Arylacetates

The possibility to electrochemically remove the film from the surface has to be mentioned. Indeed, if the coated carbon plates are polarized again in electrolyte-containing ACN solution at a potential slightly more anodic than the one for grafting, surfaces are recovered free of organic materials due to the overoxidation of the anchored layer [7, 8]. 

Nevertheless, with these compounds, the oxidation can be operated in aqueous media [9]. The advantage of dealing with water as a solvent is found in the increase of organic groups anchored onto the felt. 

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The benzoic acid may be separated by steam distillation or by saturating the aqueous mixture of sodium salts with sulphur dioxide whilst maintaining the temperature below 40° the benzoic acid precipitates and can be separated by filtration or extraction with ether. Acidification of the filtrate with hydrochloric acid liberates the pyruvic acid. The pjTuvic acid may be oxidised < lth hydrogen peroxide to the arylacetic acid, for example ... 

Nonsteroidal Antiinflammatory Drugs. Nonsteroidal antiinflammatory dmgs (NSAIDs) include, among the numerous agents of this class, aspirin (acetylsaflcyhc acid), the arylacetic acids indomethacin and sulindac, and the arylpropionic acids, (5)-(147) and (R)-(148) ibuprofen, (5)-(149) and (R)- (150), flurbiprofen naproxen (41), and fenoprofen (see Analgesics, antipyretics, and antiinflammatory agents Salicylic acid and related compounds). 

Improved syntheses from arylacetic acids and hydroquinone [123-31 -9] or substituted quinones have been devised for BDF dyes (12). 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

Ogura and colleagues have also shown that 135 can be further converted to various products such as arylacetic acids, their esters181,182 and a-bromoarylacetic acid183. The condensation product of 94 with ketones can also be converted to the corresponding methyl ester by treatment with hydrogen chloride in methanol184. 

In another nonelectrolytic process, arylacetic acids are converted to vi c-diaryl compounds 2A1CR2COOH —> ArCR2CR2Ar by treatment with sodium persulfate (Na2S20g) and a catalytic amount of AgNOs." Both of these reactions involve dimerization of free radicals. In still another process, electron-deficient aromatic acyl chlorides are dimerized to biaryls (2 ArCOCl —> ArAr) by treatment with a disilane RsSiSiRs and a palladium catalyst." " ... 

In another type of oxidative decarboxylation, arylacetic acids can be oxidized to aldehydes with one less carbon (ArCH2COOH ArCHO) by tetrabutylammonium... 

Alkyl aryl ketones can be converted to arylacetic acid derivatives in an entirely different manner. The reaction consists of treatment of the substrate with silver nitrate and I2 or Br2, ° or with thallium nitrate, MeOH, and trimethyl orthoformate adsorbed on Montmorillonite K-10 clay, an acidic clay. ... 

Arylacetate esters have been generated by coupling aryl bromides with stannyl enolates generated from silyl ketene acetals. 

Quite recently, a series of arylacetic acid derivatives has come into clinical use as potent antiinflammatory agents. In general, these compounds show profiles of activity quite similar to aspirin, and though as a rule they are more active and are less likely to cause or exacerbate gastric ulcers. 

As noted previously, a wide variety of aromatic systems serve as nuclei for arylacetic acid antiinflammatory agents. It is thus to be expected that fused heterocycles can also serve the same function. Synthesis of one such agent (64) begins with condensation of indole-3-ethanol (60) with ethyl 3-oxo-caproate (61) in the presence of tosic acid, leading directly to the pyranoindole 63. The reaction may be rationalized by assuming formation of hemiketal 62, as the first step. Cyclization of the carbonium ion... 

Landwehr, M., Hochrein, L., Otey, C.R. et al. (2006) Enantioselective a-hydroxylation of 2-arylacetic acid derivatives and buspirone catalyzed by engineered cytochrome P450 BM-3. Journal of the American Chemical Society, 128, 6058-6059. 

A process research investigation on p38 MAP kinase inhibitors examined the synthesis (on 7 mol scale) of a group of closely related pyrimidinones such as 37, by condensation of a number of arylacetic esters with 4-cyanopyridine and methyl isothiocyanate. Other nitriles were also examined but were much less successful than 4-cyanopyridine 3-cyanopyridine gave a much lower yield and both benzonitrile and 2-cyanopyridine failed completely <06T11714>. 

Conjugation with amino acids is a major route of metabolism for carboxylic acids including aromatic, heteroaromatic, arylacetic, cinnamic, and arylox-yacetic acids. Although a wide range of amino acid conjugates has been ob-... 

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