Chloroform
Chloroform displayed.svg
Chloroform-3D-balls.png
Chloroform in its liquid state shown in a test tube
Names
Preferred IUPAC name
Trichloromethane
Other names
Chloroform[1]
Methane trichloride
Methyl trichloride
Methenyl trichloride
Methenyl chloride
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 Highly refractive colorless liquid
Odor Strong smell reminiscent of dry-cleaner's shops
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)
decomposes at 450 °C
10.62 g/L (0 °C)
8.09 g/L (20 °C)
7.32 g/L (60 °C)
Solubility Soluble in benzene
Miscible in diethyl ether, oils, ligroin, alcohol, CCl4, CS2
Solubility in acetone ≥ 100 g/L (19 °C)
Solubility in dimethyl sulfoxide ≥ 100 g/L (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)
UV-vis (λmax) 250 nm, 260 nm, 280 nm
−59.30·10−6 cm3/mol
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
Pharmacology
N01AB02 (WHO)
Hazards[7]
Occupational safety and health (OHS/OSH):
Main hazards
 Carcinogen – Reproductive toxicity – Specific target organ toxicity (STOT)[2][3][4]
GHS labelling:
GHS06: Toxic
GHS08: Health hazard
Danger
H302, H315, H319, H331, H336, H351, H361d, H372
P201, P202, P235, P260, P264, P270, P271, P280, P281, P301+P330+P331, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P311, P314, P332+P313, P337+P313, P362, P403+P233, P405, P501
NFPA 704 (fire diamond)
2
0
0
Flash point Non-flammable
Lethal dose or concentration (LD, LC):
704 mg/kg (mouse, dermal)[5]
9,617 ppm (rat, 4 hr)[6]
20,000 ppm (guinea pig, 2 hr)
7,056 ppm (cat, 4 hr)
25,000 ppm (human, 5 min)[6]
NIOSH (US health exposure limits):
PEL (Permissible)
 50 ppm (240 mg/m3)[3]
REL (Recommended)
 Ca ST 2 ppm (9.78 mg/m3) [60-minute][3]
IDLH (Immediate danger)
 500 ppm[3]
Safety data sheet (SDS) [1]
Related compounds
Related chloromethanes
 Chloromethane
Dichloromethane
Tetrachloromethane
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, or trichloromethane (often abbreviated as TCM), is an organic compound with the formula CHCl3 and a common organic solvent. It is a very volatile, colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE and refrigerants[8] and is a trihalomethane that serves as a powerful anesthetic, euphoriant, anxiolytic, and sedative when inhaled or ingested. It is also part of a wider class of substances known as volatile organic compounds.[9][10]

Chloroform is miscible with many solvents but it is only very slightly soluble in water (only 8 g/L at 20 °C). Chloroform was frequently used as an anaesthetic between 1847 and the first half of the 20th century.

Structure

The molecule adopts a tetrahedral molecular geometry with C3v symmetry.[11] The chloroform molecule can be viewed as a methane molecule with three hydrogen atoms replaced with three chlorine atoms, leaving a single hydrogen atom.

Natural occurrence

The total global flux of chloroform through the environment is approximately 660000 tonnes per year,[12] and about 90% of emissions are natural in origin. Many kinds of seaweed produce chloroform, and fungi are believed to produce chloroform in soil.[13] Abiotic processes are also believed to contribute to natural chloroform productions in soils, although the mechanism is still unclear.[14]

As chloroform is a volatile organic compound,[15] it dissipates 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 half-life in air ranges from 55 to 620 days. Biodegradation in water and soil is slow. Chloroform does not significantly bioaccumulate in aquatic organisms.[16]

History

Chloroform was synthesized independently by several investigators circa 1831:

Production

Industrially, chloroform is produced by heating a mixture of chlorine and either methyl chloride (CH3Cl) or methane (CH4).[8] 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, methylene chloride (dichloromethane), trichloromethane (chloroform), and tetrachloromethane (carbon tetrachloride). This can then be separated by distillation.[8]

Chloroform may also be produced on a small scale via the haloform reaction between acetone and sodium hypochlorite:

