Carbonyl deoxygenation
Wolff-Kishner reduction
How the Wolff-Kishner reduction 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: N₂H₄; KOH (or t-BuOK). Conditions: Diethylene glycol, 180–200 °C (Huang-Minlon). Bonds formed: CH₂ (C–H ×2); N₂ gas; bonds broken: C=O; N–N / C–N. Stereochemistry: Carbanion is protonated; no stereocontrol. Rate and selectivity: N₂ loss is irreversible; needs base-stable substrate.
At a glance
Step 1: Hydrazone formation
Hydrazine condenses with a ketone or aldehyde, losing water to form a hydrazone (C=N–NH₂).
Step 2: Deprotonation and N₂ loss
Strong base deprotonates the N–H; the resulting anion pushes electron density through the N=N as it loses N₂ gas, forming a carbanion directly on the former carbonyl carbon.
Step 3: Protonation by solvent
That carbanion is immediately protonated by solvent, replacing the entire C=O with a CH₂ group — full deoxygenation, driven irreversibly by loss of N₂ gas.
Abbreviations and terms
- KOtBu
- Potassium tert-butoxide. Strong, bulky alkoxide base – favours elimination over substitution.
- KOH
- Potassium hydroxide. Strong aqueous/alcoholic base.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- Δ
- Heat. Reaction is run at elevated temperature.
How it compares with related reactions
| Wolff-Kishner reduction | Clemmensen reduction | Mozingo reduction (thioketal desulfurization) | |
|---|---|---|---|
| Reagents | N₂H₄; KOH (or t-BuOK) | Zn(Hg), conc. HCl | 1,2-Ethanedithiol, BF₃·OEt₂ (or TsOH); then Raney Ni (H-saturated) |
| Conditions | Diethylene glycol, 180–200 °C (Huang-Minlon) | Reflux, heterogeneous (metal surface) | Step 1: CH₂Cl₂, 25 °C; step 2: EtOH, reflux |
| Stereochemistry | Carbanion is protonated; no stereocontrol | Not stereocontrolled; mechanism debated | Any carbonyl stereocentre α is untouched; no new stereocentre |
| Rate / selectivity | N₂ loss is irreversible; needs base-stable substrate | Works best for aryl ketones; avoid acid-sensitive groups | Strong Ni–S bond formation drives desulfurization |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Wolff-Kishner reduction?
N₂H₄; KOH (or t-BuOK). Conditions: Diethylene glycol, 180–200 °C (Huang-Minlon).
Which bonds are formed and which are broken?
Formed: CH₂ (C–H ×2); N₂ gas. Broken: C=O; N–N / C–N.
What is the stereochemical outcome?
Carbanion is protonated; no stereocontrol
What controls the rate or the selectivity?
N₂ loss is irreversible; needs base-stable substrate
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