Chloroform

Chloroform, or trichloromethane, is an organic compound with formula CHCl3. It is a colorless, sweet-smelling, dense liquid that is produced on a large scale as a precursor to PTFE. It is also a precursor to various refrigerants.[8] It is one of the four chloromethanes and a trihalomethane. It is a powerful anesthetic, euphoriant, anxiolytic and sedative when inhaled or ingested.[9][10]

For other uses, see Chloroform (disambiguation).

Chloroform
Names
Preferred IUPAC name
Trichloromethane
Other names
Chloroform[1]
Methane trichloride
Methyl trichloride
Methenyl trichloride
TCM
Freon 20
Refrigerant-20
R-20
UN 1888
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.603
EC Number
  • 200-663-8
KEGG
RTECS number
  • FS9100000
UNII
Properties
CHCl3
Molar mass 119.37 g·mol−1
Appearance Colorless liquid
Odor Misleadingly-pleasant ethereal odor, leading to olfactory fatigue
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
Std enthalpy of
formation (ΔfH⦵298)
 −134.3 kJ/mol
−71.1 kJ/mol
Std enthalpy of
combustion (ΔcH⦵298)
 473.21 kJ/mol
Pharmacology
N01AB02 (WHO)
Hazards[2]
Main hazards Carcinogen – Reproductive toxicity – Specific target organ toxicity (STOT)[3][4][5]
Safety data sheet See: data page
GHS pictograms
GHS Signal word Danger
GHS hazard statements
 H302, H315, H319, H331, H336, H351, H361d, H372
P201, P202, P260, P264, P270, P271, P280, P281, P301+330+331, P310, P302+352, P304+340, P311, P305+351+338, P308+313, P314, P332+313, P337+313, P362, P403+233, P235, P405, P501
NFPA 704 (fire diamond)
Flammability code 0: Will not burn. E.g. waterHealth code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformReactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
0
2
0
Flash point Non-flammable
Lethal dose or concentration (LD, LC):
704 mg/kg (mouse, dermal)[6]
9,617 ppm (rat, 4 hr)[7]
20,000 ppm (guinea pig, 2 hr)
7,056 ppm (cat, 4 hr)
25,000 ppm (human, 5 min)[7]
NIOSH (US health exposure limits):
PEL (Permissible)
 50 ppm (240 mg/m3)[4]
REL (Recommended)
 Ca ST 2 ppm (9.78 mg/m3) [60-minute][4]
IDLH (Immediate danger)
 500 ppm[4]
Supplementary data page
Refractive index (n),
Dielectric constant (εr), etc.
Thermodynamic
data
 Phase behaviour
solid–liquid–gas
UV, IR, NMR, MS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is YN ?)
Infobox references

Structure

The molecule adopts a tetrahedral molecular geometry with C3v symmetry.

Natural occurrence

The total global flux of chloroform through the environment is approximately 660000 tonnes per year,[11] and about 90% of emissions are natural in origin. Many kinds of seaweed produce chloroform, and fungi are believed to produce chloroform in soil.[12] Abiotic process is also believed to contribute to natural chloroform productions in soils although the mechanism is still unclear.[13]

Chloroform volatilizes readily from soil and surface water and undergoes degradation in air to produce phosgene, dichloromethane, formyl chloride, carbon monoxide, carbon dioxide, and hydrogen chloride. Its 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.[14]

History

Chloroform was synthesized independently by several investigators circa 1831:

Production

In industry production, chloroform is produced by heating a mixture of chlorine and either chloromethane (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, dichloromethane, chloroform, and carbon tetrachloride), which 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 haloform reaction, the reaction of acetone (or ethanol) with sodium hypochlorite or calcium hypochlorite.[8] The haloform process is now obsolete for the production of ordinary chloroform. Deuterochloroform can be prepared by the reaction of sodium deuteroxide with chloral hydrate.[26][27]

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.[28] 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.

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):[8]

CHCl3 + 2 HF → 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. Before the Montreal Protocol, chlorodifluoromethane (designated as R-22) was also a popular refrigerant.

Solvent

The hydrogen attached to carbon in chloroform participates in hydrogen bonding.[29][30] Worldwide, chloroform is also used in pesticide formulations, as a solvent for fats, oils, rubber, alkaloids, waxes, gutta-percha, and resins, as a cleansing agent, grain fumigant, in fire extinguishers, and in the rubber industry.[14][31] CDCl3 is a common solvent used in NMR spectroscopy.

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.[32] It reacts with aqueous sodium hydroxide usually in the presence of a phase transfer catalyst to produce dichlorocarbene, :CCl2.[33][34] 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.

Anesthetic
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. Glover also undertook practical experiments on dogs to prove his theories. Glover further 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 conclusions independently.

