Prof. R.C.

Jagessar Lecture
Notes:
Epoxides
CHM 2206, 7th. February 2023
Epoxides

• Epoxides are three membered-cyclic ether, also called oxirane.

• Epoxides are valuable synthetic intermediates used for converting
alkenes to a variety of other functional groups.
• An alkene is converted to an epoxide by a peroxyacid, RCOOOH.
• A peroxyacid, is a carboxylic acid that has an extra oxygen atom in
a –O-O- (peroxy) linkage.
Epoxides Nomenclature

o The common name of an epoxide is formed by adding “ oxide”

to the name of the alkene that is oxidised. Consider the two
reactions below:

O
O
+ PhC O O H
+ Ph OOH
E th y le n e o x id e b e n z o ic a c id
p e ro x y b e n zo ic a cid

p e ro x y b e n zo ic a cid O c y c lo p e n e ten e o x id e
Epoxides Nomenclature

• Another systematic nomenclature names epoxides as derivatives

of the parent compound, ethylene oxide, using “ oxirane” as the
synthematic name for ethylene oxide.
• In this system, the ring atoms of a heterocyclic compound are
numbered starting with the heteroatom and moving in the
direction to give the lowest substituent numbers.
Epoxides Nomenclature

O C H 2C H 3 O CH3
O H

(H 3C )2 H C C H 2C H 3 H 3C O H
o x ira n e
2 ,2 - d ie th y l- 3 - is o p r o p y lo x ir a n e tr a n s - 2 - m e th o x y - 3 - m e th y lo x ir a n e
Epoxides: Synthesis
• Epoxides are synthesised via several means.
• Alkenes: Epoxides are synthesised via the reaction of an alkene
with peroxyacids, RCOOOH.

O
RCOOOH
+ R C O 2H
carboxylic acid
E poxide
alkene (oxirane)

R C O O O H = Peroxyacid

O m eta-chlroroperoxybenzoic acid,
M CPBA
Cl
OOH
O

Cl
O OH

alkene E poxide
(oxirane)
Epoxides: Synthesis

O
RCOO OH
+ RCO 2 H

Epoxide

M CPBA
O
CH 2 Cl 2

Cl O

M CPBA =

m eta carbon O O H
Epoxides: Synthesis

H
H
O

O
O O
H
CH 2Cl2

CH 2Cl2
Cl O

MCPBA =
Cl
O O H
Epoxides: Synthesis

• From base Promoted Cylization of Halohydrins:

• Another method for the synthesis of epoxides involves a variation
of the Williamson-Ether synthesis.
• The alkoxide is usually generated via the reaction of an halohydrin
with a base, that leads to the formation of an alkoxide.
• An halohydrin is a molecule that has an halogen bonded to the b-
carbon bearing an –OH group
• Intramolecular SN2 attack of the internal alkoxide on the carbon
bearing the halogen as the leaving group, leads to the formation of
the cylic Epoxides.
 Epoxides: Synthesis
CH 3 O H CH 3 O- O
H3C
NaOH
C C C C C C
 b H
X X

halohydrin alkoxide trans to X leaving group

CH 3 O H CH 3 O- O
H3C
NaOH
H C C H H C C H HC C H + Br -
H
Br H Br H

Internal alkoxide
X = halide (Intramolecular S N 2 reaction)
Epoxides: Synthesis

• An halohydrin is usually prepared via the reaction of an alkene

with an halogen in the presence of water.
Epoxides: Synthesis
H 2O -H +
OH H
Br-Br

H H H Br H H Br

alkene brom onium ion trans-brom ohydrin

N aO H O -N a+ H
OH H O + N aBr

H Br H Br H

trans-brom ohydrin trans-brom ohydrin Epoxides

Epoxides: Synthesis

H 2O HO-
B r-B r

H H H Br H H Br H H Br H

brom onium ion brom onium ion

brom onium ion

H N aO H O-
O O + N aB r

H H H
H Br H Br H
Other cyclic ethers
• Other cyclic ethers include, Oxetanes, Furans (oxolanes), Pyrans
(Oxanes).
O

H3C CH3
O

H3C H

Oxetane 2-ethyl-3,3-dimethyloxetane

Furans (Oxolanes) OCH3

O
O
O
3-methoxyfuran Tetrahydrofuran
Furan

H CH3 H CH3
Pyrans (Oxanes)

O O
O
4-methylpyran tetrahydropyran (THP)
Pyran
(oxane)

Dioxanes
O O
O

O CH3 O
O
4-methyl-1,3-dioxane dibenzodioxin (dioxin)
1,4-dioxane
Reactions of Epoxides

• An epoxide reacts with a Grignard reagent to produce an alcohol

bearing two more carbons than the parent Grignard molecule