Editing Epoxide

{{Short description|Organic compounds with a carbon-carbon-oxygen ring}}
[[File:Epoxide generic.svg|thumb|A generic epoxide]]

In [[organic chemistry]], an '''epoxide''' is a cyclic [[ether]], where the ether forms a three-atom [[Ring (chemistry)|ring]]: two atoms of [[carbon]] and one atom of [[oxygen]].  This triangular structure has substantial [[ring strain]], making epoxides highly [[Reactivity (chemistry)|reactive]], more so than other ethers.  They are produced on a large scale for many applications.  In general, low molecular weight epoxides are colourless and [[nonpolar]], and often [[Volatility (chemistry)|volatile]].<ref name=UllmannEpoxides>{{Ullmann | author1 = Guenter Sienel | author2 = Robert Rieth | author3 = Kenneth T. Rowbottom | title = Epoxides | doi = 10.1002/14356007.a09_531}}</ref>

==Nomenclature==
A compound containing the epoxide [[functional group]] can be called an epoxy, epoxide, oxirane, and ethoxyline.  Simple epoxides are often referred to as oxides.  Thus, the epoxide of [[ethylene]] (C<sub>2</sub>H<sub>4</sub>) is [[ethylene oxide]] (C<sub>2</sub>H<sub>4</sub>O).  Many compounds have trivial names; for instance, ethylene oxide is called "oxirane". Some names emphasize the presence of the epoxide [[functional group]], as in the compound ''1,2-epoxyheptane'', which can also be called ''1,2-heptene oxide''.

A [[polymer]] formed from epoxide precursors is called an ''[[epoxy]]''. However, few if any of the epoxy groups in the [[resin]] survive the [[Curing (chemistry)|curing process]].

==Synthesis==
The dominant epoxides industrially are [[ethylene oxide]] and [[propylene oxide]], which are produced respectively on the scales of approximately 15 and 3 million tonnes/year.<ref>{{Ullmann |author1=Siegfried Rebsdat |author2=Dieter Mayer |title=Ethylene Oxide |doi=10.1002/14356007.a10_117 }}</ref>  

Aside from ethylene oxide, most epoxides are generated when [[peroxide|peroxidized]] reagents donate a single oxygen atom to an [[alkene]]. Safety considerations weigh on these reactions because organic peroxides are prone to spontaneous decomposition or even combustion.  

Both [[t-butyl hydroperoxide]] and [[ethylbenzene]] hydroperoxide can be used as oxygen sources during propylene oxidation (although a catalyst is required as well, and most industrial producers use dehydrochlorination instead).<ref name=PO>{{cite book | doi=10.1002/14356007.a22_239 | chapter=Propylene Oxide | title=Ullmann's Encyclopedia of Industrial Chemistry | date=2000 | last1=Kahlich | first1=Dietmar | last2=Wiechern | first2=Uwe | last3=Lindner | first3=Jörg | isbn=3-527-30673-0 }}</ref>

===Ethylene oxidation===
The [[ethylene oxide]] industry generates its product from reaction of [[ethylene]] and [[oxygen]]. Modified [[heterogeneous catalysis|heterogeneous]] [[silver]] catalysts are typically employed.<ref>{{cite journal|journal = Catalysis Reviews|title = Structure Sensitivity of the Catalytic Oxidation of Ethene by Silver|last1=Sajkowski|first1= D. J.|last2 = Boudart|first2 = M.|date = 1987|volume =29|issue = 4|pages = 325–360|doi = 10.1080/01614948708078611}}</ref> According to a reaction mechanism suggested in 1974<ref name="kilty">{{cite journal
| author = Kilty P. A.|author2= Sachtler W. M. H.
| title = The mechanism of the selective oxidation of ethylene to ethylene oxide
| doi=10.1080/01614947408079624
| journal = Catalysis Reviews
| year = 1974
| volume = 10
| pages = 1–16
}}</ref> at least one ethylene molecule is totally oxidized for every six that are converted to ethylene oxide: <chem display=block>7 H2C=CH2  +  6 O2  ->  6 C2H4O  +  2 CO2  +  2 H2O</chem>  

