Epoxide

Epoxide chemistry

1. EpoxidesEpoxides
OxiranesOxiranes

2. 2
•Epoxides are cyclic three member ethers containing
oxygen atom as member of ring. Epoxides are also
called oxiranes.
•The C—O—C bond angle for an epoxide must be near to
60°, a considerable deviation from the tetrahedral bond
angle of 109.5°.
•Thus, epoxides have angle strain, making them more
reactive than other ethers.

3. 3
•Epoxides can be named in three different ways — As
epoxyalkanes, oxiranes, or alkene oxides.
•To name an epoxide as an epoxyalkane, first name the
alkane chain or ring to which the O atom is attached, and
use the prefix “epoxy” to name the epoxide as a
substituent. Use two numbers to designate the location
of the carbon atoms to which the O’s is bonded.
Nomenclature of EpoxidesNomenclature of Epoxides

4. 4
•Epoxides can also be named as derivatives of oxirane,
the simplest epoxide having two carbons and one oxygen
atom in a ring.
•The oxirane ring is numbered to put the O atom at
position one, and the first substituent at position two.
•In most of cases, no number is used for a substituent in a
monosubstituted oxirane.
O O
CH
3
oxirane
(epoxyethane)
2-methyloxirane
(epoxypropane)
O
CH
3
O
CH
3H
3C
O
CH
3
CH
3
2-ethyloxirane
(1,2-epoxybutane)
2,3-dimethyloxirane
(2,3-epoxybutane)
2,2-dimethyloxirane
(1,2-epoxy-2-methy-
propane)

5. 5
•Epoxides are also named as alkene oxides, since they
are often prepared by adding an O atom to an alkene. To
name an epoxide in this way:
Mentally replace the epoxide oxygen with a double
bond.
Name the alkene.
Add the word oxide at the end.
H
2CCH
2
O
H
2C
CH
3
O
CH
3
ethene
(ethylene)
oxirane
(ethylene oxide)
prop-1-ene
(propylene)
2-methyloxirane
(propylene oxide)

6. 6
Preparation of epoxidePreparation of epoxide
There are two main laboratory methods for the preparation of
epoxides:
 Epoxidation of alkenes by reaction with peroxy acids.
 Base-promoted ring closure of vicinal halohydrins.

7. 7
Epoxidation of alkenes – oxidation Epoxidation of alkenes – oxidation
Epoxides are very easy to prepare via the reaction of an alkene with a peroxy acid.
This process is known as epoxidation.
CC RO
O
O
H
O
RO
O
H+
+
alkene
peroxy acid
Epoxide
Carboxylic acid
oxidation
A commonly used peroxy acid is
-peroxyacetic acid (CH
3
CO
2
OH),
- peroxy trifluoroacetic acid, peroxy
- benzoic acid,
- peroxy m-chlorobenzoic acid, etc.
Also carried out by using hydrogen peroxide and NaOH.

8. 8
Epoxidation of alkenesEpoxidation of alkenes
Epoxidation of alkenes with peroxy acids is a syn addition to the double bond.
Substituents that are cis to each other in the alkene remain cis in the epoxide;
substituents that are trans in the alkene remain trans in the epoxide.
C
C
H
H
H
3CO
O
O
H
O
H
H
H
3CO
O
H+ +
oxidation
Peracetic acid
acetic acid
(E)-1,2-diphenylethene
(2R,3R)-2,3-diphenyloxirane
O
HH
(2R,3S)-2,3-diphenyloxirane
Not forming isomeric -

9. 9
Epoxidation of alkenesEpoxidation of alkenes
Addition of an O atom from either side of the trigonal planar cis-alkene leads to the same
compound - an achiral meso compound that contains two stereogenic centers.
H
3CO
O
H
+
acetic acid
O
H
H
3C CH
3
H
CC
H
CH
3
H
3C
H
(Z)-but-2-ene
H
3CO
O
O
H
+ oxidation
Peracetic acid
O
H
CH
3H
3C
H
+
O is added
below the plane
O is added
above the plane
(2R,3S)-2,3-
dimethyloxirane
(2S,3R)-2,3-
dimethyloxirane
pair of achiral meso compounds are formed
Addition of an O atom from either side of the trigonal planar trans-alkene leads to the
same compound - an enantiomeric compounds.
CC
H
CH
3
H
H
3C
H
3CO
O
O
H
O
H
H
3C
CH
3
H+ oxidation
Peracetic acid
(E)-but-2-ene
O
H
CH
3
H
3C
H
+ +H
3CO
O
H
acetic acid
O is added
below the plane
O is added
above the plane
(2R,3R)-2,3-
dimethyloxirane
(2S,3S)-2,3-
dimethyloxirane
pair of enantiomers are formed

