Chapter%2018%20Lecture%201%20Enols

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Chapter 18 Lecture 1 Enols

• Enolate Ions
• Carbonyl Reactivity
• Nucleophilic carbonyl oxygen
• Electrophilic carbonyl carbon
• a-carbon containing acidic a-protons (the
  subject of this chapter)
• Acidity of Aldehydes and Ketones
• pKa of protons alpha to an aldehyde or ketone
  carbonyl 19-21
• Ethene pKa 44
• Ethyne pKa 25
• Alcohol pKa 15-18
• Strong bases can remove a-hydrogens to produce an
  Enolate Ion

Enolate Ion
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• Why are carbonyl a-protons acidic?
• The conjugate base is stabilized by the enolate
  ion resonance structures
• The d carbon of the carbonyl destabilizes the a
  CH bond
• C. Formation of Enolate Ions
• LDA (lithium diisopropyl amide) or other strong
  bases are used
• Aprotic solvents are used to prevent solvent
  deprotonation
• Enolate Resonance Hybrid
• The a-carbon and the oxygen of an enolate ion are
  both nucleophilic
• Ambident two-fanged a species that can
  react at 2 different sites to give 2 different
  products

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• The carbon atom is the normal site of reaction by
  SN2. This type of reaction is called alkylation
  or C1-alkylation of the enolate ion.
• The oxygen atom is the normal site of
  protonation, forming an enol, which will
  tautomerize to the original ketone.
• II. Keto-Enol Equilibria
• KetoneEnol Tautomerization
• This reaction is reversible, and the extent of
  reaction depends on conditions
• Base-catalyzed Enol-Keto Equilibration
• Base removes proton from the enol
• The mechanism is the reverse of the original
  enolate formation

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• Acid Catalyzed Enol-Keto Equilibration
• Protonation occurs at the double bond
• Resonance stabilized C is next to O
• Protonated carbonyl deprotonates to give the keto
  form
• Both reaction are fast if the catalyst (B- or H)
  are present
• Keto form is usually dominant
• Keto to enol tautomerization mechanisms are the
  reverse of those above
• Effects of Substituents on Keto-Enol Equilibria
• Ketone donating substituents stabilize keto form
• Aldehyde lack of donating substituents pushes
  equilibria toward enol form

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• Deuteration of Carbonyl a-Carbons
• Dissolving an aldehyde or ketone in D2O, DO- (or
  D) replaces all of the a-Hydrogens with
  Deuteriums
• Even though the keto form dominates, a small is
  always tautomerizing to the enol. Over time,
  reprotonation at C gives the fully deuterated
  product.
• Reaction can be followed by 1H NMR as a-H signal
  disappears
• Interconversion of a-C stereochemistry
• 1) Keto-Enol tautomerization proceeds through an
  achiral intermediate

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• Loss of optical activity occurs under basic or
  acidic conditions
• Halogenation of Aldehydes and Ketones
• Acid-Catalyzed a-Halogenation of Ketones and
  Aldehydes
• In acidic conditions, only one halogen is able to
  add
• The reaction rate is independent of X2
  concentration, suggesting that the rate
  determining step depends only on the carbonyl
  compound

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• 3) Mechanism of acid catalyzed a monohalogenation
• 4) Why does the reaction stop after only one
  halogenation?
• Mechanism requires enolization
• Electron withdrawing Br prevents protonation
  needed in first step

O is no longer basic enough To attack proton.
Enolization Cant happen.
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• Base Mediated Halogenation of a-Carbon Goes to
  Completion
• Mechanism
• Electron Withdrawing Br increases a-Hydrogen
  acidity, favoring complete bromination of all
  a-Carbons
• The Iodoform test for Methyl Ketones is base
  catalyzed halogenation

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• Alkylation of Aldehydes and Ketones
• Alkylation of Ketones Using NaH
• Ketones with only one a-Hydrogen are alkylated in
  high yield
• Example
• NaH is a strong base yielding enolate ion when
  reacted with carbonyls
• Polyalkylation occurs if multiple a-Hs are
  present

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• Unsymmetric Ketones give multiple products
• Enamine Route to Ketone/Aldehyde Alkylation
• Enamine formation makes CC bonds electron rich
  by resonance
• The nucleophilic a-Carbon can then attack
  electrophiles

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• The amine is removed from the alkylated product
  by acid to give the alkylated ketone or aldehyde
• The Enamine Alkylation Route is Preferred
• No multiple alkylations
• Works on Aldehydes and Ketones