | edition=4th | publisher=Informa | year=2008 | page=774}}</ref> [[deuterated chloroform|{{chem2|CDCl3}}]] is a common solvent used in [[NMR spectroscopy]].<ref>{{cite journal|doi=10.1021/om100106e|title=NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist|journal=Organometallics|volume=29|issue=9|pages=2176–2179|year=2010|last1=Fulmer|first1=Gregory R.|last2=Miller|first2=Alexander J. M.|last3=Sherden|first3=Nathaniel H.|last4=Gottlieb|first4=Hugo E.|last5=Nudelman|first5=Abraham|last6=Stoltz|first6=Brian M.|last7=Bercaw|first7=John E.|last8=Goldberg|first8=Karen I.|s2cid=2755004 |url=https://authors.library.caltech.edu/18475/2/om100106e_si_001.pdf}}</ref>

===Refrigerant===
Chloroform is used as a precursor to make R-22 (chlorodifluoromethane). This is done by reacting it with a solution of [[hydrofluoric acid]] (HF) which fluorinates the {{chem2|CHCl3}} molecule and releases hydrochloric acid as a byproduct.<ref>{{cite web | url=https://www.ebi.ac.uk/chebi/es/searchId.do?printerFriendlyView=true&locale=null&chebiId=35255&viewTermLineage=null&structureView=&|title=Chloroform (CHEBI:35255)}}</ref> Before the [[Montreal Protocol]] was enforced, most of the chloroform produced in the United States was used in the production of [[chlorodifluoromethane]]. However, its production remains high, as it is a key precursor of PTFE.<ref>{{cite web|url=https://www.atsdr.cdc.gov/ToxProfiles/tp6-c4.pdf|title=Production, import/export, use, and disposal|access-date=5 April 2023|website=atsdr.cdc.gov}}</ref> 

Although chloroform has properties such as a low boiling point, and a low global warming potential of only 31 (compared to the 1760 of R-22), which are appealing properties for a refrigerant, there is little information to suggest that it has seen widespread use as a refrigerant in any consumer products.<ref>{{cite encyclopedia| title=Chloroform as a pollutant |encyclopedia=The Encyclopedia of World Problems | url=http://encyclopedia.uia.org/en/problem/chloroform-pollutant#:~:text=Most%20chloroform%20is%20manufactured%20to,spot%20removers%2C%20and%20various%20solvents}}</ref>

===Lewis acid===
In solvents such as {{chem2|CCl4}} and alkanes, chloroform hydrogen bonds to a variety of Lewis bases. {{chem2|HCCl3}} is classified as a [[HSAB|hard acid]], and the [[ECW model]] lists its acid parameters as E<sub>A</sub> = 1.56 and C<sub>A</sub> = 0.44.

===Reagent===
As a [[reagent]], chloroform serves as a source of the [[dichlorocarbene]] intermediate {{chem2|CCl2}}.<ref>{{cite encyclopedia|last1=Srebnik |first1=M. |last2=Laloë |first2=E. |date=2001 |encyclopedia=Encyclopedia of Reagents for Organic Synthesis |publisher=Wiley |doi=10.1002/047084289X.rc105|chapter=Chloroform |isbn=978-0-471-93623-7 }}</ref> It reacts with aqueous [[sodium hydroxide]], usually in the presence of a [[phase transfer catalyst]], to produce [[dichlorocarbene]], {{chem2|CCl2}}.<ref>{{OrgSynth|last1=Vogel |first1=E. |last2=Klug |first2=W. |last3=Breuer |first3=A.|title = 1,6-Methano[10]annulene|collvol = 6|collvolpages = 731|year = 1988|prep = cv6p0731}}</ref><ref>{{OrgSynth|last1 = Gokel |first1=G. W. |last2=Widera|first2= R. P. |last3=Weber |first3=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. In the [[Kharasch addition]], chloroform forms the {{chem2|•CHCl2}} free radical which adds to alkenes.{{citation needed|date=November 2020}}

