C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11
Reactions of Alcohols
Jo Blackburn
Richland College,Dallas,TX
Dallas County Community College District
2003,Prentice Hall
Organic Chemistry,5th Edition
L,G,Wade,Jr.
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 2
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 =>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 3
Summary Table
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 4
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
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 5
1o,2o,3o Carbons
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 6
Oxidation of 2° Alcohols
2° alcohol becomes a ketone
Reagent is Na2Cr2O7/H2SO4
Active reagent probably H2CrO4
Color change,orange to greenish-blue
C H 3 C H C H 2 C H 3
O H N a
2 C r 2 O 7 / H 2 S O 4
C H 3 C C H 2 C H 3
O
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 7
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.
C H 3 C H 2 C H 2 C H 2
O H N H C r O 3 C l
C H 3 C H 2 C H 2 C H
O
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 8
3° Alcohols Don’t Oxidize
Cannot lose 2 H’s
Basis for chromic acid test
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 9
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,=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 10
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.
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 11
Alcohol as a Nucleophile
ROH is weak nucleophile
RO- is strong nucleophile
New O-C bond forms,O-H bond breaks.
=>
C
O
H
R X
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 12
Alcohol as an Electrophile
OH- is not a good
leaving group unless it
is protonated,but most
nucleophiles are strong
bases which would
remove H+.
Convert to tosylate
(good leaving group) to
react with strong
nucleophile (base)
=>
C
O
H
+
C-Nuc bond forms,
C-O bond breaks
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 13
Formation of Tosylate Ester
p-toluenesulfonyl chloride
TsCl,“tosyl chloride”
C
O
H
C H 3
S
C l
OO
N
C H 3
S OO
OH
C
C H 3
S
O
OO
C
ROTs,
a tosylate ester
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 14
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
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 15
Summary of Tosylate
Reactions
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 16
Reduction of Alcohols
Dehydrate with conc,H2SO4,then add H2
Tosylate,then reduce with LiAlH4
C H 3 C H C H 3
O H
H 2 S O 4
C H 2 C H C H 3
H 2
P t
C H 3 C H 2 C H 3
a l c o h o l a l k e n e a l k a n e
a l c o h o l
C H 3 C H C H 3
O H
T s C l
C H 3 C H C H 3
O T s
L i A l H 4
a l k a n e
C H 3 C H 2 C H 3
t o s y l a t e
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 17
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 3 O + B r -
R O H R O H
H
R B r=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 18
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.
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 19
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,
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 20
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)
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 21
Mechanism with PBr3
P bonds to -OH as Br- leaves
Br- attacks backside (SN2)
HOPBr2 leaves =>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 22
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
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 23
Dehydration Reactions
Conc,H2SO4 produces alkene
Carbocation intermediate
Saytzeff product
Bimolecular dehydration produces ether
Low temp,140° C and below,favors ether
High temp,180° C and above,favors
alkene =>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 24
Dehydration Mechanisms
C H 3 C H C H 3
O H
H 2 S O 4
a l c o h o l
C H 3 C H C H 3
O H
H
C H 3 C H C H 3
C H 2 C H C H 3H 2 O
C H 3 O H
H 3 O +
C H 3 O H C H 3 O H 2C H 3 O
H
C H 3
H 2 O
C H 3 O C H 3
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 25
Energy Diagram,E1
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 26
Unique Reactions of Diols
Pinacol rearrangement
Periodic acid cleavage
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 27
Pinacol Rearrangement
Pinacol,2,3-dimethyl-2,3-butanediol
Dehydration with sulfuric acid
C H 3 C
C H 3
O H O H
C H 3
C C H 3
H +
C H 3 C
C H 3
O H O H
C H 3
C C H 3
H
C H 3 C
C H 3
O H
C
C H 3
C H 3
C H 3 C
C H 3
O H
C
C H 3
C H 3
C H 3 C
O H
C H 3
C C H 3
C H 3
C H 3 C
O H
C H 3
C C H 3
C H 3
C H 3 C
O
C H 3
C C H 3
C H 3
p i n a c o l o n e
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 28
Periodic Cleavage
of Glycols
Same products formed as from ozonolysis
of the corresponding alkene.
C H 3 C
H
O H O H
C H 3
C C H 3
H I O 4
C H 3 C
H
O
+ C
O
C H 3
C H 3
C C
H 3 C
H C H
3
C H 3
O s O 4
H 2 O 2
O 3
(C H 3 )2 S
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 29
Esterification
Fischer,alcohol + carboxylic acid
Tosylate esters
Sulfate esters
Nitrate esters
Phosphate esters
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 30
Fischer Esterification
Acid + Alcohol yields Ester + Water
Sulfuric acid is a catalyst.
Each step is reversible.
C H 3 C O H
O
+ C H 2 C H 2 C H C H 3
C H 3
OH
H
+
C H 3 C
O
O C H 2 C H 2 C H C H 3
C H 3
+ H O H
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 31
Tosylate Esters
Alcohol + p-Toluenesulfonic acid,TsOH
Acid chloride is actually used,TsCl
C H 3 C H 2 O H + H O S
O
O
C H 3
C H 3 C H 2 O S
O
O
C H 3
H O H+
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 32
Sulfate Esters
Alcohol + Sulfuric Acid
+H O S
O
O
O H H O C H 2 C H 3
H +
O C H 2 C H 3
O
O
SH O
C H 3 C H 2 O H + O C H 2 C H 3
O
O
SH O
H +
C H 3 C H 2 O S
O
O
O C H 2 C H 3
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 33
Nitrate Esters
+ H O C H 2 C H 3 H
+
N O H
O
O
O C H 2 C H 3N
O
O
C H 2
C H 2
C H 2
O H
O H
O H
+ 3 H O N O 2
C H 2
C H 2
C H 2
O N O 2
O N O 2
O N O 2
n it r o g ly c e r i n eg ly c e r in e =>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 34
Phosphate Esters
P
O
O H
O H
H O
C H 3 O H
P
O
O H
O H
C H 3 O
C H 3 O H
P
O
O C H 3
O H
C H 3 O
P
O
O C H 3
O C H 3
C H 3 O
C H 3 O H
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 35
Phosphate Esters in DNA
=>
O
C H
2
H
H
H
ba s e
O
P
O
O O
O
C H
2
H
H
H
ba s e
O
P
O
O O
O
C H
2
H
H
H
ba s e
O
P
O
O O
O
O
C H
2
H
H
H
ba s e
O
P
O
O O
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 36
Alkoxide Ions
ROH + Na (or NaH) yields sodium alkoxide
RO- + 1° alkyl halide yields ether
(Williamson ether synthesis)
C H 3 C H 2 C H C H 3
O
C H 3 C H 2 B r+ C H 2 C H 2 C H
C H 3
O C H 2 C H 3
=>
C H 3 C H 2 C H 2
C
HH
B r O
H
H
Chapter 11 37
End of Chapter 11