Reactions of a-Hydrogens: Condensation Reactions

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Reactions of a-HydrogensCondensation Reactions

• Chapter 21

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possible, otherwise the images are very faint!
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Assignments for Chapter 21 and 22

• Chapter 20, hardly any, attend class!
• Skip these sections from Chap. 21
• 21.4, 21.6, 21.8, 21.11, 21.17 and 21.21
• Skip these sections from Chap. 22
• 22.3, 22.4, 22.13 through 22.15
• Keep 22.16 and 22.17!!!

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Problems for Chapter 21

• In-Text Problems
• 2, 3, 4, 8, 13, 14, 18, 19, 26, 29, 30, 32, 34,
  35, 36, 37, 40, 46 and 50
• End-of-Chapter Problems
• 2, 4, 5, 9, 13, 16, 17 and 21

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Sect. 21.1 Keto-Enol Tautomerism
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Keto-Enol Tautomerism in 1,3-Dicarbonyl Compounds
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Keto-Enol Tautomerism in 1,3-Dicarbonyl Compounds

• The equilibrium lies substantially to the right
  with 1,3-dicarbonyl compounds.
• In simple ketones, such a hydrogen-bonded
  structure cannot form, and the percentage of enol
  found in an equilibrium mixture is very small
  (equilibrium lies to left).

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Some Representative Enol Percents
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Sect. 21.2 Acidity of a-Hydrogens

• The acidity of a hydrogen attached to the
  a-carbon of a carbonyl compound is much higher
  than the acidity of a typical C-H hydrogen.
• pKa values range from about 19 to 20 (compared
  with 48 to 50) for alkanes.

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Acidity of a-Hydrogens The Reason
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Acidity of a-Hydrogens

• Resonance stabilization of the enolate ion shifts
  the equilibrium to the right, thereby making the
  C-H bond more acidic.
• Once formed, the enolate ion is capable of
  reacting as a nucleophile. The a-carbon of the
  enolate ion bears substantial negative charge.

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Sect. 21.3 Halogenation of Ketones
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Mechanism
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Example
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But...

• The halogenation is difficult to stop at the
  mono-substitution stage.
• Often, poly-halogenated products are formed in
  this reaction.

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With an excess of bromine
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In base, bromoform is formed
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Section 21.5 Iodoform reaction
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Sect. 21.7 Alkylation Reactions
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Example
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Sect. 21.9 Alkylation of Active Methylene
Compounds
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Sect 21.10 Hydrolysis and decarboxylation
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Mechanism of decarboxylation
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Alkylation of ethyl acetoacetate
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Sect. 21.10 Decarboxylation
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Sect. 21.12 The Aldol Condensation
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Aldol Condensation -- Mechanism
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An example
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One More
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Synthesis Problem
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Sect. 21.13 Dehydration of Aldol products

• Aldol products easily dehydrate in acid and
  sometimes in base.

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Dehydration of Aldol Products
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Dehydration of Aldol Products
Note here that iodine is a sufficiently strong
Lewis acid to bring about dehydration.
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Also
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Synthesis of
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Synthesis of a Compound used in Perfumery
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Preparation via Aldol Condensation and reduction
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Preparation via Aldol Condensation and reduction!
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Synthesis of an Insect Repellent
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Sect. 21.14 Crossed Aldol Condensations

• Reaction of two different aldehydes
• One with an "-hydrogen (donor)
• Other with no "-hydrogen (acceptor)

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Crossed Aldol Condensations
acceptor
donor
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Chalcone formation part 1
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Chalcone Formation part 2
(formed from an aldol condensation)
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Do the synthesis of
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Sect. 21.15 The Claisen Ester Condensation
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Claisen Ester Condensation -- Mechanism (Part One)
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Claisen Ester Condensation -- Mechanism (Part
Two)
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Example
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Another Example
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Example of a Ring Formation
This reaction is known as the Dieckmann
cyclization.
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Sect. 21.16 Crossed Claisen Condensation

• In the crossed Claisen condensation, we choose
  one of the esters to be the acceptor. The
  acceptor does not have a-hydrogens.
• The other ester, the donor, does have
  a-hydrogens. It can react with base to form a
  nucleophilic enolate ion.
• With such an experimental design, the crossed
  Claisen condensation can be used successfully.

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Crossed Claisen Condensation -- An Example
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Synthesize this
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Sect. 21.18 1,2 vs. 1,4-addition
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Sect. 21.19 Conjugate addition Michael reaction
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Sect. 21.20 copper catalyzed conjugate addition
reactions