===Anaesthetic===
[[File:Chickamauga 2009, Chloroform.jpg|thumb|Antique bottles of chloroform]]
Chloroform is a powerful [[general anesthetic]], [[euphoriant]], [[anxiolytic]], and [[sedative]] when inhaled or ingested. The [[anaesthetic]] qualities of chloroform were first described in 1842 in a thesis by [[Robert Mortimer Glover]], which won the Gold Medal of the [[Harveian Society]] for that year.<ref name="Chloroform History">{{cite journal |last1=Perkins-McVey |first1=Matthew |title="A new order of poisonous substances": revisiting Robert M. Glover's dissertation on the physiological effects of bromine, chlorine, and iodine compounds |journal=Naunyn-Schmiedeberg's Archives of Pharmacology |date=10 November 2023 |volume=397 |issue=5 |pages=3343–3350 |doi=10.1007/s00210-023-02820-y |url=https://www.researchgate.net/publication/375556103 |access-date=27 January 2024|doi-access=free |pmid=37947840 }}</ref><ref>{{cite journal |last1=Glover |first1=Robert M. |title=On the Physiological and Medicinal Properties of Bromine and Its Compounds; Also on the Analogies between the Physiological and Medicinal Properties of These Bodies, and Those of Chlorine and Iodine, with Their Correspondent Compounds; Being the Harveian Prize Essay for 1842. |journal=Edinburgh Medical and Surgical Journal |date=1 October 1842 |volume=58 |issue=153 |pages=335–364 |pmid=30330609 |pmc=5789197 }}</ref> Glover also undertook practical experiments on dogs to prove his theories, refined his theories, and presented them in his doctoral thesis at the [[University of Edinburgh]] in the summer of 1847, identifying anaesthetizing halogenous compounds as a "new order of poisonous substances".<ref name="Chloroform History" />

The Scottish [[obstetrics|obstetrician]] [[James Young Simpson]] was one of those examiners required to read the thesis, but later claimed to have never read it and to have come to his own conclusions independently.<ref name="Chloroform History" /> Perkins-McVey, among others, have raised doubts about the credibility of Simpson's claim, noting that Simpson's publications on the subject in 1847 explicitly echo Glover's and, being one of the thesis examiners, Simpson was likely aware of the content of Glover's study, even if he skirted his duties as an examiner.<ref name="Chloroform History" /> In 1847 and 1848, Glover would pen a series of heated letters accusing Simpson of stealing his discovery, which had already earned Simpson considerable notoriety.<ref name="Chloroform History" /> Whatever the source of his inspiration, on 4 November 1847, Simpson argued that he had discovered the anaesthetic qualities of chloroform in humans. He and two colleagues entertained themselves by trying the effects of various substances, and thus revealed the potential for chloroform in medical procedures.<ref name="Gordon2002">{{cite book|last=Gordon|first=H. Laing|title=Sir James Young Simpson and Chloroform (1811–1870)|url=https://books.google.com/books?id=pYer05UwKBYC&pg=PA106|date=November 2002|publisher=Minerva Group|isbn=978-1-4102-0291-8|pages=106–109|access-date=5 January 2016|archive-date=6 May 2016|archive-url=https://web.archive.org/web/20160506214333/https://books.google.com/books?id=pYer05UwKBYC&pg=PA106|url-status=live}}</ref>
[[File:James Young Simpson chloroform.png|thumb|An illustration depicting James Young Simpson and his friends found unconscious.]]
A few days later, during the course of a dental procedure in [[Edinburgh]], [[Francis Brodie Imlach]] became the first person to use chloroform on a patient in a clinical context.<ref>{{cite web |last=Dingwall |date=April 2004 |url=http://historyofdentistry.co.uk/index_htm_files/2004Apr2.pdf |title=A pioneering history: dentistry and the Royal College of Surgeons of Edinburgh |website=historyofdentistry.co.uk  |archive-url=https://web.archive.org/web/20130201191323/http://historyofdentistry.co.uk/index_htm_files/2004Apr2.pdf |archive-date=1 February 2013}}</ref>

In May 1848, [[Robert Halliday Gunning]] made a presentation to the Medico-Chirurgical Society of Edinburgh following a series of laboratory [[Domestic rabbit#Experimentation|experiments on rabbits]] that confirmed Glover's findings and also refuted Simpson's claims of originality. The laboratory experiments that proved the dangers of chloroform were largely ignored.<ref>{{cite journal |url=https://www.royalsoced.org.uk/cms/files/research_awards/prizes/prize_lists/gunning_victoria_history.pdf |title=Robert Halliday Gunning and the Victoria Jubilee Prizes |year=2003 |access-date=2016-08-18  |archive-url=https://web.archive.org/web/20160822105053/https://www.royalsoced.org.uk/cms/files/research_awards/prizes/prize_lists/gunning_victoria_history.pdf |archive-date=22 August 2016 |doi=10.1177/003693300304800209 |last1=Baillie |first1=T. W. |journal=Scottish Medical Journal |volume=48 |issue=2 |pages=54–57 |pmid=12774598 |s2cid=10998512 }}</ref>