3 NaClO + (CH3)2CO → CHCl3 + 2 NaOH + CH3COONa

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 reaction of hexachloroacetone with deuterium oxide.[30] 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.[31][32]

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.[33] 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]

Uses

In terms of scale, the most important reaction of chloroform is with hydrogen fluoride to give monochlorodifluoromethane (CFC-22), a precursor in the production of polytetrafluoroethylene (Teflon) and other fluoropolymers:[8]

CHCl3 + 2HF → CHClF2 + 2 HCl

The reaction is conducted in the presence of a catalytic amount of mixed antimony halides. Chlorodifluoromethane is then converted into tetrafluoroethylene, the main precursor to Teflon.[34]

Solvent

The hydrogen attached to carbon in chloroform participates in hydrogen bonding,[35][36] thus making it a good solvent for many materials.

Worldwide, chloroform is also used in pesticide formulations, as a solvent for lipids, rubber, alkaloids, waxes, gutta-percha, and resins, as a cleansing agent, grain fumigant, in fire extinguishers, and in the rubber industry.[16][37] CDCl3 is a common solvent used in NMR spectroscopy.[38]

Refrigerant

Trichloromethane has been used as a precursor to make R-22 (Chlorodifluoromethane). This is done by reacting it with a solution of Hydrofluoric acid (HF) which will fluorinate the CHCl3 molecule and release hydrochloric acid as a byproduct.[39] Prior to the enforcement of the Montreal Protocol, the majority of the trichloromethane produced in the United States, was used for the production of Chlorodifluoromethane. [40]

Although trichloromethane has properties such as its low boiling point and its low global warming potential of only 31 (compared to the 1,760 of R-22) which result in it having good refrigeration properties, there is little information to suggest that it has seen widespread use as a refrigerant in any consumer products.[41]

Lewis acid

In solvents such as CCl4 and alkanes, chloroform hydrogen bonds to a variety of Lewis bases. HCCl3 is classified as a hard acid and the ECW model lists its acid parameters as EA = 1.56 and CA = 0.44.

Reagent

As a reagent, chloroform serves as a source of the dichlorocarbene :CCl2 group.[42] It reacts with aqueous sodium hydroxide usually in the presence of a phase transfer catalyst to produce dichlorocarbene, :CCl2.[43][44] This reagent effects 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.[citation needed]

Anaesthetic

Antique bottles of chloroform
Antique bottles of chloroform

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.[citation needed] Glover also undertook practical experiments on dogs to prove his theories, and refined his theories and presented them in the thesis for his doctorate at the University of Edinburgh in the summer of 1847.

The Scottish obstetrician James Young Simpson was one of the persons required to read the thesis, but later claimed to have never read the thesis and to have come to his own conclusions independently.[citation needed] On 4 November 1847, Simpson argued that he discovered the anaesthetic qualities of chloroform on humans. He and two colleagues entertained themselves by trying the effects of various substances, and thus revealed the potential for chloroform in medical procedures.[27]

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.[45]

In May 1848, Robert Halliday Gunning made a presentation to the Medico-Chirurgical Society of Edinburgh following a series of laboratory experiments on rabbits that confirmed Glover's findings and also refuted Simpson's claims of originality. The laboratory experiments proving the dangers of chloroform were largely ignored.[46]

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 birth of Queen Victoria's last two children.[47] In the United States, chloroform began to replace ether as an anesthetic at the beginning of the 20th century;[citation needed] it was 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.[48] One possible mechanism of action for chloroform is that it increases the movement of potassium ions through certain types of potassium channels in nerve cells.[49] 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.[citation needed]

In 1848, Hannah Greener, a 15-year-old girl who was having an infected toenail removed, died after being given the anaesthetic.[50] Her autopsy establishing the cause of death was undertaken by John Fife assisted by Robert Mortimer Glover.[26] 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.[51]

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 cardiac fibrillation.[citation needed] Despite this, between 1865 and 1920, chloroform was used in 80 to 95% of all narcoses performed in the UK and German-speaking countries. IIn Germany, the first comprehensive surveys of the fatality rate during anaesthesia were made by Gurlt between 1890 and 1897.[citation needed] 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 under chloroform the chances were between 1:3,000 and 1:6,000.[citation needed] The rise of gas anaesthesia using nitrous oxide, improved equipment for administering anaesthetics and the discovery of hexobarbital in 1932 led to the gradual decline of chloroform narcosis.[52]

