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# Favorskii Rearrangement

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 Sub Topics $\alpha$-halogenated ketones undergo skeletal rearrangement in the presence of certain nucleophiles to yield carboxylic acids or derivatives thereof. For example, 2-chlorocyclohexanone is readily converted by alkoxide ion into the ester of a cyclopentanecarboxylic acid. From the considerable amount of data collected from studies of the Favorskii rearrangement it appears that two types of mechanism are operative; the first and more general involves a symmetrical intermediate and the second involves a semi benzilic type sequence.  When $\alpha$-halo ketones are treated with base, they often rearrange to a carboxylate derivative. This is known as the Favorskii rearrangement. It is reasonably general although the yields are variable. The nature of the carboxylate function depends on the base used; hydroxide leads to a carboxylate salt, alkoxide lead to esters and amines give amides. The reaction has also been carried out with $\alpha$, $\beta$-epoxyketones.

## Reactions

Sodium ethoxide of 1,2-14C-labeled 2-chlorocyclohexanone, ethyl cyclopentanecarboxylate possessing a symmetrical distribution of the label was obtained. Loftfield favored a cyclopropanone as the symmetrical intermediate an idea originating in the early German literature and support for this is found in the recent demonstration that cyclopropanones di, in fact yield Favorskii products under Favorskii reaction conditions.

Thus tertramethyl cyclopropanone with sodium methoxide in either methanol or dimethoxy ethane (DME) yields the ester. In cases where a symmetrical intermediate is involved several studies have been carried out in an attempt to distinguish between a cyclopropanone intermediate and a zwitter intermediate.

Solvent effects, conformational effects, and stereochemical properties of the products have all been used in adducing evidence in favor of the cyclopropanone pathway. On the basis of quantum mechanical arguments, however Dewar and Burr contend that the Zwitter pathway is the more probable one.

The carboxylic ring contraction is shown below:

## Mechanism

A typical Favorskii rearrangement involves reaction of an $\alpha$-halo ketone with a base to give an ester or carboxylic acid, as in the follwing example.

Two $\alpha$-carbons, in the starting ketone, become equivalent during the course of the reaction. this means that a symmetrical intermediate must be formed. One possible mechanism, which is consistent with the result.

## Examples

Some of the examples of Favorskii rearrangement is given below:

Example 1:

In Favorskii rearrangement an $\alpha$-halo ketone (chloro or bromo) is changed into an ester using an alkoxide ion.

Example 2:

Cyclic ketones with an axial $\alpha$-halogen generally do not undergo the Favorskii rearrangement, although at least one exception is noted.

Example 3:
Favorskii rearrangement carried out in deuterium oxide that 2-bromocyclobutanone rearranges to cyclopropane carboxylic acid via a semibenzilic mechanism.