The use of chloroform during [[surgery]] expanded rapidly in Europe; for instance in the 1850s chloroform was used by the physician [[John Snow]] during the births of [[Queen Victoria]]'s last two children [[Prince Leopold, Duke of Albany|Leopold]] and [[Princess Beatrice of the United Kingdom|Beatrice]].<ref>{{cite web |url=http://www.ph.ucla.edu/epi/snow/victoria.html |title=Anesthesia and Queen Victoria |website=ph.ucla.edu |access-date=13 August 2012 |url-status=live |archive-url=https://web.archive.org/web/20120716005223/http://www.ph.ucla.edu/epi/snow/victoria.html |archive-date=16 July 2012}}</ref> In the United States, chloroform began to replace [[Diethyl ether|ether]] as an anesthetic at the beginning of the 20th century;<ref name="Chloroform History in U.S.">{{cite journal |last1=Wawersik |first1=J |title=[History of chloroform anesthesia]. |journal=Anaesthesiologie und Reanimation |date=1997 |volume=22 |issue=6 |pages=144-52 |pmid=9487785 |url=https://pubmed.ncbi.nlm.nih.gov/9487785/}}</ref> it was abandoned in favor of ether on discovery of its toxicity, especially its tendency to cause fatal [[cardiac arrhythmia|cardiac arrhythmias]] analogous to what is now termed "[[Intoxicative inhalant#Sudden sniffing death syndrome|sudden sniffer's death]]". Some people used chloroform as a recreational drug or to attempt suicide.<ref>{{cite journal|last=Martin|first=William|title=A Case of Chloroform Poisoning; Recovery|journal=British Medical Journal|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 of chloroform is that it increases the movement of [[potassium]] ions through certain types of [[potassium channel]]s 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|date = May 1999|title = Inhalational anesthetics activate two-pore-domain background K<sup>+</sup> channels|journal = Nature Neuroscience|volume = 2|pages = 422–426|doi = 10.1038/8084|pmid = 10321245|issue = 5|s2cid = 23092576}}</ref> Chloroform could also be mixed with other anesthetic agents such as ether to make C.E. mixture,<ref name="Chloroform & Ether">{{cite journal |last1=von Hintzenstern |first1=U. |last2=Schwarz |first2=W. |title=Frühe Erlanger Beiträge zur Theorie und Praxis der Ather- und Chloroformnnarkose |journal=Der Anaesthesist |date=1 February 1996 |volume=45 |issue=2 |pages=131–139 |doi=10.1007/s001010050247 |pmid=8720885 |url=https://pubmed.ncbi.nlm.nih.gov/8720885/ |access-date=17 March 2025 |trans-title=Early contributions from Erlangen to the theory and practice of ether and chloroform anesthesia. 1. Heyfelder's clinical trial with ether and chloroform |language=de}}</ref> or ether and [[Ethanol|alcohol]] to make [[A.C.E. mixture]].<ref name="Alcohol, Chloroform & Ether">{{cite journal |title=An Experience with the New Anæsthetic-Chloroform, Ether and Absolute Alcohol. |journal=The Independent practitioner |date=February 1883 |volume=4 |issue=2 |pages=97-100 |pmid=37826124 |url=https://pubmed.ncbi.nlm.nih.gov/37826124/ |access-date=17 March 2025 |language=English |pmc=10072673}}</ref><ref name="ACE Mixture">{{cite journal |last1=Shah |first1=Shrey P. |last2=Bause |first2=George S. |title=From ACE to ACENO: How America's Munson added Harley's British mixture to nitrous oxide |journal=Journal of Anesthesia History |date=September 2020 |volume=6 |issue=3 |pages=168–169 |doi=10.1016/j.janh.2020.07.006 |pmid=32921491 |url=https://pubmed.ncbi.nlm.nih.gov/32921491/ |access-date=17 March 2025}}</ref> 