Only ethylene produces an epoxide during [[incomplete combustion]]. Other alkenes fail to react usefully, even [[propylene]], though TS-1 supported [[Gold|Au]] catalysts can selectively epoxidize propylene.<ref>{{cite journal |title=The Production of Propene Oxide: Catalytic Processes and Recent Developments|first1=T. Alexander|last1=Nijhuis|first2=Michiel|last2=Makkee|first3=Jacob A.|last3=Moulijn|first4=Bert M. |last4 = Weckhuysen |date=1 May 2006|journal=Industrial & Engineering Chemistry Research |volume=45 |issue=10 |pages=3447–3459|doi=10.1021/ie0513090|hdl = 1874/20149|s2cid=94240406 |hdl-access=free}}</ref>

===Organic peroxides and metal catalysts===
Metal complexes are useful catalysts for epoxidations involving [[hydrogen peroxide]] and alkyl hydroperoxides. Metal-catalyzed epoxidations were first explored using [[tert-butyl hydroperoxide]] (TBHP).<ref name=name2>{{cite journal | year = 1965 | title =  Metal Acetylacetonate Catalyzed Epoxidation of Olefins with t-Butyl Hydroperoxide| journal =  The Journal of Organic Chemistry| volume = 30 | issue = 6| page = 2074 | doi = 10.1021/jo01017a520 | last1 = Indictor| first1 = Norman}}</ref>  Association of TBHP with the metal (M) generates the active metal peroxy complex containing the MOOR group, which then transfers an O center to the alkene.<ref>{{cite journal | author = Thiel W. R. | year = 1997 | title = Metal catalyzed oxidations. Part 5. Catalytic olefin epoxidation with seven-coordinate oxobisperoxo molybdenum complexes: A mechanistic study | journal = Journal of Molecular Catalysis A: Chemical| volume = 117 | issue = 1–3 | pages = 449–454 | doi = 10.1016/S1381-1169(96)00291-9 }}</ref>
:[[File:SimpleMOORexpxCyc2.svg|thumb|left|Simplified mechanism for metal-catalyzed epoxidation of alkenes with peroxide (ROOH) reagents]]
[[Vanadium(II) oxide]] catalyzes the epoxidation at specifically less-substituted alkenes.<ref>{{cite journal|date=25 Sep 2006|first=Douglass|last=Taber|title=Selective reactions of Alkenes|journal=Organic Chemistry Highlights|url=https://www.organic-chemistry.org/Highlights/2006/25September.shtm}}</ref>  

===Nucleophilic epoxidation===
Electron-deficient olefins, such as [[enone]]s and [[acrylic acid|acryl derivatives]] can be epoxidized using nucleophilic oxygen compounds such as peroxides. The reaction is a two-step mechanism. First the oxygen performs a [[nucleophilic conjugate addition]] to give a stabilized carbanion. This carbanion then attacks the same oxygen atom, displacing a leaving group from it, to close the epoxide ring.

===Transfer from peroxycarboxylic acids===
Peroxycarboxylic acids, which are more electrophilic than other peroxides, convert alkenes to epoxides without the intervention of metal catalysts.  In specialized applications, [[dioxirane]] reagents (e.g. [[dimethyldioxirane]]) [[epoxidation with dioxiranes|perform similarly]], but are more explosive.  

Typical laboratory operations employ the [[Prilezhaev reaction]].<ref name=March>March, Jerry. 1985. ''Advanced Organic Chemistry, Reactions, Mechanisms and Structure''. 3rd ed. John Wiley & Sons. {{ISBN|0-471-85472-7}}.</ref><ref>{{cite journal
 | author = Nikolaus Prileschajew
 | journal = Berichte der Deutschen Chemischen Gesellschaft
 | volume = 42
 | issue = 4
 | pages = 4811–4815
 | title = Oxydation ungesättigter Verbindungen mittels organischer Superoxyde
 | trans-title = Oxidation of unsaturated compounds by means of organic peroxides
 | doi = 10.1002/cber.190904204100
 | year = 1909
 | language = de
 | url = https://zenodo.org/record/1426367}}</ref> This approach involves the oxidation of the alkene with a [[peroxyacid]] such as [[Meta-Chloroperoxybenzoic acid|''m''CPBA]]. Illustrative is the epoxidation of [[styrene]] with [[perbenzoic acid]] to [[styrene oxide]]:<ref name="Harold1941">{{OrgSynth | author = Harold Hibbert and Pauline Burt | title = Styrene Oxide | collvol = 1 | collvolpages = 494 | year = 1941 | prep = cv1p0494}}</ref>
:[[File:PrilezhaevReaction.svg|Prilezhaev Reaction]]

