Organic Chemistry, 6th Edition

L. G. Wade, Jr.

Chapter 11
Reactions of Alcohols
 Types of Alcohol Reactions
Dehydration to alkene
Oxidation to aldehyde, ketone
Substitution to form alkyl halide
Reduction to alkane
Esterification
Tosylation
Williamson synthesis of ether =>

Chapter 11 2
Summary Table

Chapter 11 3 =>
 Oxidation States
Easy for inorganic salts
CrO42- reduced to Cr2O3
KMnO4 reduced to MnO2
Oxidation: loss of H2, gain of O, O2, or X2
Reduction: gain of H2 or H-, loss of O, O2,
or X2
Neither: gain or loss of H+, H2O, HX
=>
Chapter 11 4
1, 2, 3 Carbons

=>
Chapter 11 5
 Oxidation of 2 Alcohols
2 alcohol becomes a ketone
Reagent is Na2Cr2O7/H2SO4
Active reagent probably H2CrO4
Color change: orange to greenish-blue

OH O
Na2Cr2O7 / H2SO4
CH3CHCH2CH3 CH3CCH2CH3

=>
Chapter 11 6
 Oxidation of 1 Alcohols
1 alcohol 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.

OH N H CrO3Cl O
CH3CH2CH2CH2 CH3CH2CH2CH
=>
Chapter 11 7
 3 Alcohols Dont Oxidize
Cannot lose 2 Hs
Basis for chromic acid test

=>
Chapter 11 8
 Other Oxidation Reagents
Collins reagent: Cr2O3 in pyridine
Jones reagent: chromic acid in acetone
KMnO4 (strong oxidizer)
Nitric acid (strong oxidizer)
CuO, 300C (industrial dehydrogenation)
Swern oxidation: dimethylsulfoxide, with
oxalyl chloride and hindered base,
oxidizes 2 alcohols to ketones and 1
alcohols to aldehydes. =>
Chapter 11 9
 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.
Treatment for poisoning is excess ethanol.
=>
Chapter 11 10
 Alcohol as a Nucleophile
H
O
C R X

ROH is weak nucleophile

RO- is strong nucleophile
New O-C bond forms, O-H bond breaks.
=>
Chapter 11 11
 Alcohol as an Electrophile
OH- is not a good
leaving group unless it H
is protonated, but most
nucleophiles are strong O
bases which would + C
remove H+.
Convert to tosylate
(good leaving group) to
C-Nuc bond forms,
react with strong C-O bond breaks
nucleophile (base).
=>
Chapter 11 12
Formation of Tosylate Ester
H
C C
O Cl
C H O O
O S O N
O S O O S O

CH3 CH3 CH3

p-toluenesulfonyl chloride ROTs,
TsCl, tosyl chloride a tosylate ester
=>

Chapter 11 13
 SN2 Reactions of Tosylates
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 LiAlH4 produces alkane
=>

Chapter 11 14
Summary of Tosylate
Reactions

=>
Chapter 11 15
 Reduction of Alcohols
Dehydrate with conc. H2SO4, then add H2
Tosylate, then reduce with LiAlH4

OH
H2SO4 H2
CH3CHCH3 CH2 CHCH3 CH3CH2CH3
Pt
alcohol alkene alkane

OH OTs
TsCl LiAlH4
CH3CHCH3 CH3CHCH3 CH3CH2CH3 =>
alcohol tosylate alkane

Chapter 11 16
 Reaction with HBr
-OH of alcohol is protonated
-OH2+ is good leaving group
-
3 and 2 alcohols react with Br via SN1
1 alcohols react via SN2

+ H -
H3O Br
R O H R O H R Br =>

Chapter 11 17
 Reaction with HCl
Chloride is a weaker nucleophile than
bromide.
Add ZnCl2, which bonds strongly with
-OH, to promote the reaction.
The chloride product is insoluble.
Lucas test: ZnCl2 in conc. HCl
1 alcohols react slowly or not at all.
2 alcohols react in 1-5 minutes.
3 alcohols react in less than 1 minute.
=>
Chapter 11 18
Limitations of HX Reactions
HI does not react
Poor yields of 1 and 2 chlorides
May get alkene instead of alkyl halide
Carbocation intermediate may
rearrange.