In 1848, Hannah Greener, a 15-year-old girl who was having an infected toenail removed, died after being given the anaesthetic.<ref>{{cite journal|title=An Unexplained Death: Hannah Greener and Chloroform |last1=Knight |first1=Paul R. III |last2=Bacon |first2=Douglas R. |s2cid=12865865 | year=2002 |volume = 96 |issue = 5 |journal=Anesthesiology|doi=10.1097/00000542-200205000-00030|pages=1250–1253|pmid=11981167|doi-access=free }}</ref> Her autopsy establishing the cause of death was undertaken by [[John Fife (surgeon)|John Fife]] assisted by [[Robert Mortimer Glover]].<ref name=pdf1/> A number of physically fit patients died after inhaling it. In 1848, however, John Snow developed an inhaler that regulated the dosage and so successfully reduced the number of deaths.<ref>{{cite book|last1 = Snow|first1 = John|year = 1858|title = On Chloroform and Other Anaesthetics and Their Action and Administration|pages = 82–85|url = https://archive.org/stream/onchloroformothe1858snow#page/82/mode/2up/search/inhaler|url-status = live|archive-url = http://archive.wikiwix.com/cache/20151123021418/https://archive.org/stream/onchloroformothe1858snow#page/82/mode/2up/search/inhaler|archive-date = 23 November 2015|publisher = London : John Churchill}}</ref>

The opponents and supporters of chloroform disagreed on the question of whether the medical complications were due to respiratory disturbance or whether chloroform had a specific effect on the heart. Between 1864 and 1910, numerous commissions in Britain studied chloroform but failed to come to any clear conclusions. It was only in 1911 that Levy proved in experiments with animals that chloroform can cause ventricular fibrillation.<ref name="Chloroform ventricular fibrillation">{{cite journal |last1=Hutcheon |first1=D. E. |title=SUSCEPTIBILITY TO VENTRICULAR FIBRILLATION DURING CHLOROFORM AND CYCLOPROPANE ANAESTHESIA |journal=British Journal of Pharmacology and Chemotherapy |date=March 1951 |volume=6 |issue=1 |pages=31–34 |doi=10.1111/j.1476-5381.1951.tb00617.x |pmid=14821299 |url=https://pubmed.ncbi.nlm.nih.gov/37826124/ |access-date=17 March 2025 |language=English |pmc=1509204}}</ref> Despite this, between 1865 and 1920, chloroform was used in 80 to 95% of all narcoses performed in the UK and German-speaking countries. In Germany, comprehensive surveys of the fatality rate during anaesthesia were made by Gurlt between 1890 and 1897.<ref name="Chloroform History in U.S." /> At the same time in the UK the medical journal ''[[The Lancet]]'' carried out a questionnaire survey<ref>{{Cite journal |last=Anonymous. |date=1890 |title=The Lancet Inquiry into the Mortality Under Anaesthetics. |journal=Lancet |volume=145 |issue=3472 |pages=612–13}}</ref> and compiled a report detailing numerous adverse reactions to anesthetics, including chloroform.<ref>{{Cite journal |last=Anonymous. |date=1893 |title=Report of The Lancet Commission appointed to investigate the subject of the administration of chloroform and other anesthetics from a clinical standpoint. |journal=Lancet |volume=141 |issue=3629 |pages=629–38}}</ref> In 1934, Killian gathered all the statistics compiled until then and found that the chances of suffering fatal complications under ether were between 1:14,000 and 1:28,000, whereas with chloroform the chances were between 1:3,000 and 1:6,000.<ref name="Chloroform History in U.S." /> The rise of gas anaesthesia using [[nitrous oxide]], improved equipment for administering anesthetics, and the discovery of [[hexobarbital]] in 1932 led to the gradual decline of chloroform narcosis.<ref>{{cite journal | pmid = 9487785 | volume=22 | issue=6 | title=History of chloroform anesthesia | year=1997 | journal=Anesthesiology and Reanimation | pages=144–152 | last= Wawersik |first=J.}}</ref>

The latest reported anaesthetic use of chloroform in the Western world dates to 1987, when the last doctor who used it retired, about 140 years after its first use.<ref>{{cite book|last=Stratmann|first=Linda|date=2003|title=Chloroform: The Quest for Oblivion|location=Stroud|publisher=Sutton Publishing|isbn=978-0-7524-9931-4}}</ref>

