In organic chemistry a halohydrin (also a haloalcohol or β-halo alcohol) is a
functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...
in which 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 ...
and a
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
are bonded to adjacent
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon makes u ...
atoms, which otherwise bear only hydrogen or
hydrocarbyl groups (e.g.
2-chloroethanol
2-Chloroethanol (also called ethylene chlorohydrin or glycol chlorohydrin) is an organic chemical compound with the chemical formula HOCH2CH2Cl and the ''simplest'' beta-halohydrin (chlorohydrin). This colorless liquid has a pleasant ether-like od ...
,
3-chloropropane-1,2-diol). The term only applies to saturated motifs, as such compounds like
2-chlorophenol would not normally be considered halohydrins. Megatons of some chlorohydrins, e.g.
propylene chlorohydrin, are produced annually as precursors to polymers.
Halohydrins may be categorized as chlorohydrins, bromohydrins, fluorohydrins or iodohydrins depending on the halogen present.
Synthesis
From alkenes
Halohydrins are usually prepared by treatment of an
alkene
In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond.
Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
with a halogen, in the presence of water.
The reaction is a form of
electrophilic addition, similar to the
halogen addition reaction A halogen addition reaction is a simple organic reaction where a halogen molecule is added to the carbon–carbon double bond of an alkene functional group.
The general chemical formula of the halogen addition reaction is:
:C=C + X2 → X−C−C ...
and proceeds with
anti addition, leaving the newly added X and OH groups in a
trans configuration. The chemical equation for the conversion of ethylene to ethylene chlorohydrin is:
:H
2C=CH
2 + Cl
2 + H
2O → H
2(OH)C-CH
2Cl + HCl
When bromination is desired,
''N''-bromosuccinimide (NBS) can be preferable to
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 simil ...
because fewer side-products are produced.
From epoxides
Halohydrins may also be prepared from the reaction of an
epoxide
In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale f ...
with a
hydrohalic acid
In chemistry, hydrogen halides (hydrohalic acids when in the aqueous phase) are diatomic, inorganic compounds that function as Arrhenius acids. The formula is HX where X is one of the halogens: fluorine, chlorine, bromine, iodine, or astatine. A ...
, or a metal halide.
This reaction is produced on an industrial scale for the production of chlorohydrin precursors to two important epoxides,
epichlorohydrin
Epichlorohydrin (abbreviated ECH) is an organochlorine compound and an epoxide. Despite its name, it is not a halohydrin. It is a colorless liquid with a pungent, garlic-like odor, moderately soluble in water, but miscible with most polar orga ...
and
propylene oxide
Propylene oxide is an acutely toxic and carcinogenic organic compound with the molecular formula CH3CHCH2O. This colourless volatile liquid with an odour similar to ether, is produced on a large scale industrially. Its major application is its us ...
. At one time,
2-chloroethanol
2-Chloroethanol (also called ethylene chlorohydrin or glycol chlorohydrin) is an organic chemical compound with the chemical formula HOCH2CH2Cl and the ''simplest'' beta-halohydrin (chlorohydrin). This colorless liquid has a pleasant ether-like od ...
was produced on a large scale as a precursor to
ethylene oxide
Ethylene oxide is an organic compound with the formula . It is a cyclic ether and the simplest epoxide: a three-membered ring consisting of one oxygen atom and two carbon atoms. Ethylene oxide is a colorless and flammable gas with a faintly sw ...
, but the latter is now prepared by the direct oxidation of ethylene.
From 2-chloro acids
2-Chlorocarboxylic acids can be reduced with
lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic ...
to the 2-chloroalcohols. The required 2-chlorocarboxylic acids are obtained in a variety of ways, including the
Hell–Volhard–Zelinsky halogenation
The Hell–Volhard–Zelinsky halogenation reaction is a chemical transformation that involves the halogenation of a carboxylic acid at the α carbon. For this reaction to occur the α carbon must bear at least one proton. The reaction is named a ...
.
2-Chloropropionic acid is produced by chlorination of
propionyl chloride
Propionyl chloride (also propanoyl chloride) is the organic compound with the formula CH3CH2C(O)Cl. It is the acyl chloride derivative of propionic acid. It undergoes the characteristic reactions of acyl chlorides. It is a colorless, corrosive, v ...
followed by hydrolysis of the 2-chloropropionyl chloride.
