Clemmensen reduction is an organic chemical reaction that converts ketones or aldehydes into alkanes. A catalyst must be used for this reaction. It is a fusion of hydrochloric acid and zinc (mercury alloyed with zinc). Therefore, mercury alloyed with zinc does not participate in the reaction. It simply provides a clean and active surface for the reaction.
The name of the procedure comes from the Danish scientist Erik Christian Clemmensen. This method is very effective in reducing arylalkyl ketones. In addition, the reduction of zinc metals is much more effective with aliphatic or cyclic ketones. More importantly, the substrate for this reaction must be non-reactive to the strong acid conditions of the reaction.
Mechanism of Clemmensen Reduction
The mechanism of this reaction is not fully understood, but there are two suggestions.
Carbenoid Mechanism: The carbenoid mechanism is a radical process that reduces manipulation on zinc metal surfaces. The reduction occurs on the surface of the zinc catalyst. In this reaction, the corresponding alcohol is not considered an intermediate because it does not produce alkanes when exposed to the same reaction conditions.
The underlying substance must not react to acidic conditions. Acid-sensitive bases react strongly with Wolff-Kishner reduction if they are milder than Mozingo reduction.
The reaction is not due to acid sensitive substances.
Due to its non-uniform nature, its mechanism remains ambiguous despite its age, making it difficult to study the mechanism.
There are probably few studies on the specific reactions proposed, such as zinc carbenoids and organozinc intermediates.
What is Wolff Kishner Reduction?
Wolff-Kishner reduction is an organic chemical reaction used to convert a carbonyl functional group to a methylene group.
This reaction is named after two scientists, Nikolai Kirschner and Ludwig Wolff.
The main uses of this reaction are the synthesis of scopadurcinic acid B, aspidospermine, and disidiolide.
In contrast to the Clemmensen reduction, this reaction requires very basic conditions.
Therefore, the first step in the reaction process is to produce hydrazone by condensing hydrazine with a ketone or aldehyde substrate.
Next, in the second step, you need to deprotonate the hydrazone with an alkoxide base.
Following this is the step of forming the diimide anion. This anion then decays and releases N2 gas, forming an alkylation.
Finally, this alkylation can be protonated to the desired product.
Mechanism of Wolff Kishner Reduction
The hydrazone NH2 is very acidic (pKa is about 21) and can be deprotonated with strong bases at sufficiently high temperatures (the base is probably a conjugate base of ethylene glycol, not KOH). This deprotonation seems to be the rate-determining step.
The next step is the most difficult; protonation of carbon.
There is a warning that the resonance form does not actually exist, but it can be helpful to imagine forming this kind of resonance form with a negative charge on carbon and protonating it with a solvent (ethylene glycol).
This produces a species with a nitrogen-nitrogen double bond that irreversibly decays to nitrogen gas and carbanion (ie, negatively charged carbon) during base deprotonation.
Protonation of carbon completes the process.
Wolff Kishner Reduction Examples
Wolff-Kishner reduction of ketones uses hydrazine (NH2NH2) as a reducing agent in the presence of a strong base (KOH) in a high boiling aprotic solvent (ethylene glycol, HO-CH2CH2-OH, bp 197o C).
The driving force of the reaction is the conversion of hydrazine to nitrogen gas.
This is not always a gentle process.
In order for the reaction to proceed at a reasonable rate, it needs to be heated to approximately 200o C.
The first step is the formation of hydrazone from ketones (hydrazone is associated with imines, which will be discussed later in this course). Hydrazine (NH2NH2) is added to the carbonyl and water is expelled after a series of proton transfer steps.
The first step in the Wolff-Kishner reaction is the formation of a hydrazone intermediate.
Once the hydrazone is formed, the actual action of the Wolff-Kishner reaction begins.
Difference Between Clemmensen and Wolff Kishner Reduction
Both Clemmensen reduction and Wolff-Kishner reduction are performed via functional group reduction. For this reason, both reactions must meet specific conditions and catalysts for the process to function properly.
The main differences between the Clemmensen reduction and the Wolff-Kishner reaction are:
The Clemmensen reduction reaction attempts to convert ketones and aldehydes to alkanes. The Wolff-Kishner reaction, on the other hand, is used to convert carbon functional groups to methylene groups.
Clemmensen reduction uses a catalyst called fused zinc. However, no catalyst is required to perform the Wolff-Kishner reduction.
The Clemmensen and Wolff-Kishner reactions is that the former operates under strongly acidic conditions and is not suitable for acid-sensitive substrates. In contrast, the Wolff-Kishner reduction reaction uses basic conditions and is not suitable for base-sensitive substrates.
Differences between Clemmensen and Wolff Kishner Reduction
Equation of Wolff Kishner Reduction
The reaction of acetophenone (methyl phenyl ketone) in Wolff-Kishner reduction produces ethylbenzene:
or more generally, this reaction is:
This reaction also requires considerable energy in the form of heat. Moreover, it usually runs at about 200oC.
Application of Clemmensen Reduction
The reduction mechanism is often used to convert a carbonyl group to a methyl group.
It is also used in the production of polycyclic aromatic compounds and aromatic compounds containing linear hydrocarbons.
It is often used to convert acyl benzene to alkyl benzene in Friedel-Crafts acylation reactions.
The reduction reaction in the presence of zinc amalgam and concentrated hydrochloric acid converts benzaldehyde to toluene.
Application of Wolff-Kishner Reduction
Wolff-Kishner reduction was applied to the total synthesis of scopadurcinate B, aspidospermidine, and disidiolide.
Wolff-Kishner reduction is an effective tool in organic synthesis. For example, Ishibashi used the Wolff-Kishner reduction yellow minron modification as one of the final steps in the synthesis of (±) -aspidospermidine. After forming the hydrazone at 160o C, the distillable material was removed and heated at 210o C overnight.
The carbonyl group reduced by Wolff-Kishner reduction was essential for the previous synthetic step.
The tertiary amide was stable under reaction conditions and was subsequently reduced by lithium aluminium hydride.
Wolff-Kishner reduction was also used on a kilogram scale to synthesise a functionalized imidazole substrate.
Benefits of Learning the Wolff-Kishner Reduction Mechanism
Learning the Wolff-Kishner reduction mechanism will be very helpful for you. This is one of the most important concepts in Chemistry, so you need to be familiar with this topic. Before you start the Wolff-Kishner reduction mechanism, it's a good idea to first review the concept textbook description. It will give you an idea of what the concept is and why it is important in Chemistry. You should also use exercises to test your knowledge to see if you understand the Wolff-Kishner reduction mechanism.
There are various organic chemical reactions used in organic chemistry to synthesise important compounds. The Clemmensen reduction and the Wolff-Kishner reduction are two such reactions. The main difference between the Clemmensen reduction and the Wolff-Kishner reduction is that the Clemmensen reduction converts ketones or aldehydes to alkanes, whereas the Wolff-Kishner reduction converts carbonyl groups to methylene groups.