Download Reactions of Alcohols

CH3CH2CH2
Organic Chemistry, 5th Edition
L. G. Wade, Jr.
Chapter 11
Reactions of Alcohols
Jo Blackburn
Richland College, Dallas, TX
Dallas County Community College District
2003, Prentice Hall
Br
H
C O
H
H H
CH3CH2CH2
Br
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
H
C O
H
H H
=>
2
CH3CH2CH2
Br
Summary Table
Chapter 11
H
C O
H
H H
3
=>
CH3CH2CH2
Br
Oxidation States
C O
H
H H
• 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
H
4
CH3CH2CH2
1º, 2º, 3º Carbons
Br
C O
H
H H
=>
Chapter 11
H
5
CH3CH2CH2
Br
Oxidation of 2° Alcohols
•
•
•
•
C O
H
H H
2° alcohol becomes a ketone
Reagent is Na2Cr2O7/H2SO4
Active reagent probably H2CrO4
Color change: orange to greenish-blue
OH
CH3CHCH2CH3
Na2Cr2O7 / H2SO4
O
CH3CCH2CH3
=>
Chapter 11
H
6
CH3CH2CH2
Oxidation of 1° Alcohols
Br
C O
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
CH3CH2CH2CH2
O
CH3CH2CH2CH
=>
Chapter 11
H
7
CH3CH2CH2
3° Alcohols Don’t Oxidize
Br
C O
H
H H
• Cannot lose 2 H’s
• Basis for chromic acid test
Chapter 11
=>
H
8
CH3CH2CH2
Br
Other Oxidation Reagents
•
•
•
•
•
•
C O
H
H H
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
H
9
Biological Oxidation
CH3CH2CH2
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
H
10
CH3CH2CH2
Br
Alcohol as a Nucleophile
H
C
C O
H
H H
O
R X
• ROH is weak nucleophile
• RO- is strong nucleophile
• New O-C bond forms, O-H bond breaks.
=>
Chapter 11
H
11
CH3CH2CH2
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)
Br
C O
H
H H
H
+
C
O
C-Nuc bond forms,
C-O bond breaks
=>
Chapter 11
H
12
CH3CH2CH2
Br
Formation of Tosylate Ester
H
C O
H
H H
H
C
O
C
C
H O
O
Cl
O
S
O
N
O
CH3
S
O
CH3
p-toluenesulfonyl chloride
TsCl, “tosyl chloride”
Chapter 11
O
S
O
CH3
ROTs,
a tosylate ester
=>
13
CH3CH2CH2
Br
SN2 Reactions of Tosylates
•
•
•
•
•
•
C O
H
H H
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
H
14
CH3CH2CH2
Summary of Tosylate
Reactions
Br
C O
H
H H
=>
Chapter 11
H
15
CH3CH2CH2
Reduction of Alcohols
Br
C O
H
H H
• Dehydrate with conc. H2SO4, then add H2
• Tosylate, then reduce with LiAlH4
OH
CH3CHCH3
H2SO4
alcohol
OH
CH3CHCH3
alcohol
CH2
CHCH3
H2
Pt
alkene
TsCl
CH3CH2CH3
alkane
OTs
CH3CHCH3
tosylate
Chapter 11
LiAlH4
CH3CH2CH3
alkane
H
=>
16
CH3CH2CH2
Reaction with HBr
•
•
•
•
Br
C O
H
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
R O H
H3O
+
H
R O H
Chapter 11
-
Br
R Br
H
=>
17
CH3CH2CH2
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
H
18
CH3CH2CH2
Br
Limitations of HX Reactions
•
•
•
•
C O
H
H H
HI does not react
Poor yields of 1° and 2° chlorides
May get alkene instead of alkyl halide
Carbocation intermediate may
rearrange.
