Download - Chapter 11nc
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Chapter 11Reactions of Alcohols
Jo BlackburnRichland College, Dallas, TX
Dallas County Community College District 2006, Prentice Hall
Organic ChemistryL. G. Wade, Jr.
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Types of Alcohol Reactions
• Dehydration to alkene
• Oxidation to aldehyde, ketone
• Substitution to form alkyl halide
• Reduction to alkane
• Esterification
• Williamson ether synthesis
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Summary Table
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Oxidation States
• For inorganics:
! CrO42- reduced to Cr2O3
! KMnO4 reduced to MnO2
• For organics
! 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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1º, 2º, 3º Carbons
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Oxidation of 2°Alcohols• 2°alcohol becomes a ketone
• Common reagent is Na2Cr2O7/H2SO4
• Active reagent probably H2CrO4
• Color change: orange to greenish-blue
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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.)
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Oxidation of 1°Alcohols
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3°Alcohols Don’t Oxidize
• Cannot lose 2 H’s
• Basis for chromic acid test
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Other Oxidation Reagents
• HOCl (NaOCl / H+)
• Collins reagent: Cr2O3 in pyridine
• Jones reagent: chromic acid in acetone
• KMnO4 (strong oxidizer)
• CuO, 300°C (industrial dehydrogenation)
• Various methods based on dimethylsulfoxide
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Chapter 11 11
Dehydrogenation:
Swern Oxidation
There are many other oxidation reagents. Here are two of them
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And the One You Did In the Lab
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Biological Oxidation
• Catalyzed by ADH, alcohol dehydrogenase.
• Oxidizing agent is NAD+, nicotinamideadenine 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.
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Product?
1. (CH3)2CHOH
2. (CH3)2C=O
3. CH3CH2COOH
4. No reaction
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Product?
1. CH3COOH
2. CH3CH2COOH
3. CH3CH2CHO
4. No reaction
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Product?
1. CH3COOH
2. CH3CH2COOH
3. CH3CH2CHO
4. No reaction
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Product?
1. (CH3)3COH
2. (CH3)2C=O
3. CH2=C(CH3)2
4. No reaction
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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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Alcohol as an Electrophile
• OH- is very poor leaving group unless it is protonated
• Most nucleophiles are strong bases which would remove H+.
• Convert to tosylate (good leaving group) to react with strong nucleophile (base).
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∂ +
C-Nuc bond forms, C-O bond breaks
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Formation of Tosylate Ester
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p-toluenesulfonyl chlorideTsCl, “tosyl chloride”
ROTs,a tosylate ester
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(basically same as halides)
• 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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SN2 Reactions of Tosylates
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Reduction of Alcohols
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Cannot just reduce off the oxygen of an alcohol
1. Dehydrate with conc. H2SO4, then add H2
or2. Tosylate, then reduce with LiAlH4
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Conversion to Alkyl Halides
• -OH of alcohol is protonated
• -OH2+ is good leaving group
• 3°and 2°alcohols react with Br- via SN1
• 1°alcohols react via SN2
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Reaction with HBr
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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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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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Reactions with Phosphorus Halides or Thionyl Chloride
• Good yields with 1°and 2°alcohols
• SOCl2 generally best for alkyl chlorides
• PBr3 for alkyl bromide
• [P and I2 for alkyl iodide (PI3 not stable)]
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Mechanism with PBr3
• P bonds to -OH as Br- leaves
• Br- attacks backside (SN2)
• HOPBr2 leaves Chapter 11 30
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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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Product?
1. CH3CH2CH2OTs
2. CH3CH2CH2OCl
3. CH3CH2CH2Cl
4. CH3CH2CH2Ts
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Product?
1. CH3CH2CH2OSCl22. CH3CH2CH2Cl
3. CH3CH2CH2OCl
4. CH3CH2CH2SO2H
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Product?
1. CH3CH2CH2OPBr3
2. CH3CH2CH2OBr
3. CH3CH2CH2Br
4. CH3CH2CH2PBr2 0
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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
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Dehydration Mechanisms
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CH2 CHCH3
H
H2O CH2 CHCH3
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Energy Diagram, E1
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Unique Reactions of Diols
• Pinacol rearrangement
• Periodic acid cleavage
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Pinacol Rearrangement
• Pinacol: 2,3-dimethyl-2,3-butanediol
• Dehydration with sulfuric acid
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Periodic Acid Cleavage of Glycols
Same products formed as from ozonolysis of the corresponding alkene.
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Esterification
• Fischer: alcohol + carboxylic acid
• Tosylate esters
• Sulfate esters
• Nitrate esters
• Phosphate esters
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Fischer Esterification
• Acid + Alcohol yields Ester + Water
• Sulfuric acid is a catalyst.
• Each step is reversible.
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Tosylate Esters
• Alcohol + p-Toluenesulfonic acid, TsOH
• Acid chloride is actually used, TsCl
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Chapter 11 44
Why Tosylate Esters?
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Sulfate Esters
Alcohol + Sulfuric Acid
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Nitrate Esters
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Phosphate Esters
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Phosphate Esters in DNA
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Product?
1. CH3CH2COOCH3
2. CH3COOCH2CH3
3. CH3CH2COOCH2CH3
4. CH3COOCH3
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Product?
1. CH3OSO3H
2. CH3OSO3CH3
3. CH3OSO2CH3
4. CH3OSO2H
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Williamson Ether Synthesis
• ROH + Na (or NaH) yields sodium alkoxide
• RO- + 1°alkyl halide yields ether
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End of Chapter 11
Chapter 11 52