Fries rearrangement

What is Fries rearrangement?

The Fries rearrangement is a Lewis acid–promoted reaction of phenolic esters to form ortho- and/or para-acyl phenols, which was first reported in 1908 by Fries et al. The reaction can be catalyzed by both Lewis acids (e.g., AlCl3, BCl3, BF3, Bi(OTf)3, FeCl3, HgCl2, SnCl4, ZrCl4, and lanthanide triflates) and Brønsted acids (e.g., TsOH, H3PO4, HF, etc.), with lanthanide triflates being the most active and least toxic catalysts.

Fries rearrangement - general reaction scheme - photo-Fries rearrangement - photo-Fries reaction
Fries rearrangement (photo-Fries)

The reaction is typically carried out by heating a mixture of phenolic ester and acidic promoter either neat or in a solvent suitable for Friedel-Crafts acylation to 80–180 ºC. The resulting Lewis acid–acyl phenol complex decomposes to form the rearranged product. The reaction conditions and starting material structure can influence the ratio of para- and/or ortho-acyl phenols and simple phenol obtained. The reaction pathway leading to para-acyl phenol is through a 1,4-path of intermolecular rearrangement, while that leading to ortho-acyl phenol is through a 1,2-path of intramolecular rearrangement. Some interesting Fries rearrangements include Bi(OTf)3-promoted direct acylation of phenol, BF3·OEt2-catalyzed rearrangement of diacyl hydroquinone to 4-ethoxy-2-acyl phenol, and the rearrangement of acyl p-phenyl phenol to 4-acyl 4-hydroxy biphenyl.

Analogous shifts can be observed in acyloxyheteroarenes such as N-acetylcarbazole, which are referred to as the Fries-Rosenmund rearrangement. However, thioesters do not undergo this type of rearrangement even under harsh conditions. Additionally, regioselectivity limitations can be addressed through the use of metal-promoted Fries rearrangement or anionic ortho-Fries rearrangement. These modifications only convert O-aryl carbamates to ortho-hydroxy aryl amides and N-aryl carbamates to ortho-amino aryl amides. The rearrangement of arylsulfonates to hydroxyaryl sulfones is known as the thia-Fries rearrangement, which can also involve an anionic intermediate and is referred to as the anionic thia-Fries rearrangement.

Comparable rearrangements of aryl esters under photo-irradiation are reported, which are called the photo-Fries rearrangement or photo-Fries reaction. Under photo-irradiation, aryl sulfonanilides, sulfonates, carbamates, sulfamates, and cinnamates all undergo similar rearrangements. The Photo-Fries Rearrangement is known to be intramolecular and can occur through either an excited singlet state or an upper triplet state. After excitation, the homolytic cleavage of aryl ester leads to the formation of radicals that combine to rearrangement products and starting material. The product distribution can be affected by the presence of oxygen or the addition of certain materials such as pentasil zeolite, Nafion membrane, or β-cyclodextrin. The Photo-Fries rearrangement has also been extended to simple vinyl esters and 1,3-dienyl esters, which undergo both 1,3- and 1,5-acyl migration.

References

Fries, K. and Finck, G. (1908), Über Homologe des Cumaranons und ihre Abkömmlinge. [On homologs of coumaranone and their derivatives] Ber. Dtsch. Chem. Ges., 41: 4271-4284. https://doi.org/10.1002/cber.190804103146

Shares