=>
Chapter 11
H
19
CH3CH2CH2
Reactions with
Phosphorus Halides
•
•
•
•
Br
C O
H
H H
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
H
20
CH3CH2CH2
Mechanism with PBr3
Br
C O
H
H H
• P bonds to -OH as Br leaves
• Br- attacks backside (S 2)
N
• HOPBr2 leaves
Chapter 11
=>
H
21
Reaction with
Thionyl Chloride
•
•
•
•
CH3CH2CH2
Br
C O
H
H H
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
H
22
=>
CH3CH2CH2
Br
Dehydration Reactions
•
•
•
•
•
•
C O
H
H H
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
=>
Chapter 11
H
23
CH3CH2CH2
Br
Dehydration Mechanisms
C O
H
H H
H
OH
CH3CHCH3
H2SO4
OH
CH3CHCH3
CH3CHCH3
alcohol
H2O
CH3OH
H3O
CH2
CHCH3
+
CH3
CH3
OH2
O CH3
H
CH3OH
H2O
Chapter 11
H
CH3OCH3
=>
24
CH3CH2CH2
Energy Diagram, E1
Chapter 11
Br
H
C O
H
H H
25
=>
CH3CH2CH2
Br
Unique Reactions of Diols
C O
H
H H
• Pinacol rearrangement
• Periodic acid cleavage
=>
Chapter 11
H
26
CH3CH2CH2
Pinacol Rearrangement
Br
C O
H
H H
• Pinacol: 2,3-dimethyl-2,3-butanediol
• Dehydration with sulfuric acid
CH3 CH3
CH3
C
C CH3
OH
OH
H
CH3
CH3 CH3
+
CH3
C
C CH3
OH
OH
CH3
C
OH
C
CH3
CH3
H
CH3
CH3
C
OH
C
CH3
CH3
CH3
CH3
C
C CH3
OH
CH3
CH3
CH3
C
C CH3
OH
CH3
CH3
CH3
Chapter 11
C
C CH3
O
CH3
pinacolone
H
=>
27
CH3CH2CH2
Periodic Cleavage
of Glycols
Br
C O
H
H H
Same products formed as from ozonolysis
of the corresponding alkene.
CH3
H
CH3
C
C CH3
OH
OH
HIO4
CH3
CH3
H
C
+
O
O
C CH3
O3
(CH3)2S
OsO4
H2O2
H
C
H3C
C
CH3
=>
CH3
Chapter 11
H
28
CH3CH2CH2
Br
Esterification
•
•
•
•
•
C O
H
H H
Fischer: alcohol + carboxylic acid
Tosylate esters
Sulfate esters
Nitrate esters
Phosphate esters
=>
Chapter 11
H
29
CH3CH2CH2
Br
Fischer Esterification
H
C O
H
H H
• Acid + Alcohol yields Ester + Water
• Sulfuric acid is a catalyst.
• Each step is reversible.
O
CH3
C OH
CH3
+ H O CH2CH2CHCH3
+
H
O
CH3
CH3C OCH2CH2CHCH3
+ HOH
=>
Chapter 11
30
CH3CH2CH2
Br
Tosylate Esters
C O
H
H H
• Alcohol + p-Toluenesulfonic acid, TsOH
• Acid chloride is actually used, TsCl
O
CH3CH2
O H
+
HO
S
CH3
O
O
CH3CH2
O
S
O
Chapter 11
H
CH3 =>
+ HOH
31
CH3CH2CH2
Br
Sulfate Esters
H
C O
H
H H
Alcohol + Sulfuric Acid
O
HO
S
O
+
OH
H
+ H O CH2CH3
O
S
OCH2CH3
O
O
CH3CH2O H + HO
HO
S
O
+
OCH2CH3
O
Chapter 11
H
CH3CH2O
S
OCH2CH3
O
=>
32
CH3CH2CH2
Br
Nitrate Esters
O
O
+
N OH
+
H O CH2CH3
H
O
H
C O
H
H H
N OCH2CH3
O
CH2
O H
CH2
O H
CH2
O H
+
3 HO NO2
CH2
O NO2
CH2
O NO2
CH2
O NO2
nitroglycerine
glycerine
Chapter 11
33
=>
CH3CH2CH2
Br
Phosphate Esters
O
HO
P
OH
O
OH
CH3OH
CH3O
P
OH
CH3OH
C O
H
H H
O
CH3O
P
OCH3
OH
OH
CH3OH
O
CH3O
P
OCH3
OCH3
Chapter 11
H
=>
34
CH3CH2CH2
Phosphate Esters in DNA
O CH2
Br
C O
H
H H
base
O
H
H
H
O
O
CH2
O
H
P
O
base
O
H
H
O
O
CH2
O
H
P
O
base
O
H
H
O
O
CH2
O
H
P
O
base
O
H
H
O
O
P
O
Chapter 11
O
H
=>
35
CH3CH2CH2
Br
Alkoxide Ions
H
C O
H
H H
• ROH + Na (or NaH) yields sodium alkoxide
• RO- + 1° alkyl halide yields ether (Williamson
ether synthesis)
CH3
CH3CH2CHCH3
+ CH3CH2
Br
O
CH2CH2CH O CH2CH3
=>
Chapter 11
36
CH3CH2CH2
Br
C O
H
H H
End of Chapter 11
Chapter 11
H
37