Chapter 8 - F

Chapter 8: Ethers and Epoxides
© R. Spinney 2013
Ethers
General structure: R-O-R’
O atom is sp3 hybridized
with 2 lone pairs of e-
O atom: nucleophile
C atom: electrophile
Note: the term “ether” equates to diethyl ether,
CH3CH2OCH2CH3
O
8.1 Nomenclature
• The IUPAC names for ethers are based on the
alkane name of the longest chain attached to
the oxygen
• The shorter chain is named as an alkoxy
substituent
– Alkane with the -ane replaced by -oxy
– e.g., CH3CH2O = ethoxy
• CH3CH2CH2CH2CH2-O-CH3
1-methoxypentane
8.2 Ethers: Physical Properties
Colorless liquids with low BP and pleasant odor.
Compound Formula BP (°C) MW Solubility

(g/100 mL, 20 °C)
1-butanol CH3CH2CH2CH2CH2OH 118 74 7.9
Diethyl ether CH3CH2OCH2CH3 35 74 7.5
pentane CH3CH2CH2CH2CH3 36 72 0.03
Ethers: Physical Properties
Why? Ethers can accept H-bonds but not donate
them. This makes them soluble in water but
there is no H-bonding between ether molecules
so they have BPs similar to alkanes. Alcohols can
H-bond to each other, the same as water, and so
have significantly higher BPs.
8.3 Ethers: as Solvents
Ethers make good aprotic (they have no acidic H
atom) solvents because:
1. They are fairly unreactive to most dilute acids and bases
2. They are fairly unreactive to most dilute oxidizing and
reducing agents
3. Most organic compounds are soluble in ethers
4. The solvent (ether) is easy to remove afterwards due to
their low BP
5. Problem: very flammable, can easily form explosive
peroxides with atmospheric O2 (use FeSO4 to destroy
these).
8.3 Ethers: as Solvents
Commonly used ethers (BP):
O O
O
ether (35) furan (31) THF (67)

tetrahydrofuran
O O O
pyran (86) tetrahydropyran (88) 1,4-dioxane (101)

8.4 The Grignard Reaction
One of the more important uses of ethers is as a solvent in the
preparation of Grignard reagents, an organometallic
compound.
These compounds contain a carbon-metal bond, that while

covalent is VERY highly polarized, i.e.
d- d+
C M
This is a means of generating carbanions, a carbon

nucleophile!
The Grignard Reaction
The general mechanism is:
R Mg R
C X C Mg X X = Cl, Br, I
anh.
ether
The Mg atom inserts itself between the C and halide

atoms.
The anh. (anhydrous) ether used as a solvent is very
important in stabilizing the Grignard reagent by acting as a
Lewis base, i.e.
R R
O
R ..
C Mg X
..
O
R R
The two most commonly used ethers are diethyl ether and
THF (tetrahydrofuran), the choice usually based on the BP.
Since a carbanion is a very strong base the reaction
cannot be carried out in the presence of even weakly
acidic protons, i.e. even water and alcohols are too
acidic and will destroy the Grignard reagent.
R R
C Mg X H OH C H Mg2+(OH)X-
strong strong weak weak

base acid acid base
Other organometallic compounds exist;
1. acetylides from terminal alkynes and sodium amide
2. Organolithium compounds can be prepared similar to
Grignard reagents, i.e.
R 2 Li R d- d+
C X C Li Li+X-
anh. ether
8.5 Preparation of Ethers
There are a number of methods to generate
ethers, depending on the nature of the ether
desired.
1) Acid catalyzed dehydration of alcohols

– Useful for symmetric ethers
– Uses sulfuric acid (H2SO4) to remove a water
molecule
Preparation of Ethers
H2SO4
i.e. 2 OH O H2O
The mechanism:
H2SO4 +
OH OH2 +
2 O O
HO H
H2O H3O+
2) Acid catalyzed addition of an alcohol to an
alkene
– Markovnikov addition of H+ to alkene
– Acid/base reaction between carbocation and
alcohol O atom
– Useful for situations where you have a tertiary
carbocation, i.e. MTBE a common additive to
gasoline
i.e. OH
H2SO4
O
The mechanism:
H2SO4
+
O O
HO H
EtOH EtOH2+
3) Williamson Ether Synthesis
– Good for asymmetric ethers
– Generate an alkoxide in the first step
– React the alkoxide with an alkyl halide in the
second step
– Second step is an SN2, so works best if the alkyl
halide is primary or secondary, poorly if tertiary.
The alkoxide is a nucleophile.
i.e. 2 R OH 2 Na 2 R O Na+ H2
or NaH
R O Na+ R X R O R Na+ X-
The mechanism:
R O Na+ R X R O R Na+ X-
Note: 2° and 3° alkyl halides are subject to
competing elimination reactions (E2), i.e.
SN2
O I O I-
H E2
O
Cl OH Cl-
8.6 Cleaving Ethers
Ethers are subject to cleavage by nucleophilic attack
in an SN type of reaction.
RO- is a poor leaving group so for 1° & 2° ethers you