The stereochemistry of the reaction is quite sensitive.  Depending on the mechanism of the reaction and the geometry of the alkene starting material, ''cis'' and/or ''trans'' epoxide [[diastereomer]]s may be formed. In addition, if there are other stereocenters present in the starting material, they can influence the stereochemistry of the epoxidation. 

The reaction proceeds via what is commonly known as the "Butterfly Mechanism".<ref>{{cite journal | author = Paul D. Bartlett | title = Recent work on the mechanisms of peroxide reactions | journal = Record of Chemical Progress | year = 1950 | volume = 11 | pages = 47–51}}</ref> The peroxide is viewed as an [[electrophile]], and the alkene a [[nucleophile]]. The reaction is considered to be concerted. The butterfly mechanism allows ideal positioning of the {{chem2|O\sO}} [[molecular orbital|sigma star orbital]] for {{chem2|C\sC}} π electrons to attack.<ref>{{cite book|author=John O. Edwards|title=Peroxide Reaction Mechanisms | publisher=Interscience, New York| year = 1962 | pages = 67–106}}</ref> Because two bonds are broken and formed to the epoxide oxygen, this is formally an example of a [[Coarctate reaction|coarctate transition state]].
:[[File:Epoxidation butterfly mechanism.svg|center|750px|The butterfly mechanism for the Prilezhaev epoxidation reaction.]]

===Asymmetric epoxidations===
Chiral epoxides are produced by epoxidation of prochiral alkenes. When the catalyst is chiral or the alkene is chiral, then [[asymmetric epoxidation]] becomes possible.  Prominent methodologies are the [[Sharpless epoxidation]], the [[Jacobsen epoxidation]], and the [[Shi epoxidation]].<ref>{{cite journal |last1 = Berrisford |first1 = D. J. |last2 =Bolm |first2=C. |last3=Sharpless |first3=K. B. | year = 2003 | title = Ligand-Accelerated Catalysis | journal =  Angewandte Chemie International Edition in English| volume = 95 | issue = 10 | pages = 1059–1070 | doi = 10.1002/anie.199510591 }}</ref>

===Dehydrohalogenation and other γ eliminations===
[[File:Epichlorohydryna.svg|thumb|upright=0.75|right|[[Epichlorohydrin]], is prepared by the chlorohydrin method. It is a precursor in the production of [[epoxy resin]]s.<ref name="UllmannEpxyRes">{{cite encyclopedia|last1=Pham|first1=Ha Q.|last2=Marks|first2=Maurice J.|encyclopedia=Ullmann's Encyclopedia of Industrial Chemistry|doi=10.1002/14356007.a09_547.pub2|publisher=Wiley-VCH|year=2005|isbn=978-3527306732|chapter=Epoxy Resins}}</ref>]]
[[Halohydrin]]s react with base to give epoxides.<ref name="Koppenhoefer1993">{{OrgSynth | author = Koppenhoefer, B. |author2=Schurig, V. | title = (R)-Alkyloxiranes of High Enantiomeric Purity from (S)-2-Chloroalkanoic Acids via (S)-2-Chloro-1-Alkanols: (R)-Methyloxirane | collvol = 8 | collvolpages = 434 | year = 1993 | prep = cv8p0434}}</ref> The reaction is spontaneous because the energetic cost of introducing the ring strain (13 kcal/mol) is offset by the larger bond enthalpy of the  newly introduced C-O bond (when compared to that of the cleaved C-halogen bond). 