10. 10

11. 11

12. 12
•Organic compounds that contain both a hydroxy group and a halogen atom on
adjacent carbons are called halohydrins. It was synthesized by the treatment of
halogen followed by hydrolysis.
•In halohydrins, an intramolecular version of the Williamson ether synthesis can
occur to form epoxides.
From vicinal halohydrinsFrom vicinal halohydrins
CC
Alkene
CC
O
Epoxide
X
2
HOH
CC
XHO
HO
-
vicinal halohydrin

13. 13
From vicinal halohydrins - stereochemistryFrom vicinal halohydrins - stereochemistry
Substituents that are cis to each other in the alkene remain cis in the epoxide.
This is because formation of the bromohydrin involves anti addition, and the
ensuing intramolecular nucleophilic substitution reaction takes place with
inversion of configuration at the carbon that bears the halide leaving group.
CC
HH
CC
HH
O
Br
2
HOH
HO
-
vicinal halohydrin
CC
H
Br
HO
H
CC
H
Br
-
O
H
-Br
-
(Z)-but-2-ene
cis-2,3-epoxybutane
(2R,3S)-2,3-dimethyloxirane
CC
H
H
CC
H
H
O
trans-2,3-epoxybutane
Br
2
HOH
HO
-
vicinal halohydrin
CC
Br
HO
H
H
CC
Br
-
O
H
H
-Br
-
(E)-but-2-ene
(2R,3R)-2,3-dimethyloxirane

14.  Which of the following will produce the epoxide below? 
Question
A.a, b B.a, c C. b, c D. b, d E. c, d

15. 15
Reactions of EpoxidesReactions of Epoxides
•Recall that epoxides do not contain a good leaving group.
•Epoxides  do  contain  a  strained  three-membered  ring  with  two  polar 
bonds.
•Nucleophilic attack opens the strained three-membered ring, making it a 
favorable process even with a poor leaving group.

16. 16
•The reaction occurs readily with strong nucleophiles and with acids like HZ,
where Z is a nucleophilic atom.

17. 17
•Virtually all strong nucleophiles open an epoxide ring by a two-step reaction
sequence:
•In step 1, the nucleophile attacks an electron-deficient carbon, thus cleaving the
C—O bond and relieving the strain of the three-membered ring.
•In step 2 the alkoxide is protonated with water to generate a neutral product with
two functional groups on adjacent atoms.
•Common nucleophiles that open the epoxide ring include ¯OH, ¯OR, ¯CN, ¯SR
and NH
3
. With these strong nucleophiles, the reaction occurs by an S
N
2
mechanism.

18. 18
Examples:

19. 19
Let’s now consider the stereochemical consequences of the reaction of 1,2-
epoxycyclohexane with ¯OCH
3
.
Nucleophilic attack of ¯OCH
3
occurs from the backside at either C—O bond,
because both ends are similarly substituted. Since attack at either side occurs with
equal probability, an equal amount of the two enantiomers (i.e. a racemic mixture)
is formed.

20. 20
Optically inactive starting materials give optically inactive products!

21. 21
•Acids HZ that contain a nucleophile Z also open epoxide rings by a two-step
sequence.
•HCl, HBr and HI, as well as H
2
O and ROH in the presence of acid, all open an
epoxide ring in this manner.

22. 22
Figure 9.9
Opening of an unsymmetrical
epoxide ring with HCI

23. 23
•Ring opening of an epoxide with either a strong nucleophile
or an acid HZ is regioselective because one constitutional
isomer is the major or exclusive product.
•Note that the site selectivity of these two reactions is exactly
opposite.

24. •Epoxides can be opened by many strong nucleophiles.
•Both regioselectivity and stereoselectivity must be
considered.
Ring-opening of Epoxides

25. Question
•What is the product isolated when the epoxide below reacts with
NaOCH
3
in CH
3
OH?
•A) B)
•C) D)

26. NHNH
33
HH
22OO
(70%)(70%)
RR
SS
RR
RR
StereochemistryStereochemistry
HH
33CC CHCH
33
HH
33CC
CHCH
33
OO
HH
HH
HH
HH
OOHH
HH
22NN
Inversion of configuration at carbon being attacked by Inversion of configuration at carbon being attacked by
nucleophile.nucleophile.
Suggests SSuggests S
NN
2-like transition state.2-like transition state.

27. Question
•What is the product of the reaction shown?
•A) B)
•C) D)

28. What are the product(s) of the following reaction?
A. C.
B. D.
1) CH
3MgBr
2) H
2OO
HO
OH
HO OH
Question

29. Question
•What is the product isolated when the epoxide at
the right reacts with CH
3
OH and H
2
SO
4
?
•A) B)
•C) D)

30. What is the product of the following reaction?
A. C.
B. D.
HBr
OH
Br
Br
Br
OH OH
Br OH
O
Question