Wolff-Kishner reduction mechanism begins with the formation of a hydrazone anion which then releases the nitrogen molecule to form a carbanion. This carbanion then reacts with the water in the system to give a hydrocarbon. Typically, diethylene glycol is used as a solvent for this method.
This reduction is an organic reaction where aldehydes and ketones are reduced to alkanes. Some carbonyl compounds are stable in strongly basic conditions, hence they can be easily reduced to alkanes (The carbon-oxygen double bond becomes two carbon-hydrogen single bonds).
Although the mechanism usually begins with the condensation of hydrazine to give a hydrazone, the usage of a pre-formed hydrazone can have advantages such as reduced reaction time, reactions that proceed at room temperature or very mild reaction conditions. The pre-formed hydrazone substrates that can be used in this reduction also require different solvents and reaction temperatures.
Table of Contents
Wolff Kishner Reduction Mechanism
Step 1: Formation of hydrazone
The aldehyde or ketone is subjected to hydrazine. This yields the hydrazone required for the process. The reaction is illustrated below.
Step 2: Deprotonation of Nitrogen
The terminal nitrogen atom is deprotonated, and it proceeds to form a double bond with the neighbouring nitrogen atom. The released proton attaches itself to the hydroxide ion from the basic environment to form water.
Step 3: Protonation of the Carbon
Since oxygen is more electron-withdrawing than carbon, the carbon is protonated by the water molecule as shown below.
Step 4: Deprotonation of Nitrogen
The terminal nitrogen is deprotonated again, this time forming a triple bond with its neighbouring nitrogen atom. This results in the formation of a carbanion where the two triple-bonded nitrogens are released as nitrogen gas. Similar to step 2, the ejected proton forms water along with the basic environment.
Step 5: Protonation of Carbon
Similar to step 3 of the Wolff-Kishner reduction mechanism, the carbon is protonated by water, resulting in the formation of the desired hydrocarbon product as shown. Thus, the aldehyde or ketone is converted to an alkane.
The rate-determining step of this reaction is the bond formation of the terminal carbon with hydrogen (in the hydrazone anion). The carbon-hydrogen bond formation is helped by mildly electron-withdrawing substituents. Highly electron-withdrawing substituents decrease the negative charge of the terminal nitrogen, making it difficult to break the N-H bond.
The Wolff-Kishner reduction has been modified into several techniques, each with its own advantages and disadvantages. For example – the Huang Minlon modification (using the carbonyl compound, 85% hydrazine and potassium hydroxide as the reagent) offers reduced reaction time and the achievement of higher temperatures but requires distillation.
Frequently Asked Questions – FAQs
What is meant by Wolff-Kishner reduction?
The Wolff-Kishner reduction is a reaction used to convert carbonyl functionalities into methylene groups in organic chemistry. De-protonation of the hydrazone by an alkoxide base to form a diimide anion by a concerted, solvent-mediated protonation/de-protonation step is the rate deciding step of the reaction.
Does Wolff-Kishner reduce ketones?
The Wolff-Kishner reduction is a reaction used to convert carbonyl functionalities, aldehyde and ketone, into methylene groups in organic chemistry.
Why is zinc amalgamated in Clemmensen reduction?
Hydrogen gas is released (H2) when zinc reacts with hydrochloric acid. However, when this reaction occurs with zinc amalgam, the individual hydrogen molecules created by the reaction of zinc with HCl stay in a reactive state (also known as “nascent hydrogen”) and react with the ketone to create zinc nitrate. This is why zinc amalgam is used to reduce Clemmensen.
Why is ketone more reactive than aldehyde?
Owing to the following considerations, aldehydes are usually more reactive than ketones.
- Owing to the electron-donating nature of alkyl groups, the carbonyl carbon in aldehydes usually has more partial positive charges than in ketones.
- Aldehydes have only one group of e-donors, whereas ketones have two.
What is tollens reagent reaction?
Tollens’ reagent is a chemical reagent used to assess the identity of functional groups of an aldehyde, aromatic aldehyde and alpha-hydroxy ketone. The reagent is composed of silver nitrate and ammonia solution.
What do u mean by hydrazine and hydrazone
Hydrazine is a chemical compound with the formula N2H4. It consists of two singly-bonded nitrogen atoms, each bonded to two hydrogen atoms.
Hydrazone is the functional group given by R1R2C=N-NH2.
What is Application of wolff kishner reduction?
Wolff-Kishner reduction can be employed for the synthesis of aspidospermidine. The Huang Minion modification of this reaction can be used to reduce some tricyclic carbonyl compounds. Furthermore, the Wolff-Kishner reduction can also be used for the synthesis of functionalized imidazole substrates.