Criminal use

Chloroform has been used by criminals to knock out, daze, or even murder victims. Joseph Harris was charged in 1894 with using chloroform to rob people.[53] 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 sleeping.[54] In 2002, 13-year-old 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.[55] In a 2007 plea bargain, a man confessed to using stun guns and chloroform to sexually assault minors.[56]

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 in this manner.[57] It takes at least five 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 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. losing consciousness instantaneously, using chloroform.[58]

Safety

Exposure

Chloroform is known to form as a by-product of water chlorination, along with a range of other disinfection by-products, and as such is commonly present in municipal tap water and swimming pools. Reported ranges vary considerably but are generally below the current health standard for total trihalomethanes of 100μg/L.[59] Nonetheless, the presence of chloroform in drinking water at any concentration is considered controversial by some.[citation needed]

Historically, chloroform exposure may well have been higher due to its common use as an anaesthetic, as an ingredient in cough syrups, and as a constituent of tobacco smoke where DDT had previously been used as a fumigant.[60]

Pharmacology

It is well absorbed, metabolized, and eliminated rapidly by mammals after oral, inhalation, or dermal exposure. Accidental splashing into the eyes has caused irritation.[16] Prolonged dermal exposure can result in the development of sores as a result of defatting. Elimination is primarily through the lungs in the form of chloroform and carbon dioxide; less than 1% is excreted in the urine.[37]

Chloroform is metabolized in the liver by the cytochrome P-450 enzymes, by oxidation to chloromethanol and by reduction to the dichloromethyl free radical. Other metabolites of chloroform include hydrochloric acid and digluathionyl dithiocarbonate, with carbon dioxide as the predominant end product of metabolism.[61]

Like most other general anesthetics and sedative-hypnotic drugs, chloroform is a positive allosteric modulator for the GABAA receptor.[62] Chloroform causes depression of the central nervous system (CNS), ultimately producing deep coma and respiratory center depression.[61] When ingested, chloroform caused symptoms similar to those seen following inhalation. Serious illness has followed ingestion of 7.5 g (0.26 oz). The mean lethal oral dose for an adult is estimated at 45 g (1.6 oz).[16]

The anesthetic use of chloroform has been discontinued because it caused deaths due to respiratory failure and cardiac arrhythmias. Following chloroform-induced anesthesia, some patients suffered nausea, vomiting, hyperthermia, jaundice, and coma due to hepatic dysfunction. At autopsy, liver necrosis and degeneration have been observed.[16]

Chloroform has induced liver tumors in mice and kidney tumors in mice and rats.[16] The hepatotoxicity and nephrotoxicity of chloroform is thought to be due largely to phosgene.[61]

Conversion to phosgene

Chloroform converts slowly in air to the extremely poisonous phosgene (COCl2), releasing HCl in the process.[63]

2 CHCl3 + O2 → 2 COCl2 + 2 HCl

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.[64] 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,[65] and the carbonate salt neutralizes the resulting acid.[66]

Suspected samples can be tested for phosgene using filter paper (treated with 5% diphenylamine, 5% dimethylaminobenzaldehyde in ethanol, and then dried), which turns yellow in phosgene vapour. There are several colorimetric and fluorometric reagents for phosgene, and it can also be quantified with mass spectrometry.[67]

Regulation

Chloroform is suspected of causing cancer (i.e., possibly carcinogenic, IARC Group 2B) as per the International Agency for Research on Cancer (IARC) Monographs. [PDF]

It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. 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.[68]

Bioremediation of chloroform

Some anaerobic bacteria use chloroform for their respiration, termed organohalide respiration, converting it to dichloromethane.[69][70]