=== Criminal use ===
[[File:Damsels in distress chloroformed.jpg|thumb|[[Damsel in distress|Damsels in distress]] being knocked out with chloroform in various media]]
Chloroform has been used by criminals to knock out, daze, or murder victims. Joseph Harris was charged in 1894 with using chloroform to rob people.<ref>{{cite news|url=https://news.google.com/newspapers?id=Ec1VAAAAIBAJ&pg=2904,2720400&dq=chloroform+knockout&hl=en|title=Knock-out and Chloroform|newspaper=[[The Philadelphia Record]]|date=9 February 1894|access-date=31 March 2011|archive-date=20 January 2022|archive-url=https://web.archive.org/web/20220120054325/https://news.google.com/newspapers?id=Ec1VAAAAIBAJ&pg=2904,2720400&dq=chloroform+knockout&hl=en|url-status=live}}</ref> [[Serial killer]] [[H. H. Holmes]] used chloroform overdoses to kill his female victims. In September 1900, chloroform was implicated in the murder of the U.S. businessman [[William Marsh Rice]]. Chloroform was deemed a factor in the alleged murder of a woman in 1991, when she was asphyxiated while asleep.<ref>{{cite news|url=https://news.google.com/newspapers?id=I91HAAAAIBAJ&pg=2367,1007950&dq=chloroform+knockout&hl=en|title=Chloroform case retrial underway|date=7 July 1993|access-date=31 March 2011|newspaper=[[Record-Journal]]|archive-date=6 November 2021|archive-url=https://web.archive.org/web/20211106203133/https://news.google.com/newspapers?id=I91HAAAAIBAJ&pg=2367%2C1007950&dq=chloroform+knockout&hl=en|url-status=live}}</ref> In 2002, 13-year-old [[Murder of Kacie Woody|Kacie Woody]] was sedated with chloroform when she was abducted by David Fuller and during the time that he had her, before he shot and killed her.<ref>{{Cite web|url=https://www.arkansasonline.com/news/2003/dec/17/not-forgotten/|title=But not forgotten|last=Cathy Frye - [[Arkansas Democrat-Gazette]]|date=2003-12-17|website=www.arkansasonline.com|access-date=2021-12-07|archive-date=7 December 2021|archive-url=https://web.archive.org/web/20211207200713/https://www.arkansasonline.com/news/2003/dec/17/not-forgotten/|url-status=live}}</ref> In a 2007 plea bargain, a man confessed to using [[Electroshock weapon|stun guns]] and chloroform to sexually assault minors.<ref>{{cite news|url=https://www.usatoday.com/news/nation/2007-11-06-chloroform-rapes_N.htm|title=Man admits to raping friends' daughters|date=6 November 2007|access-date=31 March 2011|newspaper=[[USA Today]]|url-status=live|archive-url=https://web.archive.org/web/20110429075437/http://www.usatoday.com/news/nation/2007-11-06-chloroform-rapes_N.htm|archive-date=29 April 2011}}</ref>

The use of chloroform as an [[incapacitating agent]] has become widely recognized, bordering on [[cliché]], through the adoption by [[crime fiction]] authors of plots involving criminals' use of chloroform-soaked rags to render victims unconscious. However, it is nearly impossible to incapacitate someone using chloroform in this way.<ref name="Anaesthesia">{{cite journal|last=Payne|first=J. P.|s2cid=1718276|date=July 1998|title=The criminal use of chloroform|journal=[[Anaesthesia (journal)|Anaesthesia]]|volume=53|issue=7|pages=685–690|doi=10.1046/j.1365-2044.1998.528-az0572.x|pmid=9771177|doi-access=free}}</ref> It takes at least five minutes of inhalation of chloroform to render a person unconscious. Most criminal cases involving chloroform involve co-administration of another drug, such as [[ethanol|alcohol]] or [[diazepam]], or the victim being complicit in its administration. After a person has lost consciousness owing to chloroform inhalation, a continuous volume must be administered, and the chin must be supported to keep the tongue from obstructing the airway, a difficult procedure, typically requiring the skills of an [[anesthesiologist]]. In 1865, as a direct result of the criminal reputation chloroform had gained, the medical journal ''[[The Lancet]]'' offered a "permanent scientific reputation" to anyone who could demonstrate "instantaneous insensibility", i.e. loss of consciousness, using chloroform.<ref>{{cite journal|title=Medical Annotation: Chloroform amongst Thieves |journal=[[The Lancet]] |date=1865 |volume=2 |issue=2200 |pages=490–491|doi=10.1016/s0140-6736(02)58434-8}}</ref>

