Chloroform , or trichloromethane , is an organic compound with the formula CHCl3 . It is a colorless, strong-smelling, dense liquid that is produced extensively as a precursor to PTFE . It is also a precursor to various refrigerants . [8] It is one of four chloromethanes and one trihalomethane . It is a powerful anesthetic , stimulant , anxiolytic and sedative when inhaled or ingested.
| Property | |
|---|---|
| chemical formula | CH Cl 3 _ |
| molar mass | 119.37 g·mol −1 |
| appearance | colorless liquid |
| dirt | Deceptively-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 |
| Solubility in water | 10.62 g/l (0 °C) 8.09 g/l (20 °C) 7.32 g/l (60 °C) |
| solubility | Soluble in benzene diethyl ether, oil, ligroin, alcohol, CCl 4, CS 2 |
| 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) |
| Henry’s law constant ( k H ) | 3.67 L atm/mol (24 °C) |
| Acidity ( pKa ) | 15.7 (20 °C) |
| UV-Vis (λ max ) | 250nm, 260nm, 280nm |
| Magnetic Sensitivity (χ) | −59.30 10 −6 cm 3 /mol |
| thermal conductivity | 0.13 W/m K (20 °C) |
| Refractive Index ( ND ) | 1.4459 (20 °C) |
| viscosity | 0.563 CP (20 °C) |
structure
Molecule C adopts a tetrahedral molecular geometry with 3v symmetry.
natural phenomena
The total global flux of chloroform through the environment is approximatelyFrom 660 000 tonnes per year, [11] and about 90% of the emissions are natural in origin. Many types of seaweed produce chloroform, and fungi are believed to produce chloroform in soil. [12] Abiotic processes are also believed to contribute to natural chloroform production in soil, although the mechanism is still unclear. [13]
Chloroform is readily destabilized by soil and surface water and degradation in air to produce phosgene, dichloromethane, formyl chloride, carbon monoxide, carbon dioxide and hydrogen chloride. Its half-life in the air ranges from 55 to 620 days. Biodegradation in water and soil is slow. Chloroform does not bioaccumulate significantly in aquatic organisms. [14]
history
Chloroform was independently synthesized by several investigators around 1831:
- Moldenhauer, a German pharmacist from Frankfurt an der Oder, appears to have produced chloroform in 1830 by mixing chlorinated lime with ethanol; However, he mistook it for chlorether (chloric ether, 1,2-dichloroethane) . [15] [16]
- Samuel Guthrie, an American physician from Sacketts Harbor, New York, also appears to have produced chloroform in 1831 by reaction of chlorinated lime with ethanol, noting its anesthetic properties; However, he also believed that he had prepared chlorine ether. [17] [18] [19]
- Justus von Liebig carried out the alkaline cleavage of chloral. [20] [21]
- Eugene Sauberon obtained the compound by the action of chlorine bleach on both ethanol and acetone. [22]
- In 1834, the French chemist Jean-Baptiste Dumas determined the empirical formula for chloroform and named it. [23] In 1835, Dumas prepared the substance by alkaline cleavage of trichloroacetic acid. Chloroform prepared by Regnault for chlorination of chloromethane.
- In 1842, Robert Mortimer Glover in London discovered the anesthetic properties of chloroform on laboratory animals. [24]
- In 1847, Scottish obstetrician James Y. Simpson was the first to demonstrate the anesthetic properties of chloroform on humans, provided by local pharmacist William Flockhart of Duncan, Flockhart & Company, [25] and helped to popularize the drug for use in medicine. [26] By the 1850s, chloroform was being produced on a commercial basis, with approximately 750,000 doses a week in Britain by 1895, [27] using the Liebig process, which retained its importance until the 1960s. kept. Today, chloroform – along with dichloromethane – is prepared exclusively and extensively by chlorination of methane and chloromethane. [8]
Production
In industry production, chloroform is produced by heating a mixture of chlorine and chloromethane (CH3Cl ) or methane (CH4 ) . [8] At 400–500 °C, a free radical halogenation occurs, converting these precursors into progressively more chlorinated compounds:
CH 4 + Cl 2 → CH 3 Cl + HCl
CH 3 Cl + Cl 2 → CH 2 Cl 2 + HCl
CH 2 Cl 2 + Cl 2 → CHCl 3 + HCl
Chloroform undergoes further chlorination to yield carbon tetrachloride (CCl 4 ):
CHCl 3 + Cl 2 → CCl 4 + HCl
The production of this process is a mixture of four chloromethanes (chloromethane, dichloromethane, chloroform and carbon tetrachloride), which can then be separated by distillation.
