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Essential Organic Chemistry
Paula Yurkanis Bruice
Chapter 10
Reactions of Alcohols, Amines,
Ethers, and Epoxides
10.1 Nomenclature of Alcohols
Compounds in which a hydrogen is
replaced by an OH group.
We distinguish three types:
Naming Alcohols
Common names are the name of alkyl
group followed by the word “alcohol”
Naming
1. Longest carbon chain containing the alcohol.
2. OH suffix gets the lowest possible number.
Naming
3. Find also lowest possible number for other substituent.
4. For more than one substituent they are listed in
alphabetical order.
10.2 Substitution Reactions of Alcohols
Alcohols are not reactive in nucleophilic substitution
or elimination reactions since hydroxide is a strong base,
poor leaving group.
R OH
Nu
R
OH
X
X
R+
Nu
no reaction in
either case
+
R
HO-
+
strong
base
SN1
HO-
SN2
poor leaving
group
Substitution Reactions of Alcohols
The situation improves under acid conditions. We
change the leaving group to water, a neutral group.
R
OH
H+
R
O
H
NuNu R
+
H
neutral
O
H
neutral
H
- H2O
R+
NuNu R
10.3 Elimination Reactions of Alcohols
Elimination of water, dehydration, is commonly
obtained using sulfuric acid (H2SO4) as a catalyst.
H3C
OH
CH3
H2SO4

H3CHC CHCH3 + H2O
 The acid is mandatory to convert the poor
leaving group OH– into a good leaving group
H2O.
Elimination
First step is protonation of the hydroxyl group.
H
H3C
OH
H2SO4
CH3

H3C
O H
CH3
Loss of water leads to a carbocation.
H
H3C
O H - H2O
CH3
H3C
CH3
Elimination
Second, a base removes a proton b to the
carbocation center.
H3C
b
H H
H3CHC CHCH3

CH3
+
H2SO4
OSO3H
Notice that this reaction is an E1 reaction.
•Rate-determining step is the formation of the
carbocation.
Elimination
In case we have a choice between several bhydrogens, the most stable alkene is formed
preferentially.
CH3
H3PO4 H3C
CH3CHCH2CH3
OH

H3C
CH3 H2C
CH +
H3C
84 %
CH2
CH3
16 %
Elimination
As a result of the E1 mechanism, the ease of
dehydration follows the order:
R
H
R
R
OH
>
H
OH
>
R
H
R
R
OH
 That directly reflects the stability of the
intermediate carbocations.
R
R
R
H
R
>
H
R
>
R
H
Elimination
 Primary alcohols undergo dehydration by an E2
pathway.
 First, however, we generate the good leaving group.
H
+
OH
H
O H
The subsequent steps, removal of water and
deprotonation, take place simultaneously.
OSO3H
H
H3C
CH
H
O H
H3C
CH2
10.4 Oxidation of Alcohols
Dehydrogenation (oxidation) is possible for
1o and 2o leading to aldehydes and ketones, respectively.
O
R
H
aldehyde
O
R
R'
ketone
Oxidation of Alcohols
 Aldehydes can be further oxidized to acids.
O
R
O
R
H
aldehyde
OH
acid
Oxidation of Alcohols
 Typical oxidizing agents are chromic acid (H2CrO4)
or pyridinium chlorochromate (PCC).
O
-
O
H
O Cr Cl
HO Cr OH
N
O
O
chromic acid
PCC
Examples
H2CrO4
OH
cyclopentanol
OH
O
cyclopentanone
H2CrO4
O
H
butanol
butanal
OH
O
butanoic acid
H2CrO4
Examples
OH
PCC
O
CH2Cl2
butanol
H
butanal
PCC is a more selective oxidizing agent.
Oxidation can be stopped at the aldehyde level.
10.5 Reaction of Amines
 Amines are less reactive than alcohols.
• This can be evaluated by inspection of the pKa values of
the leaving group.
pKa
HF
HOH
HNH2
3.2
15.7
36
Protonation of the amine improves the
situation only slightly.
H
H
CH3CH2OH
pKa
-2.4
>
CH3CH2NH2
11.2
Amines
Amines are the most common organic bases.
CH3
H NH
CH2CH3
pKa 10.8
H NH
H NH2
CH3
CH3
10.9
H NH
5.07
40
10.6 Nomenclature of Ethers
 Common Name:
• Name of alkyl substituents followed by “ether”
Nomenclature of Ethers
 IUPAC
•Parent alkyl compound with RO
substituent. “-yl” is then replaced by “oxy”
10.7 Substitution Reactions of Ethers
The behavior of ethers is comparable to
alcohols.
• pKa of the leaving group is comparable.
H OCH3
H OH
pKa
15.7
15.5
Activation by acid allows substitution.
H
R O R'
R O R' + HI
R
I
+
R'
OH

Substitution of Ethers
The mechanism involves first a protonation
step.
H
R O R' + HI
R O R'
The subsequent steps are determined by the
stability of the intermediates.
• Stable carbocation  SN1
• Unstable carbocation  SN2
Substitution of Ethers
Examples
CH3
H3C
CH3 H
H+ IH3C
OCH3
CH3
OCH3
CH3
stable carbocation
CH3
H3C
SN1
CH3
I
H3C
CH3 attack of nucleophile
I
CH3
Substitution of Ethers
H3C
H+ IOCH3
H3C
H
OCH3
SN2
Primary carbocations are unstable;
thus, reaction proceeds via SN2.
H3C
H
O CH3
SN2
H3C
OH
+ CH3I
I
Reaction takes place on the less hindered of the
two alkyl groups.
Ethers
Only hydrogen halides react with ethers
Ethers commonly used as solvents
Often used solvents are:
O
O
tetrahydrofuran
THF
O
O
tetrahydropyran
1,4-dioxan
CH3CH2OCH2CH3
diethyl ether
"ether"
CH3OCH2CH2OCH3
dimethoxyethane
DME