Reactions of Alcohols, Ethers, Epoxides, Amines, and Thiols

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Chapter 11

• Reactions of Alcohols, Ethers, Epoxides, Amines,
  and Thiols

Paula Yurkanis Bruice University of California,
Santa Barbara
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More About the Families in Group II
The families in Group II all have an
electronegative atom or group that is attached to
an sp3 carbon.
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Strongly Basic Leaving Groups Cannot Be
Displaced
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Acid Converts the Poor Leaving Group into
a Good Leaving Group
Alcohols have to be activated before they can
react.
Only weakly basic nucleophiles can be
used. Strongly basic nucleophiles would react
with the proton.
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Converting Alcohols to Alkyl Halides
Primary and Secondary alcohols require heat
tertiary alcohols do not.
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The Reactions of Secondary and Tertiary Alcohols
with Hydrogen Halides are SN1 Reactions
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An SN1 Reaction Creates a Carbocation
Intermediate, So Watch Out for Carbocation
Rearrangements
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The Reactions of Primary Alcohols with
Hydrogen Halides are SN2 Reactions
Recall that Br is a good nucleophile in a protic
solvent.
Alcohols undergo SN1 reactions unless they would
have to form a primary carbocation.
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Cl is the Poorest Nucleophile of the Halide Ions
ZnCl2 increases the rate of the reaction by
creating a better leaving group than water.
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Why is It Important to Be Able to Convert
Alcohols to Alkyl Halides?
Alcohols are readily available but
unreactive. Alkyl halides are less available but
reactive and can be used to synthesized a wide
variety of compounds.
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Other Methods to Convert
Alcohols into Alkyl Halides
phosphorus tribromide, phosphorus trichloride,
thionyl chloride
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The Mechanism for the Reaction with
PBr3 or PCl3
A bromophosphite (chlorophosphite) group is a
better leaving group than a halide ion.
Pyridine is the solvent and acts as a base.
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The Mechanism for the Reaction with SOCl2
A chlorosulfite group is a better leaving group
than a halide ion.
Pyridine is the solvent and acts as a base.
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Converting Alcohols to Alkyl Halides
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Primary and Secondary Alcohols Can Be Activated
by Being Converted to Sulfonate Esters
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A Sulfonic Acid is a Strong Acid
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Common Sulfonyl Chlorides
tosyl chloride TsCl
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The Mechanism
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A Sulfonate Ester Reacts with Nucleophiles
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Activating an Alcohol
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Two SN2 Reactions or One SN2 Reaction?
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Dehydration of an Alcohol
Dehydration of an alcohol is an elimination
reaction.
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Dehydration is a Reversible Reaction
To prevent the alkene from adding water and
reforming the alcohol, the water is removed as it
is formed.
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Dehydration of Secondary and Tertiary Alcohols
are E1 Reactions
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Dehydration is a Regioselective Reaction
The major product is the more stable alkene.
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The More Stable Alkene Has the More Stable
Transition State
Leading to Its Formation
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Tertiary Alcohols are the Easiest to Dehydrate
The rate of dehydration reflects the ease of
carbocation formation.
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An E1 Reaction Creates a Carbocation
Intermediate, So Watch Out for Carbocation
Rearrangements
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Dehydration of a Primary Alcohol
is an E2 Reaction
Both E2 and SN2 products are obtained.
Alcohols undergo E1 reactions unless they would
have to form a primary carbocation.
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The Major Product is 2-Butene
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Dehydration is Stereoselective
The major product is the stereoisomer with the
largest groups on opposite sides of the double
bond.
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Dehydration Under Mild Conditions
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The Mechanism
The E1 dehydration has been changed to an E2
dehydration.
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Another Way to Do an E2 Dehydration
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Oxidation of Secondary Alcohols
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Oxidation of Primary Alcohols
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Tertiary Alcohols Cannot Be Oxidized to
a Carbonyl Compound
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Oxidation by Hypochlorous Acid (HOCl)
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The Mechanism
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Alcohols and Ethers Have Similar Leaving Groups
Alcohols and ethers have to be activated before
the compounds can react.
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The Leaving Group of an Ether Can Be Activated by
Protonation
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The Mechanism
If a relatively stable carbocation is formed when
ROH leaves, it will be
an SN1 reaction.
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The Mechanism
If a relatively stable carbocation would not be
formed when ROH leaves, it will be an SN2
reaction.
Ethers undergo SN1 reactions unless they would
have to form a primary carbocation.
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Ethers Cannot Be Activated by Other Methods
An alcohol forms an intermediate that can lose a
proton.
An ether forms an intermediate that cannot lose a
proton.
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Ethers Are Common Solvents Because
They React Only with Hydrogen Halides
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Synthesis of an Epoxide
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Synthesis of an Epoxide
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Epoxides are More Reactive Than Ethers
Because of Ring Strain
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The Acid-Catalyzed Mechanism
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If the Epoxide is Not Symmetrical, Which Carbon
Does the Nucleophile Attack?
The nucleophile attacks the more substituted ring
carbon.
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Under Acidic Conditions the Nucleophile Attacks
the More Substituted Ring Carbon
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Under Neutral or Basic Conditions the Nucleophile
Attacks the Less Substituted Carbon
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The Conditions Determine the Site of Nucleophilic
Attack
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Using Epoxides in Synthesis
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The Addition of Water to an Alkene
Carbocation rearrangements can occur during the
acid-catalyzed addition of water.
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Adding Water to an Alkene Without a Carbocation
Rearrangement
The regioselectivity is the same as the
acid-catalyzed addition of water because the
hydride ion adds to the sp2 carbon bonded to the
most hydrogens.
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Forming a trans-1,2-Diol
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Forming a cis-1,2-Diol
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The Mechanism
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Arene Oxides
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Two Pathways for Reaction
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Mechanism for Formation of Phenol
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The Epoxide Opens Preferentially in the Direction
That Forms the More Stable Carbocation
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Addition Products Can Be Carcinogenic
If formation of the addition products is faster
than formation of the phenol, the arene oxide
can be carcinogenic.
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Relative Reactivities
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Protonating an Amine Does Not Form a Compound
with a Good Leaving Group
Amines cannot undergo substitution and
elimination reactions.
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Amines are Common Organic Bases
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Amines are Common Nucleophiles
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The Hofmann Elimination Reaction
A quaternary ammonium ion can undergo an
elimination reaction with a strong base such as
hydroxide ion.
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The Hofmann Elimination is an E2 Reaction
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The Base Removes the H from the b-Carbon Bonded
to the Most Hydrogens
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Because the Leaving Group is Poor,the Transition
State Is Carbanion-Like
Recall that alkyl fluorides have carbanion-like
transition states because the leaving group is
poor.
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It Must Be a Quaternary Hydroxide
Aqueous silver oxide
converts a quaternary ammonium halide to a
quaternary ammonium hydroxide.
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Thiols
Thiols used to be called mercaptans because they
capture mercury.
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Nomenclature of Thiols
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Thiols are Good Nucleophiles in a Protic Solvent
Thiolate ions are better nucleophiles in a protic
solvent than alkoxide ions.
The product is a sulfur analogue of an ether
(thioether or a disulfide).
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Thioethers are Also Nucleophiles
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A Sulfonium Salt is an Alkylating Agent
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The Families in Group II