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Organic Chemistry, 6th Edition
L. G. Wade, Jr.
Chapter 11
Reactions of Alcohols
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Types of Alcohol Reactions
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Dehydration to alkene
Oxidation to aldehyde, ketone
Substitution to form alkyl halide
Reduction to alkane
Esterification
Tosylation
Williamson synthesis of ether
Chapter 11
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Summary Table
Chapter 11
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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
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Chapter 11
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1º, 2º, 3º Carbons
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Chapter 11
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Oxidation of 2° Alcohols
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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
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Chapter 11
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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
CH3CH2CH2CH2
O
CH3CH2CH2CH
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Chapter 11
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3° Alcohols Don’t Oxidize
• Cannot lose 2 H’s
• Basis for chromic acid test
Chapter 11
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Other Oxidation Reagents
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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.
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Chapter 11
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Biological Oxidation
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• 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.
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Chapter 11
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Alcohol as a Nucleophile
H
C
O
R X
• ROH is weak nucleophile
• RO- is strong nucleophile
• New O-C bond forms, O-H bond breaks.
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Chapter 11
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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).
H
+
C
O
C-Nuc bond forms,
C-O bond breaks
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Chapter 11
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Formation of Tosylate Ester
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
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SN2 Reactions of Tosylates
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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
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Chapter 11
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Summary of Tosylate
Reactions
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Chapter 11
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Reaction with HBr
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-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
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Br
R Br
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Reaction with HCl
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• 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.
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Chapter 11
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Limitations of HX Reactions
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HI does not react
Poor yields of 1° and 2° chlorides
May get alkene instead of alkyl halide
Carbocation intermediate may
rearrange.
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Chapter 11
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Reactions with
Phosphorus Halides
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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)
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Chapter 11
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Mechanism with PBr3
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• P bonds to -OH as Br leaves
• Br- attacks backside (S 2)
N
• HOPBr2 leaves
Chapter 11
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Reaction with
Thionyl Chloride
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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
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Dehydration Reactions
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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
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Chapter 11
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Dehydration Mechanisms
H
OH
CH3CHCH3
H2SO4
OH
CH3CHCH3
CH3CHCH3
alcohol
H2O
CH3OH
H3O
CH2
CHCH3
+
CH3
CH3
OH2
O CH3
H
CH3OH
H2O
Chapter 11
CH3OCH3
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Energy Diagram, E1
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Chapter 11
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Alkoxide Ions
• ROH + Na (or NaH) yields sodium alkoxide
• RO- + 1° alkyl halide yields ether (Williamson
ether synthesis)
CH3
CH3CH2CHCH3
+ CH3CH2
Br
O
CH2CH2CH O CH2CH3
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Chapter 11
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End of Chapter 11
Chapter 11
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