References

  1. ^ "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 661. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4. The retained names 'bromoform' for HCBr3, 'chloroform' for HCCl3, and 'iodoform' for HCI3 are acceptable in general nomenclature. Preferred IUPAC names are substitutive names.
  2. ^ "Part 3 Health Hazards" (PDF). Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Second revised edition. United Nations. Archived (PDF) from the original on 4 March 2019. Retrieved 30 September 2017.
  3. ^ a b c d NIOSH Pocket Guide to Chemical Hazards. "#0127". National Institute for Occupational Safety and Health (NIOSH).
  4. ^ Toxicity on PubChem Archived 17 August 2018 at the Wayback Machine
  5. ^ Lewis, Richard J. (2012). Sax's Dangerous Properties of Industrial Materials (12th ed.). ISBN 978-0-470-62325-1.
  6. ^ a b "Chloroform". Immediately Dangerous to Life or Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
  7. ^ "PubChem: Safety and Hazards – GHS Classification". National Center for Biotechnology Information, U.S. National Library of Medicine. Archived from the original on 17 August 2018. Retrieved 17 August 2018.
  8. ^ a b c d e Rossberg, M.; et al. "Chlorinated Hydrocarbons". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a06_233.pub2.
  9. ^ "Ether and Chloroform". Archived from the original on 24 March 2018. Retrieved 24 April 2018.
  10. ^ "Chloroform [MAK Value Documentation, 2000]". The MAK-Collection for Occupational Health and Safety. 2012. pp. 20–58. doi:10.1002/3527600418.mb6766e0014. ISBN 978-3527600410.
  11. ^ "Illustrated Glossary of Organic Chemistry - Chloroform". www.chem.ucla.edu. Retrieved 29 December 2022.
  12. ^ Gribble, Gordon W. (2004). "Natural Organohalogens: A New Frontier for Medicinal Agents?". Journal of Chemical Education. 81 (10): 1441. Bibcode:2004JChEd..81.1441G. doi:10.1021/ed081p1441.
  13. ^ Cappelletti, M. (2012). "Microbial degradation of chloroform". Applied Microbiology and Biotechnology. 96 (6): 1395–409. doi:10.1007/s00253-012-4494-1. PMID 23093177. S2CID 12429523.
  14. ^ Jiao, Yi; et al. (2018). "Halocarbon Emissions from a Degraded Forested Wetland in Coastal South Carolina Impacted by Sea Level Rise". ACS Earth and Space Chemistry. 2 (10): 955–967. Bibcode:2018ESC.....2..955J. doi:10.1021/acsearthspacechem.8b00044. S2CID 134649348.
  15. ^ "Complete list of VOC's".
  16. ^ a b c d e f Chloroform (PDF), CICAD, vol. 58, World Health Organization, 2004, archived (PDF) from the original on 31 July 2020
  17. ^ Moldenhawer (1830). "Verfahren den Spiritus von dem Fuselöl auf leichte Weise zu befreien" [Procedure for freeing ethanol of fusel oil in an easy way]. Magazin für Pharmacie. 8 (31): 222–227. Archived from the original on 29 July 2020. Retrieved 6 May 2016.
  18. ^ Defalque, Ray J.; Wright, A. J. (2000). "Was chloroform produced before 1831?". Anesthesiology. 92 (1): 290–291. doi:10.1097/00000542-200001000-00060. PMID 10638939.
  19. ^ Guthrie, Samuel (1832). "New mode of preparing a spirituous solution of chloric ether". The American Journal of Science and Arts. 21: 64–65 and 405–408. Archived from the original on 29 July 2020. Retrieved 6 May 2016.
  20. ^ Guthrie, Ossian (1887). Memoirs of Dr. Samuel Guthrie, and the History of the Discovery of Chloroform. Chicago: George K. Hazlitt & Co. p. 1.
  21. ^ Stratmann, Linda (2003). "Chapter 2". Chloroform: The Quest for Oblivion. Stroud: Sutton Publishing. ISBN 9780752499314. Archived from the original on 29 July 2020. Retrieved 6 May 2016.