Formation of epoxides from secondary halohydrins is predicted to occur faster than from primary halohydrins due to increased entropic effects in the secondary halohydrin, and tertiary halohydrins react (if at all) extremely slowly due to steric crowding.
<ref>{{cite journal | author = Silva, P.J. | year = 2023 | title = Computational insights into the spontaneity of epoxide formation from halohydrins and other mechanistic details of Williamson's ether synthesis | journal =  Chemistry Journal of Moldova| volume = 18 | issue = 2 | pages = 87–95 | doi = 10.19261/cjm.2023.1083  | doi-access = free }}</ref>

Starting with [[propylene chlorohydrin]], most of the world's supply of [[propylene oxide]] arises via this route.<ref name=PO/>  
[[File:Methyloxirane from 2-chloropropionic acid.png|frameless|center|400px]]

An intramolecular epoxide formation reaction is one of the key steps in the [[Darzens reaction]].

In the [[Johnson–Corey–Chaykovsky reaction]] epoxides are generated from [[carbonyl]] groups and [[sulfonium ylide]]s. In this reaction, a sulfonium is the leaving group instead of chloride.

===Biosynthesis===
Epoxides are uncommon in nature. They arise usually via oxygenation of alkenes by the action of [[cytochrome P450]].<ref>{{cite journal | author = Thibodeaux C. J. | year = 2012 | title = Enzymatic Chemistry of Cyclopropane, Epoxide, and Aziridine Biosynthesis | journal =  Chemical Reviews| volume = 112 | issue = 3 | pages = 1681–1709 | doi = 10.1021/cr200073d | pmid = 22017381 | pmc = 3288687 }}</ref> (but see also the short-lived [[epoxyeicosatrienoic acid]]s which act as signalling molecules.<ref name="Boron2003-108">{{cite book | first = Walter F. | last = Boron | name-list-style = vanc | title = Medical Physiology: A Cellular And Molecular Approach | publisher = Elsevier/Saunders | year = 2003 | page = 108 | isbn = 978-1-4160-2328-9 }}</ref> and similar [[epoxydocosapentaenoic acid]]s, and [[epoxyeicosatetraenoic acid]]s.)

[[Arene oxide]]s are intermediates in the oxidation of arenes by [[cytochrome P450]]. For prochiral arenes ([[naphthalene]], [[toluene]], [[benzoate]]s, [[benzopyrene]]), the epoxides are often obtained in high enantioselectivity.

== Reactions ==<!-- This section is linked from [[Organic reaction]]. -->
Ring-opening reactions dominate the reactivity of epoxides.

===Hydrolysis and addition of nucleophiles===
:[[File:Epoxide hydrolysis.svg|thumb|362px|right|Two pathways for the hydrolysis of an epoxide]]
Epoxides react with a broad range of nucleophiles, for example, alcohols, water, amines, thiols, and even halides. With two often-nearly-equivalent sites of attack, epoxides exemplify "ambident substrates".<ref>{{March6th|page=517}}</ref>  Ring-opening [[regioselectivity]] in asymmetric epoxides generally follows the S<sub>N</sub>2 pattern of attack at the least-substituted carbon,<ref>{{cite book|title=Organic Synthesis: the disconnection approach|edition=2nd|first1=Stuart|last1=Warren|first2=Paul|last2=Wyatt|publisher=Wiley|year=2008|page=39}}</ref> but can be affected by carbocation stability under acidic conditions.<ref>{{cite web|url=https://www.ch.imperial.ac.uk/rzepa/blog/?p=10237|first=Henry|last=Rzepa|author-link=Henry Rzepa|website=Chemistry with a twist|title=How to predict the regioselectivity of epoxide ring opening|date=28 April 2013}}</ref>  This class of reactions is the basis of [[epoxy]] glues and the production of glycols.<ref name="UllmannEpxyRes"/>

[[Lithium aluminium hydride]] or [[aluminium hydride]] both [[Organic reduction|reduce]] epoxides through a simple nucleophilic addition of hydride (H<sup>−</sup>); they produce the corresponding [[Alcohol (chemistry)|alcohol]].<ref>{{cite journal | title = Reduction of epoxides. II. The lithium aluminum hydride and mixed hydride reduction of 3-methylcyclohexene oxide | author = Bruce Rickborn and Wallace E. Lamke | year = 1967 | volume = 32 | issue = 3 | pages = 537–539 | journal =  The Journal of Organic Chemistry| doi = 10.1021/jo01278a005}}</ref>