Enantiomerically
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...
pure (''S'')-2-chloropropionic acid and several related compounds can be prepared from amino acids via
diazotization
Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide.
General properti ...
.
Reactions
In presence of a base halohydrins undergo internal
SN2 reaction to form
epoxide
In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale f ...
s. Industrially, the base is
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 m ...
, whereas in the laboratory, potassium hydroxide is often used.
This reaction is the reverse of the formation reaction from an
epoxide
In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale f ...
and can be considered a variant of the
Williamson ether synthesis
The Williamson ether synthesis is an organic reaction, forming an ether from an organohalide and a deprotonated alcohol (alkoxide). This reaction was developed by Alexander Williamson in 1850. Typically it involves the reaction of an alkoxide io ...
. Most of the world's supply of
propylene oxide
Propylene oxide is an acutely toxic and carcinogenic organic compound with the molecular formula CH3CHCH2O. This colourless volatile liquid with an odour similar to ether, is produced on a large scale industrially. Its major application is its us ...
arises via this route.
[Dietmar Kahlich, Uwe Wiechern, Jörg Lindner "Propylene Oxide" in Ullmann's Encyclopedia of Industrial Chemistry, 2002 by Wiley-VCH, Weinheim. Article Online Posting Date: June 15, 2000]
Such reactions can form the basis of more complicated processes, for example epoxide formation is one of the key steps in the
Darzens reaction.
Halogenated halohydrin
Compounds such as
2,2,2-trichloroethanol, which contain multiple
geminal
In chemistry, the descriptor geminal () refers to the relationship between two atoms or functional groups that are attached to the same atom. A geminal diol, for example, is a diol (a molecule that has two alcohol functional groups) attached to ...
halogens adjacent to a hydroxyl group may be considered halohydrins (although, strictly speaking, they fail the
IUPAC
The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...
definition) as they possess similar chemistry. In particular they also undergo intramolecular cyclisation to form dihaloepoxy groups. These species are both highly reactive and synthetically useful, forming the basis of the
Jocic–Reeve reaction,
Bargellini reaction and
Corey–Link reaction.
Safety
As with any functional group, the hazards of halohydrins are difficult to generalize as they may form part of an almost limitless series of compounds, with each structure having different pharmacology. In general, simpler low molecular weight compounds are often toxic and carcinogenic (e.g.
2-chloroethanol
2-Chloroethanol (also called ethylene chlorohydrin or glycol chlorohydrin) is an organic chemical compound with the chemical formula HOCH2CH2Cl and the ''simplest'' beta-halohydrin (chlorohydrin). This colorless liquid has a pleasant ether-like od ...
,
3-MCPD) by virtue of being
alkylating agent
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...
s. This reactivity can be put to good use, for instance in the anti-cancer drug
mitobronitol
Mitobronitol (1,6-dibromo-1,6-dideoxy-D-mannitol) is a brominated analog of mannitol. It is an anticancer drug that is classified as an alkylating agent
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may ...
. A number of synthetic
corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
s exist bearing a fluorohydrin motif (
triamcinolone
Triamcinolone is a glucocorticoid used to treat certain skin diseases, allergies, and rheumatic disorders among others. It is also used to prevent worsening of asthma and COPD. It can be taken in various ways including by mouth, injection int ...
,
dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ca ...
).
Misnomers
Despite their rather suggestive names
epichlorohydrin
Epichlorohydrin (abbreviated ECH) is an organochlorine compound and an epoxide. Despite its name, it is not a halohydrin. It is a colorless liquid with a pungent, garlic-like odor, moderately soluble in water, but miscible with most polar orga ...
and
sulfuric chlorohydrin are not halohydrins.
See also
*
Cyanohydrin
In organic chemistry, a cyanohydrin or hydroxynitrile is a functional group found in organic compounds in which a cyano and a hydroxy group are attached to the same carbon atom. The general formula is , where R is H, alkyl, or aryl. Cyanohydrin ...
References
{{Reflist
Functional groups