The Favorskii rearrangement is an organic reaction in which an α-haloketone reacts with a nucleophile under basic conditions to form a carboxylic acid or one of its derivatives, such as an ester.

The reaction is named after the Russian chemist Alexei Yevgrafovich Favorskii, who first reported it in 1894.

General Reaction

The usual starting material is an α-haloketone. In this compound, a halogen atom such as chlorine or bromine is attached to the carbon directly next to the ketone carbonyl group.

The reaction can be represented generally as:

α-Haloketone + nucleophile under basic conditions → carboxylic acid or carboxylic acid derivative 

The type of carboxylic acid derivative formed depends mainly on the nucleophile and reaction medium used.

Reaction with Hydroxide and Water

When the reaction is carried out with hydroxide in water, a carboxylate ion is formed under basic conditions. Acidification then converts the carboxylate ion into the corresponding carboxylic acid.

α-Haloketone + OH^–/H₂O → carboxylate ion →[H⁺] carboxylic acid

Reaction with an Alkoxide and Alcohol

When an alkoxide is used in the corresponding alcohol, the product is normally an ester.

α-Haloketone + RO^–/ROH → ester

For example, sodium methoxide converts 2-chlorocyclohexanone into methyl cyclopentanecarboxylate. Other alkoxides produce the corresponding alkyl esters.

Favorskii Rearrangement in Cyclic Compounds

The Favorskii rearrangement is especially useful for cyclic α-haloketones because it commonly causes a one-carbon ring contraction.

An n-membered cyclic α-haloketone produces a carboxylic acid derivative containing an (n − 1)-membered ring.

Cyclic α-haloketone with an n-membered ring
→ carboxylic acid derivative with an (n − 1)-membered ring

No carbon atom is removed from the molecule. Instead, the original ketone carbonyl carbon becomes the carbonyl carbon of the new carboxylic acid derivative and is positioned outside the contracted ring.

Example

When 2-chlorocyclohexanone is treated with hydroxide and then acidified, it forms cyclopentanecarboxylic acid.

In this reaction, the six-membered carbon ring of the starting compound becomes a five-membered ring. However, no carbon atom is lost. The original ketone carbonyl carbon becomes the carbon of the carboxyl group attached outside the new five-membered ring.

Mechanism

The following mechanism shows the commonly taught cyclopropanone pathway for an α-haloketone that contains an α’-hydrogen. Depending on the substrate and reaction conditions, other mechanistic pathways may also operate.

1. Deprotonation: A base removes an α’-hydrogen from the carbon adjacent to the carbonyl on the side opposite the halogen-bearing carbon. This forms an enolate ion.
2. Intramolecular Cyclization: The nucleophilic enolate carbon attacks the carbon bearing the halogen. As the halide ion leaves, a strained cyclopropanone intermediate is formed.
3. Nucleophilic Attack: A nucleophile, such as hydroxide or an alkoxide, attacks the carbonyl carbon of the cyclopropanone, producing a tetrahedral intermediate.
4. Ring Opening and Proton Transfer: The negatively charged oxygen reforms the carbonyl group while one of the carbon–carbon bonds of the three-membered ring breaks. This produces a carboxylic acid group and a carbanion intermediate. A proton transfer—shown here as occurring from the carboxylic acid group to the carbanion—then produces a carboxylate ion. Acidic workup converts the carboxylate into the corresponding carboxylic acid.