Chloroform

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For the song by Phoenix, see Chloroform (song).
Chloroform
Chloroform displayed.svg Chloroform 3D.svg
Chloroform in its liquid state shown in a test tube
Identifiers
CAS number 67-66-3 YesY
PubChem 6212
ChemSpider 5977 YesY
UNII 7V31YC746X YesY
EC number 200-663-8
KEGG C13827 YesY
ChEBI CHEBI:35255 YesY
ChEMBL CHEMBL44618 YesY
RTECS number FS9100000
ATC code N01AB02
Jmol-3D images Image 1
Properties
Molecular formula CHCl3
Molar mass 119.38 g mol−1
Appearance Colorless liquid
Odor Heavy, ethereal odor
Density 1.564 g/cm3 (-20 °C)
1.489 g/cm3 (25 °C)
1.394 g/cm3 (60 °C)
Melting point −63.5 °C (−82.3 °F; 209.7 K)
Boiling point 61.15 °C (142.07 °F; 334.30 K)
decomposes at 450 °C
Solubility in water 1.062 g/100 mL (0 °C)
0.809 g/100 mL (20 °C)
0.732 g/100 mL (60 °C)
Solubility Soluble in benzene
Miscible in diethyl ether, oils, ligroin, alcohol, CCl4, CS2
Solubility in acetone ≥ 10 g/100 mL (19 °C)
Solubility in dimethyl sulfoxide ≥ 10 g/100 mL (19 °C)
Vapor pressure 0.62 kPa (-40 °C)
7.89 kPa (0 °C)
25.9 kPa (25 °C)
313 kPa (100 °C)
2.26 MPa (200 °C)
kH 3.67 L·atm/mol (24 °C)
Acidity (pKa) 15.7 (20 °C)
Thermal conductivity 0.13 W/m·K (20 °C)
Refractive index (nD) 1.4459 (20 °C)
Viscosity 0.563 cP (20 °C)
Structure
Molecular shape Tetrahedral
Dipole moment 1.15 D
Thermochemistry
Specific
heat capacity
C
114.25 J/mol·K
Std molar
entropy
So298
202.9 J/mol·K
Std enthalpy of
formation
ΔfHo298
-134.3 kJ/mol
Gibbs free energy ΔG -71.1 kJ/mol
Std enthalpy of
combustion
ΔcHo298
473.21 kJ/mol
Hazards
MSDS External MSDS
GHS pictograms The exclamation-mark pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)The health hazard pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
GHS signal word Warning
GHS hazard statements H302, H315, H319, H332, H336, H351, H361, H373
GHS precautionary statements P261, P281, P305+351+338
EU classification Harmful Xn Irritant Xi
Carc. Cat. 2B
R-phrases R22, R38, R40, R48/20/22
S-phrases (S2), S36/37
NFPA 704
Flammability code 0: Will not burn. E.g., water Health code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroform Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
Flash point Non-flammable
U.S. Permissible
exposure limit (PEL)
50 ppm (240 mg/m3) (OSHA)
LD50 1250 mg/kg (rats, oral)
Supplementary data page
Structure and
properties
n, εr, etc.
Thermodynamic
data
Phase behaviour
Solid, liquid, gas
Spectral data UV, IR, NMR, MS
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Infobox references

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

Natural occurrence[edit]

The total global flux of chloroform through the environment is approximately 660 000 tonnes per year, and about 90 % of emissions are natural in origin. Many kinds of seaweed produce chloroform, and fungi are believed to produce chloroform in soil.

