Reactions of Alcohols
High-Yield Summary
- Primary alcohol + PCC (mild) → aldehyde only. Primary alcohol + chromic acid (H₂CrO₄) or Jones oxidation (CrO₃/H₂SO₄, strong) → carboxylic acid.
- Secondary alcohol + Na₂Cr₂O₇ (or PCC/CrO₃-pyridine) → ketone, and can't go further (no C-H left on that carbon). Tertiary alcohols don't oxidize at all — no C-H on the carbinol carbon.
- OH is a poor leaving group; converting to a mesylate (-OSO₂CH₃) or tosylate (-OSO₂C₆H₄CH₃) makes it a resonance-stabilized, easily-displaced leaving group for SN1/SN2.
- Acetal (from aldehyde) / ketal (from ketone) form from 2 equivalents of alcohol (or 1 diol) + acid catalyst — protects a reactive carbonyl; stable to base and reducing agents; removed by aqueous acid.
- Protecting-group strategy: protect ketone as ketal (diol, H⁺) → reduce ester with LiAlH₄ → deprotect ketal with aqueous acid, giving a selectively-reduced product.
Alcohol Oxidation by Class
| Alcohol | Product / reagent |
|---|---|
| Primary + PCC (mild) | → Aldehyde (RCHO) |
| Primary + H₂CrO₄ or Jones (CrO₃/H₂SO₄, strong) | → Carboxylic acid (RCOOH) |
| Secondary + Na₂Cr₂O₇ | → Ketone (R₂C=O), no further oxidation possible |
| Tertiary | No reaction — no H on the carbinol carbon |
Worked Example: Selectively Reducing an Ester in the Presence of a Ketone
- 1Protect the ketone: react with a diol + acid catalyst (H⁺) → converts ketone to a ketal, stable under the coming reduction.
- 2Reduce the ester: treat with LiAlH₄ → reduces the ester to a primary alcohol; the ketal is untouched (no longer an electrophilic carbonyl for LiAlH₄ to attack).
- 3Deprotect: hydrolyze the ketal with aqueous acid (H₂O, H⁺) → regenerates the original ketone.
- 4Result: ketone (regenerated) + primary alcohol (from the reduced ester) — without the protecting group, LiAlH₄ would have reduced both groups.
Key Terms
- Mesylate / Tosylate
- Sulfonate esters (-OSO₂CH₃ / -OSO₂C₆H₄CH₃) made from an alcohol; far better leaving groups than OH because the departing sulfonate anion delocalizes charge by resonance.
- Acetal / Ketal
- Carbon bonded to two -OR groups, formed from an aldehyde/ketone + 2 equivalents of alcohol (or 1 diol) under acid catalysis; a reversible protecting group for the carbonyl.
Common MCAT Trap
- The choice of oxidizing agent — not the alcohol itself — determines whether a primary alcohol stops at the aldehyde (PCC) or goes to the carboxylic acid (H₂CrO₄/Jones).
- Acetals/ketals are stable to base and to reducing/nucleophilic reagents but are cleaved by aqueous acid — don't expect them to survive an acidic aqueous workup.
- A tertiary alcohol resisting oxidation is a structural fact (no carbinol C-H), not a matter of using a weaker reagent — no oxidant, however strong, will oxidize it under normal conditions.
Quick Recall
What product does PCC give from a primary alcohol, and how does that differ from Jones oxidation?
Why can't a secondary alcohol be oxidized past a ketone?
Why does converting an alcohol to a tosylate improve its usefulness in SN1/SN2 reactions?
How is an acetal removed to regenerate the original aldehyde?