Arylacetic acids

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). 

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. ... 

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. 

Selected examples of the conversion of benzyl chlorides into arylacetic acids and arylpyruvic acids using molybdenum carbonyl complexes ... 

Analogous carbonylation reactions using nickel and iron carbonyl based systems also produce alkanecarboxylic acids [11, 13, 14]. The mechanism of the conversion of benzyl halides into arylacetic acids using iron pentacarbonyl is not as well defined as it is for reactions promoted by nickel or molybdenum carbonyl complexes. Iron... 

Preparation of arylacetic acids using a cobalt carbonyl complex... 

Method A The benzyl halide (0.13 mol) is added slowly with stirring at 55 °C over 1 h to NaCo(CO)4 (0.5 g, 2.6 mmol) and TEBA-C1 or TBA-C1 (4 mmol) in aqueous NaOH (40%, 50 ml) and Ph20 (50 ml) under CO (1 atmos.). Stirring is continued for a further 2 h at 55°C and the aqueous phase is then separated, washed with Et20 (2 x 25 ml) and acidified. The acidified aqueous phase is extracted with CH2C12 (3 x 25 ml) and the extracts washed with H20 (25 ml), dried (MgS04), and evaporated to produce the arylacetic acid. 

Method B Co2(CO)8 (0.17 g, 0.5 mmol) and TEBA-C1 (0.23 g, 1.0 mmol) in aqueous NaOH (5M, 25 ml) and PhH (25 ml) are stirred at room temperature for 30 min under CO (1 atmos.). The benzyl halide (25 mmol) is added and the reaction mixture is stirred at room temperature for ca. 12 h. The aqueous phase is separated, washed with PhH (2 x 25 ml) and acidified to produce the arylacetic acid (with arylpyruvic acid), which is isolated using the procedure described in 8.2.2.A. The PhH solutions contain the neutral products which are formed. 

The phase-transfer catalysed reaction of nickel tetracarbonyl with sodium hydroxide under carbon monoxide produces the nickel carbonyl dianions, Ni,(CO) 2- and Ni6(CO)162, which convert allyl chloride into a mixture of but-3-enoic and but-2-enoic acids [18]. However, in view of the high toxicity of the volatile nickel tetracarbonyl, the use of the nickel cyanide as a precursor for the carbonyl complexes is preferred. Pretreatment of the cyanide with carbon monoxide under basic conditions is thought to produce the tricarbonylnickel cyanide anion [19], as the active metal catalyst. Reaction with allyl halides, in a manner analogous to that outlined for the preparation of the arylacetic acids, produces the butenoic acids (Table 8.7). 

The toxic potential of metabolic intermediates, of the carrier moiety, or of a fragment thereof, should never be neglected. For example, some problems may be associated with formaldehyde-releasing prodrugs such as N- and 0-[(acyloxy)methy 1] derivatives or Mannich bases. Similarly, arylacetylenes assayed as potential bioprecursors of anti-inflammatory arylacetic acids proved many years ago to be highly toxic due to the formation of an intermediate ketene. 

Br a-Hydroxy-arylacetic acid esters were oxidized with bromide ion as a mediator to give a-oxo-arylacetic acid esters [37]. 

The methylation of arylacetic acid derivatives is chosen as a model reaction for the mechanistic discussion. Experimental evidence of DMC-mediated alkylation of A1CH2X (X = CN, C02Me) with DMC supports the hypothesis that the reaction does not proceed through a 8 2 displacement of the ArCH X nucleophile on DMC (Bai2 mechanism).Rather, the selectivity arises from consecutive... 

Arylacetic acids, synthesis of, 1, 2 22, 4 3-Arylacrylic acids, synthesis of, 1, 8... 

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