Fries-rearrangement

Fries rearrangement is a useful method for the preparation of phenolic ketones and is usually carried out by heating a mixture of substrate and aluminium chloride. 

The Fries rearrangement of phenyl acetate to o- and p-hydroxyacetophenone is also a very valuable reaction in the pharmaceutical industry. Nafion-silica composites containing 13 and 40% (w/w) Nafion were also studied in this reaction and compared with pure Nafion and with zeolites such as HBEA, HUSY, HZSM5, and HY. The Nafion-silica composites resulted in better conversion than the pure analog, but in this study the BEA zeolite resulted in the highest conversion and a relatively high selectivity. Unfortunately, no reactions rates were given so no conclusions can be drawn about the intrinsic activity of the different catalysts [17]. 

The Fries rearrangement is the name for the very widespread rearrangement of aryl esters to hydroxy aryl ketones,75 thus  

Hesse and H. Stahl, Chem. Ber., 2414 (1956), where previous references are cited. 

Experimentally this is a very important reaction, for on it are based many syntheses of hydroxyaryl ketones of great practical importance. The reason for this, as Fries himself remarked, is that direct introduction of an acetyl group — and particularly of a substituted acetyl group — is by no means as smooth a route as the by-way through the aryl ester since reaction of phenols with aluminum chloride sometimes leads to most unsatisfactory products. Moreover, the technique used for a Fries rearrangement requires very little modification to be suitable for a large number of esters. 

Freudenberg and Orthner have described the rearrangement of phenyl acetate to 0-hydroxyacetophenone as follows 78 

Aluminum chloride (200 g), is added in portions to phenyl acetate (100 g), initially with cooling, and when the violent reaction has moderated the mixture is heated for 5 h at 120°, then decomposed with ice, and distilled in steam superheated to 150°. Working up the distillate affords 0-hydroxyacetophenone (37 g), b.p. 91-92°/13 mm. 

Lewis acid-catalyzed rearrangement of phenol esters to 2- or 4-ketophenols. 

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. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 103, Springer-Verlag Berlin Heidelberg 2009 

Guisnet, M. Perot, G. The Fries rearrangement. In Fine Chemicals through Heterogeneous Catalysis 2001, 211—216. (Review). 

Feirini, Serena Ponticelli, Fabio Taddei, Maurizio. Org. Lett. 2007, 9, 69-72. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 lll, Springer International Publishing Switzerland 2014 

Example 6, Remote Anionic Thia-Fries rearrangement  

ZrCU as a stoichiometric reagent [15a] and Zr(OTf)4 as a catalyst [15b], and other group 3 and 4 metal compounds, have been found to be efficient mediators of the Fries rearrangement. O-Acetylnaphthol (33) was converted to C-acetylnaphthol (34) in 76 % yield by use of the best catalyst so far, Hf(OTf)4. The use of Zr(OTf)4 resulted in 71 % yield (Eq. 14). 

The Friedlander quinoline synthesis is particular useful for the preparation of 3-substituted quinolines, which are less accessible by other routes. A drawback however is the fact that the required o-atninobenzaldehydes or o-aminoarylketones are not as easy to prepare as, e.g., the anilines that are required for the Skraup synthesis. 

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. 

The reaction mechanism is not rigorously known. Evidence for an intramolecular pathway as well as an intermolecular pathway has been found  

The Lewis acid can coordinate to the substrate at either one of the oxygen centers, or even both when used in excess  

The Lewis acid complex 4 can cleave into an ion-pair that is held together by the solvent cage, and that consists of an acylium ion and a Lewis acid-bound phenolate. A fr-complex 6 is then formed, which further reacts via electrophilic aromatic substitution in the ortho- or para-position  

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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... 

Fries rearrangement (Section 24 9) Aluminum chlonde promoted rearrangement of an aryl ester to a ring acylated denvative of phenol... 

Friedlander reaction FrieUnder synthesis Fries rearrangement Frigen... 

A second process that occurs concurrently with the dissociation— redistribution process is an intermolecular rearrangement by which cyclohexadienone groups move along a polymer chain. The reaction maybe represented as two electrocycHc reactions analogous to a double Fries rearrangement. When the cyclohexadienone reaches a terminal position, the intermediate is the same as in equation 8, and enolization converts it to the phenol (eq. 9). 

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). 

Acylation of 3-alkyl-6-hydroxy-l,2-benzisoxazole has also been reported (77JIC875) under Friedel-Crafts conditions to give the 7-acyl product. Fries rearrangement of 6-acetoxy-3-methyl-1,2-benzisoxazole in the presence of AICI3 at 140 °C also provides a route to the 7-acetyl-6-hydroxy derivatives (73UC541). Reactions of these kind are rare in this series. 

Benzothiazole, 2-amino-6-thiocyanato-azo dyes from, 1, 328 Benzothiazole, 2-aryl-synthesis, 6, 321 Benzothiazole, 2-arylamino-synthesis, 6, 323 Benzothiazole, 2-aryloxy-Fries rearrangement, 6, 289 Benzothiazole, 2-benzyl-picrate, 6, 252 Benzothiazole, 2-chloro-dyes from, 1, 321-322 synthesis, 6, 323 Benzothiazole, 2,3-dihydro-oxidation, 6, 272 Benzothiazole, 2-dimethylamino-synthesis, 5, 128... 

Free Electron Molecular Orbital method colour and constitution, 1, 342 Freelingyne occurrence, 4, 706 Free radical processes in photography, 1, 387-389 Friedlander synthesis quinolines, 2, 443 thioindigo dyes, 4, 910 Fries rearrangement chroman-4-one synthesis from, 3, 850 Fructose, 1-deoxy- C NMR, 4, 575 Frusemide as diuretic, 1, 174 metabolism, 1, 245 FS-32 — see 1/f-Indazole, l-[3-... 

Beckmann rearrangement, 4, 292 pyrolysis, 4, 202 synthesis, 4, 223 Wittig reaction, 4, 294 Wolff-Kishner reduction, 4, 291 Indole, 1-acyl-2,3-disubstituted photoisomerization, 4, 204 photo-Fries rearrangement, 4, 204 photoisomerization, 4, 42 synthesis, 4, 82 Indole, 2-acyl acidity, 4, 297 synthesis, 4, 337, 360 Indole, 3-acyl-acidity, 4, 297 cleavage, 4, 289 reduction, 4, 289 synthesis, 4, 360 Indole, 7-acyl-synthesis, 4, 246... 

There is usually no reaction with nitrobenzene as solvent. However, in this medium acetoxybenzylidene azlactones undergo a Fries rearrangement [Eq. (16)]. 

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 ... 

A photochemical variant, the so-called photo-Fries rearrangement, proceeds via intermediate formation of radical species. Upon irradiation the phenyl ester molecules (1) are promoted into an excited state 11. By homolytic bond cleavage the radical-pair 12 is formed that reacts to the semiquinone 13, which in turn tautomerizes to the p-acylphenol 3. The corresponding ort/zo-derivative is formed in an analogous way ... 

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

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