Chapter 11
Alcohols & Ethers
1. Structure & Nomenclature

Alcohols have a hydroxyl (–OH) group
bonded to a saturated carbon atom
(sp3 hybridized)
1o
OH
Ethanol
2o
OH
2-Propanol
(isopropyl
alcohol)
3o
OH
2-Methyl2-propanol
(tert-butyl alcohol)
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OH
2-Propenol
(allyl alcohol)
OH
2-Propynol
(propargyl alcohol)
OH
Benzyl alcohol
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
Phenols
• Compounds that have a hydroxyl
group attached directly to a
benzene ring
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
Ethers
• The oxygen atom of an ether is
bonded to two carbon atoms
O
O
Diethyl ether
tert-Butyl methyl ether
O
O
Divinyl ether
CH3
Ethyl phenyl ether
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1A. Nomenclature of Alcohols

Rules of naming alcohols
• Identify the longest carbon chain
that includes the carbon to which
the –OH group is attached
• Use the lowest number for the
carbon to which the –OH group is
attached
• Alcohol as parent (suffix)
 ending with “ol”
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
Examples
OH
OH
OH
OH
2-Propanol
(isopropyl alcohol)
1,2,3-Butanetriol
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
Example
OH
3-Propyl-2-heptanol
8
or
1
5
2
OH
3
4
6
7
wrong
3
7
6
5
OH
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4
1
2
1B. Nomenclature of Ethers

Rules of naming ethers
• Similar to those with alkyl halides
 CH3O–
Methoxy
 CH3CH2O–
Ethoxy

Example
O
Ethoxyethane
(diethyl ether)
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
Cyclic ethers
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2. Physical Properties of
Alcohols and Ethers
Ethers have boiling points that are
roughly comparable with those of
hydrocarbons of the same molecular
weight (MW)
 Alcohols have much higher boiling
points than comparable ethers or
hydrocarbons

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
For example
O
OH
Diethyl ether
Pentane
1-Butanol
(MW = 74)
(MW = 72)
(MW = 74)
b.p. = 34.6oC
b.p. = 36oC
b.p. = 117.7oC

Alcohol molecules can associate with
each other through hydrogen bonding,
whereas those of ethers and
hydrocarbons cannot
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
Water solubility of ethers and alcohols
• Both ethers and alcohols are able to
form hydrogen bonds with water
• Ethers have solubilities in water that are
similar to those of alcohols of the same
molecular weight and that are very
different from those of hydrocarbons
• The solubility of alcohols in water
gradually decreases as the hydrocarbon
portion of the molecule lengthens; longchain alcohols are more “alkane-like”
and are, therefore, less like water
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
Physical Properties of Ethers
Name
Formula
mp
(oC)
bp (oC)
(1 atm)
Dimethyl ether
CH3OCH3
-138
-24.9
Diethyl ether
CH3CH2OCH2CH3
-116
34.6
Diisopropyl ether
(CH3)2CHOCH(CH 3)2
-86
68
1,2-Dimethoxyethane
(DME)
CH3OCH2CH2OCH3
-68
83
-112
12
-108
65.4
O
Oxirane
Tetrahydrofuran (THF)
O
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
Physical Properties of Alcohols
Name
Formula
Methanol
CH3OH
Ethanol
CH3CH2OH
Isopropyl alcohol
CH3CH(OH)CH 3
tert-Butyl alcohol
(CH3)3COH
Hexyl alcohol
CH3(CH2)4CH2OH
OH
Cyclohexanol
Ethylene glycol
HO
OH
mp
(oC)
bp (oC)
(1 atm)
*
-97
64.7
inf.
-117
78.3
inf.
-88
82.3
inf.
25
82.5
inf.
-52
156.5
0.6
24
161.5
3.6
-12.6
197
inf.
* Water solubility (g/100 mL H2O)
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3. Important Alcohols & Ethers
3A. Methanol




Methanol is highly toxic
Ingestion of even small quantities of
methanol can cause blindness
Large quantities cause death
Methanol poisoning can also occur by
inhalation of the vapors or by prolonged
exposure to the skin
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3B. Ethanol

Ethanol can be produced by
• Fermentation
• Acid-catalyzed hydration of ethene
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3D. Diethyl Ether

Diethyl ether is a very low boiling,
highly flammable liquid

Most ethers react slowly with oxygen
by a radical process called
autoxidation to form hydroperoxides
and peroxides
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4. Synthesis of Alcohols from
Alkenes