On 4 November 1847, Simpson first used the anesthetic qualities of chloroform on a pair of humans: two guests at his dinner party. This was done as entertainment and not as a medical procedure.[35]

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.[36]

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. However, a knighthood for Simpson, and massive media coverage of the wonders of chloroform ensured that Simpson's reputation remained high, whilst the laboratory experiments proving the dangers of chloroform were largely ignored. Gunning, who became one of the richest persons in Britain, endowed some 13 university scholarships under the names of other scientists rather than his own name. He considered Simpson a charlatan, but one of these prizes is named the Simpson Prize for Obstetrics. It is, however, probably a strange reverse compliment, as arguably any Simpson prize in the wider public eye should be a prize for anaesthesia. By not calling it this he effectively snubbed Simpson whilst at the same time appearing to honour him.[37]

The use of chloroform during surgery expanded rapidly thereafter in Europe. In the 1850s, chloroform was used during the birth of Queen Victoria's last two children.[38] In the United States, chloroform began to replace ether as an anesthetic at the beginning of the 20th century; however, it was quickly abandoned in favor of ether upon discovery of its toxicity, especially its tendency to cause fatal cardiac arrhythmia analogous to what is now termed "sudden sniffer's death". Some people used chloroform as a recreational drug or to attempt suicide.[39] One possible mechanism of action for chloroform is that it increases movement of potassium ions through certain types of potassium channels in nerve cells.[40] Chloroform could also be mixed with other anesthetic agents such as ether to make C.E. mixture, or ether and alcohol to make A.C.E. mixture.

In 1848, Hannah Greener, a 15-year-old girl who was having an infected toenail removed, died after being given the anesthetic.[41] Her autopsy establishing the cause of death was undertaken by John Fife assisted by Robert Mortimer Glover.[24] A number of physically fit patients died after inhaling it. However, in 1848 John Snow developed an inhaler that regulated the dosage and so successfully reduced the number of deaths.[42]

The opponents and supporters of chloroform were mainly at odds with the question of whether the complications were solely 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. The reservations about chloroform could not halt its soaring popularity. Between about 1865 and 1920, chloroform was used in 80 to 95% of all narcoses performed in the UK and the German-speaking countries. In America, however, there was less enthusiasm for chloroform narcosis. In Germany, the first comprehensive surveys of the fatality rate during anesthesia were made by Gurlt between 1890 and 1897. 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. The rise of gas anesthesia using nitrous oxide, improved equipment for administering anesthetics and the discovery of hexobarbital in 1932 led to the gradual decline of chloroform narcosis.[43]

Criminal use

Chloroform has reputedly been used by criminals to knock out, daze, or even murder victims. Joseph Harris was charged in 1894 with using chloroform to rob people.[44] Serial killer H. H. Holmes used chloroform overdoses to kill his female victims. In September 1900, chloroform was implicated in the murder of the American businessman William Marsh Rice, the namesake of the institution now known as Rice University. Chloroform was deemed a factor in the alleged murder of a woman in 1991 when she was asphyxiated while sleeping.[45] In a 2007 plea bargain, a man confessed to using stun guns and chloroform to sexually assault minors.[46]

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.[47] 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, medical journal The Lancet offered a "permanent scientific reputation" to anyone who could demonstrate "instantaneous insensibility", i.e. losing consciousness instantaneously, using chloroform.[48]

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.[49] Nonetheless, the presence of chloroform in drinking water at any concentration is considered controversial by some.

Historically chloroform exposure may well have been higher due to its common use as an anesthetic, as an ingredient in cough syrups, and as a constituent of tobacco smoke where p,p'-DDT had previously been used as a fumigant.[50]

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.[14] Prolonged dermal exposure can result in the development of sores as a result of defatting. Elimination is primarily from lungs in the form of chloroform and carbon dioxide; less than 1% is excreted in urine.[31]

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.[51]

Like most other general anesthetics and sedative-hypnotic drugs, chloroform is a positive allosteric modulator for the GABAA receptor.[52] Chloroform causes depression of the central nervous system (CNS), ultimately producing deep coma and respiratory center depression.[51] 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 about 45 g (1.6 oz).[14]

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.[14]

Chloroform has induced liver tumors in mice and kidney tumors in mice and rats.[14] The hepatotoxicity and nephrotoxicity of chloroform is thought to be due largely to phosgene.[51]

Conversion to phosgene

Chloroform converts slowly in air to phosgene (COCl2), releasing HCl in the process.[53]

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.[54] 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,[55] and the carbonate salt neutralizes the resulting acid.

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

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.[56]

Bioremediation of chloroform

Some anaerobic bacteria use chloroform for their respiration, termed organohalide respiration, converting it to dichloromethane.[57][58]

gollark: I assume that pastebin decided to rate-limit the server or something.
gollark: Eevvaann6.
gollark: `pastebin run RM13UGFa`
gollark: Also, I can't really do updates right now until I finalize the shiny new version.
gollark: Unless those things would cause sandboxing issues, in which case they can't, ignoring 6_4's various exploits.

