Acid–base & pKa
Acid–base is the fastest way to predict direction, intermediates, and whether a reagent behaves as a nucleophile or as a base.
Use pKa as a quantitative guide: for HA + B⁻ ⇌ A⁻ + HB, equilibrium favors the side with the weaker acid (higher pKa).
Four stability rules (A⁻ stability → acidity)
- Atom: negative charge is stabilized on more electronegative atoms (same row) or larger atoms (down a group).
- Resonance: delocalization stabilizes charge dramatically.
- Induction: electron-withdrawing groups stabilize nearby negative charge (distance matters).
- Orbital: higher s-character stabilizes charge (sp > sp² > sp³), so terminal alkynes are more acidic than alkenes/alkanes.
Common pKa landmarks (approx.)
| Acid (conjugate base) | pKa | What it means in practice |
|---|
| HCl (Cl⁻) | ~ -7 | strong acid; Cl⁻ is weak base |
| H₃O⁺ (H₂O) | ~ -1.7 | acidic aqueous conditions |
| carboxylic acid (carboxylate) | ~ 4–5 | deprotonated by bicarbonate/NaOH |
| phenol (phenoxide) | ~ 10 | deprotonated by strong base (NaOH) |
| alcohol (alkoxide) | ~ 16–18 | needs strong base (NaH, Na/K metal) |
| α-H next to carbonyl (enolate) | ~ 19–21 | forms enolate with LDA/NaH |
| terminal alkyne (acetylide) | ~ 25 | requires very strong base (NaNH₂) |
| amine as an acid (amide anion) | ~ 35–38 | amines are not acidic; need superbases |
| alkane (carbanion) | ~ 50 | essentially non-acidic in normal orgo |
Workflow: solve acid–base questions fast
| Step | Question | Shortcut |
|---|
| 1 | What can be protonated/deprotonated? | look for heteroatoms, α-H next to C=O, phenols, carboxylic acids |
| 2 | Compare pKas of acids on each side | equilibrium favors higher pKa (weaker acid) |
| 3 | Check solvent and counterion | protic solvents level strong bases; Li/Na/K affects aggregation |
| 4 | Use resonance/induction to refine | substituents can shift pKa by many units |