Hydride reduction — nitrile to amine
LiAlH₄ reduction of a nitrile to a primary amine
How the LiAlH₄ reduction of a nitrile to a primary amine 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 (excess), then H₂O workup. Conditions: Dry Et₂O or THF, 0 °C → reflux; then H₃O⁺ or Fieser workup. Bonds formed: C–H ×2, N–H ×2; bonds broken: C≡N (to C–N single), Al–N. Stereochemistry: None (achiral CH₂NH₂). Rate and selectivity: Second hydride addition fast relative to the first.
At a glance
Step 1: First hydride adds to C≡N
Hydride adds to the nitrile carbon, and the resulting nitrogen anion is stabilized as an aluminum ate complex — a metalated imine intermediate, not a free proton source, since the reaction runs under anhydrous conditions with no water present until workup.
Step 2: Second hydride adds to the C=N
A second equivalent of hydride adds to this metalated imine's electrophilic carbon exactly as it would to any ordinary imine, since the reaction doesn't stop after the first addition.
Step 3: Workup protonates N⁻
Aqueous workup protonates the resulting amide anion, giving a primary amine — this two-hydride reduction converts a nitrile directly into a CH₂-NH₂ group, extending the carbon chain by one nitrogen-bearing carbon relative to the starting material it was typically made from.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- 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 a nitrile to a primary amine | LiAlH₄ reduction of an ester to a primary alcohol | NaBH₄ reduction of a ketone | |
|---|---|---|---|
| Reagents | LiAlH₄ (excess), then H₂O workup | LiAlH₄ (≥ 0.5 equiv., 2 H⁻ per ester), then H₃O⁺ or Fieser workup | NaBH₄ (0.25–1 equiv) |
| Conditions | Dry Et₂O or THF, 0 °C → reflux; then H₃O⁺ or Fieser workup | Dry Et₂O or THF, 0 °C to reflux | EtOH or MeOH, 0–25 °C; aqueous workup |
| Stereochemistry | None (achiral CH₂NH₂) | No stereocentre (primary alcohol) | Hydride attacks the less hindered face of ring ketones |
| Rate / selectivity | Second hydride addition fast relative to the first | Fast; aldehyde reduces faster than the ester | 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 a nitrile to a primary amine?
LiAlH₄ (excess), then H₂O workup. Conditions: Dry Et₂O or THF, 0 °C → reflux; then H₃O⁺ or Fieser workup.
Which bonds are formed and which are broken?
Formed: C–H ×2, N–H ×2. Broken: C≡N (to C–N single), Al–N.
What is the stereochemical outcome?
None (achiral CH₂NH₂)
What controls the rate or the selectivity?
Second hydride addition fast relative to the first
Study guides that help with this reaction
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go