Chapter 8

Ethers and Epoxides

 Teaching Objectives and Requirements
 Understand: Ethers, Physical Properties,
Synthesis of Epoxides Grasp: Nomenclatu
re of Ethers, Synthesis of Ether, Reaction
s: Acid-Catalyzed Cleavage, Reactions of
Epoxides.
 Key points and Main Areas of Difficulty
 Synthesis of Ether, Reactions: Acid-Catal
yzed Cleavage, Reactions of Epoxides.
 8.1 Ethers
 Ethers contain two groups ,which may be alk
yl or aryl groups,bonded to an oxygen atom.
 The groups are the same in a symmetrical et
her and different in an un symmetrical ether.

CH3CH2 O CH2CH3 CH3CH2 O O

diethyl ether phenyl propyl ether diphenyl ether

(symmetrical ether) (unsymmetrical ether) (symmetrical ether)
 8.1 Ethers
 The oxygen atom of an ether is sp3-
hybridized,and the C—O—C bond angle
is approximately the tetrahedral bond
angle.
 8.2 Nomenclature of Ethers
 Simple ethers are named as alkyl (or aryl)
groups in alphabetical order and appending
the name ether. CH CH
3 3
CH3 CH2 CH2 CH2 O CH3 CH3 CH O CH CH3
butyl methyl ether diisopropyl ether

 IUPAC Names of Ethers

 8.2 Nomenclature of Ethers
 Ethers are named according to IUPAC no
menclature as alkoxyalkanes, where the s
maller alkyl group and the oxygen atom co
nstitute an alkoxy group.
 An alkoxy group is treated as a substitute
nt on the larger parent alkane chain or cyc
loalkane ring.
 8.2 Nomenclature of Ethers

                                                                                                      
 8.2 Nomenclature of Ethers
 Cyclic Ethers
 The three- through six-membered cyclic et
hers have common names.
 In all ring systems, the oxygen atom is as
signed the number 1,and the rings are nu
mbered in the direction that gives the first
substituent the lower number.
 Cyclic ethers with three-atom rings called
epoxides.
 8.2 Nomenclature of Ethers
 Because these compounds are formed fro
m the oxidation of an alkene, the common
name of an epoxide is derived by adding o
xide to the name of the alkene.
 8.2 Nomenclature of Ethers
 The name of the five-membered ring ether i
s tetrahydrofuran (THF),based on its relatio
nship to the aromatic compound furan.
 Similarly,tetrapyran (THP),a six-membered
ring ether, is related to pyran,an unsaturate
d ether.

O O O O
furan tetrafuran pyran tetrapyran
 8.2 Nomenclature of Ethers
 The IUPAC names for cyclic ethers havin
g three-,four-,five-,and six-membered ring
s are oxiran, oxetane, oxolane, and oxane
, respectively.
 The oxygen atom in each of these rings re
ceives the number 1.
 The ring is numbered in the direction that
gives the lowest numbers to substituents.
8.2 Nomenclature of Ethers

Cl
CH3 1 OCH3 4
3 2 4 O 4 3 5 3
O CH3 3 2
5 2
1 O 6 2
CH2CH3 O
1 1
2,2-dimethyloxiran 2-ethyloxetane 3-methoxyoxolane 4-chlorooxane
8.3 Physical Properties of Ethers
 Ethers are more polar than alkanes and
somewhat less polar than alcohols.
 Ethers are more polar than alkanes and
somewhat less polar than alcohols.
 Ethers do not have an O—H bond and th
erefore cannot serve as hydrogen bond
donors.
 As a consequence,ether molecules do n
ot hydrogen bond to each other.
8.3 Physical Properties of Ethers

 Thus,ethers have boiling points substanti

ally lower than those of alcohols of comp
arable molecular weight.
 Because ethers are polar,they are more
soluble in water than alkanes of similar
molecular weight.
 Ethers such as diethyl ether dissolve a v
ariety of nonpolar and polar compounds.
8.4 The Grignard Reagent and Ether
s
 Grignard reagent ,represented as RMgX,
which can be prepared from haloalkanes
as well as from aryl halides.
Mg
R X ether R Mg X

 Victor Grignard:
French chemist Victor Grignard
 8.4 The Grignard Reagent and
Ethers
 In a Grignard reagent, the R group maybe a
1,2,or 3 alkyl group as well as a vinyl or aryl
group.
 The halogen may be Cl, Br,or I; fluorine co
mpounds do not form Grignard reagents.
 8.4 The Grignard Reagent and
Ethers
 A Grignard reagent has a very polar
carbon-magnesium bond in which the
carbon atom has a partial negative charge
and the metal a partial positive charge.
δ- δ+
C MgX
 8.4 The Grignard Reagent and
Ethers
 Grignard reagents react rapidly with acidic
hydrogen atoms in molecules such as alcoh
ols and water to produce alkanes.
Mg H2O
R X R Mg X R H
ether
 8.5 Synthesis of Ethers
 Ethers can be prepared by a method call
ed the Williamson synthesis. In this re
action,a halide ion is displaced from an a
lkyl halide by an alkoxide ion in an SN2 r
eaction.
 The alkoxide ion is prepared by the react
ion of an alcohol with a strong base such
as sodium hydride.
 8.5 Synthesis of Ethers

H .. - +
.. : +
O NaH .. : Na + H2
O

.. - + CH3
.. : Na + CH3
O Br .. :
O + NaBr

 Because the steric hindrance,the yields are d

ecreased in the order of primary, secondary
and tertiary.
 8.5 Synthesis of Ethers
 Thus, to make an unsymmetrical ether that
has a primary and a tertiary alkyl group, a p
rimary alkyl halide and a tertiary alkoxide io
n must be used.
CH3 CH3
.. - ..
I SN2
-
CH3 C O.. : + CH3 CH3 C O.. CH3 + I
CH3 CH3
H CH3 CH3 ..
.. E2
CH3 .. + CH2
O C Cl CH2 C + CH3 .. + Cl
OH
CH3
CH3
 8.6 Reactions of Ethers
 Ethers are stable compounds that do not rea
ct with most common reagents.
 They do not react with bases because they a
re aprotic, but do react with strong acids who
se conjugate bases are good nucleophiles.

