In
chemistry
Chemistry is the scientific study of the properties and behavior of matter. It is a natural science that covers the elements that make up matter to the compounds made of atoms, molecules and ions: their composition, structure, proper ...
, the haloform reaction is a
chemical reaction
A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking ...
in which a
haloform (, where X is a
halogen
The halogens () are a group in the periodic table consisting of five or six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), astatine (At), and tennessine (Ts). In the modern IUPAC nomenclature, this grou ...
) is produced by the exhaustive
halogenation
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 ...
of an
acetyl group
In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl, ...
(, where R can be either a hydrogen atom, an
alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloa ...
or an
aryl group), in the presence of a
base.
The reaction can be used to transform acetyl groups into
carboxyl group
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
s () or to produce
chloroform
Chloroform, or trichloromethane, is an organic compound with formula C H Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE. It is also a precursor to various ...
(),
bromoform
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, ...
(), or
iodoform
Iodoform (also known as triiodomethane and, inaccurately, as carbon triiodide) is the organoiodine compound with the chemical formula C H I3. A pale yellow, crystalline, volatile substance, it has a penetrating and distinctive odor (in older ch ...
(). Note that
fluoroform () can't be prepared in this way.
Mechanism
In the first step, the halogen dis-proportionates in the presence of
hydroxide
Hydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and hydrogen atom held together by a single covalent bond, and carries a negative electric charge. It is an important but usually minor constituent of water. ...
to give the halide and hypohalite.
:
Br2 + 2 OH- -> Br- + BrO- + H2O
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 being the
leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited ...
stabilized by three
electron-withdrawing group
In chemistry, an electron-withdrawing group (EWG) is a substituent that has some of the following kinetic and thermodynamic implications:
*with regards to electron transfer, electron-withdrawing groups enhance the oxidizing power tendency of the ...
s. In the third step the 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
Chloral hydrate is a geminal diol with the formula . 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 (trichl ...
) the reaction may stop and the intermediate product isolated if conditions are acidic and hypohalite is used.
:
Scope
Substrates are broadly limited to methyl ketones and secondary
alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
s oxidizable to methyl ketones, such as
isopropanol
Isopropyl alcohol (IUPAC name propan-2-ol and also called isopropanol or 2-propanol) is a colorless, flammable organic compound with a pungent alcoholic odor. As an isopropyl group linked to a hydroxyl group (chemical formula ) it is the sim ...
. The only primary alcohol and
aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl gro ...
to undergo this reaction are
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
and
acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the ...
, respectively. 1,3-Diketones such as
acetylacetone
Acetylacetone is an organic compound with the chemical formula . It is a colorless liquid, classified as a 1,3-diketone. It exists in equilibrium with a tautomer . These tautomers interconvert so rapidly under most conditions that they are tre ...
also give the haloform reaction. β-ketoacids such as
acetoacetic acid
Acetoacetic acid (also acetoacetate and diacetic acid) is the organic compound with the formula CHCOCHCOOH. It is the simplest beta-keto acid, and like other members of this class, it is unstable. The methyl and ethyl esters, which are quite sta ...
will also give the test upon heating. Acetyl chloride and acetamide don't give this test. The halogen used may be
chlorine
Chlorine is a chemical element with the symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate between them. Chlorine i ...
,
bromine
Bromine is a chemical element with the symbol Br and atomic number 35. It is the third-lightest element in group 17 of the periodic table ( halogens) and is a volatile red-brown liquid at room temperature that evaporates readily to form a simi ...
,
iodine
Iodine is a chemical element with the Symbol (chemistry), 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 , ...
or
sodium hypochlorite
Sodium hypochlorite (commonly known in a dilute solution as bleach) is an inorganic chemical compound with the formula NaOCl (or NaClO), comprising a sodium cation () and a hypochlorite anion (or ). It may also be viewed as the sodium s ...
.
Fluoroform (CHF
3) cannot be prepared by this method as it would require the presence of the highly unstable
hypofluorite ion. However ketones with the structure RCOCF
3 do cleave upon treatment with base to produce fluoroform; this is equivalent to the second and third steps in the process shown above.
Applications
Laboratory scale
This reaction forms the basis of the iodoform test which was commonly used in history as a
chemical test
In chemistry, a chemical test is a qualitative or quantitative procedure designed to identify, quantify, or characterise a chemical compound or chemical group.
Purposes
Chemical testing might have a variety of purposes, such as to:
* Determine ...
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
Iodoform (also known as triiodomethane and, inaccurately, as carbon triiodide) is the organoiodine compound with the chemical formula C H I3. A pale yellow, crystalline, volatile substance, it has a penetrating and distinctive odor (in older ch ...
, which is a solid at room temperature and tends to precipitate out of solution causing a distinctive cloudiness.
In
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J ...
, this reaction may be used to convert a terminal methyl ketone into the analogous carboxylic acid.
Industrially
It was formerly used to produce iodoform, bromoform, and even chloroform industrially.
As a by-product of water chlorination
Water chlorination
Water chlorination is the process of adding chlorine or chlorine compounds such as sodium hypochlorite to water. This method is used to kill bacteria, viruses and other microbes in water. In particular, chlorination is used to prevent the spr ...
can result in the formation of haloforms if the water contains suitable reactive impurities (e.g.
humic acid Humic substances (HS) are organic compounds that are important components of humus, the major organic fraction of soil, peat, and coal (and also a constituent of many upland streams, dystrophic lakes, and ocean water). For a long era in the 19th an ...
).
There is a concern that such reactions may lead to the presence of carcinogenic compounds in drinking water.
History
The haloform reaction is one of the oldest
organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical ...
s known. In 1822,
Georges-Simon Serullas added potassium metal to a solution of
iodine
Iodine is a chemical element with the Symbol (chemistry), 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 , ...
in
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
and water to form potassium formate and iodoform, called in the language of that time ''hydroiodide of carbon''. In 1832,
Justus von Liebig
Justus Freiherr von Liebig (12 May 1803 – 20 April 1873) was a German scientist who made major contributions to agricultural and biological chemistry, and is considered one of the principal founders of organic chemistry. As a professor at th ...
reported the reaction of
chloral
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 ...
with
calcium hydroxide
Calcium hydroxide (traditionally called slaked lime) is an inorganic compound with the chemical formula Ca( OH)2. It is a colorless crystal or white powder and is produced when quicklime (calcium oxide) is mixed or slaked with water. It has ma ...
to form chloroform and calcium formate. The reaction was rediscovered by
Adolf Lieben
Adolf Lieben (3 December 1836 – 6 June 1914) was an Austrian Jewish chemist. He was born in Vienna the son of Ignatz Lieben. He studied at the University of Vienna, University of Heidelberg (Ph.D. 1856 with Robert Wilhelm Bunsen), and Pari ...
in 1870.
[See:
*
* ] The iodoform test is also called the Lieben haloform reaction. A review of the haloform reaction with a history section was published in 1934.
References
{{Reflist, 2
Organic redox reactions
Carbon-heteroatom bond forming reactions
Halogenation reactions