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Chloroform

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Chloroform
Names
IUPAC name
Chloroform
Systematic IUPAC name
Trichloromethane
Other names
Formyl trichloride, Methane trichloride, Methyl trichloride, Methenyl trichloride, TCM, Freon 20, R-20, UN 1888
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.000.603 Edit this at Wikidata
EC Number
  • 200-663-8
KEGG
RTECS number
  • FS9100000
  • InChI=1/CHCl3/c2-1(3)4/h1H
    Key: HEDRZPFGACZZDS-UHFFFAOYAG
  • ClC(Cl)Cl
Properties
CHCl3
Molar mass 119.38 g/mol
Appearance Colorless liquid
Density 1.483 g/cm3
Melting point -63.5 °C
Boiling point 61.2 °C
0.8 g/100 ml (20 °C)
1.4459
Structure
Tetrahedral
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Harmful (Xn), Irritant (Xi), Carc. Cat. 2B
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability (red): no hazard codeInstability (yellow): no hazard codeSpecial hazards (white): no code
2
Flash point Non-flammable
NIOSH (US health exposure limits):
PEL (Permissible)
 50 ppm (240 mg/m3) (OSHA)
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 ?)

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Chloroform in its liquid state shown in a test tube

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Chloroform is the organic compound with formula CHCl3. 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]

Occurrence

CHCl3 has a multitude of natural sources, both biogenic and abiotic. It is the estimated that greater than 90% of atmospheric CHCl3 is of natural origin.

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).[2] Similarly, the macroalga Eucheuma denticulatum, which is cultivated and harvested on a large scale for carrageenan production, produces CHCl3[3], as do Hypnea spinella, Falkenbergia hillebrandii, and Gracilara cornea along with seven indigenous macroalgae inhabiting a rock pool.[4] These studies show increased CHCl3 production with increased light intensity, presumably when photosynthesis is at a maximum. Chloroform is also produced by the brown alga Fucus vesiculosus, the green algae Cladophora glomerata, Enteromorpha ahlneriana, Enteromorpha flexuosa, and Enteromorpha intestinalis, and the diatom Pleurosira laevis [5]. Other studies observe CHCl3 in Fucus serratus, Fucus vesiculosis, Corallina officinalis, Cladophora pellucida, and Ulva lactuca [6], and Desmarestia antarctica, Lambia antarctica, Laminaria saccharina, Neuroglossum ligulatum.[7]

Production

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).[8] The American physician Samuel Guthrie prepared gallons of the material and described its "deliciousness of flavor."[9] Independently, Justus von Liebig also described the same compound.[10] All early preparations used variations of the haloform reaction. Chloroform was named and chemically characterized in 1834 by Jean-Baptiste Dumas.[11]

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 + Cl2 → CH2Cl2 + HCl
CH2Cl2 + Cl2 → CHCl3 + HCl

Chloroform undergoes further chlorination to give CCl4:

CHCl3 + Cl2 → CCl4 + HCl

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

Deuterochloroform

An archaic industrial route to chloroform involved the reaction of acetone (or ethanol) with sodium hypochlorite or calcium hypochlorite, the aforementioned haloform reaction.[1] The chloroform can be removed from the coproducts by distillation. A related reaction is still used in the production of bromoform and iodoform. Although the haloform process is obsolete for the production of ordinary chloroform, it is used to produce CDCl3.[citation needed] Deuterochloroform can also be prepared by the reaction of sodium deuteroxide with chloral hydrate,[citation needed] or from ordinary chloroform.[12]

Inadvertent formation of chloroform

The haloform reaction can also occur inadvertently in domestic settings. Sodium hypochlorite solution (chlorine bleach) mixed with common household liquids such as acetone, butanone, ethanol, or isopropyl alcohol can produce some chloroform, in addition to other compounds such as chloroacetone, or dichloroacetone.

Uses

The major use of chloroform today is in the production of the chlorodifluoromethane (R-22), 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 (R22) was also 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. Chloroform containing deuterium (heavy hydrogen), CDCl3, is a common solvent used in NMR spectroscopy. It can be used to bond pieces of acrylic glass (also known under the trade names Perspex and Plexiglas). A solvent of phenol:chloroform:isoamyl alcohol 25:24:1 is used to dissolve non-nucleic acid biomolecules in DNA and RNA extractions.

