Fries rearrangement reaction

Phenolic esters (1) of aliphatic and aromatic carboxylic acids, when treated with a Lewis acid as catalyst, do undergo a rearrangement reaction to yield ortho- and para-acylphenols 2 and 4 respectively. This Fries rearrangement reaction is an important method for the synthesis of hydroxyaryl ketones. 

As catalysts for the Fries rearrangement reaction are for example used aluminum halides, zinc chloride, titanium tetrachloride, boron trifluoride and trifluoromethanesulfonic acid7... 

Arylketones are generally prepared by acylation of aromatics (reaction 1) or by the related Fries rearrangement (reaction 2) ... 

PC also shows photolytic (in this case photo-Fries) and photo-oxidation reactions, but when PC is irradiated with wavelengths above 300 nm, photolysis only plays a minor role. Photo-oxidation is the major degradation mechanism it was shown that the initiation of this photo-oxidation is not due to the photo-Fries rearrangement reaction. 

Wang, H., Zou, Y. Modified 3-Zeolite as Catalyst for Fries Rearrangement Reaction. Catal. Lett. 2003, 86,163-167. 

Fig. 1. Scheme for the SAM formation of MUAP, the photo-Fries rearrangement reaction upon irradiation with UV-light, and the post-modification reaction with perfluorobutyryl chloride. Below images of water droplets and CH2I2 droplets on each surface. 

Acid-catalyzed reactions of the phenol esters resulting in the formation of phenolic ketones are known as Fries rearrangements. Aluminum chloride was the first catalyst used but other Lewis acids are also effective. Examples from the recent literature are shown in equations (44) to (48). A nitrogen analog, that is the rearrangement of an acyl derivative of an arylamine, is shown in equation (49). Photo-Fries rearrangement reactions have also been studied in detail and are exemplified in equations (50) to (55). 

An unusual sodium hydride-mediated remote anionic 1,5-thia-Fries rearrangement reaction was developed by Xu and eoworkers recently [82]. Their method provides an effieient approach for the regioseleetive synthesis of not only 2-(2-hydroxyphenyl)-3-indole triflones but also the related 3-sulfonylindoles (164 165) (Figure 18.10) [82]. 

Scheme 11.6 Anionic Fries rearrangement reaction in the synthesis of Camptothecin.

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