Perkow reaction

What is Perkow reaction?

The Perkow reaction is a method for preparing vinyl (or enol) phosphates from α-halo carbonyl compounds and trivalent phosphorus reagents. It was first reported by Perkow in 1952 and is also known as the Perkow synthesis, Perkow rearrangement, anomalous Arbuzov reaction, Perkow-Arbuzov reaction, or vinyl ester reaction.

Perkow reaction - general reaction scheme - Perkow synthesis - Perkow rearrangement - anomalous Arbuzov reaction -  Perkow-Arbuzov reaction - vinyl ester reaction
Perkow reaction
  • R1, R2 = H, alkyl, aryl
  • R3 = alkyl
  • R4, R5 = alkyl, alkoxyl, phenoxy
  • X = Cl, Br, I (see list of acronyms)

α-Halo aldehydes are more reactive than α-halo ketones, while α-halo esters are the least reactive species for the Perkow reaction, and α-halo amides do not react at all. The α-halo carbonyl compounds show a general reactivity scale of I > Br > Cl, and the more α-halo atoms in the carbonyl compound, the faster the reaction occurs.

For example, chloral and bromal undergo the Perkow reaction most readily, and such a vigorous reaction is usually controlled by either lowering the reaction temperature or carrying it out in an inert solvent. The trivalent phosphorus reagent should contain at least one alkoxy group, whose alkyl group is capable of evolving as a carbonium ion, and should not have a hydrogen or hydroxy group attaching to a phosphorus atom. Trialkyl phosphites, dialkyl ethylphosphonites, dialkyl phenylphosphonites, and methyl diphenylphosphinite are all possible reagents for this reaction, but trialkylphosphines, triaryl phosphates, and phosphorotriamidites do not undergo the Perkow reaction.

The electronic character of phosphorus and the steric effects are prominent in the Perkow reaction, as indicated by the predominant trans-configuration in vinyl phosphates, resulting from the initial attack of trialkyl phosphite from the less hindered side of halogen in eclipsed or gauched form of the α-halo ketones. The reaction rate of triisopropyl phosphite is slower than that of triethyl phosphite in the Perkow reaction. However, this reaction is often complicated by the Michaelis-Arbuzov rearrangement, by which phosphonate is formed instead of phosphate. The course of the reaction depends on the nature and position of halogen on the carbonyl compounds as well as the reaction temperature.

In general, more Perkow products are produced from α-iodo ketones, even at low temperature, whereas more Michaelis-Arbuzov products are generated from α-chloroketone at high temperature. α-Halo ketones with a halogen atom at the primary carbon prefer Michaelis-Arbuzov products, whereas ketones with a halogen atom at the secondary carbon yield more Perkow products. Moreover, the ketones containing more than one α-halogen atom give exclusively or almost exclusively Perkow products.

References

Perkow, W., Ullerich, K. and Meyer, F. Neue Phosphorsäureester mit pupillenverengender Wirkung.[New phosphoric acid esters with pupil constricting effectNaturwissenschaften 39, 353 (1952). DOI: 10.1007/BF00589945

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