Chapter 11
Alcohols & Ethers
Created by
Professor William Tam & Dr. Phillis Chang
Ch. 11 - 1
About The Authors
These Powerpoint Lecture Slides were created and prepared by Professor
William Tam and his wife Dr. Phillis Chang.
Professor William Tam received his B.Sc. at the University of Hong Kong in
1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an
NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard
University (USA). He joined the Department of Chemistry at the University of
Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and
Associate Chair in the department. Professor Tam has received several awards
in research and teaching, and according to Essential Science Indicators, he is
currently ranked as the Top 1% most cited Chemists worldwide. He has
published four books and over 80 scientific papers in top international journals
such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem.
Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her
M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She
lives in Guelph with her husband, William, and their son, Matthew.
Ch. 11 - 2
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 - 3
OH
2-Propenol
(allyl alcohol)
OH
2-Propynol
(propargyl alcohol)
OH
Benzyl alcohol
Ch. 11 - 4

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 - 5

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 - 6
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 - 7

Examples
OH
OH
OH
OH
2-Propanol
(isopropyl alcohol)
1,2,3-Butanetriol
Ch. 11 - 8

Example
OH
3-Propyl-2-heptanol
8
or
1
5
2
OH
3
4
6
7
wrong
3
7
6
5
OH
4
1
2
Ch. 11 - 9
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 - 10

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 - 11
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

Ch. 11 - 12

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
Ch. 11 - 13

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 - 14

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 - 15

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 - 16
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
C
C
H
O
H
H
Ch. 11 - 17

Acid-Catalyzed Hydration of Alkenes
● Markovnikov regioselectivity
● Free carbocation intermediate
● Rearrangement of carbocation
possible
Ch. 11 - 18

Oxymercuration–Demercuration
C
C
Hg(OAc) 2
H2O, THF
OH
C
C
HgOAc
NaBH4
NaOH
OH
C
C
H
● Markovnikov regioselectivity
● Anti stereoselectivity
● Generally takes place without the
complication of rearrangements
● Mechanism
 Discussed in Section 8.6
Ch. 11 - 19

Hydroboration–Oxidation
1. BH3 THF
2. H2O2, OH
OH
H
● Anti-Markovnikov regioselectivity
● Syn-stereoselectivity
● Mechanism
 Discussed in Section 8.7
Ch. 11 - 20
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
Ch. 11 - 21

Example
Synthesis?
(1)
OH
OH
Synthesis?
(2)
Ch. 11 - 22

Synthesis (1)
H
OH
● Need anti-Markovnikov addition of
H–OH
● Use hydroboration-oxidation
H
OH
1. BH3 • THF
2. H2O2, NaOH
Ch. 11 - 23

Synthesis (2)
OH
H
● Need Markovnikov addition of H–OH
● Use either
 acid-catalyzed hydration or
 oxymercuration-demercuration
● Acid-catalyzed hydration is NOT
desired due to rearrangement of
carbocation
Ch. 11 - 24

Acid-catalyzed hydration
HO
⊕
H
H2O
H
o
(2 cation)
Rearrangement
of carbocation
Ch. 11 - 25

Oxymercuration-demercuration
OH
H
Hg(OAc) 2
H2O, THF
NaBH4
NaOH
OH
HgOAc
Ch. 11 - 26
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 - 27

 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 - 28

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 - 29
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 - 30
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 - 31
7. Conversion of Alcohols into
Alkyl Halides
R
OH
R
X
● HX (X = Cl, Br, I)
● PBr3
● SOCl2
Ch. 11 - 32

Examples
OH
conc. HCl
Cl
o
25 C
+
HOH
(94%)
OH
PBr3
Br
(63%)
Ch. 11 - 33
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 - 34
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 - 35
8A. Mechanisms of the Reactions of
Alcohols with HX
Secondary, tertiary, allylic, and benzylic
alcohols appear to react by a
mechanism that involves the formation
of a carbocation
 Step 1

O
H + H
O
H
H
fast
O
H
H +
O
H
H
Ch. 11 - 36

Step 2
+
H
O
slow
H
H
H

O
Step 3
+
Cl
fast
Cl
Ch. 11 - 37

X
Primary alcohols and methanol react to
form alkyl halides under acidic
conditions by an SN2 mechanism
+ R
H
H
C
O
H
H
H
protonated 1o alcohol
X
C
H
H
R +
O
H
(a good
leaving group)
or methanol
Ch. 11 - 38
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 - 39

Reaction of alcohols with PBr3
● Phosphorus tribromide is often
preferred as a reagent for the
transformation of an alcohol to the
corresponding alkyl bromide
Ch. 11 - 40

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 - 41

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 - 42

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 - 43

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 - 44
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 - 45

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 - 46

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 - 47

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 - 48

SN2 displacement of the mesylate or
tosylate with a nucleophile is possible
OTs
Nu
+
+
Nu
OTs
Ch. 11 - 49