==Safety==
===Exposure===
Chloroform is formed as a by-product of [[water chlorination]], along with a range of other [[disinfection by-product]]s, and it is therefore often present in municipal tap water and swimming pools. Reported ranges vary considerably, but are generally below the current health standard for total [[trihalomethanes]] (THMs) of 100 μg/L.<ref>{{cite journal|last1=Nieuwenhuijsen|first1=MJ|last2=Toledano|first2=MB|last3=Elliott|first3=P|title=Uptake of chlorination disinfection by-products; a review and a discussion of its implications for exposure assessment in epidemiological studies.|journal=Journal of Exposure Analysis and Environmental Epidemiology|date=8 August 2000|volume=10|issue=6 Pt 1|pages=586–99|pmid=11140442|doi=10.1038/sj.jea.7500139|doi-access=free}}</ref> However, when considered in combination with other trihalomethanes often present in drinking water, the concentration of THMs often exceeds the recommended limit of exposure.<ref>{{Cite web |title=EWG's Tap Water Database: Contaminants in Your Water |url=https://www.ewg.org/tapwater/reviewed-disinfection-byproducts.php |access-date=2023-08-08 |website=www.ewg.org |language=en}}</ref>


Historically, chloroform exposure may well have been higher, owing to its common use as an anesthetic, as an ingredient in cough syrups, and as a constituent of [[tobacco smoke]], where [[DDT]] had previously been used as a [[fumigant]].<ref>Yin-Tak Woo, David Y. Lai, Joseph C. Arcos [https://books.google.com/books?id=25H-BAAAQBAJ&dq=Chloroform+tobacco&pg=PA98 Aliphatic and Polyhalogenated Carcinogens: Structural Bases and Biological] {{webarchive|url=https://web.archive.org/web/20180605033237/https://books.google.com/books?id=25H-BAAAQBAJ&pg=PA98&lpg=PA98&dq=Chloroform+tobacco&source=bl&ots=GGoHCH5uup&sig=vJAm_Ecl4J_XuHn5EXIZ9Jpik4E&hl=en&sa=X&ved=0ahUKEwjPrLX9hbvUAhXDDsAKHeIOC3gQ6AEILzAC |date=5 June 2018 }}</ref>

===Pharmacology===
Chloroform is well absorbed, metabolized, and eliminated rapidly by mammals after oral, inhalation, or dermal exposure. Accidental splashing into the eyes has caused irritation.<ref name="cicad" /> Prolonged dermal exposure can result in the development of sores as a result of [[Defatting (medical)|defatting]]. Elimination is primarily through the lungs as chloroform and carbon dioxide; less than 1% is excreted in the urine.<ref name="pth" />

Chloroform is metabolized in the liver by the [[cytochrome P-450]] enzymes, by oxidation to trichloromethanol and by reduction to the dichloromethyl [[free radical]]. Other metabolites of chloroform include [[hydrochloric acid]] and diglutathionyl dithiocarbonate, with [[carbon dioxide]] as the predominant end-product of metabolism.<ref name="eot">{{cite encyclopedia| first=Anna M. |last=Fan | title=Chloroform | encyclopedia=Encyclopedia of Toxicology | edition=2nd | volume=1 | publisher=Elsevier | year=2005 | pages=561–565}}</ref>

Like most other general anesthetics and sedative-hypnotic drugs, chloroform is a [[Allosteric modulator|positive allosteric modulator]] at [[GABAA receptor|GABA<sub>A</sub> receptors]].<ref>{{Cite journal|last1=Jenkins|first1=Andrew|last2=Greenblatt|first2=Eric P.|last3=Faulkner|first3=Howard J.|last4=Bertaccini|first4=Edward|last5=Light|first5=Adam|last6=Lin|first6=Audrey|last7=Andreasen|first7=Alyson|last8=Viner|first8=Anna|last9=Trudell|first9=James R.|last10=Harrison|first10=Neil L.|date=2001-03-15|title=Evidence for a Common Binding Cavity for Three General Anesthetics within the GABAA Receptor|journal=Journal of Neuroscience|language=en|volume=21|issue=6|pages=RC136|doi=10.1523/JNEUROSCI.21-06-j0002.2001|issn=0270-6474|pmid=11245705|pmc=6762625|doi-access=free}}</ref> Chloroform causes depression of the [[central nervous system]] (CNS), ultimately producing deep [[coma]] and respiratory center depression.<ref name="eot" /> When ingested, chloroform causes symptoms similar to those seen after inhalation. Serious illness has followed ingestion of {{convert|7.5|g|oz|abbr=on}}. The mean lethal oral dose in an adult is estimated at {{convert|45|g|oz|abbr=on}}.<ref name="cicad" />

