MCAT Organic Chemistry: Aldehydes and Ketones Part Two

Introduction

• Presenter: Iman
• Apology for lack of recent uploads due to grad school commitments
• Future plans: Complete MCAT organic chemistry playlist, last two chapters of MCAT physics, and refilm two MCAT general chemistry videos

Previous Chapter Recap

• Focused on electrophilic carbon in aldehydes and ketones

Chapter Objectives

1. General Principles
   • Acidity of alpha hydrogens
   • Steric hindrance
2. Enolate Chemistry
   • Keto-enol tautomerization
   • Kinetic vs Thermodynamic enolates
   • Enamines
3. Aldol Condensation
   • Mechanism and implications

General Principles

• Alpha Carbon/Hydrogen Definition
  • Alpha carbon is adjacent to the carbonyl carbon
  • Hydrogens attached to the alpha carbon are alpha hydrogens
• Acidity and Resonance Stabilization
  • Oxygen's electron-withdrawing effect deprotonates alpha hydrogens
  • Extra electrons resonate between alpha carbon, carbonyl carbon, and carbonyl oxygen
• Comparing Aldehydes and Ketones
  • Aldehyde alpha hydrogens are more acidic than those in ketones
  • Ketones less reactive to nucleophiles due to steric hindrance
• Steric Hindrance
  • Ketones have two R groups, creating more crowded intermediate steps

Enolate Chemistry

• Tautomerization
  • Aldehydes and ketones can exist as keto and enol forms
  • Example: Keto and Enol forms differ in proton and double bond placements
  • Equilibrium: Lies towards keto form
• Enolate Formation and Stability
  • Formed by deprotonation with a strong base (e.g., hydroxide, LDA, KH)
  • Resonance stabilization distributes negative charge
• Michael Addition
  • Enolate attacks alpha-beta unsaturated carbonyl
  • Steps: Base deprotonates alpha hydrogen, enolate intermediate forms, enolate attacks double bond
• Kinetic vs Thermodynamic Enolates
  • Kinetic: Less substituted double bond, forms quickly, less stable
  • Thermodynamic: More substituted double bond, forms slowly, more stable
  • Conditions:
    • Kinetic favored in rapid, irreversible reactions, low temperature, strong bases
    • Thermodynamic favored in slow, reversible reactions, high temperature, weaker, smaller bases
• Enamines
  • Tautomers of imines (nitrogen-containing compounds)
  • Analogous to enol forms; less common than imines

Aldol Condensation

• Follows nucleophilic addition to a carbonyl mechanism
• Mechanism
  • Aldehyde or ketone acts as both electrophile and nucleophile
  • Initial Product: 3-hydroxybutanal (aldol)
  • Step 1: Base treatment forms enolate, which reacts with another carbonyl compound
  • Step 2: Dehydration occurs, forming alpha-beta unsaturated carbonyl
• Conditions for Pure Products
  • Preferable to use one type of aldehyde/ketone
  • Issue: Mixed products if multiple types are present
• Retro-aldol Reaction
  • Reverse of aldol condensation
  • Catalyzed by aqueous base and heat
  • Breaks bond between alpha and beta carbon of carbonyl

Review

• Key Points Summary
  • Alpha hydrogens are acidic and easily deprotonated
  • Ketones less reactive to nucleophiles
  • Keto-enol tautomers interconvert
  • Michael addition: Enolate nucleophile attacks carbonyl
  • Kinetic vs thermodynamic enolates: Differences in stability and formation conditions
  • Aldol condensation: Nucleophilic and electrophilic action, dehydration step
  • Retro-aldol: Cleaves alpha-beta carbon bond under heat and base

Conclusion

• Chapter 7 covered in detail
• Next video: Problem set
• Encouragement for further questions and study

Happy studying and good luck!