Chloroform

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Chloroform
Identifiers
CAS number67-66-3 YesY
PubChem6212
ChemSpider5977 YesY
UNII7V31YC746X YesY
EC number200-663-8
KEGGC13827 YesY
ChEBICHEBI:35255 YesY
ChEMBLCHEMBL44618 YesY
RTECS numberFS9100000
ATC codeN01AB02
Jmol-3D imagesImage 1
Properties
Molecular formulaCHCl3
Molar mass119.38 g mol−1
AppearanceColorless liquid
Density1.483 g/cm3
Melting point

-63.5 °C, 210 K, -82 °F

Boiling point

61.2 °C, 334 K, 142 °F

Solubility in water0.8 g/100 mL (20 °C)
Refractive index (nD)1.4459
Structure
Molecular shapeTetrahedral
Hazards
MSDSExternal MSDS
R-phrasesR22, R38, R40, R48/20/22
S-phrases(S2), S36/37
Main hazardsHarmful (Xn), Irritant (Xi), Carc. Cat. 2B
NFPA 704
NFPA 704.svg
0
2
0
Flash pointNon-flammable
U.S. Permissible
exposure limit (PEL)
50 ppm (240 mg/m3) (OSHA)
Supplementary data page
Structure and
properties
n, εr, etc.
Thermodynamic
data
Phase behaviour
Solid, liquid, gas
Spectral dataUV, IR, NMR, MS
 YesY (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references
 
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Chloroform
Identifiers
CAS number67-66-3 YesY
PubChem6212
ChemSpider5977 YesY
UNII7V31YC746X YesY
EC number200-663-8
KEGGC13827 YesY
ChEBICHEBI:35255 YesY
ChEMBLCHEMBL44618 YesY
RTECS numberFS9100000
ATC codeN01AB02
Jmol-3D imagesImage 1
Properties
Molecular formulaCHCl3
Molar mass119.38 g mol−1
AppearanceColorless liquid
Density1.483 g/cm3
Melting point

-63.5 °C, 210 K, -82 °F

Boiling point

61.2 °C, 334 K, 142 °F

Solubility in water0.8 g/100 mL (20 °C)
Refractive index (nD)1.4459
Structure
Molecular shapeTetrahedral
Hazards
MSDSExternal MSDS
R-phrasesR22, R38, R40, R48/20/22
S-phrases(S2), S36/37
Main hazardsHarmful (Xn), Irritant (Xi), Carc. Cat. 2B
NFPA 704
NFPA 704.svg
0
2
0
Flash pointNon-flammable
U.S. Permissible
exposure limit (PEL)
50 ppm (240 mg/m3) (OSHA)
Supplementary data page
Structure and
properties
n, εr, etc.
Thermodynamic
data
Phase behaviour
Solid, liquid, gas
Spectral dataUV, IR, NMR, MS
 YesY (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references
Chloroform in its liquid state shown in a test tube

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 somewhat hazardous. Several million tons are produced annually as a precursor to Teflon and refrigerants, but its use for refrigerants is being phased out.[1]

Contents

Occurrence

Chloroform has a multitude of natural sources, both biogenic and abiotic. It is estimated that greater than 90% of atmospheric chloroform is of natural origin.[2]

Marine

In particular, chloroform is produced by brown seaweeds (Laminaria digitata, Laminaria saccharina, Fucus serratus, Pelvetia canaliculata, Ascophyllum nodosum), red seaweeds (Gigartina stellata, Corallina officinalis, Polysiphonia lanosa), and green seaweeds (Ulva lactuca, Enteromorpha sp., Cladophora albida).[3] Similarly, the macroalga Eucheuma denticulatum, which is cultivated and harvested on a large scale for carrageenan production, produces chloroform,[4] as do Hypnea spinella, Falkenbergia hillebrandii, and Gracilara cornea along with seven indigenous macroalgae inhabiting a rock pool.[5] These studies show increased chloroform production with increased light intensity, presumably when photosynthesis is also increased. Chloroform is also produced by the brown algae Fucus vesiculosus, the green algae Cladophora glomerata, Enteromorpha ahlneriana, Enteromorpha flexuosa, and Enteromorpha intestinalis, and the diatom Pleurosira laevis.[6] Other studies observe chloroform in Fucus serratus, Corallina officinalis, Cladophora pellucida, and Ulva lactuca,[7] and Desmarestia antarctica, Lambia antarctica, Laminaria saccharina, Neuroglossum ligulatum.[8]