The anesthetic use of chloroform has been discontinued, because it caused deaths from respiratory failure and cardiac arrhythmias. Following chloroform-induced anesthesia, some patients suffered [[nausea]], [[vomiting]], [[hyperthermia]], [[jaundice]], and coma owing to [[hepatic dysfunction]]. At autopsy, liver [[necrosis]] and degeneration have been observed.<ref name="cicad" /> The hepatotoxicity and nephrotoxicity of chloroform is thought to be due largely to [[phosgene]], one of its metabolites.<ref name="eot" />

===Conversion to phosgene===
Chloroform converts slowly in the presence of UV light and air to the extremely poisonous gas [[phosgene]] ({{chem2|COCl2}}), releasing [[HCl]] in the process.<ref name="earlham">{{cite web|url=http://www.earlham.edu/chemical-hygiene-and-safety/safety-topics/chloroform-and-phosgene/|title=Chloroform and Phosgene, Chemical Hygiene and Safety|website=Earlham College|access-date=17 August 2017|url-status=live|archive-url=https://web.archive.org/web/20170819102644/http://www.earlham.edu/chemical-hygiene-and-safety/safety-topics/chloroform-and-phosgene/|archive-date=19 August 2017}}</ref>

{{block indent|{{chem2|2 CHCl3 + O2 → 2 COCl2 + 2 HCl}}}}

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. Amylene has been found to be ineffective, and the phosgene can affect analytes in samples, lipids, and nucleic acids dissolved in or extracted with chloroform.<ref>{{cite journal|url=http://pubs.acs.org/cen/safety/19980302.html|last=Turk|first=Eric|title=Phosgene from Chloroform|journal=Chemical & Engineering News|date=2 March 1998|volume=76|issue=9|page=6|doi=10.1021/cen-v076n009.p006|doi-access=free|access-date=13 August 2012|archive-date=24 July 2008|archive-url=https://web.archive.org/web/20080724065839/http://pubs.acs.org/cen/safety/19980302.html|url-status=live}}</ref> When ethanol is used as a stabiliser for chloroform, it reacts with phosgene (which is soluble in chloroform) to form the relatively harmless [[diethyl carbonate]] ester:

{{block indent|{{chem2|2 CH3CH2OH + COCl2 → CO3(CH2CH3)2 + 2 HCl}}}}

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,<ref>{{cite web |url=https://www.britannica.com/EBchecked/topic/457363/phosgene |title=phosgene (chemical compound) |website=Encyclopædia Britannica |access-date=16 August 2013 |url-status=live |archive-url=https://web.archive.org/web/20130605183448/https://www.britannica.com/EBchecked/topic/457363/phosgene |archive-date=5 June 2013}}</ref> and the carbonate salt [[Neutralization (chemistry)|neutralizes]] the resulting acid.<ref>{{Cite journal |last1=Manogue |first1=W. H. |last2=Pigford |first2=R. L. |date=September 1960 |title=The kinetics of the absorption of phosgene into water and aqueous solutions |url=https://onlinelibrary.wiley.com/doi/10.1002/aic.690060329 |journal=AIChE Journal |language=en |volume=6 |issue=3 |pages=494–500 |doi=10.1002/aic.690060329 |bibcode=1960AIChE...6..494M |issn=0001-1541|url-access=subscription }}</ref>

Suspected samples can be tested for phosgene using filter paper which when treated with 5% [[diphenylamine]], 5% [[dimethylaminobenzaldehyde]] in [[ethanol]], and then dried, turns yellow in the presence of phosgene vapour.<ref>{{Cite web |title=American Chemical Society: Chemical & Engineering Safety Letters |url=https://pubsapp.acs.org/cen/safety/19980302.html#:~:text=Filter%20paper%20strips,%20wetted%20with,alkenes,%20reacts%20quickly%20with%20phosgene. |access-date=2024-03-18 |website=pubsapp.acs.org}}</ref> There are several [[colorimetry|colorimetric]] and [[fluorometry|fluorometric]] reagents for phosgene, and it can also be quantified using [[mass spectrometry]].<ref>{{Cite journal |last1=Cheng |first1=Xueheng |last2=Gao |first2=Quanyin |last3=Smith |first3=Richard D. |last4=Simanek |first4=Eric E. |last5=Mammen |first5=Mathai |last6=Whitesides |first6=George M. |date=1996 |title=Characterization of Hydrogen-Bonded Aggregates in Chloroform by Electrospray Ionization Mass Spectrometry |url=https://www.academia.edu/33298377 |archive-url=https://archive.today/20220731041555/https://www.academia.edu/33298377/Characterization_of_Hydrogen_Bonded_Aggregates_in_Chloroform_by_Electrospray_Ionization_Mass_Spectrometry |archive-date=2022-07-31 |url-status=live |journal=The Journal of Organic Chemistry |volume=61 |issue=6 |pages=2204–2206 |doi=10.1021/jo951345g |issn=0022-3263}}</ref>