===Polymerization and oligomerization===
Polymerization of epoxides gives [[polyether]]s. For example [[ethylene oxide]] polymerizes to give [[polyethylene glycol]], also known as polyethylene oxide. The reaction of an alcohol or a phenol with ethylene oxide, [[ethoxylation]], is widely used to produce surfactants:<ref name=UllmannSurf>{{cite encyclopedia| author = Kosswig, Kurt | year = 2002 | encyclopedia= Ullmann's Encyclopedia of Industrial Chemistry | chapter = Surfactants |editor = Elvers, Barbara |display-editors=etal | doi = 10.1002/14356007.a25_747 | location = Weinheim, GER | publisher = Wiley-VCH | ref = published online, 15 June 2000 | isbn = 978-3527306732 }}</ref>
:ROH  +  n C<sub>2</sub>H<sub>4</sub>O   →   R(OC<sub>2</sub>H<sub>4</sub>)<sub>n</sub>OH

With anhydrides, epoxides give polyesters.<ref>{{cite journal|title=Ring-Opening Copolymerization of Epoxides and Cyclic Anhydrides with Discrete Metal Complexes: Structure–Property Relationships|author=Julie M. Longo |author2=Maria J. Sanford |author3=[[Geoffrey W. Coates]]|journal= Chemical Reviews|year=2016|volume=116|issue=24|pages=15167–15197|doi=10.1021/acs.chemrev.6b00553|pmid=27936619}}</ref>

===Metallation and deoxygenation===
[[Lithiation]] cleaves the ring to β-lithioalkoxides.<ref>{{cite journal | title = 1,3-Diols From Lithium Β-lithioalkoxides Generated By The Reductive Lithiation Of Epoxides: 2,5-dimethyl-2,4-hexanediol |author1=B. Mudryk |author2=T. Cohen | journal =  Organic Syntheses| year = 1995 | volume = 72 | pages = 173 | doi = 10.15227/orgsyn.072.0173}}</ref>

Epoxides can be deoxygenated using [[oxophilic]] reagents, with loss or retention of configuration.<ref><!--placeholder until a secondary source is located-->{{cite journal|title=Stereospecific Deoxygenation of Aliphatic Epoxides to Alkenes under Rhenium Catalysis|author1=Takuya Nakagiri |author2=Masahito Murai |author3=Kazuhiko Takai |journal= Organic Letters|year=2015|volume=17|issue=13|pages=3346–9|doi=10.1021/acs.orglett.5b01583|pmid=26065934}}</ref> The combination of [[tungsten hexachloride]] and [[N-Butyllithium|''n''-butyllithium]] gives the [[alkene]].<ref>{{cite journal | title = Deoxygenation of Epoxides with Lower Valent Tungsten Halides: ''trans''-Cyclododecene | author = [[K. Barry Sharpless]], Martha A. Umbreit | journal = Organic Syntheses| year = 1981 | volume = 60| page = 29 | doi = 10.15227/orgsyn.060.0029}}</ref><ref>{{cite journal | title = Lower valent tungsten halides. New class of reagents for deoxygenation of organic molecules |author1=K. Barry Sharpless |author1-link=Karl Barry Sharpless |author2=Martha A. Umbreit |author3=Marjorie T. Nieh |author4=Thomas C. Flood | journal = Journal of the American Chemical Society| year = 1972 | volume = 94 | issue = 18 | pages = 6538–6540 | doi = 10.1021/ja00773a045|bibcode=1972JAChS..94.6538S }}</ref>

When treated with [[thiourea]], epoxides convert to the [[episulfide]] (thiiranes).

===Other reactions===
* Epoxides undergo ring expansion reactions, illustrated by the insertion of carbon dioxide to give [[Carbonate ester|cyclic carbonates]].
* An epoxide adjacent to an alcohol can undergo the [[Payne rearrangement]] in base.