HX
R O R' R O H + X R'
HX
R O H R X
 8.6 Reactions of Ethers
 In general,the less substituted alkyl halide is for
med by an SN2 reaction.
 The halide ion attacks the less hindered carbon
atom, and the displaced alkoxy group has the o
xygen atom bonded to the more substituted car
bon atom.
 The cleavage reaction does not occur with a ha
lide salt: a proton from the halogen acid is requ
ired to protonate the oxygen atom and provide
an alcohol as the leaving group.
8.6 Reactions of Ethers

.. fast
.. .. :
+ H Br .. +
O
.. +O

less hindered H

.. - slow ..
.. + : Br
.. : .. + : Br
..
+
O SN2 O:
H H
more hindered
 8.7 Synthesis of Epoxides
 The synthesis and reaction of cyclic ethe
rs containing four or more atoms are sim
ilar to those of acyclic ethers.
 The three-membered cyclic ethers,which
are important intermediates in synthesis,
can be synthesized by oxidizing an alken
e with a peroxyacid(RCO3H).
 8.7 Synthesis of Epoxides

O O
H Cl C OOH H Cl C
CH2Cl2 OH
+ O +
25 ¡æ
H H

 In the epoxidation of alkenes with m-chlorope

roxybenzoic acid(MCPBA), the stererochemi
stry of the groups in the alkene is retained.
 8.7 Synthesis of Epoxides
 That is,groups that are cis in the alkene are c
is in the epoxide, and groups that are trans in
the alkene remain trans in the epoxide.
CH3 CH3 CH3 O CH3
C C MCPBA
H H H H
 8.8 Reaction of Epoxides
 Epoxides are highly reactive because th
e three-member ring has considerable b
ond angle strain.
 Acid-Catalyzed Ring Opening
 The acid-catalyzed ring opening of epoxi
des occurs by an SN2 process in which
water is the nucleophile and the leaving
group is the protonated oxygen atom of t
he epoxide.
 8.8 Reaction of Epoxides
O H3O
+ HO HH
C C
H H H
H H H OH
H .. .. .. .. +
.. :
H O + H O+ CH2CH2 OH
.. H O
.. CH2CH2 OH
.. + H3 O
O:
H
H

 Ring Opening by Nucleophiles

 Ethers do not generally react with nucleophil
es under neutral or basic conditions.
 8.8 Reaction of Epoxides
 However,epoxides are so reactive that the r
ing is opened even by nucleophiles such as
OH-,SH-,or NH3 or the related organic speci
es RO-.RS-,and RNH2.
O HO HH
NH3 + C C
H H H
H H H NH2
 8.8 Reaction of Epoxides
ether
R Br + Mg R MgBr
O HO H
R MgBr + C C H
H H H -+
H H H O MgBr

HO H
C C H + H2O RCH2CH2OH + HOMgBr
H -+
H O MgBr
 8.8 Reaction of Epoxides
 Direction of Ring Opening
 Unsymmetrical epoxides give different produ
cts under acid-catalyzed and base-catalyzed
conditions. OH
-
CH3O
CH3O CH2 C CH3
CH3OH
O CH3
H C C CH3 1-methoxy-2-methyl-2-propanol
H CH3 +
OCH3
H
HO CH2 C CH3
CH3OH
CH3
2-methoxy-2-methl-1-propanol
 8.8 Reaction of Epoxides
 In the case of the ring opening by a nucl
eophile under basic conditions,the reacti
on is controlled by the same features as
the SN2 displacement reactions we consi
dered in Chapter 7.
 The nucleophile attacks the less hindere
d primary carbon atom instead of the tert
iary carbon atom.
 8.8 Reaction of Epoxides
 The resulting alkoxide ion then exchanges a
proton with the solvent,and the methoxide ba
se is regenerated.
.. -
.. - HH .. :
O
O:
CH3 .. :
O C C
H CH3 CH3O CH
H CH3 3
CH3
.. - ..
HH .. :
O H HH :OH - ..
C C :O C C + :O.. CH3
CH .. CH3 CH
CH3O CH3 3 CH3O CH3 3
 8.8 Reaction of Epoxides
 Under acid-catalyzed conditiongs,the proto
nated epoxide has some positive charge on
each carbon atom in the ring.
H H H
:O+ :O : :O :
+ +
H CH3 H CH3 H CH3
H CH3 H CH3 H CH3
oxonium ion primary carbocation tertiary carbocation
 8.8 Reaction of Epoxides
 The positive charge is more stable on the tert
iary carbon atom than on the primary carbon
atom.
 This tertiary carbocation resonance form is a
more important contributor than the primary o
ne.
 Thus,the tertiary carbocation center combine
s with the nucleophile to give the conjugate a
cid of the observed product of the acid-cataly
zed ring opening.
 8.8 Reaction of Epoxides
 The conjugete acid then exchanges a proto
n with the solvent.
H
+ HO CH3
:O H CH3
:O
.. CH3 H
H CH3 H O:
H CH3 CH3 + H

HO CH3 HO CH3
CH3 H CH3 +
H :O + CH3 OH2
H O: .. CH3 H
H :O
.. CH3
CH3 + H