As a reagent in organic synthesis

As a reagent, chloroform serves as a source of the dichlorocarbene CCl2 group.[13] It reacts with aqueous sodium hydroxide usually in the presence of a phase transfer catalyst to produce dichlorocarbene, CCl2.[14][15] 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

Chloroform was once a popular anesthetic; its vapor depresses the central nervous system of a patient, allowing a doctor to perform various otherwise painful procedures. In 1847, the Bathgate obstetrician James Young Simpson first used chloroform for general anesthesia during childbirth. The use of chloroform during surgery expanded rapidly thereafter in Europe. 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 (~1.5–2.2) [16] 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[17]. 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.

Veterniary Use

In veterniary medicine it is used externally to kill maggots in wounds.

Safety

A fatal oral dose of chloroform is about 10 mL (14.8 g), with death due to respiratory or cardiac arrest.[18]

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 to the kidneys, and some people develop sores when the skin is immersed in chloroform.

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.[19] Cough syrups containing Chloroform can still be legally purchased in pharmacies and supermarkets in the UK.

The US National Toxicology Program's eleventh report on carcinogens[20] implicates it as reasonably anticipated to be a human carcinogen, a designation equivalent to International Agency for Research on Cancer class 2A. It has been most readily associated with hepatocellular carcinoma.[21][22] 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 and ultraviolet light, 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. Suspicious samples can be tested for phosgene using 5% diphenylamine, 5% dimethylaminobenzaldehyde, and then dried, turn yellow in phosgene vapor.

References

  1. ^ a b c d 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. ^ Nightingale PB, Malin G, Liss PS (1995). "Production of Chloroform and Other Low- Molecular-Weight Halocarbons by Some Species of Macroalgae". Limnology and Oceanography. 40 (4). American Society of Limnology and Oceanography: 680.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ 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: 89. doi:10.1080/09670269600651241.
  4. ^ Ekdahl A, Pedersen M, Abrahamsson K (1998). "A Study of the Diurnal Variation of Biogenic Volatile Halocarbons". Mar Chem. 63: 1.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ 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. PMID 13679095.
  6. ^ 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: 93. doi:10.1016/S1465-9972(00)00021-0.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ 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. PMID 15669318.
  8. ^ Eugène Soubeiran (1831). Ann. Chim. 48: 131. {{cite journal}}: Missing or empty |title= (help)
  9. ^ Samuel Guthrie (1832). "New mode of preparing a spirituous solution of Chloric Ether". Am. J. Sci. And Arts. 21: 64.
  10. ^ 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.
  11. ^ 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.
  12. ^ Canadian Patent 1085423
  13. ^ Srebnik, M.; Laloë, E. "Chloroform" Encyclopedia of Reagents for Organic Synthesis" 2001 John Wiley.doi:10.1002/047084289X.rc105
  14. ^ "1,6-Methano[10]annulene". Organic Syntheses. 1988; Collected Volumes, vol. 6, p. 731.
  15. ^ Gokel, G. W.; Widera, R. P.; Weber, W. P. (1988). "Phase-Transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide". Organic Syntheses{{cite journal}}: CS1 maint: multiple names: authors list (link); Collected Volumes, vol. 6, p. 232.
  16. ^ Calderone, F.A. (1935). J. Pharmacology Experimental Therapeutics. 55: 24 http://jpet.aspetjournals.org/cgi/reprint/55/1/24.pdf. {{cite journal}}: Missing or empty |title= (help)
  17. ^ 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. {{cite journal}}: More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); More than one of |author5= and |last5= specified (help); More than one of |author6= and |last6= specified (help)CS1 maint: date and year (link)
  18. ^ Chloroform, US Environmental Potection Agency
  19. ^ "The National Toxicology Program: Substance Profiles: Chloroform CAS No. 67-66-3" (pdf). Retrieved 2007-11-02.
  20. ^ "11th Report on Carcinogens". Retrieved 2007-11-02.
  21. ^ "Centers for Disease Control and Prevention: Current Intelligence Bulletin 9".
  22. ^ "National Toxicology Program: Report on the carcinogenesis bioassay of chloroform" (PDF).


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