Aldehydes & Ketones II

7.1 General Principles of Enolates

This section explains the acidity of alpha-hydrogens in aldehydes and ketones, formation of enolate intermediates, and the influence of steric hindrance on reactivity.

• Acidity of alpha-Hydrogens
  • Alpha carbon = adjacent to carbonyl carbon
  • H attached to alpha-C = alpha-H
  • O atom pulls e⁻ from C-H bonds → easier deprotonation
  • Conjugate base stabilized by resonance (a-C, carbonyl C, carbonyl O) → enolate intermediate
  • E⁻ withdrawing O stabilizes carbanion (negatively charged C atom)
  • Alpha-H ketones slightly less acidic than aldehydes
  • Alkyl groups destabilize carbanions (opposite effect to carbocation stabilization)
• Steric Hindrance
  • Aldehydes more reactive to nucleophiles than ketones
  • Ketone alkyl groups hinder nucleophile approach → higher energy, crowded intermediate → less likely to react

7.2 Enolate Chemistry

Enolate chemistry covers keto-enol tautomerization, enolate formation, Michael addition, kinetic vs. thermodynamic enolates, and enamine intermediates.

• Keto-Enol Tautomerization
  • Enol = C=C bond + alcohol (-OH)
  • Tautomers differ in proton placement and double bond
  • Equilibrium favors keto form
  • Chiral alpha-C → racemic mixture during interconversion (alpha-racemization)
  • Enols = key intermediates in aldehyde/ketone reactions

  

• Deprotonation of alpha-C
  • Strong bases: OH⁻, LDA, KH
• Michael Addition
  • Carbanion attacks alpha,beta-unsaturated carbonyl (C=C next to carbonyl)
  • Resonance stabilization of intermediate drives reaction
• Kinetic vs. Thermodynamic Enolates
  • Two enolate forms possible with asymmetric ketone
  • Kinetic = rapid, less stable, less substituted → low temp, bulky strong base, irreversible
  • Thermo = slow, more stable, more substituted → high temp, small base, reversible
• Enamines
  • Tautomers of imines (C=N)
  • N may be bonded to alkyl group or substituent

7.3 Aldol Condensation

Aldol condensation is nucleophilic addition where aldehydes/ketones act as both nucleophile (enolate) and electrophile (keto). The reaction can produce beta-hydroxy carbonyls and alpha,beta-unsaturated carbonyls via dehydration.

• Mechanism
  • Nucleophilic enolate attacks electrophilic carbonyl of another molecule
  • Forms 3-hydroxybutanal (aldol, contains aldehyde + alcohol)

• Dehydration
  • Strong base + high temp → E1/E2 elimination of water
  • Produces alpha,beta-unsaturated carbonyl
• Reaction Control
  • Best with single type of aldehyde/ketone
  • Multiple types → uncontrolled products
  • Prevented if molecule has no alpha-H (quaternary alpha-C)
• Terminology
  • Condensation = joining 2 molecules with loss of small molecule (water)
  • Dehydration = water eliminated
• Retro-Aldol Reaction
  • Reverse aldol
  • Aqueous base + heat
  • Useful for breaking alpha/beta carbon-carbon bonds
  • Stabilized via enolate intermediate

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