Chloroform can also be produced on a smaller scale via the haloform reaction between acetone and sodium hypochlorite:
3 NaClO + (CH 3 ) 2 CO → CHCl 3 + 2 NaOH + CH 3 COONa
deuterochloroform
Deuterated chloroforms is an isotopologue of chloroform with a single deuterium atom. CdCl is a common solvent used in 3 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 for the production of common chloroform is now obsolete. Deuterochloroform can be prepared by the reaction of sodium deuteroxide with chloral hydrate. [28] [29]
unintentional formation of chloroform
The haloform reaction can also occur unintentionally in home settings. Bleaching with hypochlorite generates halogenated compounds in side reactions; Chloroforms is the main byproduct. [30] Sodium hypochlorite solution (chlorine bleach) can be mixed with common household liquids such as acetone, methyl ethyl ketone, ethanol or isopropyl alcohol to produce some chloroforms in addition to other compounds such as chloroacetone or dichloroacetone.
Use
In terms of scale, the most important reaction of chloroform is with monochlorodifluoromethane (CFC-22), to give hydrogen fluoride (a precursor in the production of polytetrafluoroethylene (Teflon): [8]CHCl 3 + 2 HF → CHClF 2 + 2 HCl
The reaction is conducted in the presence of a catalytic amount of mixed antimony halide. Chlorodifluoromethane is then converted to tefluoroethylene, the main precursor of Teflon. Before the Montreal Protocol, chlorodifluoromethane (designated as R-22) was also a popular refrigerant.
solvent
In the chloroform part in the carbon hydrogen bond to the hydrogen bond. [31] [32] Worldwide, chloroform is also used in pesticide formulations, as a solvent for fats, oils, rubber, alkaloids, waxes, gutta-percha, and resins, as a cleaning agent. , grain fumigant, in fire extinguishers, and in the rubber industry. [14] [33] CdCl is a common solvent used in 3 NMR spectroscopy.
Lewis acid
In solvents such as CCl and alkanes, chloroform hydrogen bonds to various Lewis bases. HCl3 is classified as a hard acid and the ECW model lists its acid parameters as E A = 1.56 and C A = 0.44.
reagent
As a reagent, chloroform serves as a source of the dichlorocarbene : CCl2 group. [34] It reacts with aqueous sodium hydroxide, usually in the presence of a phase transfer catalyst, to produce dichlorocarbene, :CCl 2 . [35] [36] This reagent affects the ortho-formylation of active aromatic rings such as phenol, producing aryl aldehyde in a reaction known as the Reimer–Tiemann reaction. Alternatively, the carbene may be implicated by an alkene to form a cyclopropane derivative. In Kharasch addition, chloroform forms CHCl 2 in free radical addition to alkenes. ,citation needed ]
anesthetic drug
The properties of the anesthetic 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 conducted practical experiments on dogs to prove his theories. Glover further refined his theories and presented them in the summer of 1847 for his doctoral thesis at the University of Edinburgh. Scottish obstetrician James Young Simpson was one of the men required to read the thesis, but later claimed he never read it. thesis and arrived at its own conclusions independently.
