Hydride reduction — exhaustive
LiAlH₄ reduction of an ester to a primary alcohol
How the LiAlH₄ reduction of an ester to a primary alcohol works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: LiAlH₄ (≥ 0.5 equiv., 2 H⁻ per ester), then H₃O⁺ or Fieser workup. Conditions: Dry Et₂O or THF, 0 °C to reflux. Bonds formed: two C–H; C–OH (alcohol); bonds broken: C=O π; C–OEt; Al–H. Stereochemistry: No stereocentre (primary alcohol). Rate and selectivity: Fast; aldehyde reduces faster than the ester.
At a glance
Step 1: First hydride gives an aldehyde
LiAlH₄'s far more reactive, more nucleophilic hydride attacks the ester's carbonyl carbon, forming a tetrahedral intermediate that collapses by expelling alkoxide — the same addition-elimination pattern as any nucleophilic acyl substitution, generating an aldehyde in the process.
Step 2: Second hydride attacks the aldehyde
Unlike the milder Weinreb amide, this aldehyde is not protected from further attack: a second equivalent of hydride immediately adds to it, since LiAlH₄ is reactive enough that the reaction doesn't stop at the aldehyde stage.
Step 3: Workup protonates the alkoxide
Protonation on aqueous workup gives a primary alcohol — this exhaustive, two-hydride reduction is why LiAlH₄ is the reagent of choice whenever a carboxylic acid derivative needs to be taken all the way down to the alcohol, in contrast to the Rosenmund reduction's deliberately stopped, milder alternative.
Abbreviations and terms
- OEt
- Ethoxy. –OCH₂CH₃.
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- Et2O
- Diethyl ether. Low-boiling ether solvent, classic for Grignard reagents.
- LiAlH4
- Lithium aluminium hydride. Powerful hydride (H⁻) donor; reduces esters, acids, amides to alcohols/amines.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
How it compares with related reactions
| LiAlH₄ reduction of an ester to a primary alcohol | LiAlH₄ reduction of a nitrile to a primary amine | NaBH₄ reduction of a ketone | |
|---|---|---|---|
| Reagents | LiAlH₄ (≥ 0.5 equiv., 2 H⁻ per ester), then H₃O⁺ or Fieser workup | LiAlH₄ (excess), then H₂O workup | NaBH₄ (0.25–1 equiv) |
| Conditions | Dry Et₂O or THF, 0 °C to reflux | Dry Et₂O or THF, 0 °C → reflux; then H₃O⁺ or Fieser workup | EtOH or MeOH, 0–25 °C; aqueous workup |
| Stereochemistry | No stereocentre (primary alcohol) | None (achiral CH₂NH₂) | Hydride attacks the less hindered face of ring ketones |
| Rate / selectivity | Fast; aldehyde reduces faster than the ester | Second hydride addition fast relative to the first | Aldehydes > ketones; esters and amides untouched |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the LiAlH₄ reduction of an ester to a primary alcohol?
LiAlH₄ (≥ 0.5 equiv., 2 H⁻ per ester), then H₃O⁺ or Fieser workup. Conditions: Dry Et₂O or THF, 0 °C to reflux.
Which bonds are formed and which are broken?
Formed: two C–H; C–OH (alcohol). Broken: C=O π; C–OEt; Al–H.
What is the stereochemical outcome?
No stereocentre (primary alcohol)
What controls the rate or the selectivity?
Fast; aldehyde reduces faster than the ester
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go