Download - Chapter 11 Reactions of Alcohols
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Chapter 11Reactions of Alcohols
Organic Chemistry, 6th EditionL. G. Wade, Jr.
Chapter 11 2
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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 3
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Summary Table
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Chapter 11 4
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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 =>
Chapter 11 5
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1º, 2º, 3º Carbons
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Chapter 11 6
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Oxidation of 2° Alcohols• 2° alcohol becomes a ketone• Reagent is Na2Cr2O7/H2SO4
• Active reagent probably H2CrO4
• Color change: orange to greenish-blue
CH3CHCH2CH3
OHNa2Cr2O7 / H2SO4
CH3CCH2CH3
O
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Chapter 11 7
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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.
CH3CH2CH2CH2
OH N H CrO3Cl
CH3CH2CH2CH
O
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Chapter 11 8
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3° Alcohols Don’t Oxidize• Cannot lose 2 H’s• Basis for chromic acid test
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Chapter 11 9
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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 10
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+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.
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Chapter 11 11
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Alcohol as a Nucleophile
• ROH is weak nucleophile• RO- is strong nucleophile• New O-C bond forms, O-H bond breaks.
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CO
H
R X
Chapter 11 12
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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). =>
CO
H
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C-Nuc bond forms, C-O bond breaks
Chapter 11 13
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Formation of Tosylate Ester
p-toluenesulfonyl chlorideTsCl, “tosyl chloride”
CO
H
CH3
S
Cl
OO N
CH3
S OO
OH
C
CH3
S
O
OO
C
ROTs,a tosylate ester
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Chapter 11 14
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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
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Chapter 11 15
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Summary of Tosylate Reactions
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Chapter 11 16
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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
H3O+ Br-
R O H R O H
H
R Br =>
Chapter 11 17
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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.
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Chapter 11 18
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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.
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Chapter 11 19
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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)
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Chapter 11 20
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Mechanism with PBr3
• P bonds to -OH as Br- leaves• Br- attacks backside (SN2)
• HOPBr2 leaves =>
Chapter 11 21
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+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
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Chapter 11 22
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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
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Dehydration Mechanisms
CH3CHCH3
OHH2SO4
alcoholCH3CHCH3
OHH
CH3CHCH3
CH2 CHCH3H2O
CH3OH
H3O+
CH3OH CH3 OH2 CH3 O
H
CH3
H2OCH3OCH3
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Chapter 11 24
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Energy Diagram, E1
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Chapter 11 25
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Alkoxide Ions• ROH + Na (or NaH) yields sodium alkoxide• RO- + 1° alkyl halide yields ether (Williamson
ether synthesis)
CH3CH2CHCH3
OCH3CH2 Br+ CH2CH2CH
CH3
O CH2CH3
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Chapter 11 26
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End of Chapter 11
