Chapter 11
Alcohols & Ethers
Created by
Professor William Tam & Dr. Phillis Chang
Ch. 11 - 1
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)
Ch. 11 - 2
OH
2-Propenol
(allyl alcohol)
OH
2-Propynol
(propargyl alcohol)
OH
Benzyl alcohol
Ch. 11 - 3

Phenols
● Compounds that have a hydroxyl
group attached directly to a
benzene ring
OH
OH
Cl
OH
H3C
Phenol
4-Methylphenol
2-Chlorophenol
Ch. 11 - 4

Ethers
● The oxygen atom of an ether is
bonded to two carbon atoms
O
O
Diethyl ether
O
Divinyl ether
CH3
tert-Butyl methyl ether
O
Ethyl phenyl ether
Ch. 11 - 5
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”
Ch. 11 - 6

Examples
OH
OH
OH
OH
2-Propanol
(isopropyl alcohol)
1,2,3-Butanetriol
Ch. 11 - 7

Example
1
5
2
3
4
7
6
3-Propyl-2-heptanol
OH
Ch. 11 - 8
1B. Nomenclature of Ethers

Rules of naming ethers
● Similar to those with alkyl halides
 CH3O–
Methoxy
 CH3CH2O–
Ethoxy

Example
O
Ethoxyethane
(diethyl ether)
Ch. 11 - 9

Cyclic ethers
O
Oxacyclopropane
or oxirane
(ethylene oxide)
O
Oxacyclobutane
or oxetane
O
O
Oxacyclopentane
(tetrahydrofuran or THF)
O
1,4-Dioxacyclohexane
(1,4-dioxane)
Ch. 11 - 10
2. Physical Properties of
Alcohols and Ethers
Ch. 11 - 11

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
Ch. 11 - 12

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
Oxirane
O
Tetrahydrofuran (THF)
O
Ch. 11 - 13

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
* Water solubility (g/100 mL H2O)
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.
Ch. 11 - 14
4. Synthesis of Alcohols from Alkenes

Acid-catalyzed Hydration of Alkenes
C
C
H
H2O
C
C
H
OH
Ch. 11 - 15

Hydroboration–Oxidation
1. BH3 THF
2. H2O2, OH
OH
H
Ch. 11 - 16
OH
H+, H2O or
1. Hg(OAc)2, H2O, THF
2. NaBH4, NaOH
R
H
Markovnikov regioselectivity
R
1. BH3 • THF
2. H2O2, NaOH
H
R
OH
Anti-Markovnikov regioselectivity
Ch. 11 - 17
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
Ch. 11 - 18

 O

C–O & O–H bonds of an
alcohol are polarized
H
Protonation of the alcohol converts a
⊖
poor leaving group (OH ) into a good
one (H2O)
H
C
O
alcohol
H + H
A
strong
acid
C
O
H + A
protonated
alcohol
Ch. 11 - 19

Once the alcohol is protonated
substitution reactions become possible
H
Nu +
C
O
protonated
alcohol
H
SN2
H
Nu
C
+ O
H
The protonated –OH
group is a good leaving
group (H2O)
Ch. 11 - 20
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
Ch. 11 - 21
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
⊖
OH is the weakest
acid in this series
C
> RO > HO
Increasing basicity
Ch. 11 - 22
7. Conversion of Alcohols into
Alkyl Halides
R
OH
R
X
● HX (X = Cl, Br, I)
● PBr3
● SOCl2
Ch. 11 - 23

Examples
OH
conc. HCl
Cl
o
25 C
+
HOH
(94%)
OH
PBr3
Br
(63%)
Ch. 11 - 24
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)

Ch. 11 - 25
R
OH + NaX
No Reaction!
⊖
OH is a poor
leaving group
R
OH + NaX
R
⊕
H
H3O is a good
leaving group
O
R
H
X
X
H
Ch. 11 - 26
9.

Alkyl Halides from the Reaction
of Alcohols with PBr3 or SOCl2
Reaction of alcohols with PBr3
3 R OH + PBr3
o
o
(1 or 2 )
R
Br + H3PO3
● The reaction does not involve the
formation of a carbocation and usually
occurs without rearrangement of the
carbon skeleton (especially if the
temperature is kept below 0°C)
Ch. 11 - 27

Mechanism
Br
R
Br
OH +
+ R
Br
P
O
Br
PBr2
H
a good
leaving group
R
O
PBr2
+ Br
H
protonated
alkyl dibromophosphite
R
Br + HOPBr2
Ch. 11 - 28