Acid-catalyzed Hydration of Alkenes
C
C
⊕
H
H
H2O
C
C
H
OH
H2O
C
H
C
H2O
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C
C
H
O
H
H

Acid-Catalyzed Hydration of Alkenes
• Markovnikov regioselectivity
• Free carbocation intermediate
• Rearrangement of carbocation
possible
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
Oxymercuration–Demercuration
C
C
Hg(OAc) 2
H2O, THF
OH
C
C
HgOAc
NaBH4
NaOH
• Markovnikov regioselectivity
• Anti stereoselectivity
• Generally takes place without the
complication of rearrangements
• Mechanism
 Discussed in Section 8.5
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OH
C
C
H

Hydroboration–Oxidation
• Anti-Markovnikov regioselectivity
• Syn-stereoselectivity
• Mechanism
 Discussed in Section 8.7
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Markovnikov regioselectivity
OH
+
H , H2O or
1. Hg(OAc)2, H2O, THF
2. NaBH4, NaOH
R
H
R
1. BH3 • THF
2. H2O2, NaOH
H
R
OH
Anti-Markovnikov regioselectivity
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
Example
Synthesis?
(1)
OH
OH
Synthesis?
(2)
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
Synthesis (1)
H
OH
• Need anti-Markovnikov addition of
H–OH
• Use hydroboration-oxidation
H
OH
1. BH3 • THF
2. H2O2, NaOH
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
Synthesis (2)
OH
H
• Need Markovnikov addition of H–OH
• Thus, could potentially use either
 acid-catalyzed hydration or
 oxymercuration-demercuration
• However, acid-catalyzed hydration is
NOT reasonable here due to likely
rearrangement of carbocation
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
Oxymercuration-demercuration
OH
H
Hg(OAc) 2
H2O, THF
NaBH4
NaOH
OH
HgOAc
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5. Reactions of Alcohols

The reactions of alcohols have mainly
to do with the following:
• The oxygen atom of the –OH group
is nucleophilic and weakly basic
• The hydrogen atom of the –OH
group is weakly acidic
• The –OH group can be converted to
a leaving group so as to allow
substitution or elimination reactions
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
 O


H
C–O & O–H bonds of an
alcohol are polarized
Protonation of the alcohol converts a
⊖
poor leaving group (HO ) into a good
one (H2O)
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
Once the alcohol is protonated
substitution reactions become possible
H
Nu +
C
O
protonated
alcohol
H
SN2
H
Nu
C
+ O
The protonated –OH
group is a good leaving
group (H2O)
© 2014 by John Wiley & Sons, Inc. All rights reserved.
H
6. Alcohols as Acids

Alcohols have acidities similar to that of
water
pKa Values for Some Weak Acids
Acid
pKa
CH3OH
15.5
H2O
15.74
CH3CH2OH
15.9
(CH3)3COH
18.0
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Relative Acidity
H2O & alcohols are the
strongest acids in this series
H2O > ROH > RC
CH > H2 > NH3 > RH

Increasing acidity

Relative Basicity
R > NH2 > H > RC
⊖
HO is the weakest
acid in this series
C
> RO > HO
Increasing basicity
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7. Conversion of Alcohols into
Alkyl Halides
R
OH
R
• HX (X = Cl, Br, I)
• PBr3
• SOCl2
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X

Examples
OH
conc. HCl
Cl
o
25 C
+
HOH
(94%)
OH
PBr3
Br
(63%)
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8. Alkyl Halides from the Reaction
of Alcohols with Hydrogen
Halides
R
OH + HX
R
X + H2O
The order of reactivity of alcohols
• 3o > 2o > 1o < methyl
 The order of reactivity of the hydrogen
halides
• HI > HBr > HCl
(HF is generally unreactive)

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R
OH + NaX
No Reaction!
⊖
HO is a poor
leaving group
⊕
H3O is a good
leaving group
© 2014 by John Wiley & Sons, Inc. All rights reserved.
11. Synthesis of Ethers
11A. Ethers by Intermolecular
Dehydration of Alcohols
H2SO4
180oC
Ethene
OH
H2SO4
o
140 C
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O
Diethyl ether

Mechanism
OH + H
OSO3H
O
H + OSO3H
H
OH
O
O
H 2O
H
• This method is only good for the
synthesis of symmetrical ethers
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+ H2O

