Chapter 11 Revisited Reactions of Alcohols

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Chapter 11 Revisited ?Reactions of Alcohols
Organic Chemistry, 5th EditionL. G. Wade, Jr.
Jo Blackburn Richland College, Dallas, TX Dallas
County Community College District ã 2003,
Prentice Hall
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Summary Table
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1º, 2º, 3º Carbons
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Summary of Oxidation
Weak Oxidants Strong oxidants
1o alcohol ? aldehyde 2o alcohol ? ketone PCC
_________ Jones
_________ Collins ________ Swern ________
1o alcohol ? acid 2o alcohol ? ketone Chromic
Acid _________ Nitric Acid
_________ Permanganate ________ Copper Oxide
________
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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 not a good leaving group unless it is
  protonated, but most nucleophiles are strong
  bases which would remove H.
• Trick - Convert alcohol to tosylate (good leaving
  group) to react with strong nucleophile

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Nuc-C bond forms as C-O bond breaks SN2 reaction
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Formation of Tosylate Ester
p-toluenesulfonyl chloride TsCl, tosyl chloride
ROTs, a tosylate ester
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SN2 Reactions of Tosylates

• With hydroxide (-OH) produces alcohol.
• With cyanide (-CN) produces nitrile.
• With halide ion (-X) produces alkyl halide.
• With alkoxide ion (-OR) produces ether.
• With ammonia (NH3) produces amine salt.
• With LiAlH4 (-H) produces alkane.

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Summary of Tosylate Reactions
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Reduction of Alcohols

• Dehydrate with conc. H2SO4, then add H2
• Tosylate, then reduce with LiAlH4

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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

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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 (Lucas Reagent).
• 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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Lucas Mechanism
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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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Better - Reactions with Phosphorus Halides (PX3)

• 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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Mechanism with PBr3/PI3/PCl3

• P bonds to -OH as Br- leaves
• Br- attacks backside (SN2) if.
• HOPBr2 leaves

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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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Dehydration Reactions

• 1
• Conc. H2SO4 produces alkene
• Carbocation intermediate
• Saytzeff product
• 2
• Bimolecular dehydration produces ether
• Carbocation Intermediate
• Low temp, 140C and below, favors ether
• High temp, 180C and above, favors alkene

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Dehydration Mechanisms
1. Formation of Alkene
H
O
2
C
H
C
H
C
H
2
3
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Dehydration Mechanisms
2. Formation of Ether
C
H
O
H
H
O
3
2
C
H
O
C
H
3
3
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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 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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Fischer Esterification - Mechanism
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Tosylate Esters

• Alcohol p-Toluenesulfonic acid, TsOH
• Acid chloride is actually used, TsCl

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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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Alkoxide Ions

• ROH Na (or NaH) yields sodium alkoxide
• RO- 1 alkyl halide yields ether (Williamson
  ether synthesis)

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End of Chapter 11