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Beckmanns Rearrangement, Schmidt Rearrangement and Claisen-Schmidt Condensation

An oxime-based reaction that can result in either nitriles or amides, depending on the starting material, is the Beckmann Rearrangement.

Beckmanns Rearrangement

An oxime-based reaction that can result in either nitriles or amides, depending on the starting material, is the Beckmann Rearrangement. Those oximes that are obtained from ketones get transformed into amides; whereas those derived from aldehydes become nitriles.

An oxime can be changed into an amide through the Beckmann Rearrangement process under some acidic conditions. A protonation reaction eventually takes place, leading to the formation of a preferred leaving group resulting from the alcohol group.

A transition from the R group to the leaving species occurs at the nitrogen, which introduces carbocation and a water molecule. An attack of the water atom on the carbocation results in the formation of the amide, followed by deprotonation and tautomerization.

Beckmann Rearrangement, in simple terms, is when an oxime is changed into an amide. Hydroxylamine is used to process an aldehyde or ketone into an oxime. There is a reaction in science called the Beckmann rearrangement, which is named after a German scientist.

Mechanism



Beckmann Rearrangement consists of the following steps:
  • A cyclohexanone reacts with hydroxylamine to form an oxime.
  • When an alkyl substituent changed from "trans" to "nitrogen" at the hydroxyl of the oxime, protonation happened
  • Expulsion of water also causes the breakage of N-O bonds.
  • Later, the nitrogen molecule is protonated, which results in the formation of amine through isomerization.


Schmidt Rearrangement

This chemical reaction involves azides reacting with carbonyl groups of a compound to produce amines or amides. Schmidt reported the reaction first in 1924.

Examples
If an azide reacts with a ketone, it can be used to produce amides, but if an azide reacts with a carboxylic acid, it can be used to produce amines.

Schmidt reaction for carboxylic acid
A reaction that produces amines from azides and carboxylic acids looks like this:



Schmidt reaction for ketones
When an azide reacts with a ketone, an amide is produced. This is another example of the Schmidt reaction. It looks like this:



From benzophenone and hydrogen azide, benzanilide can be prepared by the Schmidt reaction. This is an example of a ketone and azide being combined to produce an amide.

Mechanism

The Schmidt reaction can be used either to make amides or to make amines, as discussed earlier. It is necessary to add a different functional group to these two products (ketones or carboxylic acids). Below is a detail of the mechanisms of each process.

Schmidt reaction mechanism for producing amines
  • From the protonation of the carboxylic acid, an acylium ion is formed, and then water is removed.
  • The protonated azido ketone is formed after this acylium ion reacts with hydrazoic acid.
  • This is followed by the rearrangement of the protonated azido ketone and the R group, resulting in the removal of dinitrogen and migration of the carbon-nitrogen bond.
  • By attacking the protonated isocyanate with water, a carbamate is formed.
  • The carbamate then deprotonates. By removing CO2, the amine is produced.
Here is an illustration of how this mechanism works:



Schmidt reaction mechanism for producing amines
  • A bond between the proton and hydrogen is formed during protonation of the ketone.
  • After nucleophilic addition of the azide, an intermediate is formed.
  • This temporary imine is now formed by an elimination reaction, thereby removing the water from the intermediate.
  • Alkyl groups present in the original ketone migrate to nitrogen in the imine, which is an alkyl group. Nitrogen is thus eliminated.
  • Now, water attacks the resulting compound, and the deprotonation that follows yields the desired amide tautomer.
  • The final amide product results from the relocation of a proton from the tautomer.


Claisen-Schmidt Condensation

The first thing that one needs to understand is what the Claisen Schmidt reaction is. Due to the improvement in aromaticity in this case, it is highly possible for the reaction to occur. An aldol condensation reaction involves four steps.

A Claisen-Schmidt condensation takes place when an aldehyde or ketone has an *-hydrogen and an aromatic carbonyl compound does not have one. During this reaction, aromatic aldehydes are formed as a product. This makes it quite feasible and successful in practice. NaOHNaOH reacts with acetaldehyde to produce benzaldehyde. Cross-aldol condensation happens here.

Basically, there are four steps to the entire process. Those steps are as follows:

Step 1 - To produce the negatively charged compound that will be used for further reactions, the acetaldehyde is reacted with a base.


Step 2 - A negatively charged aldehydic compound is then produced by reacting this compound with benzaldehyde. The aromatic ring is added now.

Step 3 - After the compound has been obtained, it needs to be treated in acid.

Step 4 - During this stage, the water molecules are separated from the entire compound, resulting in the production of the aromatic aldehyde.

Benzaldehydes were used as a base in combination with sodium hydroxide to obtain quantitative yields in Claisen-Schmidt reactions in the absence of solvent. The reaction is attainable since the product is subsequently converted into a stable aromatic compound.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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