Reaction of alcohols with SOCl2
● SOCl2 converts 1o and 2o alcohols to
alkyl chlorides
● As with PBr3, the reaction does not
involve the formation of a
carbocation and usually occurs
without rearrangement of the
carbon skeleton (especially if the
temperature is kept below 0°C)
● Pyridine (C5H5N) is often included to
promote the reaction
Ch. 11 - 29

Mechanism
O
R
O
H + Cl
S
R
Cl
H
O
O
S
N
Cl
Cl
 Cl
(C5H5N)
O
N +R
O
S
Cl
R
H
O
O
S
Cl
Ch. 11 - 30

Mechanism
O
N +R
O
S
Cl
 Cl
O
R
O
S
N
⊖
Cl
O
O
+
N
S
O
R
Cl + O
S
N
Ch. 11 - 31
10. Tosylates, Mesylates, & Triflates:
Leaving Group Derivatives of
Alcohols
O
OTs =
O
S
CH3
(Tosylate)
O
O
OMs =
O
S
CH3
(Mesylate)
O
Ch. 11 - 32

Direct displacement of the –OH group
with a nucleophile via an SN2 reaction
⊖
is not possible since OH is a very poor
leaving group
OH + Nu

No Reaction!
⊖
Thus we need to convert the OH to a
better leaving group first
Ch. 11 - 33

Mesylates (OMs) and Tosylates (OTs)
are good leaving groups and they can
be prepared easily from an alcohol
(methane sulfonyl chloride)
+
OH
CH3
O
S
Cl
pyridine
O
O
O
same as
S
CH3 +
O
OMs
N
+ Cl
H
(a mesylate)
Ch. 11 - 34

Preparation of Tosylates (OTs) from an
alcohol
(p-toluene sulfonyl chloride)
O
+
OH
H3C
S
Cl
pyridine
O
O
O
same as
OTs
CH3 +
S
O
N
+ Cl
H
(a tosylate)
Ch. 11 - 35

SN2 displacement of the mesylate or
tosylate with a nucleophile is possible
OTs
Nu
+
+
Nu
OTs
Ch. 11 - 36

Example
OH
TsCl
Retention of
OTs configuration
pyridine
NaCN
DMSO
Inversion of
configuration
CN
+ NaOTs
Ch. 11 - 37

Example
Retention of
configuration
OH
OMs
MsCl
pyridine
NaSMe
DMSO
Inversion of
configuration
SMe
Ch. 11 - 38
11. Synthesis of Ethers
11A. Ethers by Intermolecular
Dehydration of Alcohols
H2SO4
180oC
Ethene
OH
H2SO4
o
140 C
O
Diethyl ether
Ch. 11 - 39

Mechanism
OH + H
OSO3H
O
H + OSO3H
H
OH
O
O
H2O
+ H2O
H
● This method is only good for
synthesis of symmetrical ethers
Ch. 11 - 40

For unsymmetrical ethers
ROH + R'OH
H2SO4
R
R'
+
o
1 alcohols
O
R
O
R
+
R'
O
Mixture
of ethers
R'
Ch. 11 - 41

R
Exception
OH +
cat. H2SO4
HO
R
O
+ HO
H
R
H
(good yield)
OH
Ch. 11 - 42
11B. The Williamson Synthesis of
Ethers
R
X
R'O
R
O
R'
(SN2)

Via SN2 reaction, thus R is limited to 1o
(but R' can be 1o, 2o or 3o)
Ch. 11 - 43

Example 1
Na H
O
O Na
+ H2
H
Br
O
Ch. 11 - 44

Example 2
Cl
HO
Cl
NaOH
H2O
O
O
Ch. 11 - 45

Example 3
I
OH

NaOH
H2O
O
However
I
OH
NaOH
H2O
No epoxide observed!
Ch. 11 - 46
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)
Ch. 11 - 47

Example
i
1. Hg(O2CCF3)2, PrOH
O
2. NaBH4, NaOH
Ch. 11 - 48
11D. tert-Butyl Ethers by Alkylation
of Alcohols: Protecting Groups
R


OH +
H2SO4
R
O
tert-butyl
A tert-butyl ether can be used to
protecting
“protect” the hydroxyl group of a 1o
group
alcohol while another reaction is carried
out on some other part of the molecule
A tert-butyl protecting group can be removed
easily by treating the ether with dilute aqueous
acid
Ch. 11 - 49

Example
Synthesis of
from
and
1
3
HO
2
1
5
4
3
HO
Br
2
5
BrMg
4
Ch. 11 - 50
● Direct reaction will not work
BrMg
☓
+
(Not Formed)
HO
Br
HO
● Since Grignard reagents are basic
and alcohols contain acidic proton
BrMg
+
H
O
BrMg O
Br
+ H
Br
Ch. 11 - 51
● Need to “protect” the –OH group
first
tert-butyl protected alcohol
HO
Br
1. H2SO4
2.
O
Br
BrMg
H
HO
H2O
deprotonation
O
Ch. 11 - 52
12. Reactions of Ethers

