Haloform reaction | |
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Named after | Adolf Lieben |
Reaction type | Substitution reaction |
Identifiers | |
Organic Chemistry Portal | haloform-reaction |
RSC ontology ID | RXNO:0000689 |
In chemistry, the haloform reaction is a chemical reaction in which a haloform (CHX3, where X is a halogen) is produced by the exhaustive halogenation of an acetyl group (R−C(=O)CH3, where R can be either a hydrogen atom, an alkyl or an aryl group), in the presence of a base. [1] [2] [3] The reaction can be used to transform acetyl groups into carboxyl groups (R−C(=O)OH) or to produce chloroform (CHCl3), bromoform (CHBr3), or iodoform (CHI3). Note that fluoroform (CHF3) can't be prepared in this way.
In the first step, the halogen dis-proportionates in the presence of hydroxide to give the halide and hypohalite.
If a secondary alcohol is present, it is oxidized to a ketone by the hypohalite:
If a methyl ketone is present, it reacts with the hypohalite in a three-step process:
1. Under basic conditions, the ketone undergoes keto-enol tautomerisation. The enolate undergoes electrophilic attack by the hypohalite (containing a halogen with a formal +1 charge).
2. When the α(alpha) position has been exhaustively halogenated, the molecule undergoes a nucleophilic acyl substitution by hydroxide, with −CX3 being the leaving group stabilized by three electron-withdrawing groups. In the third step the −CX3 anion abstracts a proton from either the solvent or the carboxylic acid formed in the previous step, and forms the haloform. At least in some cases (chloral hydrate) the reaction may stop and the intermediate product isolated if conditions are acidic and hypohalite is used.
Substrates are broadly limited to methyl ketones and secondary alcohols oxidizable to methyl ketones, such as isopropanol. The only primary alcohol and aldehyde to undergo this reaction are ethanol and acetaldehyde, respectively. 1,3-Diketones such as acetylacetone also give the haloform reaction. β-ketoacids such as acetoacetic acid will also give the test upon heating. Acetyl chloride and acetamide don't give this test. The halogen used may be chlorine, bromine, iodine or sodium hypochlorite. [4] Fluoroform (CHF3) cannot be prepared by this method as it would require the presence of the highly unstable hypofluorite ion. However ketones with the structure RCOCF3 do cleave upon treatment with base to produce fluoroform; this is equivalent to the second and third steps in the process shown above.
This reaction forms the basis of the iodoform test which was commonly used in history as a chemical test to determine the presence of a methyl ketone, or a secondary alcohol oxidizable to a methyl ketone. When iodine and sodium hydroxide are used as the reagents a positive reaction gives iodoform, which is a solid at room temperature and tends to precipitate out of solution causing a distinctive cloudiness.
In organic chemistry, this reaction may be used to convert a terminal methyl ketone into the analogous carboxylic acid.
It was formerly used to produce iodoform, bromoform, and even chloroform industrially.[ citation needed ]
Water chlorination can result in the formation of haloforms if the water contains suitable reactive impurities (e.g. humic acid). [5] [6] There is a concern that such reactions may lead to the presence of carcinogenic compounds in drinking water. [7]
The haloform reaction is one of the oldest organic reactions known. [8] In 1822, Georges-Simon Serullas added potassium metal to a solution of iodine in ethanol and water to form potassium formate and iodoform, called in the language of that time hydroiodide of carbon. [9] In 1832, Justus von Liebig reported the reaction of chloral with calcium hydroxide to form chloroform and calcium formate. [10] The reaction was rediscovered by Adolf Lieben in 1870. [11] The iodoform test is also called the Lieben haloform reaction. A review of the haloform reaction with a history section was published in 1934. [2]
Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at 114 °C (237 °F), and boils to a violet gas at 184 °C (363 °F). The element was discovered by the French chemist Bernard Courtois in 1811 and was named two years later by Joseph Louis Gay-Lussac, after the Ancient Greek Ιώδης 'violet-coloured'.
The haloalkanes are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely used commercially. They are used as flame retardants, fire extinguishants, refrigerants, propellants, solvents, and pharmaceuticals. Subsequent to the widespread use in commerce, many halocarbons have also been shown to be serious pollutants and toxins. For example, the chlorofluorocarbons have been shown to lead to ozone depletion. Methyl bromide is a controversial fumigant. Only haloalkanes that contain chlorine, bromine, and iodine are a threat to the ozone layer, but fluorinated volatile haloalkanes in theory may have activity as greenhouse gases. Methyl iodide, a naturally occurring substance, however, does not have ozone-depleting properties and the United States Environmental Protection Agency has designated the compound a non-ozone layer depleter. For more information, see Halomethane. Haloalkane or alkyl halides are the compounds which have the general formula "RX" where R is an alkyl or substituted alkyl group and X is a halogen.
Chloroform, or trichloromethane (often abbreviated as TCM), is an organic compound with the formula CHCl3 and a common organic solvent. It is a very volatile, colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE and refrigerants and is a trihalomethane that serves as a powerful anesthetic, euphoriant, anxiolytic, and sedative when inhaled or ingested. Chloroform was frequently used as an anaesthetic between 1847 and the first half of the 20th century. It is also part of a wider class of substances known as volatile organic compounds. Chloroform is miscible with many solvents but it is only very slightly soluble in water (only 8 g/L at 20 °C).
Chloral hydrate is a geminal diol with the formula C2H3Cl3O2. It is a colorless solid. It has limited use as a sedative and hypnotic pharmaceutical drug. It is also a useful laboratory chemical reagent and precursor. It is derived from chloral (trichloroacetaldehyde) by the addition of one equivalent of water.
