The Favorskii rearrangement is principally a rearrangement of

cyclopropanone Cyclopropanone is an organic compound with molecular formula (CH2)2CO consisting of a cyclopropane carbon framework with a ketone functional group. The parent compound is labile, being highly sensitive toward even weak nucleophiles. Surrogates ...

s and α-halo ketones that leads to carboxylic acid derivatives. In the case of cyclic α-halo ketones, the Favorskii rearrangement constitutes a ring contraction. This rearrangement takes place in the presence of a base, sometimes

hydroxide Hydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and hydrogen atom held together by a single covalent bond, and carries a negative electric charge. It is an important but usually minor constituent of water. I ...

, to yield a carboxylic acid but most of the time either an alkoxide base or an

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen Hydrogen is the chemical element wi ...

to yield an

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

or an

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...

, respectively. α,α'-Dihaloketones eliminate HX under the reaction conditions to give α,β-unsaturated carbonyl compounds.

History

The reaction is named for the Russian chemist Alexei Yevgrafovich Favorskii

Reaction mechanism

The reaction mechanism is thought to involve the formation of an

enolate In organic chemistry, enolates are organic anions derived from the deprotonation of carbonyl () compounds. Rarely isolated, they are widely used as reagents in the synthesis of organic compounds. Bonding and structure Enolate anions are electr ...

on the side of the ketone away from the

chlorine Chlorine is a chemical element with the symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate between them. Chlorine i ...

atom. This enolate cyclizes to a

intermediate which is then attacked by the hydroxide nucleophile. The second step has also been proposed to be stepwise process, with chloride anion leaving first to produce a zwitterionic oxyallyl cation before a disrotatory electrocyclic ring closure takes place to afford the cyclopropanone intermediate. Usage of alkoxide anions such as sodium methoxide, instead of sodium hydroxide, yields the ring-contracted

product. When enolate formation is impossible, the Favorskii rearrangement takes place by an alternate mechanism, in which addition to hydroxide to the ketone takes place, followed by concerted collapse of the tetrahedral intermediate and migration of the neighboring carbon with displacement of the halide. This is sometimes known as the pseudo-Favorskii rearrangement, although previous to labeling studies, it was thought that all Favorskii rearrangements proceeded through this mechanism.

Wallach degradation

In the related Wallach degradation (

Otto Wallach Otto Wallach (; 27 March 1847 – 26 February 1931) was a German chemist and recipient of the 1910 Nobel Prize in Chemistry for his work on alicyclic compounds. Biography Wallach was born in Königsberg, the son of a Prussian civil servant. Hi ...

, 1918) not one but two halogen atoms flank the ketone resulting in a new contracted ketone after oxidation and decarboxylation

Photo-Favorskii reaction

The reaction type also exists as a

photochemical reaction Organic photochemistry encompasses organic reactions that are induced by the action of light. The absorption of ultraviolet light by organic molecules often leads to reactions. In the earliest days, sunlight was employed, while in more modern times ...

. The photo-Favorskii reaction has been used in the photochemical unlocking of certain

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

s (for instance those of ATP)

protected Protection is any measure taken to guard a thing against damage caused by outside forces. Protection can be provided to physical objects, including organisms, to systems, and to intangible things like civil and political rights. Although th ...

by so-called ''p-hydroxyphenacyl'' groups. The deprotection proceeds through a triplet

diradical In chemistry, a diradical is a molecular species with two electrons occupying molecular orbitals (MOs) which are degenerate. The term "diradical" is mainly used to describe organic compounds, where most diradicals are extremely reactive and i ...

(3) and a dione spiro intermediate (4) although the latter has thus far eluded detection. :

References

{{Reflist Rearrangement reactions Name reactions Ring contraction reactions

History

Reaction mechanism

Wallach degradation

Photo-Favorskii reaction

See also

Further reading

References