  22. ^ Liebig, Justus von (1831). "Ueber die Zersetzung des Alkohols durch Chlor" [On the decomposition of alcohol by chlorine]. Annalen der Physik und Chemie. 99 (11): 444. Bibcode:1831AnP....99..444L. doi:10.1002/andp.18310991111. Archived from the original on 10 May 2017. Retrieved 6 May 2016.
  23. ^ Liebig, Justus von (1832). "Ueber die Verbindungen, welche durch die Einwirkung des Chlors auf Alkohol, Aether, ölbildendes Gas und Essiggeist entstehen" [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]]. Annalen der Physik und Chemie. 100 (2): 243–295. Bibcode:1832AnP...100..243L. doi:10.1002/andp.18321000206.
    On pages 259–265, Liebig describes Chlorkohlenstoff ("carbon chloride", chloroform), but on p. 264, Liebig incorrectly states that the empirical formula of chloroform is C2Cl5.
  24. ^ Soubeiran, Eugène (1831). "Recherches sur quelques combinaisons du chlore" [Investigations into some compounds of chlorine]. Annales de Chimie et de Physique. Série 2. 48: 113–157. Archived from the original on 10 May 2017. Retrieved 6 May 2016.
  25. ^ Dumas, J.-B. (1834). "Récherches rélative à l'action du chlore sur l'alcool" [Experiments regarding the action of chlorine on alcohol]. L'Institut, Journal Général des Sociétés et Travaux Scientifiques de la France et de l'Étranger. 2: 106–108 and 112–115.
    "Es scheint mir also erweisen, dass die von mir analysirte Substance, … zur Formel hat: C2H2Cl6." (Thus it seems to me to show that the substance [that was] analyzed by me … has as [its empirical] formula: 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].)
  26. ^ a b Defalque, R. J.; Wright, A. J. (2004). "The short, tragic life of Robert M. Glover" (PDF). Anaesthesia. 59 (4): 394–400. doi:10.1111/j.1365-2044.2004.03671.x. PMID 15023112. S2CID 46428403. Archived (PDF) from the original on 9 March 2016.
  27. ^ a b Gordon, H. Laing (November 2002). Sir James Young Simpson and Chloroform (1811–1870). Minerva Group. pp. 106–109. ISBN 978-1-4102-0291-8. Archived from the original on 6 May 2016. Retrieved 5 January 2016.
  28. ^ "Sir James Young Simpson". Encyclopædia Britannica. Archived from the original on 27 July 2013. Retrieved 23 August 2013.
  29. ^ Worling, P.M. (1998). "Duncan and Flockhart: the Story of Two Men and a Pharmacy". Pharmaceutical Historian. 28 (2): 28–33. PMID 11620310.
  30. ^ Paulsen, P. J.; Cooke, W. D. (1 September 1963). "Preparation of Deuterated Solvents for Nuclear Magnetic Resonance Spectrometry". Analytical Chemistry. 35 (10): 1560. doi:10.1021/ac60203a072.
  31. ^ Breuer, F. W. (1935). "Chloroform-d (Deuteriochloroform)1". Journal of the American Chemical Society. 57 (11): 2236–2237. doi:10.1021/ja01314a058.
  32. ^ Kluger, Ronald (1964). "A Convenient Preparation of Chloroform-d1". The Journal of Organic Chemistry. 29 (7): 2045–2046. doi:10.1021/jo01030a526.
  33. ^ Süss, Hans Ulrich. "Bleaching". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH.
  34. ^ "Chlorodifluoromethane | chemical compound". Encyclopedia Britannica. Archived from the original on 17 July 2021. Retrieved 8 September 2021.
  35. ^ Wiley, G. R.; Miller, S. I. (1972). "Thermodynamic parameters for hydrogen bonding of chloroform with Lewis bases in cyclohexane. Proton magnetic resonance study". Journal of the American Chemical Society. 94 (10): 3287–3293. doi:10.1021/ja00765a001.