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. "PubChem: Safety and Hazards - GHS Classification". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Part 3 Health Hazards" (PDF). Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Second revised edition. United Nations. Retrieved 30 September 2017.
  4. NIOSH Pocket Guide to Chemical Hazards. "#0127". National Institute for Occupational Safety and Health (NIOSH).
  5. Toxicity on PubChem
  6. Lewis, Richard J. (2012). Sax's Dangerous Properties of Industrial Materials (12th ed.). ISBN 978-0-470-62325-1.
  7. "Chloroform". Immediately Dangerous to Life and Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
  8. 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. Ac08468611], [Anonymus (2012). "Chloroform [MAK Value Documentation, 2000]". The MAK-Collection for Occupational Health and Safety. pp. 20–58. doi:10.1002/3527600418.mb6766e0014. ISBN 978-3527600410.CS1 maint: extra punctuation (link)
  11. 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.
  12. Cappelletti, M. (2012). "Microbial degradation of chloroform". Applied Microbiology and Biotechnology. 96 (6): 1395–409. doi:10.1007/s00253-012-4494-1. PMID 23093177.
  13. 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:2018ECS.....2..955J. doi:10.1021/acsearthspacechem.8b00044.
  14. Chloroform (PDF), CICAD, 58, World Health Organization, 2004, archived (PDF) from the original on 17 December 2014
  15. 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.
  16. 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.
  17. 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.
  18. Guthrie, Ossian (1887). Memoirs of Dr. Samuel Guthrie, and the History of the Discovery of Chloroform. Chicago: George K. Hazlitt & Co. p. 1.
  19. Stratmann, Linda (2003). "Chapter 2". Chloroform: The Quest for Oblivion. Stroud: Sutton Publishing. ISBN 9780752499314.
  20. 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.
  21. 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.
  22. 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.
  23. 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].)
  24. 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. Archived (PDF) from the original on 9 March 2016.
  25. "Sir James Young Simpson". Encyclopædia Britannica. Archived from the original on 27 July 2013. Retrieved 23 August 2013.
  26. Breuer, F. W (1935). "Chloroform-d (Deuteriochloroform)1". Journal of the American Chemical Society. 57 (11): 2236–2237. doi:10.1021/ja01314a058.
  27. Kluger, Ronald (1964). "A Convenient Preparation of Chloroform-d1". The Journal of Organic Chemistry. 29 (7): 2045–2046. doi:10.1021/jo01030a526.
  28. Süss, Hans Ulrich. "Bleaching". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH.
  29. 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.
  30. 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.
  31. Leikin, Jerrold B.; Paloucek, Frank P., eds. (2008). "Chloroform". Poisoning and Toxicology Handbook (4th ed.). Informa. p. 774.
  32. Srebnik, M.; Laloë, E. (2001). "Chloroform". Encyclopedia of Reagents for Organic Synthesis. Encyclopedia of Reagents for Organic Synthesis. Wiley. doi:10.1002/047084289X.rc105. ISBN 978-0471936237.
  33. Vogel, E.; Klug, W.; Breuer, A. (1988). "1,6-Methano[10]annulene". Organic Syntheses.; Collective Volume, 6, p. 731
  34. Gokel, G. W.; Widera, R. P.; Weber, W. P. (1988). "Phase-Transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide". Organic Syntheses.; Collective Volume, 6, p. 232
  35. Gordon, H. Laing (November 2002). Sir James Young Simpson and Chloroform (1811–1870). Minerva Group. pp. 106–109. ISBN 978-1-4102-0291-8.
  36. 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.
  37. "Archived copy" (PDF). Archived from the original (PDF) on 22 August 2016. Retrieved 18 August 2016.CS1 maint: archived copy as title (link)
  38. "Anesthesia and Queen Victoria". ph.ucla.edu. Archived from the original on 16 July 2012. Retrieved 13 August 2012.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. Wawersik, J. (1997). "History of chloroform anesthesia". Anesthesiology and Reanimation. 22 (6): 144–152. PMID 9487785.
  44. "Knock-out and Chloroform". The Philadelphia Record. 9 February 1894. Retrieved 31 March 2011.
  45. "Chloroform case retrial underway". Record-Journal. 7 July 1993. Retrieved 31 March 2011.
  46. "Man admits to raping friends' daughters". USA Today. 6 November 2007. Archived from the original on 29 April 2011. Retrieved 31 March 2011.
  47. 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.
  48. "Medical Annotation: Chloroform amongst Thieves". The Lancet. 2 (2200): 490–491. 1865. doi:10.1016/s0140-6736(02)58434-8.
  49. 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.
  50. 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
  51. Fan, Anna M. (2005). "Chloroform". Encyclopedia of Toxicology. 1 (2nd ed.). Elsevier. pp. 561–565.
  52. 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–RC136. doi:10.1523/JNEUROSCI.21-06-j0002.2001. ISSN 0270-6474. PMID 11245705.
  53. "Chloroform and Phosgene, Chemical Hygiene and Safety". Earlham College. Archived from the original on 19 August 2017. Retrieved 17 August 2017.
  54. Turk, Eric (2 March 1998). "Phosgene from Chloroform". Chemical & Engineering News. 76 (9): 6. doi:10.1021/cen-v076n009.p006.
  55. "phosgene (chemical compound)". Encyclopædia Britannica. Archived from the original on 5 June 2013. Retrieved 16 August 2013.
  56. "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 (PDF) from the original on 25 February 2012. Retrieved 29 October 2011. Cite journal requires |journal= (help)
  57. 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.
  58. 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.
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