The Fries rearrangement

The Fries rearrangement is the acid-catalyzed transformation of aryl esters into hydroxy ary Iketones [1] and often plays an important role in the production of hydro-xyarylketones by acylation of phenols with carboxylic acids, anhydrides, or acyl chlorides. 

Three different mechanisms have been proposed [1] for the Fries rearrangement with AICI3 (i) an intramolecular mechanism with a direct acyl shift from the oxygen atom to a carbon atom of the ring (ii) a monomolecular deacylation-acylation mechanism with an acyl chloride intermediate and (iii) an intermolecular mechanism (transacylation). 

The most simple example of the Fries reairangement is the transformation of phenylacetate (PA) into hydroxyacetophenones (o- and /7-HAP Eq. 1). 

The para isomer is a key intermediate in the Hoechst Celanese process for the manufacture of paracetamol (p-acetaminophenol) [2] the ortho isomer can be used for the synthesis of salicylic acid. Other hydroxyarylketones of commercial importance also result from the Fries rearrangement, e. g. 2,4-dihydroxybenzophe-none, an intermediate in the preparation of UV absorbents [3], and diphenol monomers which can be used for the manufacture of advaneed polymers [4], etc. 

Most studies in which acid solids were used concern the synthesis of hydroxyacetophenones either by Fries rearrangement of phenyl acetate [3,5-15] or by acylation of phenol with acetic acid or acetic anhydride [11,16-21]. These reactions were conducted in the gas or liquid phase, zeolites being generally chosen as catalysts (Section 5.3.1). These shape-selective catalysts can also be used 

The production of aromatic hydroxyketones can also be performed by the Fries rearrangement in this case, the mode of para-acylation is probably different from that of ortho-acylation. Indeed, the ortho-isomer is a primary product, whereas the para-isomer seems to be a secondary product. Of course, other methods for 

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The preference for O acylation of phenols arises because these reactions are kmetically controlled O acylation is faster than C acylation The C acyl isomers are more stable how ever and it is known that aluminum chloride is a very effective catalyst for the conversion of aryl esters to aryl ketones This isomerization is called the Fries rearrangement... 

The title compounds also undergo the Claisen rarrangement (5-allyloxypyrazoles 4-allyl-5-pyrazolones) and are readily transformed into 5-chloropyrazoles by means of phosphorus oxychloride (8OCHE1). In the presence of aluminum chloride 5-acyloxypyrazoles (481) undergo the Fries rearrangement affording 4-acyl-5-hydroxypyrazoles (482). 

Since the Fries rearrangement is a equilibrium reaction, the reverse reaction may be used preparatively under appropriate experimental conditions. An instructive example, which shows how the regioselectivity depends on the reaction temperature, is the rearrangement of m-cresyl acetate 8. At high temperatures the ortho-product 9 is formed, while below 100°C the para-derivative 10 is formed ... 

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

The Fries rearrangement can be viewed as a type of Friedel-Crafts acylation reaction. Two examples of this reaction are given in Scheme 5.1-61. The first is the rearrangement of 4,4 -diacetoxybiphenyl to 4,4 -dihydroxy-3,3 -diacetoxybiphenyl in a NaCl/AlCl3 (X(A1C13) = 0.69) molten salt [93]. The second example is the rearrangement of phenyl 3-chloropropionate to 2 -hydroxy-3-chloropropiophenone, followed by cyclization to an indanone [94]. 

Scheme 5.1-61 The Fries rearrangement in chloroaluminate(lll) molten salts.

On the basis of all these experiments various mechanisms have at some stage been advanced for the Fries rearrangement involving the free acylium ion or as a tightly bound ion pair, Ji-complexes and cyclic intermediates. It is clearly impossible to reconcile all the experimental data by one reaction mechanism. It is probable that many such mechanisms are possible, each one operative under a certain set of conditions. 

For example /-butyl phenyl ether with aluminium chloride forms para-t-butyl phenol155. Often the de-alkylated phenol is also formed in considerable quantity. The reaction formally resembles the Fries and Claisen rearrangements. Like the Fries rearrangement the question of inter- or intramolecularity has not been settled, although may experiments based on cross-over studies156, the use of optically active ethers157 and comparison with product distribution from Friedel-Crafts alkylation of phenols158 have been carried out with this purpose in view. 

