Epoxide

In organic chemistry, an epoxide is a cyclic ether, where the ether forms a

three-atom ring: two atoms of carbon and one atom of oxygen. This
triangular structure has substantial ring strain, making epoxides highly
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 volatile.[1]

Nomenclature
A generic epoxide
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 (C2H4) is ethylene oxide (C2H4O). 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, but such materials do not contain epoxide
groups (or contain only a few residual epoxy groups that remain unreacted in the formation of the resin).

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.[2]

Heterogeneously catalyzed oxidation of alkenes

The epoxidation of ethylene involves its reaction with oxygen. According to a reaction mechanism suggested in
1974[3] at least one ethylene molecule is totally oxidized for every six that are converted to ethylene oxide:

The direct reaction of oxygen with alkenes is useful only for this epoxide. Modified heterogeneous silver
catalysts are typically employed.[4] Other alkenes fail to react usefully, even propylene, though TS-1 supported
Au catalysts can perform propylene epoxidation selectively.[5]

Olefin (alkene) oxidation using organic peroxides and metal catalysts

Aside from ethylene oxide, most epoxides are generated by treating alkenes with peroxide-containing
reagents, which donate a single oxygen atom. Safety considerations weigh on these reactions because organic
peroxides are prone to spontaneous decomposition or even combustion.

Metal complexes are useful catalysts for epoxidations involving hydrogen peroxide and alkyl hydroperoxides.
Peroxycarboxylic acids, which are more electrophilic, convert alkenes to epoxides without the intervention of
metal catalysts. In specialized applications, other peroxide-containing reagents are employed, such as
dimethyldioxirane. Depending on the mechanism of the reaction and the geometry of the alkene starting
material, cis and/or trans epoxide diastereomers may be formed. In addition, if there are other stereocenters
present in the starting material, they can influence the stereochemistry of the epoxidation. Metal-catalyzed
epoxidations were first explored using tert-butyl hydroperoxide (TBHP).[6] 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.[7]

Organic peroxides are used for the production of propylene oxide

from propylene. Catalysts are required as well. Both t-butyl
hydroperoxide and ethylbenzene hydroperoxide can be used as
oxygen sources.[8]

Simplified mechanism for metal- Olefin peroxidation using peroxycarboxylic acids

catalyzed epoxidation of alkenes
with peroxide (ROOH) reagents More typically for laboratory operations, the Prilezhaev reaction is
employed.[9][10] This approach involves the oxidation of the alkene
with a peroxyacid such as mCPBA. Illustrative is the epoxidation of
styrene with perbenzoic acid to styrene oxide:[11]

The reaction proceeds via what is commonly known as the "Butterfly Mechanism".[12] 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 O−O sigma star orbital for C−C π electrons to attack.[13] Because
two bonds are broken and formed to the epoxide oxygen, this is formally an example of a coarctate transition
state.

Hydroperoxides are also employed in catalytic enantioselective epoxidations, such as the Sharpless
epoxidation and the Jacobsen epoxidation. Together with the Shi epoxidation, these reactions are useful for
the enantioselective synthesis of chiral epoxides. Oxaziridine reagents may also be used to generate epoxides
from alkenes.

Homogeneously catalysed asymmetric epoxidations

Arene oxides are intermediates in the oxidation of arenes by cytochrome P450. For prochiral arenes
(naphthalene, toluene, benzoates, benzopyrene), the epoxides are often obtained in high enantioselectivity.

Chiral epoxides can often be derived enantioselectively from prochiral alkenes. Many metal complexes give
active catalysts, but the most important involve titanium, vanadium, and molybdenum.[14][15]
The Sharpless epoxidation reaction is one of the premier
enantioselective chemical reactions. It is used to prepare
2,3-epoxyalcohols from primary and secondary allylic
alcohols.[16][17]

Dehydrohalogenation
Halohydrins react with base to give epoxides.[19] 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
The Sharpless epoxidation
(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. [20]
Epichlorohydrin, is prepared
by the chlorohydrin method.
It is a precursor in the
Starting with propylene chlorohydrin, most of the world's supply of propylene production of epoxy
oxide arises via this route.[8] resins.[18]

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
ylides. In this reaction, a sulfonium is the leaving group instead of chloride.

Nucleophilic epoxidation
Electron-deficient olefins, such as enones and 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..

Biosynthesis
Epoxides are uncommon in nature. They arise usually via oxygenation of alkenes by the action of cytochrome
P450.[21] (but see also the short-lived epoxyeicosatrienoic acids which act as signalling molecules.[22] and
similar epoxydocosapentaenoic acids, and epoxyeicosatetraenoic acids.)

Reactions
Ring-opening reactions dominate the reactivity of epoxides.

Hydrolysis and addition of nucleophiles

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 are examples "ambident
substrates."[23] The regioselectivity of ring-opening in
asymmetric epoxides generally follows the SN2 pattern
of attack at the least-substituted carbon,[24] but can be
affected by carbocation stability under acidic
conditions.[25] This class of reactions is the basis of Two pathways for the hydrolysis of an epoxide
epoxy glues and the production of glycols.[18]

Polymerization and oligomerization

Polymerization of epoxides gives polyethers. 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:[26]

ROH + n C2H4O → R(OC2H4)nOH

With anhydrides, epoxides give polyesters.[27]

Deoxygenation
Epoxides can be deoxygenated using oxophilic reagents. This reaction can proceed with loss or retention of
configuration.[28] The combination of tungsten hexachloride and n-butyllithium gives the alkene.[29][30]

Other reactions
Reduction of an epoxide with lithium aluminium hydride or aluminium hydride produces the corresponding
alcohol.[31] This reduction process results from the nucleophilic addition of hydride (H−).
Reductive cleavage of epoxides gives β-lithioalkoxides.[32]
Epoxides undergo ring expansion reactions, illustrated by the insertion of carbon dioxide to give cyclic
carbonates.
When treated with thiourea, epoxides convert to the episulfide, which are called thiiranes.
An epoxide adjacent to an alcohol can undergo the Payne rearrangement in base.

Uses
Illustrative epoxides
 Bisphenol A diglycidyl ether is a The chemical structure of the
component in common household epoxide glycidol, a common
"epoxy". chemical intermediate.

Epothilones are naturally occurring 3,4-Epoxycyclohexylmethyl-3’,4’-

epoxides. epoxycyclohexane carboxylate,
precursor to coatings.[33]

Epoxidized linolein, a major Benzene oxide exists in equilibrium

component of epoxidized soybean with the oxepin isomer.
oil (ESBO), a commercially important
plasticizer.

Ethylene oxide is widely used to generate detergents and surfactants by ethoxylation. Its hydrolysis affords
ethylene glycol. It is also used for 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).

Safety
Epoxides are alkylating agents, making many of them highly toxic.[34]

See also
Epoxide hydrolase
 Juliá–Colonna epoxidation

Further reading
Massingill, J. L.; Bauer, R. S. (2000-01-01). "Epoxy Resins" (https://www.sciencedirect.com/science/article/
pii/B9780080434179500234). In Craver, Clara D.; Carraher, Charles E. (eds.). Applied Polymer Science:
21st Century. Oxford: Pergamon. pp. 393–424. doi:10.1016/b978-008043417-9/50023-4 (https://doi.org/1
0.1016%2Fb978-008043417-9%2F50023-4). ISBN 978-0-08-043417-9. Retrieved 2023-12-20.

References
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a09_531). ISBN 978-3527306732.
2. Siegfried Rebsdat; Dieter Mayer. "Ethylene Oxide". Ullmann's Encyclopedia of Industrial Chemistry.
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