CH3CH_2CH2 +

 H
Br C O
Organic Chemistry, 6th Edition H H
H

L. G. Wade, Jr.

Chapter 11
Reactions of Alcohols

Jo Blackburn
Richland College, Dallas, TX
Dallas County Community College District
2006,Prentice Hall
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
H
H H
Summary Table

Chapter 11 3 =>
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
1º, 2º, 3º Carbons H H
H

=>
Chapter 11 5
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
Oxidation of 1° Alcohols H H
H

• 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
 CH3CH_2CH2 +
 H
Br C O
3° Alcohols Don’t Oxidize H H
H

• Cannot lose 2 H’s

• Basis for chromic acid test

=>
Chapter 11 8
 CH3CH_2CH2 +
 H
Br C O
H
H H
Other Oxidation Reagents
• Collins reagent: Cr2O3 in pyridine
• Jones reagent: chromic acid in acetone
• KMnO4 (strong oxidizer)
• Nitric acid (strong oxidizer)
• CuO, 300°C (industrial dehydrogenation)
• Swern oxidation: dimethylsulfoxide, with
oxalyl chloride and hindered base,
oxidizes 2 alcohols to ketones and 1
alcohols to aldehydes. =>
Chapter 11 9
 CH3CH_2CH2 +
H
Biological Oxidation

Br C O
H
H H

• 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
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
H
Alcohol as an Electrophile H H

• OH- is not a good leaving

group unless it is H
protonated, but most
nucleophiles are strong O
bases which would + C
remove H+.
• Convert to tosylate (good
leaving group) to react
with strong nucleophile C-Nuc bond forms,
C-O bond breaks
(base).
=>
Chapter 11 12
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
Summary of Tosylate H H
H

Reactions

=>
Chapter 11 15
 CH3CH_2CH2 +
 H
Br C O
Reduction of Alcohols H H
H

• 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
 CH3CH_2CH2 +
 H
Br C O
H
Reaction with HBr H H

• -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
 CH3CH_2CH2 +
 H
Reaction with HCl Br C O
H H
H

• 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
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
Reactions with H H
H

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
 CH3CH_2CH2 +
 H
Mechanism with PBr3 Br C O
H H
H

• P bonds to -OH as Br- leaves

• Br- attacks backside (SN2)
• HOPBr2 leavesChapter 11
=> 21
 CH3CH_2CH2 +
Reaction with  H
Br C O
H
H H
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
=>
 CH3CH_2CH2 +
 H
Br C O
H
H H
Dehydration Reactions
• Conc. H2SO4 produces alkene
• Carbocation intermediate
• Zaitsev product
• Bimolecular dehydration produces ether
• Low temp, 140°C and below, favors ether
• High temp, 180°C and above, favors
alkene =>
Chapter 11 23
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Energy Diagram, E1 Br C O
H H
H

=>
Chapter 11 25
 CH3CH_2CH2 +
 H
Br C O
H
H H
Unique Reactions of Diols
• Pinacol rearrangement
• Periodic acid cleavage

=>

Chapter 11 26
 CH3CH_2CH2 +
 H
Br C O
Pinacol Rearrangement H H
H

• 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
 CH3CH_2CH2 +
 H
Periodic Cleavage Br C O
H H
H

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
 CH3CH_2CH2 +
 H
Br C O
H
H H
Esterification
• Fischer: alcohol + carboxylic acid
• Tosylate esters
• Sulfate esters
• Nitrate esters
• Phosphate esters
=>

Chapter 11 29
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
H
H H
Nitrate Esters
O +
H O
N OH + H O CH2CH3 N OCH2CH3
O O

=>
Chapter 11 33
 CH3CH_2CH2 +
 H
Br C O
H
H H
Phosphate Esters

=>
Chapter 11 34
 CH3CH_2CH2 +
 H
Br C O
Phosphate Esters in DNA H H
H

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
 CH3CH_2CH2 +
 H
Br C O
H
H H
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
 CH3CH_2CH2 +
 H
Br C O
H
H H

End of Chapter 11

Chapter 11 37