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

History[edit]

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

Production[edit]

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

CH4 + Cl2 → CH3Cl + HCl
CH3Cl + Cl2CH2Cl2 + HCl
CH2Cl2 + Cl2 → CHCl3 + HCl

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

CHCl3 + Cl2 → CCl4 + HCl

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

Deuterochloroform[edit]

Main article: Deuterated chloroform

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

Inadvertent formation of chloroform[edit]

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

Uses[edit]

The major use of chloroform today is in the production of the chlorodifluoromethane, a major precursor to tetrafluoroethylene:

CHCl3 + 2 HF → CHClF2 + 2 HCl

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

Solvent[edit]

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

Reagent[edit]

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

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

Anesthetic[edit]

Antique bottles of chloroform

Chloroform was once a widely used anesthetic. On 4 November 1847, the Scottish obstetrician James Young Simpson discovered the anesthetic qualities of chloroform.[9] The use of chloroform during surgery expanded rapidly thereafter in Europe. In the 1850s, chloroform was used during the birth of Queen Victoria's last two children.[10] In the United States, chloroform began to replace ether as an anesthetic at the beginning of the 20th century; however, it was quickly abandoned in favor of ether upon discovery of its toxicity, especially its tendency to cause fatal cardiac arrhythmia analogous to what is now termed "sudden sniffer's death". Some people used chloroform as a recreational drug or to attempt suicide.[11] One possible mechanism of action for chloroform is that it increases movement of potassium ions through certain types of potassium channels in nerve cells.[12] Chloroform could also be mixed with other 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.[13] A number of physically fit patients died after inhaling it. However, in 1848 John Snow developed an inhaler that regulated the dosage and so successfully reduced the number of deaths.[14]

Criminal use[edit]

Chloroform has been reputed to be used by criminals to knock out, daze or even murder their victims. Joseph Harris was charged in 1894 with using chloroform to rob people.[15] In 1901, chloroform was also implicated in the murder of the American businessman William Marsh Rice, the namesake of the institution now known as Rice University. Chloroform was also deemed to be a factor in the alleged murder of a woman in 1991 when she was asphyxiated while sleeping.[16] In a 2007 plea bargain a man confessed to using stun guns and chloroform to sexually assault minors.[17] Use of chloroform as an incapacitating agent has become widely recognized, bordering on clichéd, due to the popularity of crime fiction authors having criminals use chloroform-soaked rags to render victims unconscious. However, it is nearly impossible to incapacitate someone using chloroform.[18] It takes at least 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 in order to keep the tongue from obstructing the airway, a difficult procedure even for an anesthesiologist. In 1865 as a direct result of the criminal reputation chloroform had gained, medical journal The Lancet offered a "permanent scientific reputation" to anyone who could demonstrate "instantaneous insensibility" using chloroform,[19] and as of 1998 no such demonstration has been forthcoming.[18]

Safety[edit]

Chloroform is well absorbed, metabolized, and eliminated rapidly by mammals after oral, inhalation, or dermal exposure. Accidental splashing into the eyes has caused irritation.[2] 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.[5]

Chloroform is metabolized in the liver by the cytochrome P-450 enzymes, by oxidation to phosgene and by reduction to the dichloromethyl free radical. Other metabolites of chloroform include chloromethanol, hydrochloric acid, hydrogen chloride, and digluathionyl dithiocarbonate, with carbon dioxide as the predominant end product of metabolism.[20]

Chloroform causes depression of the central nervous system (CNS), ultimately producing deep coma and respiratory center depression.[20] When ingested, chloroform caused symptoms similar to those seen following inhalation. Serious illness has followed ingestion of 7.5 g. The mean lethal oral dose for an adult is estimated to be about 45 g.[2]

The anesthetic use of chloroform has been discontinued because it caused deaths due to respiratory and cardiac arrhythmias and failure. Following chloroform-induced anesthesia, some patients suffered nausea, vomiting, prostration, jaundice, and coma due to hepatic dysfunction. At autopsy, liver necrosis and degeneration have been observed.[2]

Chloroform has induced liver tumors in mice and kidney tumors in mice and rats.[2] The hepatotoxicity and nephrotoxicity of chloroform is thought to be due largely to phosgene.[20]

Conversion to phosgene[edit]

During prolonged storage in the presence of oxygen, chloroform converts slowly to phosgene, releasing HCl in the process. To prevent accidents, commercial chloroform is stabilized with ethanol or amylene, but samples that have been recovered or dried no longer contain any stabilizer. Amylene has been found ineffective, and the phosgene can affect analytes in samples, lipids, and nucleic acids dissolved in or extracted with chloroform.[21] 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,[22] and the carbonate salt neutralizes the resulting acid.