Dialkyl ethers react with very few
reagents other than acids
O
+ HBr
+ Br
O
H
an oxonium salt
Ch. 11 - 53
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
Br + H2O
Cleavage of an ether
Ch. 11 - 54

Mechanism
+ H
O
Br
+ Br
O
H
Br
+ Br
O
H
O
H
+
Br
H
H
O
H
+
Br
Ch. 11 - 55
13. Epoxides

Epoxide (oxirane)
● A 3-membered ring containing an
oxygen
O
Ch. 11 - 56
13A. Synthesis of Epoxides:
Epoxidation

Electrophilic epoxidation
C
C
O
peroxy
acid
C
C
Ch. 11 - 57

Peroxy acids (peracids)
O
R
C
O
OH
● Common peracids
Cl
O
C
O
O
OH
meta-chloroperbenzoid acid
(MCPBA)
H3C
C
O
OH
peracetic acid
Ch. 11 - 58
13B. Stereochemistry of Epoxidation
Addition of peroxy acid across a C=C
bond
 A stereospecific syn (cis) addition

MCPBA
(trans)
(trans)
MCPBA
(cis)
O
O
(cis)
Ch. 11 - 59
14. Reactions of Epoxides

The highly strained three-membered
ring of epoxides makes them much
more reactive toward nucleophilic
substitution than other ethers
Ch. 11 - 60

Acid-catalyzed ring opening of epoxide
C
+ H
C
O
O
C
H
+
C
O
H
O
C
H
O
O
H
H
+
H
H
H
H
O
H
H
H
O
H
O
C
C
H
H
C
O
Ch. 11 - 61

Base-catalyzed ring opening of epoxide
RO
R
O
+
C
C
C
C
O
O
R
O
H
RO
C
+ R
C
O
OH
Ch. 11 - 62

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
EtOH
EtO
+ Et
OH
O
Ch. 11 - 63

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
Ch. 11 - 64
15. Anti 1,2-Dihydroxylation of
Alkenes via Epoxides

Synthesis of 1,2-diols

cold KMnO4, OH or
OH
1. OsO4
2. NaHSO3
OH
1. MCPBA
2. H, H2O
OH
OH
Ch. 11 - 65

Anti-Dihydroxylation
● A 2-step procedure via ring-opening
of epoxides
H
MCPBA
O
H
H
O
H2O
H
H
H
OH
OH
H2O
Ch. 11 - 66
16. Crown Ethers

Crown ethers are heterocycles
containing many oxygens

They are able to transport ionic
compounds in organic solvents –
phase transfer agent
Ch. 11 - 67

Crown ether names: x-crown-y
● x = ring size
● y = number of oxygen
O
O
O
O
O
O
O
(18-crown-6)
O
O
O
O
O
O
O
O
(15-crown-5)
(12-crown-4)
Ch. 11 - 68

Different crown ethers accommodate
different guests in this guest-host
relationship
+
● 18-crown-6 for K
+
● 15-crown-5 for Na
+
● 12-crown-4 for Li

1987 Nobel Prize to Charles Pedersen
(Dupont), D.J. Cram (UCLA) and J.M.
Lehn (Strasbourg) for their research on
ion transport, crown ethers
Ch. 11 - 69

Many important implications to
biochemistry and ion transport
O
O
O
O
O
O
KMnO4
benzene
O
O
K
O
MnO4
O
O
O
(18-crown-6)
(purple benzene)
Ch. 11 - 70
17. Summary of Reactions of
Alkenes, Alcohols, and Ethers

Synthesis of alcohols
X
OH
O
1.
2. H2O
MgBr
OH
(1o alcohol)
1. BH3 THF
2. H2O2, NaOH
Ch. 11 - 71

Synthesis of alcohols
1. BH3 THF
2. H2O2, NaOH
+
H , H2O
OH
(2o alcohol)
1. Hg(OAc)2, H2O
2. NaBH4
or
Ch. 11 - 72

Synthesis of alcohols
X
H2O
H+, H2O
OH
1. Hg(OAc)2, H2O
2. NaBH4
(3o alcohol)
Ch. 11 - 73

Reaction of alcohols
OR
Br
PBr3
1. base
2. R-X
H+, heat
OH
SOCl 2
Cl
(1o alcohol)
H-X
TsCl
pyridine
OTS
X
Ch. 11 - 74

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
H
R'
X
ROH + R'X
Ch. 11 - 75