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Chapter 11
Reactions of Alcohols
Jo Blackburn
Richland College, Dallas, TX
Dallas County Community College District
! 2006, Prentice Hall
Organic Chemistry
L. G. Wade, Jr.
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Types of Alcohol Reactions
Dehydration to alkene
Oxidation to aldehyde, ketone
Substitution to form alkyl halide
Reduction to alkane
Esterification
Williamson ether synthesis
Chapter 11 2
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Summary Table
Chapter 11 3
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Oxidation States
For inorganics:
! CrO
4
2-
reduced to Cr
2
O
3
! KMnO
4
reduced to MnO
2
For organics
! Oxidation: loss of H
2
, gain of O, O
2
, or X
2
! Reduction: gain of H
2
or H
-
, loss of O, O
2
, or X
2
! Neither: gain or loss of H
+
, H
2
O, HX
Chapter 11 4
2
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1, 2, 3 Carbons
Chapter 11 5
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Oxidation of 2Alcohols
2alcohol becomes a ketone
Common reagent is Na
2
Cr
2
O
7
/H
2
SO
4
Active reagent probably H
2
CrO
4
Color change: orange to greenish-blue
Chapter 11 6
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Oxidation of 1Alcohols
1alcohol to aldehyde to carboxylic acid
Difficult to stop at aldehyde
Use pyridinium chlorochromate (PCC)
to limit the oxidation.
(PCC can also be used to oxidize 2
alcohols to ketones.)
Chapter 11 7
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Oxidation of 1Alcohols
Chapter 11 8
3
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3Alcohols Dont Oxidize
Cannot lose 2 Hs
Basis for chromic acid test
Chapter 11 9
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Other Oxidation Reagents
HOCl (NaOCl / H
+
)
Collins reagent: Cr
2
O
3
in pyridine
Jones reagent: chromic acid in acetone
KMnO
4
(strong oxidizer)
CuO, 300C (industrial dehydrogenation)
Various methods based on dimethylsulfoxide
Chapter 11 10
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Chapter 11 11
Dehydrogenation:
Swern Oxidation
There are many other oxidation
reagents. Here are two of them
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And the One You Did In the Lab
Chapter 11 12
4
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Biological Oxidation
Catalyzed by ADH, alcohol dehydrogenase.
Oxidizing agent is NAD
+
, nicotinamide
adenine dinucleotide.
Ethanol oxidizes to acetaldehyde, then acetic
acid, a normal metabolite.
Methanol oxidizes to formaldehyde, then
formic acid, more toxic than methanol.
Ethylene glycol oxidizes to oxalic acid, toxic.
Chapter 11 13
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Product?
1. (CH
3
)
2
CHOH
2. (CH
3
)
2
C=O
3. CH
3
CH
2
COOH
4. No reaction
!
"#
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Product?
1. CH
3
COOH
2. CH
3
CH
2
COOH
3. CH
3
CH
2
CHO
4. No reaction
!
$%
"#
5
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Product?
1. CH
3
COOH
2. CH
3
CH
2
COOH
3. CH
3
CH
2
CHO
4. No reaction
! $% "#
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Product?
1. (CH
3
)
3
COH
2. (CH
3
)
2
C=O
3. CH
2
=C(CH
3
)
2
4. No reaction
!
"#
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Alcohol as a Nucleophile
ROH is weak nucleophile
RO
-
is strong nucleophile
New O-C bond forms, O-H bond breaks.
Chapter 11 19
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Alcohol as an Electrophile
OH
-
is very poor leaving
group unless it is
protonated
Most nucleophiles are
strong bases which
would remove H
+
.
Convert to tosylate
(good leaving group) to
react with strong
nucleophile (base).
Chapter 11 20
+
C-Nuc bond forms,
C-O bond breaks
6
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Formation of Tosylate Ester
Chapter 11 21
p-toluenesulfonyl chloride
TsCl, tosyl chloride
ROTs,
a tosylate ester
=>
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S
N
2 Reactions of Tosylates
(basically same as halides)
With hydroxide produces alcohol
With cyanide produces nitrile
With halide ion produces alkyl halide
With alkoxide ion produces ether
With ammonia produces amine salt
With LiAlH
4
produces alkane
Chapter 11 22
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S
N
2 Reactions of Tosylates
Chapter 11 23
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Reduction of Alcohols
Chapter 11 24
Cannot just reduce off the oxygen of an alcohol
1. Dehydrate with conc. H
2
SO
4
, then add H
2
or
2. Tosylate, then reduce with LiAlH
4
7
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Conversion to Alkyl Halides
-OH of alcohol is protonated
-OH
2
+
is good leaving group
3and 2alcohols react with Br
-
via S
N
1
1alcohols react via S
N
2
Chapter 11 25
Reaction with HBr
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Reaction with HCl
Chloride is a weaker nucleophile than
bromide.