Iodoform (also known as triiodomethane and, inaccurately, as carbon triiodide) is the organoiodine compound with the chemical formula CHI3. A pale yellow, crystalline, volatile substance, it has a penetrating and distinctive odor (in older chemistry texts, the smell is sometimes referred to as that of hospitals, where the compound is still commonly used) and, analogous to chloroform, sweetish taste. It is occasionally used as a disinfectant.
In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, drugs. This kind of conversion is in fact so common that a comprehensive overview is challenging. This article mainly deals with halogenation using elemental halogens (F2, Cl2, Br2, I2). Halides are also commonly introduced using salts of the halides and halogen acids. Many specialized reagents exist for and introducing halogens into diverse substrates, e.g. thionyl chloride.
Bromoform (CHBr3) is a brominated organic solvent, colorless liquid at room temperature, with a high refractive index, very high density, and sweet odor is similar to that of chloroform. It is one of the four haloforms, the others being fluoroform, chloroform, and iodoform. Currently its main use is as a laboratory reagent. It is soluble in about 800 parts water and is miscible with alcohol, benzene, chloroform, ether, petroleum ether, acetone and oils.
In chemistry, trihalomethanes (THMs) are chemical compounds in which three of the four hydrogen atoms of methane are replaced by halogen atoms. Many trihalomethanes find uses in industry as solvents or refrigerants. THMs are also environmental pollutants, and many are considered carcinogenic. Trihalomethanes with all the same halogen atoms are called haloforms.
In chemistry, a chemical test is a qualitative or quantitative procedure designed to identify, quantify, or characterise a chemical compound or chemical group.
In organic chemistry, α-keto halogenation is a special type of halogenation. The reaction may be carried out under either acidic or basic conditions in an aqueous medium with the corresponding elemental halogen. In this way, chloride, bromide, and iodide functionality can be inserted selectively in the alpha position of a ketone.
Chloral, also known as trichloroacetaldehyde or trichloroethanal, is the organic compound with the formula Cl3CCHO. This aldehyde is a colourless oily liquid that is soluble in a wide range of solvents. It reacts with water to form chloral hydrate, a once widely used sedative and hypnotic substance.
Bromoacetone is an organic compound with the formula CH3COCH2Br. It is a colorless liquid although impure samples appear yellow or even brown. It is a lachrymatory agent and a precursor to other organic compounds.
The Favorskii rearrangement is principally a rearrangement of cyclopropanones and α-halo ketones that leads to carboxylic acid derivatives. In the case of cyclic α-halo ketones, the Favorskii rearrangement constitutes a ring contraction. This rearrangement takes place in the presence of a base, sometimes hydroxide, to yield a carboxylic acid but most of the time either an alkoxide base or an amine to yield an ester or an amide, respectively. α,α'-Dihaloketones eliminate HX under the reaction conditions to give α,β-unsaturated carbonyl compounds.
The benzilic acid rearrangement is formally the 1,2-rearrangement of 1,2-diketones to form α-hydroxy–carboxylic acids using a base. This reaction receives its name from the reaction of benzil with potassium hydroxide to form benzilic acid. First performed by Justus von Liebig in 1838, it is the first reported example of a rearrangement reaction. It has become a classic reaction in organic synthesis and has been reviewed many times before. It can be viewed as an intramolecular redox reaction, as one carbon center is oxidized while the other is reduced.
Bromine compounds are compounds containing the element bromine (Br). These compounds usually form the -1, +1, +3 and +5 oxidation states. Bromine is intermediate in reactivity between chlorine and iodine, and is one of the most reactive elements. Bond energies to bromine tend to be lower than those to chlorine but higher than those to iodine, and bromine is a weaker oxidising agent than chlorine but a stronger one than iodine. This can be seen from the standard electrode potentials of the X2/X− couples (F, +2.866 V; Cl, +1.395 V; Br, +1.087 V; I, +0.615 V; At, approximately +0.3 V). Bromination often leads to higher oxidation states than iodination but lower or equal oxidation states to chlorination. Bromine tends to react with compounds including M–M, M–H, or M–C bonds to form M–Br bonds.
Iodine can form compounds using multiple oxidation states. Iodine is quite reactive, but it is much less reactive than the other halogens. For example, while chlorine gas will halogenate carbon monoxide, nitric oxide, and sulfur dioxide, iodine will not do so. Furthermore, iodination of metals tends to result in lower oxidation states than chlorination or bromination; for example, rhenium metal reacts with chlorine to form rhenium hexachloride, but with bromine it forms only rhenium pentabromide and iodine can achieve only rhenium tetraiodide. By the same token, however, since iodine has the lowest ionisation energy among the halogens and is the most easily oxidised of them, it has a more significant cationic chemistry and its higher oxidation states are rather more stable than those of bromine and chlorine, for example in iodine heptafluoride.
Organoiodine compounds are organic compounds that contain one or more carbon–iodine bonds. They occur widely in organic chemistry, but are relatively rare in nature. The thyroxine hormones are organoiodine compounds that are required for health and the reason for government-mandated iodization of salt.
Radical theory is an obsolete scientific theory in chemistry describing the structure of organic compounds. The theory was pioneered by Justus von Liebig, Friedrich Wöhler and Auguste Laurent around 1830 and is not related to the modern understanding of free radicals. In this theory, organic compounds were thought to exist as combinations of radicals that could be exchanged in chemical reactions just as chemical elements could be interchanged in inorganic compounds.
Georges-Simon Serullas was a professor of pharmacy notable for being the first to publish a work on Iodoform, an early antiseptic and disinfectant.
Acetyl hypochlorite, also known as chlorine acetate, is a chemical compound with the formula CH3COOCl. It is a photosensitive colorless liquid that is a short lived intermediate in the Hunsdiecker reaction.