Ketones Fries rearrangement

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... 

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.1 Rearrangement of phenyl esters with Lewis acids results in a mixture of ortho- and para-phenolic ketones. In contrast, reaction of an o-bromophenyl ester with sec-butyllithium results in exclusive formation of the orf/jo-phenolic ketone by an intramolecular acyl rearrangement.2... 

Dialkylquinazolines 825 are available by microwave-assisted amination and ring closure of 2-acylamino phenyl-ketones 824 with ammonium formate <20070L69>. The 2-aminophenyl ketone precursors of the amides 824 are available by a photochemically induced Fries rearrangement of anilides 823, which enables a variety of different alkyl substituents to be incorporated at the 4-position of the quinazoline <20070L69>. 

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. 

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. 

Another example of the effect of confined medium is found during photo-Fries rearrangement of naphthyl esters in zeolites [103,104]. Upon photolysis in isotropic solution 1-naphthyl benzoate undergoes the photo-Fries rearrangement to yield both ortho (2-) and para (4-) phenolic ketones (Sch. 4). When this ester is included in NaY zeolite and irradiated the main product (96%) is the ortho isomer. This remarkable ortho-selectivity within zeolites has been rationalized on the basis of interactions of the reactant 1-naphthyl benzoate and intermediate radicals with the sodium ion. Due to restrictions imposed by the medium the benzoyl radical, once formed, is compelled to react only with the accessible ortho position. 

Photochemical processes of CD complexes,1 Differences in photochemical reactions conducted in solution and in CD complexes have been reviewed. For example, photo-Fries rearrangement of phenyl esters in solvents results in a mixture of o- and p-phenolic ketones via a radical reaction. Rearrangement of the same encapsulated ester results in exclusive rearrangement to the ortho-position (equa-... 

Amides cyclise directly to ketones such as 80 the carbamates on the other hand pass through a cyclic transition state which collapses to an amide 82 (an anionic ortho-Fries rearrangement - section 2.3.2.1.4) which lactonises to 83. 

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). 

The benzene derivative (2) has been shown to undergo photo-Fries rearrangement followed by cyclization. Scaiano et al." have shown that the photostability of the aromatic ketones (3) is due to highly efficient triplet deactivation. 

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. " ... 

Although phenolic ketones can be made by direct acylation of phenols, they are more often prepared in two steps by means of the Fries rearrangement (Sec. 24.9). 

---