Chloroform
Chloroform, or trichloromethane, is an organochloride with the formula and a common solvent. It is a volatile, colorless, sweet-smelling, dense liquid produced on a large scale as a precursor to refrigerants and polytetrafluoroethylene. Chloroform was once used as an inhalational anesthetic between the 19th century and the first half of the 20th century. It is miscible with many solvents but it is only very slightly soluble in water.
Structure and name
The molecule adopts a tetrahedral molecular geometry with C3v symmetry. The chloroform molecule can be viewed as a methane molecule with three hydrogen atoms replaced with three chlorine atoms, leaving a single hydrogen atom.The name "chloroform" is a portmanteau of terchloride and formyle, an obsolete name for the methylylidene radical derived from formic acid.
Natural occurrence
Many kinds of seaweed produce chloroform, and fungi are believed to produce chloroform in soil. Abiotic processes are also believed to contribute to natural chloroform productions in soils, although the mechanism is still unclear.History
Chloroform was synthesized independently by several investigators :- Moldenhawer, 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 Chloräther.
- Samuel Guthrie, a U.S. physician from Sackets Harbor, New York, also appears to have produced chloroform in 1831 by reacting chlorinated lime with ethanol, and noted its anaesthetic properties; however, he also believed that he had prepared chloric ether.
- Justus von Liebig carried out the alkaline cleavage of chloral. Liebig incorrectly states that the empirical formula of chloroform was and named it "Chlorkohlenstoff".
- Eugène Soubeiran obtained the compound by the action of chlorine bleach on both ethanol and acetone.
In 1835, Dumas prepared the substance by alkaline cleavage of trichloroacetic acid.
In 1842, Robert Mortimer Glover in London discovered the anaesthetic qualities of chloroform on laboratory animals.
In 1847, Scottish obstetrician James Y. Simpson was the first to demonstrate the anaesthetic properties of chloroform in humans, and helped to popularize the drug for use in medicine.
The application of chloroform remained dangerous, and many deaths occurred through accidental overdose. In 1848, John Snow developed an inhaler that regulated the dosage.
By the 1850s, chloroform was being produced on a commercial basis. An apparatus that could apply it safely and controllably was invented by Joseph Thomas Clover in 1862.
In Britain, about 750,000 doses a week were being produced by 1895, using the Liebig procedure, which retained its importance until the 1960s. Today, chloroform – along with dichloromethane – is prepared exclusively and on a massive scale by the chlorination of methane and chloromethane.
Production
Industrially, chloroform is produced by heating a mixture of chlorine and either methyl chloride or methane. At 400–500 °C, free radical halogenation occurs, converting these precursors to progressively more chlorinated compounds:Chloroform undergoes further chlorination to yield carbon tetrachloride :
The output of this process is a mixture of the four chloromethanes: chloromethane, methylene chloride, trichloromethane, and tetrachloromethane. These can then be separated by distillation.
Chloroform may also be produced on a small scale via the haloform reaction between acetone and sodium hypochlorite:
Deuterochloroform
is an isotopologue of chloroform with a single deuterium atom. is a common solvent used in NMR spectroscopy. Deuterochloroform is produced by the reaction of hexachloroacetone with heavy water. The haloform process is now obsolete for production of ordinary chloroform. Deuterochloroform can also be prepared by reacting sodium deuteroxide with chloral hydrate.Inadvertent formation of chloroform
The haloform reaction can also occur inadvertently in domestic settings. Sodium hypochlorite solution 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, a precursor in the production of polytetrafluoroethylene and other fluoropolymers:The reaction is conducted in the presence of a catalytic amount of mixed antimony halides. Chlorodifluoromethane is then converted to tetrafluoroethylene, the main precursor of Teflon.
Solvent
The hydrogen attached to carbon in chloroform participates in hydrogen bonding, making it a good solvent for many materials.Worldwide, chloroform is also used in pesticide formulations, as a solvent for lipids, rubber, alkaloids, waxes, gutta-percha, and resins, as a cleaning agent, as a grain fumigant, in fire extinguishers, and in the rubber industry. deuterated chloroform| is a common solvent used in NMR spectroscopy.
