Reductive amination — formate variant
Leuckart-Wallach reaction
How the Leuckart-Wallach reaction 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: Ketone, HCO₂NH₄ (or HCONH₂ / R₂NH + HCO₂H). Conditions: Neat, 160–185 °C. Bonds formed: C–N; C–H; CO₂; bonds broken: C=O; H–CO₂H. Stereochemistry: Racemic product at a new stereocentre. Rate and selectivity: High temperature needed; iminium formation reversible, hydride transfer irreversible.
At a glance
Step 1: Ketone + NH₃ → iminium ion
A ketone condenses with ammonium formate (or an amine plus formic acid) to form an iminium ion, again through ordinary Schiff-base chemistry.
Step 2: Formate transfers hydride, loses CO₂
Formate transfers hydride to the iminium carbon, decarboxylating as it does — mechanistically identical to the hydride-transfer step of Eschweiler-Clark, just applied to a ketone-derived iminium rather than formaldehyde's.
Step 3: N-Formyl amide hydrolysed to the amine
The product is a primary or secondary amine — this reaction was historically one of the most economical ways to convert cheap ketones into amines at industrial scale, using formic acid as both reductant and (via ammonium formate) nitrogen source.
Abbreviations and terms
- NaOH
- Sodium hydroxide. Strong aqueous base and nucleophile.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
How it compares with related reactions
| Leuckart-Wallach reaction | Eschweiler-Clark reaction | Borch reductive amination | |
|---|---|---|---|
| Reagents | Ketone, HCO₂NH₄ (or HCONH₂ / R₂NH + HCO₂H) | Amine, excess CH₂O (formalin), excess HCO₂H | Amine, ketone/aldehyde, NaBH₃CN |
| Conditions | Neat, 160–185 °C | Aqueous, 80–100 °C | MeOH, pH 6–7 (AcOH), 25 °C |
| Stereochemistry | Racemic product at a new stereocentre | Chiral centres α to N are not racemised | New stereocentre usually racemic (unless chiral amine/ketone) |
| Rate / selectivity | High temperature needed; iminium formation reversible, hydride transfer irreversible | Hydride transfer to the iminium is rate-limiting; CO₂ loss makes it irreversible | Iminium formation is rate-limiting; iminium reduced much faster than ketone at this pH |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Leuckart-Wallach reaction?
Ketone, HCO₂NH₄ (or HCONH₂ / R₂NH + HCO₂H). Conditions: Neat, 160–185 °C.
Which bonds are formed and which are broken?
Formed: C–N; C–H; CO₂. Broken: C=O; H–CO₂H.
What is the stereochemical outcome?
Racemic product at a new stereocentre
What controls the rate or the selectivity?
High temperature needed; iminium formation reversible, hydride transfer irreversible
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