Production

Chloroform was discovered by three researchers independently of one another. Chloroform was reported in 1831 by the French chemist Eugène Soubeiran, who prepared it from acetone (2-propanone) as well as ethanol through the action of chlorine bleach powder (calcium hypochlorite).[9] The American physician Samuel Guthrie prepared gallons of the material and described its "deliciousness of flavor."[10] Independently, Justus von Liebig also described the same compound.[11] All early preparations used variations of the haloform reaction. Chloroform was named and chemically characterized in 1834 by Jean-Baptiste Dumas.[12]

Industrial routes

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

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.[13]

Inadvertent formation of chloroform

The haloform reaction can also occur inadvertently in domestic settings.[citation needed] 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.[citation needed]

Uses

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

CHCl3 + 2 HF → CHClF2 + 2 HCl

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

As a solvent

Chloroform is a common solvent in the laboratory because it is relatively unreactive, miscible with most organic liquids, and conveniently volatile. Chloroform is used as a solvent in the pharmaceutical industry and for producing dyes and pesticides. Chloroform is an effective solvent for alkaloids in their base form and thus plant material is commonly extracted with chloroform for pharmaceutical processing. For example, it is used in commerce to extract morphine from poppies and scopolamine from Datura plants.

It can be used to bond pieces of acrylic glass (also known under the trade names Perspex and Plexiglas).

A solvent of phenol, chloroform, and isoamyl alcohol in a 25:24:1 ratio is used to dissolve non-nucleic acid biomolecules in DNA and RNA extractions.

Chloroform containing deuterium (heavy hydrogen), CDCl3, is a common solvent used in NMR spectroscopy.

As a reagent in organic synthesis

As a reagent, chloroform serves as a source of the dichlorocarbene CCl2 group.[14] It reacts with aqueous sodium hydroxide usually in the presence of a phase transfer catalyst to produce dichlorocarbene, CCl2.[15][16] 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.

As an anesthetic

Antique bottles of Chloroform

Chloroform was once a widely used anesthetic. Its vapor depresses the central nervous system of a patient, allowing a doctor to perform various otherwise painful procedures. On 4 November 1847, the Scottish obstetrician James Young Simpson discovered the anaethestic qualities of chloroform when he and his friends were experimenting with different substances on themselves in search of a replacement for ether as a general anesthetic. He was so astounded by the success of his own trial that the next morning he hired a chemist and within the next few days was administering it to his patients during childbirth.[17] 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.[18] 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". Ether is still the preferred anesthetic in some developing nations due to its high therapeutic index, and low price. One possible mechanism of action for chloroform is that it increases movement of potassium ions through certain types of potassium channels in nerve cells.[19] 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.

Hannah Greener, a 15 year old girl who was having an infected toenail removed, died after being given the anesthetic.[20] 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.[citation needed]

Chloroform has been used by criminals to knock out, daze or even murder their victims. Joseph Harris was charged with using chloroform in 1894 to rob people.[21] Chloroform was used to murder a woman in 1991 as a toxic dose was delivered while she was sleeping.[22] In 2007 a man was convicted of using chloroform to sexually assault minors.[23][24]

As a working fluid in a heat engine

At least one experimental heat engine has been constructed using chloroform as a working fluid in place of steam; similar experiments had been conducted using ether as a low-boiling-point working fluid, but its highly flammable nature caused difficulties, so chloroform was tried as a non-flammable alternative. Such experiments were apparently inspired by the misconception that a fluid with a lower boiling point than water, being easier to vaporise, would allow the construction of a more efficient engine; in fact the reverse is the case,[25] but this was not widely appreciated in the days when thermodynamics was a young science. Grandiose claims for the efficiency of this engine were reported in Scientific American in 1848, along with an editorial comment casting grave doubts on them; it appears that the development of the invention did not proceed further.[26]

Safety

A fatal oral dose of chloroform may be as small as 10 mL (14.8 g), with death due to respiratory or cardiac arrest.[27]

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

Animal studies have shown that miscarriages occur in rats and mice that have breathed air containing 30 to 300 ppm of chloroform during pregnancy and also in rats that have ingested chloroform during pregnancy. Offspring of rats and mice that breathed chloroform during pregnancy have a higher incidence of birth defects, and abnormal sperm have been found in male mice that have breathed air containing 400 ppm chloroform for a few days. The effect of chloroform on reproduction in humans is unknown.