Refrigerant
Chloroform is used as a precursor to make R-22. This is done by reacting it with hydrofluoric acid which fluorinates the molecule and releases hydrochloric acid as a byproduct. Before the Montreal Protocol was enforced, most of the chloroform produced in the United States was used in the production of chlorodifluoromethane. However, its production remains high, as it is a key precursor of PTFE.Although chloroform has properties such as a low boiling point, and a low global warming potential of only 31, which are appealing properties for a refrigerant, there is little information to suggest that it has seen widespread use as a refrigerant in any consumer products.
Lewis acid
In solvents such as and alkanes, chloroform hydrogen bonds to a variety of Lewis bases. 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 intermediate. It reacts with aqueous sodium hydroxide, usually in the presence of a phase transfer catalyst, to produce dichlorocarbene,. 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 free radical which adds to alkenes.Anaesthetic
Chloroform is a powerful general anesthetic, euphoriant, anxiolytic, and sedative when inhaled or ingested. 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, refined his theories, and presented them in his doctoral thesis at the University of Edinburgh in the summer of 1847, identifying anaesthetizing halogenous compounds as a "new order of poisonous substances".The Scottish James Young Simpson, an obstetrician, was one of those examiners required to read the thesis, but later claimed to have never read it and to have come to his own conclusions independently. Perkins-McVey, among others, have raised doubts about the credibility of Simpson's claim, noting that Simpson's publications on the subject in 1847 explicitly echo Glover's and, being one of the thesis examiners, Simpson was likely aware of the content of Glover's study, even if he skirted his duties as an examiner. In 1847 and 1848, Glover would pen a series of heated letters accusing Simpson of stealing his discovery, which had already earned Simpson considerable notoriety. Whatever the source of his inspiration, on 4 November 1847, Simpson argued that he had discovered the anaesthetic qualities of chloroform in humans. He and two colleagues entertained themselves by trying the effects of various substances, and thus revealed the potential for chloroform in medical procedures.
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.
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. The laboratory experiments that proved the dangers of chloroform were largely ignored.
The use of chloroform during surgery expanded rapidly in Europe; for instance in the 1850s chloroform was used by the physician John Snow during the births of Queen Victoria's last two children Leopold and Beatrice. In the United States, chloroform began to replace ether as an anesthetic at the beginning of the 20th century; it was abandoned in favor of ether on discovery of its toxicity, especially its tendency to cause fatal cardiac arrhythmias analogous to what is now termed "sudden sniffer's death". Some people used chloroform as a recreational drug or to attempt suicide. 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. 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 anaesthetic. Her autopsy establishing the cause of death was undertaken by John Fife assisted by Robert Mortimer Glover. A number of physically fit patients died after inhaling it. In 1848, however, John Snow developed an inhaler that regulated the dosage and so successfully reduced the number of deaths. Joseph Thomas Clover improved on the design in 1862, further reducing the risk of accidental overdose.
The opponents and supporters of chloroform disagreed on the question of whether the medical complications were 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 ventricular fibrillation. Despite this, between 1865 and 1920, chloroform was used in 80 to 95% of all narcoses performed in the UK and German-speaking countries. In Germany, comprehensive surveys of the fatality rate during anaesthesia were made by Gurlt between 1890 and 1897. At the same time in the UK the medical journal The Lancet carried out a questionnaire survey and compiled a report detailing numerous adverse reactions to anesthetics, including chloroform. 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 with chloroform the chances were between 1:3,000 and 1:6,000. The rise of gas anaesthesia using nitrous oxide, improved equipment for administering anesthetics, and the discovery of hexobarbital in 1932 led to the gradual decline of chloroform narcosis.
The latest reported anaesthetic use of chloroform in the Western world dates to 1987, when the last doctor who used it retired, about 140 years after its first use.