On 4 November 1847, Simpson first discovered the anesthetic properties of chloroform on humans. He and two of his colleagues were entertaining themselves by testing the effects of various substances, and thus discovered the potential of chloroform in medical procedures. [25]
A few days later, during a dental procedure in Edinburgh, Francis Brody Emlach became the first person to use chloroform on a patient in a clinical context. [37]
In May 1848, Robert Holliday Gunning made a presentation to the Medico-Chirsurgical Society of Edinburgh after a series of laboratory experiments on rabbits, which confirmed Glover’s findings and also refuted Simpson’s claims of originality. However, the knighthood for Simpson and the widespread media coverage of the wonders of chloroform ensured that Simpson’s reputation remained high, while laboratory experiments proving the dangers of chloroform were largely ignored. Gunning, who went on to become one of Britain’s richest men, awarded some 13 university scholarships to other scientists instead of his own name. He considered Simpson a charlatan, but one of these awards is named the Simpson Prize for Obstetrics. Although, this is probably a strange counter-compliment, Because arguably any Simpson Award should be an award for anesthesia in the eyes of the wider public. By not calling it quits, he effectively rebuffed Simpson, while at the same time appearing to honor him.[38]
After this, the use of chloroform during surgery increased rapidly in Europe. In the 1850s, chloroform was used by physician John Snow during the birth of Queen Victoria’s last two children. [39] In the United States, chloroform began to replace ether as an anesthetic in the early 20th century; However, it was quickly abandoned in favor of ether upon discovery of its toxicity, particularly its tendency to cause fatal cardiac arrhythmias now known as “sudden detectable death”. Some people have used chloroform as a recreational drug or to attempt suicide. [40] One possible mechanism of action of chloroform is that it increases the movement of potassium ions through certain types of potassium channels in nerve cells. [41]Chloroform can also be mixed with other anesthetic agents such as ether to form a CE mixture, or ether and alcohol to form an ACE mixture.
In 1848, Hannah Greiner, a 15-year-old girl who was removing an infected toenail, died after being given an anesthetic. [42] His autopsy, which established the cause of death, was performed by John Fife with the assistance of Robert Mortimer Glover. [24] Many physically healthy patients died after inhalation. However, in 1848 John Snow developed an inhaler that controlled the dosage and thus successfully reduced the number of deaths. [43]
Opponents and supporters of chloroform mainly disagreed over the question of whether complications were due to respiratory disturbances alone or whether chloroforms had a specific effect on the heart. Several commissions in Britain studied chloroforms between 1864 and 1910, but failed to reach any clear conclusions. It was only in 1911 that Levi proved in experiments with animals that chloroform could cause cardiac fibrillation. Reservations about chloroforms could not stop its growing popularity. Between about 1865 and 1920, chloroform was used in 80 to 95% of narcotics made in the UK and German-speaking countries. In the US, however, there was less enthusiasm for chloroform intoxication. In Germany, the first comprehensive survey of mortality during anesthesia was conducted by Gerlt between 1890 and 1897. In 1934, Killian gathered all the data collected by then and found that the probability of suffering fatal complications under ether was between 1:14,000 and 1:28,000, while under chloroform the probability was between 1:3,000 and 1:6,000. Was. The rise of gas anesthesia using nitrous oxide, improved equipment for administering anesthetics, and the discovery of hexobarbital in 1932 led to a gradual decline in chloroform narcosis.[44]
criminal use
Chloroform is also used by criminals to chase, dodge or even murder victims of murder. Joseph Harris was accused of using chloroform to rob people in 1894. [45] Serial killer H. H. Holmes used chloroform overdose to kill his female victims. In September 1900, chloroform was implicated in the murder of American businessman William Marsh Rice at what is now known as Rice University. Chloroform was thought to be a factor in the alleged murder of a woman in 1991, when she suffocated while sleeping. [46] In a 2007 plea deal, a man confessed to using stun guns and chloroform to sexually assault minors. [47]
The use of chloroform as a disabling agent has become widely recognized, bordering on clichés, due to the popularity of crime fiction writers with criminals using rags soaked with chloroform to sedate victims. However, it is nearly impossible to disable someone using chloroform in this way. [48]It takes at least five minutes to inhale an object soaked in chloroform to make a person unconscious. Most criminal cases involving chloroform have also involved co-administration of another drug, such as alcohol or diazepam, or the victim was found to be complicit in its administration. After a person has lost consciousness due to chloroform inhalation, a constant volume must be administered and the chin supported to prevent the tongue from obstructing the airway, a difficult procedure usually requiring the skill of an anesthesiologist. it occurs . As a direct result of chloroform’s criminal reputation in 1865, the medical journal The Lancet offered “permanent scientific reputation” to anyone who could demonstrate “immediate insensitivity”,[49]
Security
Infection
Chloroform is known to be a by-product of chlorination of water 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 greatly but are generally below the current health standard for total trihalomethane of 100μg/L. [50] Nevertheless, the presence of chloroform in any concentration in drinking water is considered controversial by some.