=>

Chapter 11 19
 Reactions with
Phosphorus Halides
Good yields with 1 and 2 alcohols
PCl3 for alkyl chloride (but SOCl2 better)
PBr3 for alkyl bromide
P and I2 for alkyl iodide (PI3 not stable)

=>

Chapter 11 20
 Mechanism with PBr3

-
P bonds to -OH as Br leaves
Br- attacks backside (S 2)
N
HOPBr2 leaves =>
Chapter 11 21
 Reaction with
Thionyl Chloride

Produces alkyl chloride, SO2, HCl

-
S bonds to -OH, Cl leaves
Cl- abstracts H+ from OH
-
C-O bond breaks as Cl transferred to C
Chapter 11 22
=>
 Dehydration Reactions
Conc. H2SO4 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 23
 Dehydration Mechanisms
H
OH OH
H2SO4
CH3CHCH3 CH3CHCH3 CH3CHCH3
alcohol
H2O
CH2 CHCH3
+
H3O
CH3OH CH3 OH2 CH3 O CH3
H
CH3OH CH3OCH3
H2O
=>
Chapter 11 24
Energy Diagram, E1

=>
Chapter 11 25
 Unique Reactions of Diols
Pinacol rearrangement
Periodic acid cleavage

=>

Chapter 11 26
 Pinacol Rearrangement
Pinacol: 2,3-dimethyl-2,3-butanediol
Dehydration with sulfuric acid
CH3 CH3 CH3 CH3 CH3
+
H CH3
CH3 C C CH3 CH3 C C CH3 CH3 C C
CH3
OH OH OH OH OH
H
CH3 CH3 CH3
CH3
CH3 C C CH3 C C CH3 CH3 C C CH3
CH3
OH OH CH3 OH CH3

CH3
CH3 C C CH3 =>
O CH3
Chapter 11 27
pinacolone
 Periodic Cleavage
of Glycols
Same products formed as from ozonolysis
of the corresponding alkene.
H CH3 CH3
HIO4 H
CH3 C C CH3 CH3 C C CH3
+
OH OH O O

OsO4 O3
H2O2 (CH3)2S

H CH3
C C =>
H3C CH3
Chapter 11 28
 Esterification
Fischer: alcohol + carboxylic acid
Tosylate esters
Sulfate esters
Nitrate esters
Phosphate esters
=>

Chapter 11 29
 Fischer Esterification
Acid + Alcohol yields Ester + Water
Sulfuric acid is a catalyst.
Each step is reversible.
O CH3 + O CH3
H
CH3 C OH + H O CH2CH2CHCH3 CH3C OCH2CH2CHCH3

+ HOH

=>

Chapter 11 30
 Tosylate Esters
Alcohol + p-Toluenesulfonic acid, TsOH
Acid chloride is actually used, TsCl
O
CH3CH2 O H + HO S CH3
O

O
CH3CH2 O S CH3 =>
O
+ HOH
Chapter 11 31
 Sulfate Esters
Alcohol + Sulfuric Acid
O +
O
H
HO S OH + H O CH2CH3 HO S OCH2CH3
O O

O + O
H
CH3CH2O H + HO S OCH2CH3 CH3CH2O S OCH2CH3
O O =>

Chapter 11 32
 Nitrate Esters
O +
H O
N OH + H O CH2CH3 N OCH2CH3
O O

=>
Chapter 11 33
Phosphate Esters

=>
Chapter 11 34
Phosphate Esters in DNA
O CH2 base
O
H
H H
O O CH2 base
O
P
O O H
H H
O O CH2 base
O
P
O O H
H H
O O CH2 base
O
P
O O H
H H
O O
P
O O =>
Chapter 11 35
 Alkoxide Ions
ROH + Na (or NaH) yields sodium alkoxide
RO- + 1 alkyl halide yields ether (Williamson
ether synthesis)

CH3
CH3CH2CHCH3 + CH3CH2 Br CH2CH2CH O CH2CH3
O
=>

Chapter 11 36