  36. ^ Kwak, K.; Rosenfeld, D. E.; Chung, J. K.; Fayer, M. D. (2008). "Solute-solvent complex switching dynamics of chloroform between acetone and dimethylsulfoxide-two-dimensional IR chemical exchange spectroscopy". The Journal of Physical Chemistry B. 112 (44): 13906–13915. doi:10.1021/jp806035w. PMC 2646412. PMID 18855462.
  37. ^ a b Leikin, Jerrold B.; Paloucek, Frank P., eds. (2008). "Chloroform". Poisoning and Toxicology Handbook (4th ed.). Informa. p. 774.
  38. ^ Fulmer, Gregory R.; Miller, Alexander J. M.; Sherden, Nathaniel H.; Gottlieb, Hugo E.; Nudelman, Abraham; Stoltz, Brian M.; Bercaw, John E.; Goldberg, Karen I. (2010). "NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist" (PDF). Organometallics. 29 (9): 2176–2179. doi:10.1021/om100106e.
  39. ^ "Chloroform (CHEBI:35255)".
  40. ^ https://www.atsdr.cdc.gov/ToxProfiles/tp6-c4.pdf
  41. ^ http://encyclopedia.uia.org/en/problem/chloroform-pollutant#:~:text=Most%20chloroform%20is%20manufactured%20to,spot%20removers%2C%20and%20various%20solvents.
  42. ^ Srebnik, M.; Laloë, E. (2001). "Chloroform". Encyclopedia of Reagents for Organic Synthesis. Wiley. doi:10.1002/047084289X.rc105. ISBN 978-0471936237.
  43. ^ Vogel, E.; Klug, W.; Breuer, A. (1988). "1,6-Methano[10]annulene". Organic Syntheses.; Collective Volume, vol. 6, p. 731
  44. ^ Gokel, G. W.; Widera, R. P.; Weber, W. P. (1988). "Phase-Transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide". Organic Syntheses.; Collective Volume, vol. 6, p. 232
  45. ^ Dingwall (April 2004). "A pioneering history: dentistry and the Royal College of Surgeons of Edinburgh" (PDF). historyofdentistry.co.uk. Archived from the original (PDF) on 1 February 2013.
  46. ^ Baillie, T. W. (2003). "Robert Halliday Gunning and the Victoria Jubilee Prizes" (PDF). Scottish Medical Journal. 48 (2): 54–57. doi:10.1177/003693300304800209. PMID 12774598. S2CID 10998512. Archived from the original (PDF) on 22 August 2016. Retrieved 18 August 2016.
  47. ^ "Anesthesia and Queen Victoria". ph.ucla.edu. Archived from the original on 16 July 2012. Retrieved 13 August 2012.
  48. ^ Martin, William (3 July 1886). "A Case of Chloroform Poisoning; Recovery". British Medical Journal. 2 (1331): 16–17. doi:10.1136/bmj.2.1331.16-a. PMC 2257365. PMID 20751619.
  49. ^ 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. S2CID 23092576.
  50. ^ Knight, Paul R., III; Bacon, Douglas R. (2002). "An Unexplained Death: Hannah Greener and Chloroform". Anesthesiology. 96 (5): 1250–1253. doi:10.1097/00000542-200205000-00030. PMID 11981167. S2CID 12865865.
  51. ^ Snow, John (1858). On Chloroform and Other Anaesthetics and Their Action and Administration. London : John Churchill. pp. 82–85. Archived from the original on 23 November 2015.
  52. ^ Wawersik, J. (1997). "History of chloroform anesthesia". Anesthesiology and Reanimation. 22 (6): 144–152. PMID 9487785.
  53. ^ "Knock-out and Chloroform". The Philadelphia Record. 9 February 1894. Archived from the original on 20 January 2022. Retrieved 31 March 2011.
  54. ^ "Chloroform case retrial underway". Record-Journal. 7 July 1993. Archived from the original on 6 November 2021. Retrieved 31 March 2011.
  55. ^ Cathy Frye - Arkansas Democrat-Gazette (17 December 2003). "But not forgotten". www.arkansasonline.com. Archived from the original on 7 December 2021. Retrieved 7 December 2021.
  56. ^ "Man admits to raping friends' daughters". USA Today. 6 November 2007. Archived from the original on 29 April 2011. Retrieved 31 March 2011.