Chloroform once appeared in toothpastes, cough syrups, ointments, and other pharmaceuticals, but it has been banned as a consumer product in the US since 1976.[28] Cough syrups containing chloroform can still be legally purchased in pharmacies and supermarkets in the UK.

The US National Toxicology Program's twelfth report on carcinogens[29] implicates it as reasonably anticipated to be a human carcinogen, a designation equivalent to International Agency for Research on Cancer class 2A. The IARC itself classifies chloroform as possibly carcinogenic to humans, a Group 2B designation.[30] It has been most readily associated with hepatocellular carcinoma.[31][32] Caution is mandated during its handling in order to minimize unnecessary exposure; safer alternatives, such as dichloromethane, have resulted in a substantial reduction of its use as a solvent.

Conversion to phosgene

During prolonged storage in the presence of oxygen, chloroform converts slowly to phosgene. 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.[33] Dissolved phosgene cannot be removed by distillation or carbon filters, but it is removed by calcium hydroxide or activated alumina.[34]

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

References

  1. ^ a b c d e M. Rossberg et al. “Chlorinated Hydrocarbons” in Ullmann’s Encyclopedia of Industrial Chemistry, 2006, Wiley-VCH, Weinheim. doi:10.1002/14356007.a06_233.pub2
  2. ^ Naturally-Occurring Organochlorines. eurochlor.org
  3. ^ Nightingale PB, Malin G, Liss PS (1995). "Production of Chloroform and Other Low- Molecular-Weight Halocarbons by Some Species of Macroalgae". Limnology and Oceanography (American Society of Limnology and Oceanography) 40 (4): 680. JSTOR 2838303. 
  4. ^ Mtolera, Matern; Collén, Jonas; Pedersén, Marianne; Ekdahl, Anja; Abrahamsson, Katarina; Semesi, Adelaida (1996). "Stress-induced production of volatile halogenated organic compounds in Eucheuma denticulatum (Rhodophyta) caused by elevated pH and high light intensities". European Journal of Phycology 31 (1): 89. doi:10.1080/09670269600651241. 
  5. ^ Ekdahl A, Pedersen M, Abrahamsson K (1998). "A Study of the Diurnal Variation of Biogenic Volatile Halocarbons". Mar Chem 63: 1. 
  6. ^ Abrahamsson, K; Choo, KS; Pedersén, M; Johansson, G; Snoeijs, P (2003). "Effects of temperature on the production of hydrogen peroxide and volatile halocarbons by brackish-water algae.". Phytochemistry 64 (3): 725–34. doi:10.1016/S0031-9422(03)00419-9. PMID 13679095. 
  7. ^ Baker JM, Sturges WT, Sugier J, Sunnenberg G, Lovett AA, Reeves CE, Nightingale PD, Penkett SA (2001). "Emissions of CH3Br, Organochlorines, and Organoiodines from Temperate Macroalgae". Chemosphere – Global Change Science 3 (1): 93. doi:10.1016/S1465-9972(00)00021-0. 
  8. ^ Laturnus, F; Svensson, T; Wiencke, C; Oberg, G (2004). "Ultraviolet radiation affects emission of ozone-depleting substances by marine macroalgae: results from a laboratory incubation study.". Environmental Science & Technology 38 (24): 6605–9. doi:10.1021/es049527s. PMID 15669318. 
  9. ^ Eugène Soubeiran (1831). Ann. Chim. 48: 131. 
  10. ^ Samuel Guthrie (1832). "New mode of preparing a spirituous solution of Chloric Ether". Am. J. Sci. And Arts 21: 64. 
  11. ^ Justus Liebig (1832). "Ueber die Verbindungen, welche durch die Einwirkung des Chlors auf Alkohol, Aether, ölbildendes Gas und Essiggeist entstehen". Annalen der Pharmacie 1 (2): 182–230. doi:10.1002/jlac.18320010203. 