===Regulation===
Chloroform is suspected of causing [[cancer]] (i.e. it is possibly [[carcinogen]]ic, [[IARC Group 2B]]) as per the [[International Agency for Research on Cancer]] (IARC) Monograph. There is no convincing evidence that chloroform causes cancer in humans.<ref>{{Cite web |title=Chloroform |url=https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono73-10.pdf |access-date=December 5, 2023}}</ref>

It is classified as an [[List of extremely hazardous substances|extremely hazardous substance]] in the United States, as defined in Section 302 of the US [[Emergency Planning and Community Right-to-Know Act]] (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities that produce, store, or use it in significant quantities.<ref name="gov-right-know">{{Cite journal |journal = [[Code of Federal Regulations]]| publisher = [[United States Government Publishing Office|Government Printing Office]] | title = 40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities | url = http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | edition = 1 July 2008 | access-date = 29 October 2011  | archive-url = https://web.archive.org/web/20120225051612/http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | archive-date = 25 February 2012}}</ref>

==Bioremediation of chloroform==
Some [[Anaerobic organism|anaerobic bacteria]] use chloroform for respiration, termed [[Halorespiration|organohalide respiration]], converting it to [[dichloromethane]].<ref>{{cite journal|journal=Philos Trans R Soc Lond B Biol Sci|year=2013|volume=368|issue=1616|page=20120318|
doi=10.1098/rstb.2012.0318|pmid=23479748|pmc=3638459|title=Identification of Dehalobacter reductive dehalogenases that catalyse dechlorination of chloroform, 1,1,1-trichloroethane and 1,1-dichloroethane |author=Shuiquan Tang |author2=Elizabeth A. Edwards}}</ref><ref>{{Cite journal|last1=Jugder|first1=Bat-Erdene|last2=Ertan|first2=Haluk|last3=Wong|first3=Yie Kuan|last4=Braidy|first4=Nady|last5=Manefield|first5=Michael|last6=Marquis|first6=Christopher P.|last7=Lee|first7=Matthew|date=2016-08-10|title=Genomic, transcriptomic and proteomic analyses of Dehalobacter UNSWDHB in response to chloroform|journal=Environmental Microbiology Reports|language=en|volume=8|issue=5|pages=814–824|doi=10.1111/1758-2229.12444|pmid=27452500|bibcode=2016EnvMR...8..814J |issn=1758-2229}}</ref>

==Gallery==
<gallery>
File:CHCl3 mm.png|{{chem2|CHCl3}} measured by the Advanced Global Atmospheric Gases Experiment ([http://agage.mit.edu/ AGAGE]) in the lower atmosphere ([[troposphere]]) at stations around the world. Abundances are given as pollution free monthly mean mole fractions in [[Parts-per notation|parts-per-trillion]] (ppt).
</gallery>

== See also ==
* [[Joseph Thomas Clover]]

== References ==
{{Reflist}}

==External links==
{{Commons category|Chloroform}}
*[http://www.chm.bris.ac.uk/motm/chloroform/chloroformv.htm Chloroform "The Molecular Lifesaver"] – An article at Oxford University providing facts about chloroform.
*[https://archive.org/details/0055-0000-7637-0000-0-0000-0000-0 Chloroform Administration] – a short film of anaesthetic chloroform application, filmed in  the 1930s
*[http://www.inchem.org/documents/cicads/cicads/cicad58.htm Concise International Chemical Assessment Document 58]
*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://webbook.nist.gov/cgi/cbook.cgi?ID=67-66-3&Units=SI&cTG=on&cTC=on&cTP=on NIST Standard Reference Database]

{{Halomethanes}}
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