Arylacetic acids, preparation

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

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 bis-deprotonation of arylacetic acids by Grignard reagents is known and the resulting bis(bromomagnesinm) salts (equation 49) have been nsed for preparing / -hydroxy acids (Ivanov reaction). 

On the preparative side, template reactions are again useful for example, the template condensation of phthalimide (or its potassium salt) with malonic acid or arylacetic acids in the presence of zinc or cadmium acetate has been shown to result in the formation of [ML] (H2L = tetrabenzoporphyrin or maso-tetraaryltetrabenzoporphyrin).1134,1135... 

Anthraquinones. A new regioselective route to highly substituted anthraquinones (4) involves the reaction of diketene in the presence of sodium hydride with ethyl 4-uryl-3-oxobutanoates (1) prepared as shown from arylacetic acids. The products, after mcthylation, are cyclized to anthrones (3), which are oxidized to anthraquinones.1... 

The dianions of arylacetic acids 997 undergo alkylation reactions with l-bromo-3-chloropropane, with the resulting 5-chloropentanoic acids 998 cyclizing upon treatment with DBU providing a one-pot preparation of 3-aryltetrahy-dropyran-2-ones 999 (Scheme 259) <2003TL365>. 

The vinamidinium salts needed were prepared from the corresponding arylacetic acids by formylation with dimethylformamide phosphoryl chloride, like (7/)ls ... 

The condensation of rhodanine (42) with aldehydes is an important reaction closely related to the Er-lenmeyer azalactone synthesis (equation 22) the resulting condensation products are particularly useful intermediates for the preparation of various functionalized arylacetic acids and derivatives via standard manipulations of the nitrile (43), which is available as illustrated in Scheme 11. Similarly, aldehydes... 

Coupling reactions. Benzyl ketones and arylacetic acid derivatives of the type ArCH(R)COY are prepared from RCH(X)COY by coupling with ArB(OH)2 using (Ph3P)4Ni as catalyst. ... 

Among the different synthetic procedures available for the preparation of hydratropic acids (e.g., indirect methylation of arylacetic acids,4 asymmetric hydroformylation of styrenes,5 rearrangements of a-bromoalkyl aryl ketals,6 etc.), direct methylation of arylacetic acid derivatives seems the most attractive from both economical and synthetic aspects the reagents are easily accessible and a one-pot reaction is involved. Nevertheless, this procedure is seldom used since the yields of the monomethyl derivatives are severely limited by the low selectivity of the reaction. Sizeable amounts of dimethylated by-products form.2 Even under phase-transfer catalysis conditions, high selectivity in monomethylation is elusive.7-8... 

The ketene 25g prepared by dehydrochlorination has been produced on an industrial scale and gives a highly stereoselective reaction with R-panto-lactone forming the product ester in 64% yield (Eqn (4.11)). Related chiral 2-arylacetic acid derivatives have important pharmaceutical appHca-tions, of which ibuprofen, now sold as Advil, and naproxen, now sold as Aleve, are synthesized by this general route.Stereoselective additions to ketenes of appropriate chiral alcohols provide usefiil routes to the particular enantiomers needed for pharmaceutical application. 

At least two other methods are available for preparing arylacetic acids from aromatic aldehydes. One involves the condensation of the aldehyde with rhodanine, and the other involves the formation of the... 

The Willgerodt reaction is useful in the preparation of arylacetic acids and amides from substituted methyl aryl ketones or vinyl aromatic compounds. The aliphatics and acetylenes give lower yields. The conversion is effected by heating aromatic compounds at 160°-200°C in an aqueous solution under pressure using ammonium polysulfide. In the Kindler modification, the ketone or styrene is refluxed with a mixture of sulfur and an amine, usually morpholine, to give a thioamide, ArCHjCSNRj. 

Although acetic anhydride is often used in the Perkin reaction as the acid anhydride component, other acid anhydrides can be used in the Perkin reaction as well. Oglialoro reported that sodium phenylacetate 21 and acetic anhydride give a-phenylcinnamic acid 22. The Oglialoro modification generates a mixed anhydride in situ and is a convenient preparative method that obviates the necessity of using the arylacetic anhydride as a starting material.2... 

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