Add ZnCl
2
, which bonds strongly with
-OH, to promote the reaction.
The chloride product is insoluble.
Lucas test: ZnCl
2
in conc. HCl
! 1alcohols react slowly or not at all.
! 2 alcohols react in 1-5 minutes.
! 3 alcohols react in less than 1 minute.
Chapter 11 26
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Limitations of HX Reactions
HI does not react
Poor yields of 1and 2chlorides
May get alkene instead of alkyl halide
Carbocation intermediate may !"#!!#$%".
Chapter 11 28
8
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Reactions with Phosphorus
Halides or Thionyl Chloride
Good yields with 1and 2alcohols
SOCl
2
generally best for alkyl chlorides
PBr
3
for alkyl bromide
[P and I
2
for alkyl iodide (PI
3
not stable)]
Chapter 11 29
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Mechanism with PBr
3
P bonds to -OH as Br
-
leaves
Br
-
attacks backside (S
N
2)
HOPBr
2
leaves
Chapter 11 30
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Reaction with Thionyl Chloride
Produces alkyl chloride, SO
2
, HCl
S bonds to -OH, Cl
-
leaves
Cl
-
abstracts H
+
from OH
C-O bond breaks as Cl
-
transferred to C
Chapter 11 31
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Product?
1. CH
3
CH
2
CH
2
OTs
2. CH
3
CH
2
CH
2
OCl
3. CH
3
CH
2
CH
2
Cl
4. CH
3
CH
2
CH
2
Ts
!
$%
"#
9
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Product?
1. CH
3
CH
2
CH
2
OSCl
2
2. CH
3
CH
2
CH
2
Cl
3. CH
3
CH
2
CH
2
OCl
4. CH
3
CH
2
CH
2
SO
2
H
!
"
#
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Product?
1. CH
3
CH
2
CH
2
OPBr
3
2. CH
3
CH
2
CH
2
OBr
3. CH
3
CH
2
CH
2
Br
4. CH
3
CH
2
CH
2
PBr
2 !
"#
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Dehydration Reactions
Conc. H
2
SO
4
produces alkene
Carbocation intermediate
Zaitsev product
Bimolecular dehydration produces ether
Low temp, 140C and below, favors ether
High temp, 180C and above, favors alkene
Chapter 11 35
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Dehydration Mechanisms
Chapter 11 36
CH
2
CHCH
3
H
H
2
O CH
2
CHCH
3
10
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Energy Diagram, E1
Chapter 11 37
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Unique Reactions of Diols
Pinacol rearrangement
Periodic acid cleavage
Chapter 11 38
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Pinacol Rearrangement
Pinacol: 2,3-dimethyl-2,3-butanediol
Dehydration with sulfuric acid
Chapter 11 39
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Periodic Acid Cleavage of Glycols
Same products formed as from ozonolysis of
the corresponding alkene.
Chapter 11 40
11
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Esterification
Fischer: alcohol + carboxylic acid
Tosylate esters
Sulfate esters
Nitrate esters
Phosphate esters
Chapter 11 41
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Fischer Esterification
Acid + Alcohol yields Ester + Water
Sulfuric acid is a catalyst.
Each step is reversible.
Chapter 11 42
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Tosylate Esters
Alcohol + p-Toluenesulfonic acid, TsOH
Acid chloride is actually used, TsCl
Chapter 11 43
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Chapter 11 44
Why Tosylate Esters?
12
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Sulfate Esters
Alcohol + Sulfuric Acid
Chapter 11 45
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Nitrate Esters
Chapter 11 46
=>
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Phosphate Esters
Chapter 11 47
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Phosphate Esters in DNA
Chapter 11 48
13
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Product?
1. CH
3
CH
2
COOCH
3
2. CH
3
COOCH
2
CH
3
3. CH
3
CH
2
COOCH
2
CH
3
4. CH
3
COOCH
3
!
$%
"#
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Product?
1. CH
3
OSO
3
H
2. CH
3
OSO
3
CH
3
3. CH
3
OSO
2
CH
3
4. CH
3
OSO
2
H
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Williamson Ether Synthesis
ROH + Na (or NaH) yields sodium alkoxide
RO
-
+ 1alkyl halide yields ether
Chapter 11 51
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End of Chapter 11
Chapter 11 52