Malonic acids aryl derivatives

When an aromatic ring is treated with diethyl oxomalonate (Et00C)2C=0, the product is an arylmalonic acid derivative ArC(OH)(COOEt)2, which can be converted to an aryl-malonic acid ArCH(COOEt)2.329 This is therefore a way of applying the malonic ester synthesis (0-94) to an aryl group (see also 3-14). Of course, the opposite mechanism applies here the aryl species is the nucleophile. 

Solid phase synthesis of highly substituted thiophene derivatives 15 using a cyclic malonic acid ester resin 14 was also reported. Highly pure thiophene derivatives were reported to have been prepared by this solid phase synthesis <0314851>. While alkyl or aromatic substitutions on the P position to the carbonyl yielded the corresponding 5-alkyl/aryl substituted 2-acyl aminothiophene, acetaldehyde did not produce the corresponding 2,3- disubstituted thiophene. 

Acetic, succinic and malonic acids (Table 1) are reported (4) to derive from Ar-CHa, Ar(CH2)2Ar (including hydroaromatic) and Ar-CH2 Ar (Ar - aromatic ring) units respectively. Examination of the concentrations of these major aliphatic products suggests that the medium lithotypes contain the highest concentrations of aryl methyl and Ar(CH2)2Ar structures. Diaryl methane units are proposed to be most significant in the pale lithotype possibly reflecting a resin input. 

The most frequently used procedures for preparation of 5-imino-3-pyrazolidines can all be considered as variations of cyclization of malonic acid derivatives. Various hydrazines react with ethyl /3-amino-/ -ethoxyacrylate to form 2-substituted-5-imino-3-pyrazolidinones (eq. 261). Complex alkyl groups,706 aryl groups693,695,922,1140,1601 and... 

The major part of the reactions of a-arylation which have been reported were performed on substrates containing active methylene groups, such as p-diketones, p-ketoesters, P-ketonitriles and malonic acid derivatives. Less activated compounds, such as P-ketosulfides have also been efficiently arylated on the a-carbon. (Table 5.3) The yield of the arylated product can be increased by addition of 1,1-diphenylethylene, acting as a free radical trap. For example, in the reaction of phenylation of ethyl cyclohexanonecarboxylate, addition of 1,1-diphenylethylene reduced the radical chain decomposition in such a way that an 80% yield was obtained instead of 55% in absence of 1,1-diphenylethylene. ... 

Under the classical conditions (pyridine, CHCI3, room temperature or 40-60 C), diethyl malonate did not react with aryllead triacetates and the a-methyl and a-phenyl derivatives reacted slowly to give poor yields (-25%) of the corresponding a-aryl a-substituted malonic acid diesters. Moderate to good yields were obtained by reacting the sodium salt of substituted malonic esters with aryllead triacetates in THF in the presence of pyridine, but the sodium salt of diethyl malonate again failed to react. 

Other C-arylation reactions have been accomphshed with vinylogues of P dicarbonyls [93], malonic acid derivatives [94], a-cyano esters and malonitriles [95]. The a-arylation of ketone enolates/enamines and nitroalkanes has also been achieved [96-98]. 

The arylation of malonic acid derivatives with ArPb(OAc)3 has been applied to the synthesis of the important anti-inflammatory drug ibuprofen (Scheme 21). ... 

Reaction XLIV. (b) Condensation of Alkyl and Aryl Halogen Compounds with the Sodio- and other Metallo-derivatives of Ethyl Aceto-acetate and its Homolognes. (A., 186, 214 201, 143 213, 143.)—Like malonic ester, acetoacetic ester contains two 1 3-carbonyl groups with a methylene group in position 2. It is only to be expected then that it yields with metallic sodium or sodium alcoholate sodio-derivatives from which mono- and di-, alkyl and aryl homologues can be obtained by treatment with a suitable halide, including halogen esters. Acetoacetic acid... 

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