As an anesthetic, as an ingredient in cough syrups, and as a component of tobacco smoke, where DDT was previously used as a fumigant, historically chloroform exposure may well have been higher. Is . [51]
Medicine
It is well absorbed, metabolized, and rapidly eliminated by mammals following oral, inhalation, or cutaneous exposure. Irritation due to accidental splash in eyes. [14] Prolonged dermal exposure may result in the development of lesions as a result of defatting. Elimination occurs mainly from the lungs in the form of chloroform and carbon dioxide; Less than 1% is excreted in the urine. [33]
Chloroform is metabolized in the liver by cytochrome P-450 enzymes, by oxidation to chloromethanol and by reduction to dichloromethyl free radicals. Other metabolites of chloroform include hydrochloric acid and diglutionyl dithiocarbonate, with carbon dioxide as the major end product of metabolism. [52]
Like most other general anesthetics and sedative-hypnotic drugs, chloroforms is a positive allosteric modulator for the GABA A receptor. [53] Chloroform causes depression of the central nervous system (CNS), eventually leading to deep coma and respiratory center depression. [52] When ingested, symptoms similar to those seen after inhaling chloroform. Serious illness has occurred after ingestion of 7.5 grams (0.26 oz). The average lethal oral dose for an adult is estimated at about 45 grams (1.6 oz). [14]
The anesthetic use of chloroforms has been discontinued because it has led to death due to respiratory failure and cardiac arrhythmias. Following chloroform-induced anesthesia, some patients experienced nausea, vomiting, hyperthermia, jaundice and coma due to hepatic dysfunction. At autopsy, hepatic necrosis and degeneration have been observed. [14]
Chloroform has induced liver tumors in rats and kidney tumors in rats and mice. [14] The hepatotoxicity and nephrotoxicity of chloroform are thought to be largely due to phosgene. [52]
conversion to phosgene
Chloroform slowly converts into the highly toxic phosgene (COCl 2 ) in the air, releasing HCl in the process.
2 CHCl 3 + O 2 → 2 CoCl 2 + 2 HCl
To prevent accidents, commercial chloroform is stabilized with ethanol or amylin, but samples that have been recovered or dried now contain no stabilizer. Amylin has been found to be ineffective, and may affect analysis in samples, lipids and nucleic acids dissolved or removed with phosgene chloroform. [55] Phosphine and HCl can be removed from chloroform by washing with a solution of saturated aqueous carbonate such as sodium bicarbonate. This process is simple and results in harmless products. Phosgene reacts with water to form carbon dioxide and HCl, [56] and the carbonate salt neutralizes the resulting acid.
Suspicious samples can be tested for phosgene by 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
According to the International Agency for Research on Cancer (IARC) monograph, chloroform is suspected to be carcinogenic (ie, possibly carcinogenic, IARC group 2B). [PDF]
It is classified as an extremely hazardous substance in the United States, as defined in section 302 of the US Emergency Planning and Community Right-to-Know Act (42 USC 11002), and by facilities that produce, store Subject to strict reporting requirements. Or use it in significant amounts. [57]
Bioremediation of Chloroform
Some anaerobic bacteria use chloroform for their respiration, called organohalide respiration, converting it to dichloromethane.
