Clemmensen Reduction
The reduction of carbonyl groups of aldehydes and ketones to methylene groups with amalgamated zinc and concentrated hydrochloric acid is known as Clemmensen reduction.
The reduction consists in refluxing the carbonyl compounds with amalgamated zinc and excess of concentrated hydrochloric acid. The reduction is useful especially for ketones containing phenolic or carboxylic groups which remain unaffected. Ketones are reduced more often than aldehydes. Such reduction is also observed in Wolff–Kishner reduction but Clemmensen reduction is easier to perform. The reduction, however, fails with acid-sensitive and high molecular weight substrates. The α,β-unsaturated ketones undergo reduction of both the olefinic and carbonyl groups. However, the reduction is specific for carbonyl groups of aldehydes and ketones containing other functional and reducible groups.
Mechanism of Clemmensen Reduction
Various mechanisms have been suggested which are so contradictory that no conclusion can be drawn. A mechanism suggesting the intermediate formation of alcohol was rejected since the reagent fails to reduce most alcohols to hydrocarbons.
Tadaaki Nakabayashi has suggested a mechanism on the assumption that the reduction under acid condition involves protonated carbonyl group to which electrons are transferred from the metal.
Certain types of aldehydes and ketones do not give the normal reduction products alone. Thus, α-hydroxy ketones give either ketones through hydrogenolysis of OH group or olefins and 1, 3-diketones give exclusively monoketones with rearrangement.
Certain cyclic 1, 3-diketones give under Clemmensen reduction a fully reduced product along with a monoketone with ring contraction.
Applications of Clemmensen Reduction
1. Reduction of aliphatic and mixed aliphatic–aromatic carbonyl compounds.
The reaction is useful for introducing straight-chain (without rearrangement) alkyl groups in aromatic rings by acylation and subsequent reduction.
2. Reduction of keto acids.
α- and β-keto acids are generally not reduced.
3. Reduction of phenolic carbonyl compounds.
4. Synthesis of cycloparaffins.
