Malonic acid aryl esters

Hydroxycoumarins from malonic acid aryl esters... 

Ring closure with malonic acid aryl esters Resorcinol ring... 

Keywords aromatic aldehyde, primary amine, malonic acid monoethyl ester, Rodionov reaction, microwave irradiation, / -aryl-/ -amino acid ester, ethyl cinna-mate... 

Indanones are very useful and versatile intermediates in the synthesis of metallocene catalysts. Scheme 1 has the synthetic scheme originally used for the preparation of 2-alkyl-4-aryl-substituted ansa metallocenes [9-11]. In the first part of this sequence, the biaryl unit is assembled and the missing carbon atoms are introduced as a side chain. The reaction of 2-phenylbenzyl bromide with malonic acid ethyl ester under basic conditions, followed by a decarboxylation, affords the 2-(2-phenylbenzyl)propionic acid. Chlorination and Friedel-Crafts acylation yields the 2-methyl-4-phenylindanone in 93 % yield. From here, only a few standard transformations are required to complete the synthesis, finally yielding the desired metallocene. 

Although azide reagents have been utilized in a number of chemical transformations, to date PS-TsA has only been utilized for the direct transfer of a diazo function to methylene groups flanked by either two carbonyls (eq 2), a carbonyl and an aryl sulfonyl (eq 3), or the methylene of lO/ anthracen-9-one. Diazodicarbonyl compounds such as 5-diazo-2,2-dimethyl-[l,3]dioxane-4,6-dione, 2-diazo-3-oxo-butyric acid ethyl ester, lO-diazo-lO/ anthracen-9-one, 2-diazo malonic acid diethyl ester, and 2-diazo-3-oxo-butyric acid ter/-butyl ester, as well as... 

CH OfiSj, H2C(S03H)2- a colourless, crystalline solid which readily absorbs water vapour decomposes on distillation. The potassium salt is prepared by heating methylene chloride with an aqueous solution of potassium sulphite under pressure at 150-I60" C. The free acid is obtained by decomposing the sparingly soluble barium salt with sulphuric acid. The aryl esters are very stable, but the alkyl esters decompose on heating to give ethers. Resembles malonic acid in some of its reactions. 

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. 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

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. 

Anhydrides—Continued reduction to alcohols, 155 reduction to lactones, 535 Arenes, see Hydrocarbons, aromatic Amdt-Eistert reaction, 433, 487, 573 Aryl esters. Fries rearrangement, 344 hydrolysis, 169 preparation, 169 Aryl halides, see Halides Atyloxy acids, preparation, by aceto-acetic ester synthesis, 430 by malonic ester synthesis, 429 from atyloxy alcohols, 419 from atyloxy cyanides, 414 preparations listed in table 48, 460 Aryloxy acyl halides, preparation, 547 preparations listed in table 61, 553 Aryloxy esters, preparations listed in table 55, 516... 

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. 

The general approach can be enlarged and conditions for condensation made milder by the use of further-activated esters, thus condensation with methyl nitroacetate produces 3-nitro-coumarins, condensations with Wittig ylides " allow orffto-hydroxyaryl ketones to be used ° and the use of diethyl malonate (or malonic acid ) (a 3-ester can be removed by hydrolysis and decarboxylation ), malononitrile, ethyl trifluo-roacetoacetate, or substituted acetonitriles in a Knoevenagel condensation, produces coumarins with a 3-ester, 3-trifluoroacetyl, " 3-cyano, or 3-alkyl or -aryl substituent. Condensation with IV-acetylglycine generates 3-acetylamino-coumarins. ... 

Recently a further method of alkaline nitration has been developed. It involves acetone cyanohydrin nitrate, which is readily obtained from acetone cyanohydrin and fuming nitric acid, and applies to compounds such as aryl-acetonitriles and malonic and acetoacetic esters that contain active methylene groups.130... 

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]. 

Michael additions. In this sense, the preferred formation of the (S)-diastereomers of the Michael adducts 17 generated from the enolate 15 of the diacetone-glucose dithiane-2-carboxylic acid ester with arylidene malonic acid esters 16 can be explained by assuming that the electrophile attacks from the lithium site in a way, which minimizes the steric repulsion between the dithiane ring and the aryl group ( formula A) ... 

The a-arylation of carbonyl compounds (sometimes in enantioselective version) such as ketones,107-115 amides,114 115 lactones,116 azlactones,117 malonates,118 piperidinones,119,120 cyanoesters,121,122 nitriles,125,124 sul-fones, trimethylsilyl enolates, nitroalkanes, esters, amino acids, or acids has been reported using palladium catalysis. The asymmetric vinylation of ketone enolates has been developed with palladium complexes bearing electron-rich chiral monodentate ligands.155... 

According to Thurston (702), the lower dibasic esters yield pure carbox5unonoguanamines so readily that this reaction is an excellent synthetic route, when confined to the lower esters. It has been apphed to 1-aryl- and alkyl-biguanides as usual, and to the alkali metal salts of half esters. The reaction involving diethyl malonate is represented below succinic acid esters (292, 699) react similarly. 

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... 

A highly enantioselective direct Mannich reaction of simple /V-Boc-aryl and alkyl- imines with malonates and /1-kclo esters has been reported.27 Catalysed by cinchona alkaloids with a pendant urea moiety, bifunctional catalysis is achieved, with the urea providing cooperative hydrogen bonding, and the alkaloid giving chiral induction. With yields and ees up to 99% in dichloromethane (DCM) solvent, the mild air- and moisture-tolerant method opens up a convenient route to jV-Boc-amino acids. 

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