Example
OH
TsCl
Retention of
OTs configuration
pyridine
NaCN
DMSO
Inversion of
configuration
CN
+ NaOTs
Ch. 11 - 50

Example
Retention of
configuration
OH
OMs
MsCl
pyridine
NaSMe
DMSO
Inversion of
configuration
SMe
Ch. 11 - 51
11. Synthesis of Ethers
11A. Ethers by Intermolecular
Dehydration of Alcohols
H2SO4
180oC
Ethene
OH
H2SO4
o
140 C
O
Diethyl ether
Ch. 11 - 52

Mechanism
OH + H
OSO3H
O
H + OSO3H
H
OH
O
O
H 2O
+ H2O
H
● This method is only good for
synthesis of symmetrical ethers
Ch. 11 - 53

For unsymmetrical ethers
ROH + R'OH
H2SO4
R
R'
+
o
1 alcohols
O
R
O
R
+
R'
O
Mixture
of ethers
R'
Ch. 11 - 54

R
Exception
OH +
cat. H2SO4
HO
R
O
+ HO
H
R
H
(good yield)
OH
Ch. 11 - 55
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 - 56

Example 1
Na H
O
O Na
+ H2
H
Br
O
Ch. 11 - 57

Example 2
Cl
HO
Cl
NaOH
H2O
O
O
Ch. 11 - 58

Example 3
I
OH

NaOH
H2O
O
However
I
OH
NaOH
H2O
No epoxide observed!
Ch. 11 - 59
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 - 60

Example
1. Hg(O2CCF3)2, iPrOH
O
2. NaBH4, NaOH
Ch. 11 - 61
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 - 62

Example
Synthesis of
from
and
1
3
HO
2
1
5
4
3
HO
Br
2
5
BrMg
4
Ch. 11 - 63
● 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 - 64
● 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 - 65
11E. Silyl Ether Protecting Groups

R
A hydroxyl group can also be protected
by converting it to a silyl ether group
O
H +
Me
Me
Si t
Cl
Bu
tert-butylchloro
imidazole
DMF
(HCl)
Me
R
(R
Me
Si t
O
Bu
O
TBS )
dimethylsilane
(TBSCl)
Ch. 11 - 66

The TBS group can be removed by
treatment with fluoride ion (tetrabutylammonium fluoride or aqueous HF is
frequently used)
Me
R
(R
Me
Si t
O
Bu
O
Bu4NF
THF
R
O
H +
Me
Me
Si t
F
Bu
TBS )
Ch. 11 - 67

Example
Synthesis of
2
HO
4
1
from
HO
Ph
I
3
6
Ph
4
1
and
5
3
2
6
5
Na
Ch. 11 - 68
● Direct reaction will not work
Ph
Na
☓
+
H
O
(Not Formed)
HO
Ph
I
● Instead
Na
H
Ph
H
O
+
+
O
Ph
I
O
I
Ch. 11 - 69
● Need to “protect” the –OH group
first
HO
I
TBSCl
TBSO
imidazole
DMF
I
Na
Ph
TBSO
Ph
Bu4N F
THF
HO
Ph
Ch. 11 - 70
12. Reactions of Ethers

Dialkyl ethers react with very few
reagents other than acids
O
+ HBr
+ Br
O
H
an oxonium salt
Ch. 11 - 71
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 - 72

Mechanism
+ H
O
Br
+ Br
O
H
Br
+ Br
O
H
O
H
+
Br
H
H
O
H
+
Br
Ch. 11 - 73
13. Epoxides

Epoxide (oxirane)
● A 3-membered ring containing an
oxygen
O
Ch. 11 - 74
13A. Synthesis of Epoxides:
Epoxidation

Electrophilic epoxidation
C
C
O
peroxy
acid
C
C
Ch. 11 - 75

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 - 76

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
Ch. 11 - 77
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 - 78

Electron-rich double reacts faster
MCPBA
(1 eq.)
O
Ch. 11 - 79
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 - 80

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 - 81

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 - 82

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 - 83

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 - 84
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 - 85

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 - 86
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 - 87

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 - 88

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 - 89

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 - 90

Several antibiotics call ionophores are
large ring polyethers and polylactones
Me
Me
O
Me
O
O
O
O
O
Me
Me
O
O
O
O
O
O
Me
Me
Me
Nonactin
Ch. 11 - 91
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 - 92

Synthesis of alcohols
1. BH3 THF
2. H2O2, NaOH
+
H , H2O
OH
(2o alcohol)
1. Hg(OAc)2, H2O
2. NaBH4
or
Ch. 11 - 93

Synthesis of alcohols
X
H2O
H+, H2O
OH
1. Hg(OAc)2, H2O
2. NaBH4
(3o alcohol)
Ch. 11 - 94

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 - 95

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 - 96
 END OF CHAPTER 11 
Ch. 11 - 97