Rearrangement Friedel-Crafts acylation

Trienone-pbenol rearrangement. Friedel-Crafts acylation of the rearranged product B. Pelc, J. Holubek, T. Wittstruck and E. Caspi, Coll. Czech. Chem. Commun., 33 (1968) 1131. 

Representative synthetic methods include Claisen rearrangement, Friedel-Crafts acylation and directed metallation. Bicyclic arylsulfonamides are used to prepare herbicidally active sulfonylureas. Biological activity of these sulfonylureas is discussed. 

Because acylation of an aromatic ring can be accomplished without rearrangement it is frequently used as the first step m a procedure for the alkylation of aromatic compounds by acylation-reduction As we saw m Section 12 6 Friedel-Crafts alkylation of ben zene with primary alkyl halides normally yields products having rearranged alkyl groups as substituents When a compound of the type ArCH2R is desired a two step sequence IS used m which the first step is a Friedel-Crafts acylation... 

The initial series of major tranquilizers consists of alkylated derivatives of 4-aryl-4-hydroxypiperidines. Construction of this ring system is accomplished by a set of rather unusual reactions. Condensation of methylstyrenes with formaldehyde and ammonium chloride afford the corresponding hexahydro-1,3-oxazines (119). Heating these oxazines in the presence of acid leads to rearrangement with loss of water to the tetrahydropyridines. Scheme 1 shows a possible reaction pathway for these transformations. Addition of hydrogen bromide affords the expected 4-bromo compound (121). This last is easily displaced by water to lead to the desired alcohol (122) The side chain (123) is obtained by Friedel-Crafts acylation of p-fluorobenzene with 4-chloro-butyryl chloride. Alkylation of the appropriate arylpiperidinol with 123 affords the desired butyrophenone derivative. Thus,... 

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]. 

Hydroxyalkyl)porphyrins,84-85 I07b 109 easily accessible from porphyrins by Friedel-Crafts acylation and subsequent reduction, undergo a stereoselective Claisen rearrangement with N,N-dimethylacetamide dimethyl acetal. The substitution pattern and the stereochemical arrangement of the derived chlorins match those of naturally occurring chlorins9 (see Section 1.2.1.2.). 

Friedel-Crafts acylation, 314, 331, 332, 335, 374 Fries rearrangement, 314 Furaltadone, 229 Furazolidone, 229 Furethidine, 301 Furosemide, 134... 

A Friedel-Crafts acylation is a synthetic method that avoids the problem of rearrangement of the cation. Figure 7-10 illustrates the generation of the electrophile (the acylium ion) from an acid chloride. The presence of resonance stabilizes the acylium ion, and that reduces the possibility of rearrangement. 

Figure 7-11 shows a Friedel-Crafts acylation reaction. The reaction produces an aryl ketone, which is useful in synthesis because it makes it relatively easy to convert the ketone (RCOR) group to an alkyl (R) group. The procedure involves the catalytic hydrogenation of the aryl ketone, and it s particularly useful when the electrophile in a Friedel-Crafts alkylation is susceptible to rearrangement. 

The Friedel-Crafts acylation of alkanes requires hydride abstraction, which can be induced by the acylium ion itself, to form the corresponding carbocation. This may undergo carbocationic rearrangements prior to a proton loss to form an alkene, which then reacts with the acylating agent. Similar to the acylation of alkenes, the product is an unsaturated ketone. The reaction is limited to alkanes that are prone to undergo hydride transfer. 

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. 

The various methods for introducing a formyl group (—COH) into a phenolic nucleus are discussed in Section 6.10.1, p. 990. The formation of phenolic ketones (e.g. HO-C6H4-COR) by the standard Friedel-Crafts acylation procedure (i.e. the reaction of a phenol with an acid chloride in the presence of aluminium chloride) does not always give acceptable yields except in the case of polyhydroxyphenols (p. 1006). The preferred method is to convert the phenol into the phenyl ester and to subject this to rearrangement (the Fries reaction) in the presence of aluminium chloride. 

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