A. Groups Cleaving from Oxygen 11-30 The Fries Rearrangement... 

The availability of Nafion on silica has not only lowered the cost of the resin but also has made it versatile (Sun et al., 1997 Harmer et al., 1998). A number of industrially important reactions have been attempted, with considerable success, with these catalysts. Consider the Fries rearrangement of phenyl acetate to p-acetyl phenol (/t-hydroxy acetophenone). This has been accomplished by Hoelderich and co-workers (Heidekum, 1998). In the ca.se of alkylation of benzene with benzyl alcohol, Amberlyst-15 and p-toluene sulphonic acid are ineffective and Nafion on silica works well at 80 °C. 

A special case of aromatic acylation is the Fries rearrangement, which is the conversion of an ester of a phenol to an o-acyl phenol by a Lewis acid. 

Prior to solving the structure for SSZ-31, the catalytic conversion of hydrocarbons provided information about the pore structure such as the constraint index that was determined to be between 0.9 and 1.0 (45, 46). Additionally, the conversion of m-xylene over SSZ-31 resulted in a para/ortho selectivity of <1 consistent with a ID channel-type zeolite (47). The acidic NCL-1 has also been found to catalyze the Fries rearrangement of phenyl acetate (48). The nature of the acid sites has recently been evaluated using pyridine and ammonia adsorption (49). Both Br0nsted and Lewis acid sites are observed where Fourier transform-infrared (FT IR) spectra show the hydroxyl groups associated with the Brpnsted acid sites are at 3628 and 3598 cm-1. The SSZ-31 structure has also been modified with platinum metal and found to be a good reforming catalyst. 

An increase of char yield is generally reflected as an improvement in oxygen index. In the styrylpyridine based polyesters and polycarbonate an intermolecular thermally induced Diels-Alder reaction has occurred through the double bond, this increased the char yield and decreased the flammability. The Fries rearrangement, as well as dimerization and isomerization, occurred simultaneously during the UV irradiation of p-VPPB, but no dimerization or isomerization occurred for p,p -BVPDPC, probably due to steric effects. 

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. 

Toluene or EtN02, 110 °C Scheme 9 Bi(0Tf)3-xH20 catalysis of the Fries rearrangement... 

More recently, Mouhtady et al. demonstrated that Bi(0Tf)3xH20 and other metal triflates interact with methanesulfonic acid (MSA) to form an efficient synergic catalytic system for the Fries rearrangement of naphthyl acetate [70, 71]. 

Benzoylcarbazole has been prepared in poor yield using anhydrous zinc chloride and benzoic acid at 160°C, ° using zinc chloride-benzoic anhydride at 150°C, and more efficiently by the Fries rearrangement of 9-ben-zoylcarbazole. A mixture of 3-mono- and 3,6-di-o-toluylcarbazoles resulted from the use of aluminium chloride in combination with acid chloride. ... 

New synthetic routes (Scheme 9) to photosensitive linear and angular furocoumarins, furoquinolones, furoquino-lines, and their analogs were the subject of a review <2004MOL50>. It focuses on the Fries rearrangement of acyloxyheteroarenes, like 70 — 71, the condensation of acylhydroxyheteroarenes with a-carbonyl compounds, like 72 73, and the transformations of dihydrofuroheteroarenes, like 74 75. 

Problem 19.16 Phenyl acetate undergoes the Fries rearrangement with AlCl, to form ortho- and para-hydroxyacetophenone. The ortho isomer is separated from the mixture by its volatility with steam. 

This type of duality of action is presumably present in other situations, such as the Fries rearrangement (78), the Friedel-Crafts reaction with acid chlorides (65) or acid anhydrides (21), and the catalytic chlorination of nitrobenzene (17). In these reactions it appears that the uncoordinated Lewis acid is the effective catalyst. The same situation is illustrated by recent work on aromatic amination (32, 33) and halogenation (57, 58, 71) and seems to be general feature of Lewis acid-catalyzed electrophilic reactions of aromatic compounds containing suitable donor groups. 

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