==Uses==
{{Gallery
|title=Illustrative epoxides
|width=220 |height=100
|align=
|footer=
|File:Bisphenol A diglycidyl ether 200.svg
 |[[Bisphenol A diglycidyl ether]] is a component in common household "epoxy".
|File:Glycidol structure.svg
 |The chemical structure of the epoxide [[glycidol]], a common chemical intermediate.
|File:Epothilone A B.svg
 |[[Epothilone]]s are naturally occurring epoxides.
|File:Diepoxyester.svg|[[3,4-Epoxycyclohexylmethyl-3',4'-epoxycyclohexane carboxylate]], precursor to coatings.<ref name="Sasaki-2007">{{cite journal |last1=Sasaki |first1=Hiroshi |title=Curing properties of cycloaliphatic epoxy derivatives |journal=Progress in Organic Coatings |date=February 2007 |volume=58 |issue=2–3 |pages=227–230 |doi=10.1016/j.porgcoat.2006.09.030}}</ref>
|File:Epoxidized linolein.svg
 |Epoxidized [[linolein]], a major component of [[epoxidized soybean oil]] (ESBO), a commercially important [[plasticizer]].
|File:Oxepin-benzene oxide.png|[[Benzene oxide]] exists in equilibrium with the oxepin isomer.
}}

[[Ethylene oxide]] is widely used to generate detergents and surfactants by [[ethoxylation]]. Its hydrolysis affords [[ethylene glycol]]. It is also used for [[Sterilization (microbiology)|sterilisation]] of medical instruments and materials.

The reaction of epoxides with amines is the basis for the formation of [[epoxy]] glues and structural materials. A typical amine-hardener is [[triethylenetetramine]] (TETA).

<!--==Perepoxides==
Perepoxides are epoxides with an additional oxygen atom attached to the epoxide-oxygen.  They are [[isoelectronic]] and isostructural with the cyclic sulfoxides derived from [[episulfide]]s.  Perepoxides are proposed intermediates in the [[photosensitizer|photosensitized]] oxidation of alkenes, as occurs when [[drying oil]]s (a component of some paints and varnishes) are exposed to air in light.  Such intermediates arise from the addition of [[singlet oxygen]] to the double bond.  Perepoxides rapidly rearrange to allylic [[hydroperoxide]]s.<ref name="March" />-->

==Safety==
Epoxides are [[alkylating agent]]s, making many of them highly toxic.<ref>{{cite journal |title= Mechanistic approaches for evaluating the toxicity of reactive organochlorines and epoxides in green algae |first1= Christian |last1= Niederer |first2= Renata |last2= Behra |first3= Angela |last3= Harder |first4= René P. |last4= Schwarzenbach |first5= Beate I. |last5= Escher |journal= Environmental Toxicology and Chemistry |volume= 23 |issue= 3 |pages= 697–704 |year= 2004 |doi= 10.1897/03-83 |pmid= 15285364 |bibcode= 2004EnvTC..23..697N |s2cid= 847639 }}</ref>

== See also ==
* [[Epoxide hydrolase]]
* [[Juliá–Colonna epoxidation]]
* [[Aziridine]] (nitrogen analogue) and [[thiirane]] (sulfur one)
* [[Cyclopropane]]
* [[Oxaziridine]] (cyclic three-membered ring with C, N, and O)

==Further reading==
* {{Cite book |last1=Massingill |first1=J. L. |chapter=Epoxy Resins |date=2000-01-01 |chapter-url=https://www.sciencedirect.com/science/article/pii/B9780080434179500234 |title=Applied Polymer Science: 21st Century |pages=393–424 |editor-last=Craver |editor-first=Clara D. |access-date=2023-12-20 |place=Oxford |publisher=Pergamon |doi=10.1016/b978-008043417-9/50023-4 |isbn=978-0-08-043417-9 |last2=Bauer |first2=R. S. |editor2-last=Carraher |editor2-first=Charles E.}}

== References ==
{{Reflist}}

{{Functional Groups}}
{{Authority control}}

[[Category:Epoxides| ]]
[[Category:Functional groups]]