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

References[edit]

  1. ^ a b c d e f g Rossberg, M. et al. “Chlorinated Hydrocarbons” in Ullmann’s Encyclopedia of Industrial Chemistry, 2006, Wiley-VCH, Weinheim. doi:10.1002/14356007.a06_233.pub2
  2. ^ a b c d e f Chloroform, CICAD 58, World Health Organization, 2004 
  3. ^ Koch, Hans A. Cholorofom Deuteration Process. Canadian Patent 1085423. Patents.ic.gc.ca. Issued: 1980-09-09. Retrieved on 2012-08-13.
  4. ^ Hans Ulrich Süss (2007), "Bleaching", Ullmann's Encyclopedia of Industrial Chemistry (7th ed.), Wiley, p. 5 
  5. ^ a b Jerrold B. Leikin; Frank P. Paloucek, eds. (2008), "Chloroform", Poisoning and Toxicology Handbook (4th ed.), Informa, p. 774 
  6. ^ Srebnik, M.; Laloë, E. (2001) "Chloroform" in Encyclopedia of Reagents for Organic Synthesis, Wiley, doi:10.1002/047084289X.rc105
  7. ^ 1,6-Methano[10]annulene, Org. Synth., 1988 ; Coll. Vol. 6: 731 
  8. ^ Gokel, G. W.; Widera, R. P.; Weber, W. P. (1988), Phase-Transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide, Org. Synth. ; Coll. Vol. 6: 232 
  9. ^ Gordon, H. Laing (November 2002). Sir James Young Simpson and Chloroform (1811–1870). The Minerva Group, Inc. pp. 106–109. ISBN 978-1-4102-0291-8. Retrieved 11 November 2011. 
  10. ^ Anesthesia and Queen Victoria. Ph.ucla.edu. Retrieved on 2012-08-13.
  11. ^ Martin, William (3 July 1886). "A Case of Chloroform Poisoning; Recovery". Br Med J 2 (1331): 16–17. doi:10.1136/bmj.2.1331.16-a. PMC 2257365. PMID 20751619. 
  12. ^ Patel, Amanda J.; Honoré, Eric; Lesage, Florian; Fink, Michel; Romey, Georges; Lazdunski, Michel (May 1999). "Inhalational anesthetics activate two-pore-domain background K+ channels". Nature Neuroscience 2 (5): 422–426. doi:10.1038/8084. PMID 10321245. 
  13. ^ Knight, Paul R. III and Bacon, Douglas R. (2002). "An Unexplained Death: Hannah Greener and Chloroform". Anesthesiology 96 (5): 1250–3. doi:10.1097/00000542-200205000-00030. PMID 11981167. 
  14. ^ Snow, John (1858). "On Chloroform and Other Anaesthetics and Their Action and Administration". pp. 82–85. 
  15. ^ "Knock-out and Chloroform". The Philadelphia Record. 9 February 1894. Retrieved 31 March 2011. 
  16. ^ "Chloroform case retrial underway". Record-Journal. 7 July 1993. Retrieved 31 March 2011. 
  17. ^ "Man admits to raping friends' daughters". USA Today. 6 November 2007. Retrieved 31 March 2011. 
  18. ^ a b 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. 
  19. ^ Medical Annotation. Chloroform amongst Thieves. The Lancet, 1865; 2: 490 – 1.
  20. ^ a b c Anna M Fan (2005), "Chloroform", Encyclopedia of Toxicology 1 (2nd ed.), Elsevier, pp. 561–565 
  21. ^ Turk, Eric (2 March 1998). "Phosgene from Chloroform". Chemical & Engineering News 76 (9): 6. doi:10.1021/cen-v076n009.p006. 
  22. ^ phosgene (chemical compound). Encyclopædia Britannica. Retrieved on 2013-08-16.

External links[edit]