FRIES Phenol ester rearrangement

FRIEDLANDER Quinoline synthesis t32 FRIES Phenol ester rearrangement 133 FRITSCH. BUTTENBERG - WIECHELL Acetylene synthesis 134... 

FRIES Phenol Ester Rearrangement Rearrangement of phenol esters to o or p ketophenols Lewis acid catalyzed... 

Subsequent work by Ruwet and co-workers proposed something similar to the proposal 1 mechanism, albeit they did not think that the phenolate ester rearranged via a Fries reaction. Ruwet and co-workers studied the heteroatom displacement of the phenol oxygen with S and Se. They suggested that the first step could be esterification followed by nucleophilic attack of the phenol on the more electrophilic carbon of the ketone moiety. Ruwet and co-workers prepared the phenolate 22a-c from the diketene and the corresponding phenols la-c. Treatment of la-c (X = O, S or Se) and diketene 21 with PPA (polyphosphoric acid) did indeed provide the chromone 23a-c in about 40% yield.This was the first reported use of PPA for this transformation. 

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. 

Fries rearrangement org chem The conversion of a phenolic ester into the corresponding 0- and p-hydroxyketone by treatment with catalysts of the type of aluminum chloride. frez re a ranj-mant)... 

Lewis acid-catalyzed rearrangement of phenol esters and lactams to 2- or 4-ketophenols. Also known as the Fries-Finck rearrangement. 

Fries, K. Finck, G. Ber. Dtsch. Chem. Ges. 1908, 41, 4271. Karl Theophil Fries (1875-1962) was born in Kiedrich near Wiesbaden on the Rhine. He earned his doctorate under Theodor Zincke. Although G. Finck co-discovered the rearrangement of phenolic esters, somehow his name has been forgotten by history. In all fairness, the Fries rearrangement should really be the Fries-Finck rearrangement. 

Fries rearrangement of phenolic esters to phenolic ketones (Problem 19.16). 

The Fries rearrangement of phenol esters gives a mixture of 2- and 4-acylphenols. Similarly, enol esters undergo rearrangement to give the corresponding 1,2-di ketones. 

The Fries rearrangement of phenol esters gives a mixture of 2- and 4-acylphenols (56). The reaction is catalyzed by Lewis acids such as aluminum chloride or by Brmnsted acids like hydrogen fluoride. This reaction is used in the production of 4-hydroxyacetophenone [99-93-4], a raw material for... 

Fries rearrangement—that is, the transformation of phenolic esters to isomeric hydroxyphenyl ketones—is related to Friedel-Crafts acylations.392,393 Olah et al.394 have found a convenient way to perform the Fries rearrangement of a variety of substituted phenolic esters in the presence of Nafion-H in nitrobenzene as solvent [Eq. (5.153)]. A catalytic amount of Nafion-H is satisfactory, and the catalyst can be recycled. In contrast, Nafion-silica nanocomposites, in general, exhibit low activities in the Fries rearrangement of phenyl acetate to yield isomeric hydroxyacetophe-nones.239,395 In a recent study, BF3-H20 was found to be highly efficient under mild conditions (80°C, 1 h) to transform phenolic esters of aliphatic and aromatic carboxylic acids to ketones (71-99% yields).396 In most cases the para-hydroxyphenyl isomers are formed with high (up to 94%) selectivity. 

Phenolic ketones may be prepared by the Hoesch acylation reaction, which may be regarded as an extension of the Gattermann aldehyde synthesis (Section 6.10.1, p. 990). The procedure involves reaction of a nitrile with a phenol (or phenolic ether) in the presence of zinc chloride and hydrogen chloride best results are usually obtained with polyhydric phenols or their ethers, as for example in the preparation of phloroacetophenone (Expt 6.125). The formation of phenolic ketones by means of the Fries rearrangement of phenolic esters with aluminium chloride is discussed on p. 976. 

When treated with acid chlorides and acid anhydrides, phenols form esters. Under Friedel-Crafts conditions, phenolic esters undergo a Fries rearrangement in which the acyl group migrates to the 2- and 4-positions. Thus, treatment of the ester 11 with aluminium chloride in an inert solvent gives a mixture of 2- and 4-hydroxyacetophenones [(hydroxy-phenyl)ethanones] C-acylation has occurred (Scheme 4.7). The two isomers are separable and this is a useful method for the production of phenolic ketones. The mechanism remains uncertain, but it would appear that the acylium ion (RCO" ) is generated and that a Friedel-Crafts mechanism operates. 

Schotteii Baumanii). The acylation of phenols without a basic solvent is promoted by small amounts of sulfuric acid or stannic chloride. Care must be exercised to prevent rearrangement of the phenolic ester to a phenolic ketone (Fries reaction, method 209). 

Boron trifluoride catalyzes the condensation of phenol and propylene to isopropyl phenyl ether and the subsequent rearrangement of this compound to o-isopropyl phenol. This rearrangement of an aryl alkyl ether is similar to the Fries reaction of phenolic esters (method 209). 

The exact mechanism has still not been completely worked out. " Opinions have been expressed that it is completely intermolecular, ° completely intramolecular, and partially inter- and intramolecular. One way to decide between inter- and intramolecular processes is to run the reaction of the phenolic ester in the presence of another aromatic compound, say, toluene. If some of the toluene is acylated, the reaction must be, at least in part, intermolecular. If the toluene is not acylated, the presumption is that the reaction is intramolecular, though this is not certain, for it may be that the toluene is not attacked because it is less active than the other. A number of such experiments (called crossover experiments) have been carried out sometimes crossover products have been found and sometimes not. As in 11-17, an initial complex (68) is formed between the substrate and the catalyst, so that a catalyst/substrate molar ratio of at least 1 1 is required. In the presence of aluminum chloride, the Fries rearrangement can be induced with micro-wave irradiationSimply heating phenyl acetate with microwave irradiation gives the Fries rearrangement. " The Fries rearrangement has been carried out in ionic melts. 

Heating a phenol ester in the presence of Nafion-H gave good yields of the hydroxy phenyl ketone.This Fries rearrangement gave a mixture of the ortho and para hydroxy compounds in a 1 2-2.5 ratio (Eqn. 22.19). A study of the rearrangement of phenyl benzoate over a number of solid acid catalysts indicated that Nafion-H was more effective than montmorilIonite or amorphous aluminum silicate for this reaction. " ... 

The Fries rearrangement proceeds via ionic intermediates but the exact mechanistic pathway (whether it is inter- or intramolecular) is still under debate. There are many reports in the literature that present evidence to support either of the pathways, but it appears that the exact route depends on the structure of the substrates and the reaction conditions. The scheme depicts the formation of an ortho-acylated phenol from a substituted phenolic ester in the presence of aluminum trihalide catalyst. The photo-Fries rearrangement proceeds via radical intermediates. ... 

Research in the laboratory of P. Magnus showed that the macrocyclic skeleton of diazonamide could be synthesized with the use of macroiactonization followed by a photo-Fries rearrangement. First, the aromatic carboxylic acid and the phenol were coupled with EDCI to form the macrolactone (phenolic ester), which was then exposed to light at high-dilution to cleanly afford the macrocyclic ortho-acylated phenol skeleton of diazonamide. 

Fries rearrangement Conversion of phenolic esters to the corresponding phenolic ketones and aldehydes. 180... 

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