Ch. 18 - 1

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Chapter 18

• Reactions at the a Carbon
• of Carbonyl Compounds
• Enols and Enolates

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Keto, enol and enolate structures

• What is a keto form ?
• A structure that contains a carbonyl. E.g.
  aldehyde, ketone, ester, acid, etc.
• What is an enol ?
• A compound that has an alkene and an OH
  attached to the same carbon atom.
• What is an enolate ?
• An enol with the proton removed. May be formed
  by removing a proton from the a carbon atom of a
  keto form.

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The a carbon and a hydrogens

• What is an a carbon ?
• A carbon atom adjacent to a carbonyl.
• What is an a hydrogen ?
• A hydrogen attached to an a carbon atom.

a Hydrogens are weakly acidic (pKa 19 20) due
to the e-withdrawing CO.
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Reactions at the a Carbon of Carbonyl
CompoundsEnols and Enolates
This shows a reaction at the carbonyl carbon
atom.
Tetrahedral intermediate
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1. The Acidity of the a Hydrogens of Carbonyl
   Compounds Enolate Anions

Comparison of pKas.
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Deprotonation
Removal of a H forms a resonance stabilized
enolate.
Resonance structures for the delocalized enolates
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Protonation
Protonation of a carbon.
Protonation of oxygen.
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1. Keto and Enol Tautomers

• Interconvertible keto and enol forms are called
  tautomers, and their interconversion is called
  tautomerization.
• The keto and enol forms are in equilibrium (not
  resonance structures) because a proton transfer
  occurs.

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E.g.
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E.g.
Resonance stabilization of the enol form
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1. Reactions via Enols Enolates

3A. Racemization
Racemization at an a carbon takes place in the
presence of acids or bases
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• Base-Catalyzed Enolization

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• Acid-Catalyzed Enolization

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3B. Halogenation at the a Carbon
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• Base-Promoted Halogenation

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• Acid-Promoted Halogenation

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3C. The Haloform Reaction
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• The Iodoform reaction

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• Mechanism

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• Acyl Substitution Step

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3D. a-Halo Carboxylic Acids The
HellVolhardZelinski Reaction
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• Example

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• Mechanism

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Further reaction of an a halo acid
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1. Lithium Enolates

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• Prep. of lithium diisopropylamide (LDA)

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4A. Regioselective Formation of Enolates

• Formation of a Kinetic Enolate

(Dimethoxyethane)
This enolate is formed faster because the
hindered strong base removes the less hindered
proton faster.
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• Formation of a Thermodynamic Enolate

This enolate is more stable because the double
bond is more highly substituted. It is the
predominant enolate at equilibrium.
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4B. Direct Alkylation of Ketones via Lithium
Enolates
Lithium diisopropylamide LDA or LiN(iPr)2.
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4C. Direct Alkylation of Esters
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• Examples

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1. Enolates of b-Dicarbonyl Compounds

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• Recall

• a-hydrogens of b-dicarbonyl compounds are more
  acidic

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Contributing resonance structures
Resonance hybrid
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1. Synthesis of Methyl Ketones The Acetoacetic
   Ester Synthesis

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• Synthesis of monosubstituted methyl ketones

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• Synthesis of disubstituted methyl ketones

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(No Transcript)
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• Synthesis of g-keto acids and g-diketones

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6A. Acylation

• Synthesis b-diketones

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1. Synthesis of Substituted Acetic Acids The
   Malonic Ester Synthesis

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• Synthesis of substituted acetic acid

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• Synthesis of monoalkylacetic acid

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• Synthesis of dialkylacetic acid

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• Example 1

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• Example 2

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1. Further Reactions of Active Hydrogen Compounds

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• Example

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1. Synthesis of Enamines Stork Enamine Reactions

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• 2 amines most commonly used to prepare enamines

• e.g.

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(a)
(b)
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• Synthesis of b-diketones

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• Synthesis of g-keto esters

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• Enamines can also be used in Michael additions

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1. Summary of Enolate Chemistry

1. Formation of an Enolate

Resonance-stabilized enolate
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1. Racemization

Enantiomers
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1. Halogenation of Aldehydes Ketones

• Specific example haloform reaction

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1. Halogenation of Carboxylic Acids The HVZ
   Reaction

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1. Direct Alkylation via Lithium Enolates

• Specific example

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1. Direct Alkylation of Esters

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1. Acetoacetic Ester Synthesis

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1. Malonic Ester Synthesis

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1. Stork Enamine Reaction

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? END OF CHAPTER 18 ?