need a strong nucleophile (SN2 mechanism) and an
acid catalyst to turn it into a good leaving group, an
alcohol, as well as heat.
3° and phenolic ethers can react by SN1 (or E1)

mechanisms so don’t require strong nucleophiles,
and don’t require heat.
• Ethers are generally unreactive
• Strong acid will cleave an ether at elevated temperature
• HI, HBr produce an alkyl halide from less hindered
component by SN2 (tertiary ethers undergo SN1)
Cleaving Ethers
H+ +
i.e. R O R R O R R OH R Nu
H Nu:
8.7 Epoxides (Oxirane)
Epoxides are cyclic ethers in a 3-membered ring.
The ring is highly strained and can be broken
easily in an SN type of reaction. The oxygen is
subject to an electrophilic addition, and the C
atoms to a nucleophilic attack.
Epoxides (Oxirane)
The most important epoxide commercially is
ethylene oxide. It is a starting material for many
other commercial organic molecules. Produced
from ethene using a silver catalyst, i.e.
Ag
O2 O
250 °C
high pressure
Epoxides (Oxirane)
Other epoxides are produced using
peroxycarboxylic acids. The most common are:
O
Peroxyacetic acid H
O O
O
H
m-chlorophenyl peroxy acid O O
(MCPBA)
Cl
Epoxides
i.e.
R H R
O
O O O
R' O OH
R'
8.8 Reactions of Epoxides
The ring is highly strained so easy to break open in a
nucleophilic attack. However acid catalysts are
usually used to create a better leaving group
H
O H+ O+ R OH
Nu:-
R R' R R' Nu R'
Nu: can be any nucleophile

Reactions of Epoxides
i.e. O H+
H
O+ H2O HO
+
O H
H
HO H2O HO
SN1 type reaction
+
O H OH
H
H H H
O+ O O
+ +
oxonium ion 1° carbocation 2° carbocation

Reactions of Epoxides
Base catalyzed reaction are also possible, i.e.
O H O
O O H
O
O
O
O
SN2 type reaction

Regioselectivity
Acid catalyzed reaction proceed as if through a carbocation
intermediate, while base reaction will be controlled by steric
hindrance to the electrophilic C atoms, i.e.
CH3O- OH
O
CH3OH
H+ HO
CH3OH
O
Addition of Grignards to Ethylene
Oxide
• Adds –CH2CH2OH to the Grignard reagent’s hydrocarbon chain
• Acyclic and other larger ring ethers do not react
8.9 Cyclic Ethers
Tetrahydrofuran (THF), tetrahydropyran and
1,4-dioxane are all common ethers used as
solvents. THF is better than ether for Grignard
reactions as it solvate the Mg atom better. THF
and 1,4-dioxane are also both soluble in water
as well as organic solvents.
O O
O
THF tetrahydropyran 1,4-dioxane

Crown Ethers
Crown ethers are cyclic structures where every
third atom is an oxygen. They are:
– Highly water soluble
– Size selective binding with metal cations
– Used in chelation therapy to selectively remove
heavy metals
O O
O O
12-crown-4 18-crown-6

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Chapter 8: Ethers and Epoxides

Compound Formula BP (°C) MW Solubility

ether (35) furan (31) THF (67)

pyran (86) tetrahydropyran (88) 1,4-dioxane (101)

These compounds contain a carbon-metal bond, that while

This is a means of generating carbanions, a carbon

The Mg atom inserts itself between the C and halide

strong strong weak weak

1) Acid catalyzed dehydration of alcohols

RO- is a poor leaving group so for 1° & 2° ethers you

3° and phenolic ethers can react by SN1 (or E1)

R R' R R' Nu R'

Nu: can be any nucleophile

oxonium ion 1° carbocation 2° carbocation

SN2 type reaction

THF tetrahydropyran 1,4-dioxane

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