Phenylacetic acid esters alkylation

Anionicallv Activated Alumina. At this time we had also developed an interest in anionically activated alumina. These basic reagents were active in promoting alkylation(42), condensation(43) and hydrolysis(44) reactions. Thus, we impregnated alumina with sodium hydroxide and used this combination both with and without a phase transfer catalyst (benzyltriethyl ammonium chloride). When BTEAC was added, the conversion to ether was decreased and the formation of ester was noted. In the absence of a phase transfer catalyst, the ether became a minor product and methyl phenylacetate became the major product with coproduction of phenylacetic acid. This ester does not result from esterification of the acid as simple stirring of phenylacetic acid with Na0H/A1203 in methanol does not produce methyl phenylacetate. 

Properties. Phenethyl alcohol is a colorless liquid with a mild rose odor. It can be dehydrogenated catalytically to phenylacetaldehyde and oxidized to phenylacetic acid (e.g., with chromic acid). Its lower molecular mass fatty acid esters as well as some alkyl ethers, are valuable fragrance and flavor substances. 

Diastereoselective a-alkylation of arylacetic acids.1 The binaphthyl ester (1) of phenylacetic acid undergoes highly diastereoselective methylation on treatment of... 

Under similar conditions, alkyl esters of phenylacetic acid were also easily nitrated to give a high proportion of the ortho isomers in good yields [27] ... 

Oxalic and malonic acids, as well as a-hydroxy acids, easily react with cerium(IV) salts (Sheldon and Kochi, 1968). Simple alkanoic acids are much more resistant to attack by cerium(IV) salts. However, silver(I) salts catalyze the thermal decarboxylation of alkanoic acids by ammonium hexanitratocerate(IV) (Nagori et al., 1981). Cerium(IV) carboxylates can be decomposed by either a thermal or a photochemical reaction (Sheldon and Kochi, 1968). Alkyl radicals are released by the decarboxylation reaction, which yields alkanes, alkenes, esters and carbon dioxide. The oxidation of substituted benzilic acids by cerium(IV) salts affords the corresponding benzilic acids in quantitative yield (scheme 19) (Hanna and Sarac, 1977). Trahanovsky and coworkers reported that phenylacetic acid is decarboxylated by reaction with ammonium hexanitratocerate(IV) in aqueous acetonitrile containing nitric acid (Trahanovsky et al., 1974). The reaction products are benzyl alcohol, benzaldehyde, benzyl nitrate and carbon dioxide. The reaction is also applicable to substituted phenylacetic acids. The decarboxylation is a one-electron process and radicals are formed as intermediates. The rate-determining step is the decomposition of the phenylacetic acid/cerium(IV) complex into a benzyl radical and carbon dioxide. 

The introduction of the trimethylsilyl chloride trapping technique" led to improved yields in the case of simple aliphatic esters. The initial silylated products are easily isolated and can be converted into the acyloins simply and in high yield. For simple aliphatic esters the yields are in the range 56-92%. Use of trimethylsilyl esters, rather than simple alkyl esters, leads to faster reactions, but lower yields.Substituted esters which have been successfully used in the newer procedure include ethyl 2-ethylhexanoate (83%), ethyl trimethylsilylacetate (90%)," ethyl 3-trimethylsilylpropionate (65%)," ethyl phenylacetate (48%)," ethyl 3-phenylpropionate (79%)" and 2-(2-methoxycarbonylethyl)-2-methyl-l,3-dioxolane derived from levulinic acid (65%)." In the case of ethyl adamantane-l-carboxylate the yield using the newer procedure is reported to be inferior to that using the earlier procedure. 

Although alkylation of alkyl phenylacetates does proceed under PTC conditions, complexation of the benzene ring with chromium tricarbonyl moiety increases substantially their C-H acidity hence PTC alkylation proceeds much easier and faster than ester hydrolysis (eq. 191). 

A simple demonstration of the ability of the Cr(CO)3 unit to stabilize a negative charge in the benzylic position is in the alkylation behaviour of methyl phenylacetate (Scheme 10.54). Treatment of the uncom-plexed ester with sodium hydride and 1,3-dibromopropane gave no product as the benzylic protons are not sufficiently acidic to be removed. Under the same conditions, the Cr(CO)3 complex 10.214 gave the expected cyclobutane 10.215. 

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