REACTIONS OF ETHER

-Normally ether is used as a solvent as they are not very

reactive towards chemical rxns.
-Ethers undergo a limited number of characteristic rxns:
NOTE:
Ether DO NOT REACT with bases, oxidizing/reducing agents
and reactive metals.

A. Rxns with Strong Acids (HBr, HI)

-Ethers are cleaved by heating with concn HBr or HI to give
alky bromides or alkyl iodides.
-Ethers react with conn HBr & HI because these reagents
are sufficiently acidic to protonate the ether, while the Br -
and I- are good nucleophiles for the substitution
General Eqn:

HX

Mechanism:

R R H R
H-Br R-Br
O O O
R R H
Br

via SN1 or SN2 H-Br

R-Br + H2O
Example:
Cleavage of cyclopentyl ether by HBr

H
O-CH2CH3 H-Br O-CH2 CH3

Br-

H H
Br -
S N1 O H -Br- O H-Br
H or SN2 H H
CH3CH2Br

Br

B. Autooxidation of Ether
-Ether exposed to air undergo is spontaneously oxidized to
formed peroxide. This process is called autooxidation.
-Hence, ethers should be bought in small quantities.
General Eqn:
Example:

Question
Compound A, C7H8O do not react with Na and SOCl 2. When
cmpd A is heated with HI, C
H3I and cmpd B are obtained having molecular formula of
C6H6O. Compound B dissolves in aqueous NaOH. Deduce
the structures of A & B and write the rxn equation of
formation of cmpd A to B.

Answer
a. Compound A, C7H8O is probably alcohol or ether. Since
cmpd A is not reactive towards Na metal and SOCl 2, hence,
cmpd A is ether.

b. Heating cmpd A with HI gave 2 products, CH 3I and cmpd

B (C6H6O). Cmpd B is soluble in aqueous NaOH. Hence, B is
phenol.
I-
ROR H-I R-O-R RI ROH
H
Rxn Eqn:
I-

OCH3 H-I O CH3

H
A

OH CH3 I

B
 SYNTHESIS OF EPOXIDES
-Epoxides are easily made from alkenes, as they can
undergo a variety of useful synthetic rxn.
-Epoxides are very useful rxn intermediates.
-Peroxides can be prepared by 2 ways:
A. Peroxyacid epoxidation
B. Base-promoted Cyclization of Halohydrins

A. Peroxyacid epoxidation
-Peroxyacids are used to convert alkenes to epoxides & rxn
medium is in aqueous acid.
-Weakly acidic peroxyacids in soluble aprotic solvents i.e
CH2Cl2 are used. Usually, meta-chloroperoxybenzoic acid
(MCPBA) is often used for these epoxidations.
General eqn:

-epoxidation is a one-step, concerted rxn that maintains

stereochemistry of substituents on the C=C.
- The peroxyacid epoxidation is quite general, with electron
rich double bonds reacting faster. This selectivity makes
difficult transformations possible.

Example:
a.
H H
MCPBA MCPBA =
O
CH2 Cl2 Cl
H H
O
cyclohexene epoxycyclohexane
(100%) C O O H
b.
1
Ph CH3 Ph O
MCPBA 3 2 CH3
C=C C C
H NO2 CH2Cl2, 25oC
H NO2
(E)-2-nitro-1-phenylpropene (E)-2-methyl-2-nitro-1-phenyloxirane

Reaction mechanism:

B. Base-promoted Cyclization of Halohydrins

-It is a variation of the Williamson ether synthesis.
General eqn:

-If an alkoxide ion & a X atom are located in the same

molecule, the alkoxide may displace a halide ion to form a
ring.
-Treatment of halohydrin with give epoxide through an
internal SN2 attack.
Halohydrins are generated by treating alkenes with aqueous
halogens (Br/Cl water) whereby the Br/Cl water add across
the C=C by Markonikov orientation.
Example: Rxn of cyclopentene with Cl water

Notes:
Halohydrins are synthesized by treating alkenes with
aqueous solutions of halogens (X2/H2O). In terms of cyclic
ether formation, a 3-membered ring is formed faster than
5- or 6-membered ones.
 REACTIONS OF EPOXIDES
-Epoxides are more reactive than dialkyl ether because of
large strain energy of the three membered ring of
epoxides..
-Opening of epoxide rings can be done in acid or base
medium.

A. Acid-catalyzed Ring Opening of Epoxides

-Mechanism of this hydrolysis involves protonation of O (to
form good leaving grp), followed by SN2 attack by water.
-Product is anti stereochemistry results from a backside
attack of water on the protonated epoxide.
Example: Acid-catalyzed Opening of Epoxides in Water.
-Epoxides open in acidic solutions to form glycols.

Mechanism of rxn:

H H
O H O H O H2O OH H

H H H H H O
H H
1,2-epoxycyclopentane

OH H
H3O+

H OH

trans-cyclopentane-1,2-diol
Example: Opening of Epoxides with Hydrohalic Acids
-When an epoxide reacts with a hydrohalic acid (HBr, HCl,
HI), a halide ion attacks the protonated epoxide. This
reaction is similar to cleavage of ethers by HBr or HI.

Notes:
-The epoxide is protonated by the acid, and the halide ion
displaced will acts as a nucleophile attacking and opening
the epoxide to form a halohydrin.

B. Base-catalyzed Ring Opening of Epoxides

-base attacks the LESS HINDERED C of epoxide.
-Example:
Reaction of 1,2-epoxypropane with ethoxide base in
ethanol.

O O-
OCH2CH3
CH3 C CH2 H3C CHCH2OCH2CH3
CH3CH2OH
H
CH3 CH2 O H
1,2-epoxypropane

OH
H3C CHCH2OCH2CH3

1,2-ethoxy-2-propanol
C. Reaction of Epoxides with Grignard &
Organolithium Reagents
-Grignard reagent (i) & alkyl lithium (ii) are strong
nucleophiles which attacks the C of epoxides to cause ring
opening.
-product of rxn is alcohol.
Examples:

CH3 CH3 CH3

OMgBr OH
H2O
OH CH3 CH2 -MgBr

CH2 CH3 CH2CH3

2-ethyl-1-methylcyclohexanol

O OLi OH
CH3 Li HC CH CH3 H2C CH CH3 H2C CH CH3
H H H
2-butanol