For unsymmetrical ethers
ROH + R'OH
H2SO4
R
R'
+
o
1 alcohols
O
R
O
R
+
R'
O
R'
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Mixture
of ethers

R
Exception
OH +
cat. H2SO4
HO
R
O
+ HO
(good yield)
H
R
H
OH
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11B. The Williamson Ether Synthesis
R
X
R'O
R
O
R'
(SN2)

Via SN2 reaction, thus R is limited to 1o
and some 2o (but R' can be 1o, 2o or 3o)
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
Example 1
Na H
O
O Na
+ H2
H
Br
O
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
Example 2
Cl
HO
Cl
NaOH
H2O
O
O
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
Example 3
I
NaOH
OH

O
H2O
However
I
NaOH
OH
H2O
No epoxide observed!
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11C. Synthesis of Ethers by Alkoxymercuration–Demercuration
Markovnikov regioselectivity
OR'
1. Hg(O2CCF3)2, R'OH
R
2. NaBH4, NaOH
(1)
R
(2)
OR'
R
Hg(O2CCF 3)
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
Example
1. Hg(O2CCF3)2, iPrOH
2. NaBH4, NaOH
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O
12. Reactions of Ethers

Dialkyl ethers react with very few
reagents other than acids
O
+ HBr
O
H
an oxonium salt
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+ Br
12A. Cleavage of Ethers

Heating dialkyl ethers with very strong
acids (HI, HBr, and H2SO4) causes
them to undergo reactions in which the
carbon–oxygen bond breaks
O
+ 2 HBr
2
Cleavage of an ether
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Br + H2O

Mechanism
+ H
O
Br
+ Br
O
H
Br
H
+ Br
O
O
H
H
O
H
+
Br
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H
+
Br
13. Epoxides

Epoxide (oxirane)
• A 3-membered ring containing an
oxygen
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13A. Synthesis of Epoxides:
Epoxidation

Electrophilic epoxidation
C
C
O
peroxy
acid
C
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C

Peroxy acids (peracids)
O
R
C
O
OH
• Common peracids
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
Mechanism
peroxy acid
O
O
H
R
O
O
O
O
O
carboxylic
acid
R
R
O
H
O
H
epoxide
alkene
concerted
transition
state
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14. Reactions of Epoxides

The highly strained three-membered
ring of epoxides makes them much
more reactive toward nucleophilic
substitution than other ethers
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
Acid-catalyzed ring opening of epoxide
C
+ H
C
O
O
C
H
+
C
O
H
H
H
H
O
C
H
O
O
H
H
+
H
H
O
H
O
C
C
H
O
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O
C
H
H
H

Base-catalyzed ring opening of epoxide
RO
R
O
+
C
C
C
C
O
O
R
O
H
RO
C
+ R
C
OH
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O

If the epoxide is unsymmetrical, in the
base-catalyzed ring opening, attack
by the alkoxide ion occurs primarily at
the less substituted carbon atom
EtO
Et
O
+
O
O
o
1 carbon atom is
less hindered
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
In the acid-catalyzed ring opening of an
unsymmetrical epoxide the nucleophile
attacks primarily at the more substituted
carbon atom
cat. HA
MeOH +
O
MeO
OH
O
MeO
OH
MeOH +
(protonated
epoxide) H
H
o
This carbon resembles a 3 carbocation
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15. Anti 1,2-Dihydroxylation of
Alkenes via Epoxides

Synthesis of 1,2-diols
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
Anti-Dihydroxylation
• A 2-step procedure via ring-opening
of epoxides
OH
OH
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H2O
17. Summary of Reactions of
Alkenes, Alcohols, and Ethers

Synthesis of alcohols
O
1.
2. H2O
OH
(1o alcohol)
MgBr
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1. BH3 THF
2. H2O2, NaOH

Synthesis of alcohols
1. BH3 THF
2. H2O2, NaOH
+
H , H2O
OH
(2o alcohol)
1. Hg(OAc)2, H2O
2. NaBH4
or
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
Synthesis of alcohols
OH
1. Hg(OAc)2, H2O
2. NaBH4
(3o alcohol)
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
Reaction of alcohols
OR
Br
PBr3
1. base
2. R-X
OH
SOCl 2
(1o alcohol)
Cl
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
Synthesis of ethers
R
RO
R

R
O
conc. H2SO4
R
140oC
R
X
OH
Cleavage reaction of ethers
O
R'
H
X
R
O
R'
X
H
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ROH + R'X
END OF CHAPTER 11
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