Wolff-Kishner Reduction: History, Mechanism, and Applications

Wolff-kishner reduction is the condensation of aldehyde or ketone with hydrazine to form hydrazone. Later, the base reduces the carbon into the corresponding alkanes. The Clemmensen reduction can do the same conversion but under strongly acidic conditions. The reaction is very effective in organic synthesis. For example, it is applied in the synthesis of aspidospermidine.

Introduction of Wolff-kishner reduction

“The reduction of carbonyl compounds (aldehyde and ketone) into the hydrocarbons by using hydrazine and a base like KOH or potassium tert-butoxide is known as Wolff kishner reduction.”

This reduction is made under basic conditions. Therefore, it can be used for acid-sensitive compounds.

History of Wolff-kishner reduction

The N. Kishner and Ludwig Wolff discovered the Wolff kishner reduction in 1911 and 1912 respectively. The N.kishner predicted that when hydrazones are added to the KOH. The corresponding hydrocarbons are formed.

Later, Wolff heated the ethanol solution of semicarbazone and hydrazone in the presence of sodium ethoxide. The same results are obtained.

Mechanism of Wolff-kishner reduction

The mechanism of Wolff kishner reduction was studied by Szmant and coworkers.

Step 1

In the first step, aldehyde or ketones are treated with hydrazine. Resulting in the formation of hydrazones.

Step 2

The base abstract is the proton of terminal nitrogen of hydrazones.

Step 3

In this step, the carbon atom is protonated by the water molecule.

Step 4

The terminal nitrogen is deprotonated again by the base. Hence, carbanion is formed.

Step 5

In the last step, the carbanion is protonated by the water. It yields the desired hydrocarbon.

Modifications

Some of the modifications are made to improve Wolff-kishner reduction.

Huang Minton modification

Huang Minton modifies the Wolff kishner reduction by using 85% hydrazine hydrate in NaOH and ethylene glycol. After hydrazone formation, the excess hydrazine and water are removed by distillation.

Barton modification

This modification plays an important role in the reduction of sterically hindered carbonyl groups. This method uses sodium in diethylene glycol instead of the base. For example, in steroidal compound carbon-11 is reduced by the barton modification.

Applications of Wolff-kishner reduction

Wolff kishner reduction is widely used in many syntheses.

It is used for the reduction of aliphatic carbonyl compounds.
The cyclic ketones can also be reduced by this method. For example, Cyclohexanone is reduced into cyclohexane.
This method is used for the reduction of 𝞪,𝞫-unsaturated ketone.
It can also be used for the reduction of high molecular weight carbonyl compounds. For example, 24-ketocholesterol is reduced into cholesterol.
The carbonyl group of keto acid can be reduced by Wolff-kishner reduction. Whereas the carboxyl group remains unaffected.
The long straight-chain alkyl groups can be introduced into the aromatic ring by this method.

Concepts Berg

What is used in Wolff-Kishner reduction?

The reagents used in the Wolff kishner reduction are hydrazine and potassium hydroxide. Although, a high boiling solvent ethylene glycol is also used.

What do we get by using the Wolff Kishner reduction in benzaldehyde?

We get toluene by the reduction of benzaldehyde.

Can a Wolff-Kishner Reduction change haloarenes to phenols?

The haloarenes can be converted into phenol by the nucleophilic substitution reaction. Whereas Wolff kishner reduction is the conversion of carbonyl compounds into the alkanes.

What is Wolff-kishner reduction?

The conversion of aldehyde or ketones into hydrocarbons under basic conditions is known as Wolff kishner reduction.

What is the difference between Clemmenson and wolf kishner reduction?

The Wolff kishner reduction is done under basic conditions. whether the Clemmensen reduction carries out under acidic conditions.

Reference Books

Organic Chemistry twelfth edition by T.W. Graham Solomons (University of South Florida) Craig B. Fryhle (Pacific Lutheran University) Scott A. Snyder (University of Chicago)

Reference links