General Principles
High-Yield Summary
- Carbons are named relative to the carbonyl with Greek letters: α (directly attached to carbonyl C) → β → γ. Hydrogens on the α-carbon are α-hydrogens.
- α-hydrogens are unusually acidic — pKa ≈ 19-20 (ketone) vs. ≈ 50 for a typical alkane C-H — because the carbonyl's electron-withdrawing polarization weakens the adjacent C-H bond.
- A strong base removes an α-hydrogen → resonance-stabilized carbanion (negative charge delocalizes onto the carbonyl oxygen) = an enolate ion.
- Hydroxide (conjugate acid pKa ≈ 15.7) only partially deprotonates — too close to the α-hydrogen's pKa. LDA (conjugate acid pKa ≈ 36) drives deprotonation essentially to completion.
- Aldehydes > ketones in nucleophile reactivity: one alkyl/aryl group (vs. two) means less steric hindrance and less electron-donation, so more partial positive charge on the carbonyl carbon.
Base Strength → Deprotonation Extent
| Base (conjugate acid pKa) | Effect on carbonyl compound |
|---|---|
| Hydroxide, OH⁻ (water pKa ≈ 15.7) | Only a small equilibrium fraction deprotonated — too close to α-H pKa (≈19-20) |
| LDA (diisopropylamine pKa ≈ 36) | Deprotonation driven essentially to completion — irreversible |
Key Terms
- α, β, γ carbons
- Positions named by distance from the carbonyl carbon: α is directly attached, β is next, γ after that.
- α-hydrogen
- A hydrogen on the α-carbon; acidic (pKa ≈ 19-20 for a ketone) due to the adjacent carbonyl's electron withdrawal.
- Enolate ion
- Resonance-stabilized carbanion formed by deprotonating an α-hydrogen; negative charge delocalized between the α-carbon and carbonyl oxygen.
- LDA (lithium diisopropylamide)
- Strong, bulky, non-nucleophilic base; its high conjugate-acid pKa (≈36) drives carbonyl deprotonation to completion.
Common MCAT Trap
- Don't assume any strong base fully converts a ketone to its enolate — hydroxide is strong but its conjugate acid's pKa is too close to the α-hydrogen's, so equilibrium favors mostly starting material.
- Aldehyde > ketone reactivity is driven by BOTH sterics (fewer alkyl groups) and electronics (less alkyl electron-donation) — don't attribute it to only one factor.
Quick Recall
Why are α-hydrogens more acidic than typical alkane C-H bonds?
Why doesn't hydroxide fully convert a ketone to its enolate, while LDA does?
Why are aldehydes more reactive than ketones toward nucleophiles?