  57. ^ Payne, J. P. (July 1998). "The criminal use of chloroform". Anaesthesia. 53 (7): 685–690. doi:10.1046/j.1365-2044.1998.528-az0572.x. PMID 9771177. S2CID 1718276.
  58. ^ "Medical Annotation: Chloroform amongst Thieves". The Lancet. 2 (2200): 490–491. 1865. doi:10.1016/s0140-6736(02)58434-8.
  59. ^ Nieuwenhuijsen, MJ; Toledano, MB; Elliott, P (8 August 2000). "Uptake of chlorination disinfection by-products; a review and a discussion of its implications for exposure assessment in epidemiological studies". Journal of Exposure Analysis and Environmental Epidemiology. 10 (6 Pt 1): 586–99. doi:10.1038/sj.jea.7500139. PMID 11140442.
  60. ^ Yin-Tak Woo, David Y. Lai, Joseph C. Arcos Aliphatic and Polyhalogenated Carcinogens: Structural Bases and Biological Archived 5 June 2018 at the Wayback Machine
  61. ^ a b c Fan, Anna M. (2005). "Chloroform". Encyclopedia of Toxicology. Vol. 1 (2nd ed.). Elsevier. pp. 561–565.
  62. ^ Jenkins, Andrew; Greenblatt, Eric P.; Faulkner, Howard J.; Bertaccini, Edward; Light, Adam; Lin, Audrey; Andreasen, Alyson; Viner, Anna; Trudell, James R.; Harrison, Neil L. (15 March 2001). "Evidence for a Common Binding Cavity for Three General Anesthetics within the GABAA Receptor". Journal of Neuroscience. 21 (6): RC136. doi:10.1523/JNEUROSCI.21-06-j0002.2001. ISSN 0270-6474. PMC 6762625. PMID 11245705.
  63. ^ "Chloroform and Phosgene, Chemical Hygiene and Safety". Earlham College. Archived from the original on 19 August 2017. Retrieved 17 August 2017.
  64. ^ Turk, Eric (2 March 1998). "Phosgene from Chloroform". Chemical & Engineering News. 76 (9): 6. doi:10.1021/cen-v076n009.p006. Archived from the original on 24 July 2008. Retrieved 13 August 2012.
  65. ^ "phosgene (chemical compound)". Encyclopædia Britannica. Archived from the original on 5 June 2013. Retrieved 16 August 2013.
  66. ^ Manogue, W. H.; Pigford, R. L. (September 1960). "The kinetics of the absorption of phosgene into water and aqueous solutions". AIChE Journal. 6 (3): 494–500. doi:10.1002/aic.690060329. ISSN 0001-1541.
  67. ^ Cheng, Xueheng; Gao, Quanyin; Smith, Richard D.; Simanek, Eric E.; Mammen, Mathai; Whitesides, George M. (1996). "Characterization of Hydrogen-Bonded Aggregates in Chloroform by Electrospray Ionization Mass Spectrometry". The Journal of Organic Chemistry. 61 (6): 2204–2206. doi:10.1021/jo951345g. ISSN 0022-3263. Archived from the original on 31 July 2022.
  68. ^ "40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities" (PDF) (1 July 2008 ed.). Government Printing Office. Archived from the original (PDF) on 25 February 2012. Retrieved 29 October 2011. ((cite journal)): Cite journal requires |journal= (help)
  69. ^ Shuiquan Tang; Elizabeth A. Edwards (2013). "Identification of Dehalobacter reductive dehalogenases that catalyse dechlorination of chloroform, 1,1,1-trichloroethane and 1,1-dichloroethane". Philos Trans R Soc Lond B Biol Sci. 368 (1616): 20120318. doi:10.1098/rstb.2012.0318. PMC 3638459. PMID 23479748.
  70. ^ Jugder, Bat-Erdene; Ertan, Haluk; Wong, Yie Kuan; Braidy, Nady; Manefield, Michael; Marquis, Christopher P.; Lee, Matthew (10 August 2016). "Genomic, transcriptomic and proteomic analyses of Dehalobacter UNSWDHB in response to chloroform". Environmental Microbiology Reports. 8 (5): 814–824. doi:10.1111/1758-2229.12444. ISSN 1758-2229. PMID 27452500.

External links

Wikimedia Commons has media related to Chloroform.
Halomethanes
General anesthetics (N01A)
Hallucinogens
Pharmacodynamics
Chloroform committees and commissions
Authority control: National
Categories