Carbonyl Compounds III

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Chapter 19 Carbonyl Compounds III Reactions at
the a-Carbon
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The a-Hydrogen Is Acidic
the anion is stabilized by resonance
A carbon acid is a compound with a relatively
acidic hydrogen bonded to an sp3-hybridized carbon
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Esters Are Less Acidic Than Aldehydes and Ketones
The electrons are not as readily delocalized
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In these compounds, the electrons left behind
from deprotonation can be delocalized onto a
more electronegative atom
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The acidity of the a-hydrogens is attributed to
charge stabilization by resonance
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KetoEnol Tautomerism
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The enol tautomer can be stabilized by
intramolecular hydrogen bonding
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An Enol Is a Better Nucleophile Than an Alkene
Carbonyl compounds that form enol undergo
substitution reactions at the a-carbon an
a-substitution reaction
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An Acid-Catalyzed a-Substitution Reaction
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A Base-Catalyzed a-Substitution Reaction
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An Enolate Is an Ambident Nucleophile
Reaction at the C or O site depends on the
electrophile and on the reaction condition
Protonation occurs preferentially on the O site
Otherwise, the C site is likely the nucleophile
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Acid-Catalyzed Halogenation
Under acidic conditions, one a-hydrogen is
substituted for a bromine
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Base-Promoted Halogenation
Under basic conditions, all the a-hydrogens
are substituted for bromines
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Conversion of a Methyl Ketone to a Carboxylic Acid
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Halogenation of the a-Carbon of Carboxylic Acids
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When the a-carbon is halogenated, it becomes
electrophilic
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Using LDA to Form an Enolate
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Alkylation of the a-Carbon of Carbonyl Compounds
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Two different products can be formed if the
ketone is not symmetrical
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The less substituted a-carbon can be alkylated if

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Enamine Reacts with Electrophiles
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The alkylation step is an SN2 reaction
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Direct alkylation of a carbonyl compound yields
several products
In contrast, alkylation of an aldehyde or a
ketone using an enamine intermediate yields the
monoalkylated product
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Aldehydes and ketones can be acylated via an
enamine intermediate
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The Michael Addition
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Mechanism of the Michael Reaction
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The Stork Enamine Reaction
Enamines are used in place of enolates in Michael
reactions
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One molecule of a carbonyl compound acts as a
nucleophile and the other carbonyl compound acts
as an electrophile
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Ketones are less susceptible than aldehydes to
attack by nucleophiles
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An aldol addition product loses water to form an
aldol condensation product
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The Mixed Aldol Addition
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One product will be formed if one of the carbonyl
compounds does not have any a-hydrogen
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Primarily one product can be formed by using LDA
to deprotonate one of the carbonyl compounds
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Condensation of Two Ester Molecules
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The reaction can be driven to completion by
removal of a proton from the b-keto ester
The Claisen condensation requires an ester with
two a-hydrogens and an equivalent amount of base
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The Mixed Claisen Condensation
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Because of the difference in the acidities of the
a-hydrogens in the two carbonyl compounds,
primarily one product is obtained
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Intramolecular Aldol Additions
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The Robinson Annulation
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Decarboxylation of 3-Oxocarboxylic Acids
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Acid catalyzes the intramolecular transfer of the
proton
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A malonic ester synthesis forms a carboxylic acid
with two more carbon atoms than the alkyl halide
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Preparation of Carboxylic Acids with Two
Substituents Bonded to the a-Carbon
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Synthesis of Methyl Ketone by Acetoacetic Ester
Synthesis
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Designing a Synthesis to Make New CarbonCarbon
Bonds
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Preparation of the Ester
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A Biological Aldol Condensation
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A Biological Claisen Condensation
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