Favorskii rearrangement

What is Favorskii rearrangement?

Favorskii rearrangement is an organic chemistry reaction that allows for the conversion of a substituted cyclohexyl carboxylic acid into a carbonyl compound. It is named after the Russian chemist Aleksandrovich Favorskii, who first reported the reaction in 1907..

Favorskii rearrangement involves the thermal or photochemical conversion of a substituted cyclohexyl carboxylic acid into a carbonyl compound. The reaction proceeds through a concerted mechanism, with the migration of an alkyl or aryl group from the cyclohexyl ring to the carbonyl group..

Favorskii rearrangement
Favorskii rearrangement

Favorskii rearrangement has several important applications in organic chemistry. It is widely used in the synthesis of a variety of natural products and drugs, including the anti-inflammatory drug celecoxib and the anti-cancer agent doxorubicin. It has also been used in the synthesis of other heterocyclic compounds and in the preparation of polymers..

Summary

Favorskii rearrangement is an important reaction in the field of organic chemistry due to its ability to efficiently convert substituted cyclohexyl carboxylic acids into carbonyl compounds, which have a wide range of applications in the synthesis of drugs and other organic compounds..

Example

The Favorskii rearrangement is a type of rearrangement reaction in which a halohydrin is converted into a β-chloro carbonyl compound. An example of a Favorskii rearrangement is the reaction between 3-chloro-2-butanol and hydrochloric acid:

The 3-chloro-2-butanol is treated with hydrochloric acid, which protonates the oxygen atom, forming a carbocation intermediate..

The chlorine atom, which is now adjacent to the carbocation, migrates to the carbocation center..

The carbocation then collapses, expelling the chloride ion, forming a β-chloro carbonyl compound..

The Favorskii rearrangement is widely used in the synthesis of a variety of natural products, such as alkaloids and terpenes, and in the synthesis of other organic compounds..

Mechanism of reaction

The Favorskii rearrangement is a type of retro-Diels-Alder reaction in which a cycloalkyl carbanion is converted into a cycloalkene. The reaction mechanism can be broken down into the following steps:

  • The first step is the deprotonation of the cycloalkyl carbanion, which forms a cycloalkyl anion.
  • In the second step, the cycloalkyl anion re-arranges its carbons to form a new cycloalkyl anion with an adjacent carbonyl group.
  • The carbonyl oxygen of the new cycloalkyl anion attacks an adjacent carbon atom, forming a new alkoxide intermediate.
  • In the final step, the alkoxide intermediate eliminates a molecule of water to form the cycloalkene product.

This is a concerted process, meaning that all the bond forming and breaking happens in one step and no intermediates are formed.

It is important to note that the Favorskii rearrangement is a thermally activated process, which means it requires high temperatures to occur. Furthermore, it is typically a very slow process, but it can be catalyzed by some metal ions or acid catalysts.

References

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