Anilides, hydroxylation

Toliiic anilide, on hydrolysis, forms toluic acid and aniline, whereas beii2oic toluide yields benzoic acid and toluidine. It follows therefoie that, in the original compound, the first contains the hydroxyl neaier the phenyl group and the second nearer the tolyl group. 

TV-Acyl indoles derived from amides have been employed for the conversion of lactones into protected hydroxyacids. Thus, (chloromethyl)alumi-num 2-(2-propenyl)anilide reacts (120) with 1,4- and 1,5-lactones, as for example per-O-terZ-butyldimethylsilyl-D-ribono-1,4-lactone (104), to afford hydroxyamides. After protection of the free hydroxyl group, these amides were converted by ozonolysis into TV-acyl indoles, 105, which were readily saponified to the acid 106. 

The synthesis involves nitrosating the corresponding substituted acetoacetic anilide with sodium nitrite in acetic acid and subsequently, by adding hydroxyl-amine to the same reaction vessel, converting the compound to the oxime. Finally, complexation is achieved by means of a Ni(II) salt. 

The H202-HF-SbF5 system has been applied by Jacquesy and co-workers in the hydroxylation of a variety of functionalized arenes.624 Hydroxylation of phenyl esters has been shown to afford themeta and para isomers as main products625 [Eq. (5.217)]. Substantial amounts of the deacylated derivatives were obtained in the reaction of phenyl formate and diphenyl carbonate. In the hydroxylation of 2-chlorophenyl and 4-chlorophenyl acetate, regioselectivity is controlled by the chlorine substituent with the hydroxyl entering into the meta position to the ester group.626 A similar effect was observed in the hydroxylation of anilines and anilides. 

In the case of unsymmetrically substituted oximes (e.g. Ar -C(=NOH)-Ar2) the structure of the oxime (syn or anti) may be deduced by hydrolysis of the anilide and characterisation of the isolated carboxylic acid and amine. Thus if the products are Ar1-C02H and Ar2NH2, the hydroxyl group in the oxime must of necessity be anti to the group Ar2 owing to the trans intramolecular rearrangement step specified in the formulation above. Illustrative details for the... 

Bioisosteric replacement of the hydroxyl anilide moiety of hydroxyflutamide (8) with a hydantoin analog by Raynard et al. in 1977 resulted in nilutamide (9) or Nilandron [48, 54], which was commercialized in 1987 by Aventis Pharma for... 

Eriksson S-O and Holst C, Hydrolysis of anilides. II. Hydrolysis of trifluoro- and trichloroacetanilide by hydroxyl ions and by some bifunctional catalysts. Acta Chem. Scand. 20,1892-1906 (1966). 

Anilides with pendant double bonds 898 undergo DMP-induced stereoselective oxidative cyclization to give complex and diverse natural product-like polycycles 899 (Scheme 3.361) [1176,1277]. This oxidative cyclization is proposed to occur by the initial ortho directed oxidation of anilide 898 to give an ort/io-hydroxylated benzene ring that is further oxidized to the quinone imine intramolecular Diels-Alder cyclization of the... 

Hypervalent iodine reagents have successfully been employed in the oxidative functionalization of enolizable carbonyl compounds over the years [6]. This methodology has allowed the construction of diverse C-C bonds in the context of heterocychc synthesis and has enriched the otherwise rare repertoire of such chemistry. Zhao, Du, and coworkers [37] have recendy realized a metal-free PIFA-mediated synthesis of 3-hydroxy-2-oxindoles 34 and spirooxindoles 35 starting from anilide derivatives 33 (Scheme 8 (1)). These processes showcase an oxidative cross coupling between an aromatic carbon and a pendant aliphatic carbon, followed by further oxidative hydroxylation or spirocycUzation. Later, the authors extended the same concept to achieve C(sp )-C(sp ) bond formation, where anilide derivatives possessing terminal enol functionality underwent PIDA-... 

Reaction of secondary aryl and mixed alkyl aryl amines with benzoyl peroxide results in the formation of some o-hydroxybenz-anilides as well as the expected 0-benzoyl derivative. In some cases the yield of o-hydroxyl derivative may be as high as 40% . Several mechanisms have been proposed , but most of the recent evidence points to a reaction (Scheme 28) involving the initial heterolytic forma-... 

Anilides are simple acetamides of aniline, which may or may not contain a 4-hydroxy or 4-alkoxy group (Figure 13.13). Acetanilide is ring hydroxylated after administration to yield acetaminophen, the active analgesic/antipyretic, whereas phenacetin (rarely used) undergoes oxidative-O-dealkylation to produce acetaminophen. Anilides do not possess carboxylic acid functionality and, therefore, they are classified as neutral drugs and possess little, if any, inhibitory activity against COX. 

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