Leuckart reaction

The Leuckart reaction is the chemical reaction that converts aldehydes or ketones to amines by reductive amination, using an ammonium salt or an amide at high temperatures.

Description

The reaction, named after Rudolf Leuckart, proceeds via two mechanisms:

• Using ammonium formate as reducing agent, at temperatures, between 120-130 °C
• Using formamide as the reducing agent, at temperatures around and above 165 °C

The first method gives a better performance and is more widely employed.

Mechanism

Ammonium formate route

Upon heating, ammonium formate first dissociates into formic acid and ammonia. Ammonia then performs a nucleophilic attack on the carbonyl carbon. The oxygen deprotonates the hydrogen from nitrogen to form a hydroxyl. The hydroxyl is protonated using hydrogen from formic acid, which allows for water molecule to leave. This forms a carbocation, which is resonance stabilized. The compound attacks hydrogen from the deprotonated formic acid from previous step, forming a carbon dioxide and an amine.

Formamide route

Formamide first nucleophilically attacks the carbonyl carbon. The oxygen is protonated by abstracting hydrogen from the nitrogen atom, subsequently forming a water molecule that leaves, forming N-formyl derivative, which is resonance stabilized. Water hydrolyzes formamide to give ammonium formate, which acts as a reducing agent and adds on to the N-formyl derivative. Hydride shift occurs, resulting in loss of carbon dioxide. Ammonium ion is added forming an imine and releasing ammonia. The imine goes through hydrolysis to form the amine.

Procedure

The general procedure used for aromatic aldehydes/ketones: In a reaction flask, like a round bottom flask, add the predetermined amounts of ketone and ammonium formate. Attach a reflux condenser. Slowly heat the reaction mixture until you reach the necessary temperature and maintain it for a few hours until completion. Remove the flask and extract the amine.

For aliphatic aldehydes or ketones, you will need to add the ammonium formate in the reaction flask first and heat it until it melts. Using a dropping funnel, slowly add the ketone/aldehyde to the melt and make sure to maintain the temperature at around 120 °C. After the reaction has completed, hydrolyze the formyl derivate and purify the compound.

Boric acid, anhydrous aluminium chloride and magnesium chloride can be used as catalysts.

Projects

• Make amines
• Make isopropylamine

References

Relevant Sciencemadness threads

• Leuckart reaction
• revised question of leuckart reaction
• DMF in Leuckart reaction?
• Leuckart reaction and acyloins (particularly L-PAC)