  12. ^ Jean-Baptiste Dumas (1834). "Untersuchung über die Wirkung des Chlors auf den Alkohol". Annalen der Pharmacie 107 (41): 650–656. doi:10.1002/andp.18341074103. 
  13. ^ Koch, Hans A. Cholorofom Deuteration Process. Canadian Patent 1085423. Patents.ic.gc.ca. Issued: 1980-09-09. Retrieved on 2012-08-13.
  14. ^ Srebnik, M.; Laloë, E. "Chloroform" Encyclopedia of Reagents for Organic Synthesis" 2001 John Wiley.doi:10.1002/047084289X.rc105
  15. ^ "1,6-Methano[10]annulene", Org. Synth., 1988, http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0731 ; Coll. Vol. 6: 731 
  16. ^ Gokel, G. W.; Widera, R. P.; Weber, W. P. (1988), "Phase-Transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0232 ; Coll. Vol. 6: 232 
  17. ^ Gordon, H. Laing (2002-11). Sir James Young Simpson and Chloroform (1811–1870). The Minerva Group, Inc.. pp. 106–109. ISBN 978-1-4102-0291-8. http://books.google.com/books?id=pYer05UwKBYC&pg=PA106. Retrieved 11 November 2011. 
  18. ^ Anesthesia and Queen Victoria. Ph.ucla.edu. Retrieved on 2012-08-13.
  19. ^ 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. 
  20. ^ An Unexplained Death: Hannah Greener and Chloroform
  21. ^ "Knock-out and Chloroform". The Philadelphia record. 9 February 1894. http://news.google.com/newspapers?id=Ec1VAAAAIBAJ&sjid=sEANAAAAIBAJ&pg=2904,2720400&dq=chloroform+knockout&hl=en. Retrieved 31 March 2011. 
  22. ^ "Chloroform case retrial underway". Record-Journal. 7 July 1993. http://news.google.com/newspapers?id=I91HAAAAIBAJ&sjid=4f8MAAAAIBAJ&pg=2367,1007950&dq=chloroform+knockout&hl=en. Retrieved 31 March 2011. 
  23. ^ "Man Uses Chloroform In Sex Attacks Of Teens". News 5. 6 November 2007. http://www.wlwt.com/news/14519857/detail.html. Retrieved 31 March 2011. 
  24. ^ "Man admits to raping friends' daughters". USA Today. 6 November 2007. http://www.usatoday.com/news/nation/2007-11-06-chloroform-rapes_N.htm. Retrieved 31 March 2011. 
  25. ^ "Carnot efficiency". http://www.douglas-self.com/MUSEUM/POWER/thermo/thermo.htm#ce. Retrieved 2012-09-24. 
  26. ^ "Ether and Chloroform Engines". http://www.douglas-self.com/MUSEUM/POWER/ether/ether.htm. Retrieved 2012-09-24. 
  27. ^ Chloroform, US Environmental Potection Agency
  28. ^ "The National Toxicology Program: Substance Profiles: Chloroform CAS No. 67-66-3" (PDF). http://ntp.niehs.nih.gov/ntp/roc/twelfth/profiles/Chloroform.pdf. Retrieved 2012-05-21. 
  29. ^ "Substances Listed in the Twelfth Report on Carcinogens" (PDF). http://ntp.niehs.nih.gov/ntp/roc/twelfth/ListedSubstancesReasonablyAnticipated.pdf. Retrieved 2012-05-21. 
  30. ^ "International Agency for Research on Cancer (IARC) – Summaries & Evaluations: Chloroform". http://www.inchem.org/documents/iarc/vol73/73-05.html. Retrieved 2010-09-02. 
  31. ^ "Current Intelligence Bulletin 9: Chloroform (DDM)". Centers for Disease Control and Prevention cdc.gov. http://www.cdc.gov/niosh/docs/1970/78127_9.html. 
  32. ^ "National Toxicology Program: Report on the carcinogenesis bioassay of chloroform". http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/trChloroform.pdf. 
  33. ^ Turk, Eric (2 March 1998). "Phosgene from Chloroform". Chemical & Engineering News 76 (9): 6. http://pubs.acs.org/cen/safety/19980302.html. 
  34. ^ Cone, EJ; Buchwald, WF; Darwin, WD (1982). "Analytical controls in drug metabolic studies. II. Artifact formation during chloroform extraction of drugs and metabolites with amine substituents". Drug metabolism and disposition: the biological fate of chemicals 10 (6): 561–7. PMID 6130900. 

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