Diethylmalonate preparation

Barbituric acid and 2-thiobarbituric acid are readily prepared by the condensation of diethylmalonate with urea and thiourea respectively, in the presence of sodium ethoxide. The use of substituted derivatives of urea and thiourea and of diethyl malonate will clearly lead to a wide range of barbituric and thiobarbituric acids having substituents in the i, 3, or 5 positions. 

Ethylmalonic Acid.—Like acetoacetic ester (see p. 83), diethylmalonate contains the gioup CO.CHj.CO. By the action of sodium or sodium alroholate, the hydrogen atoms of the methylene group are successively replaceable by sodium. The sodium atoms are in turn replaceable by alkyl or acyl groups. Thus, in the present preparation, ethyl malonic ester is obtained by the action of ethyl iodide on the monosodium compound. If this substance be treated with a second molecule of sodium alcoholate and a second molecule of alkyl iodide, a second radical would be in roduced, and a compound formed of the general formula... 

A fully unsaturated tricyclic indole derivative serves as the aromatic moiety for a nonsteroid antiinflammatory agent. Preparation of this compound starts with the Michael addition of the anion from methyl diethylmalonate to cyclohexanone. The product (32) is then hydrolyzed and decarboxylated to give ketoester 33. Fischer condensation with p-chlorophenylhydrazine leads to the indole This is then esterified (35) and dehydrogenated to the carbazole 36. Saponification leads... 

Another route to the preparation of Cgo derivatives involves the reaction of a halogen derivative of diethylmalonate in the presence of a strong base with fullerenes, which results in a... 

Freshly distilled diethylmalonate (DEM) was used as a solvent. SAMPLE PREPARATION... 

Substitution of the nine position is a common transformation for acridines. An optimized method for preparing the 9-carboxamides uses BOP/DMF <99SC4341>. Reaction of 9-isothioacridines with the sodium anion of diethylmalonate is followed by alkylation with bromoacetate to afford the spiro[dihydroacridine-9(10i/)-thiazolidines] <99H(51)137>. 

Bromo-2-isopropylanisole (191) was prepared from p-bromoanisole (190). It was caused to react with magnesium and ethylene oxide to obtain the alcohol (192). Its bromoderivative on heating with diethylmalonate and sodium ethoxide followed by hydrolysis with alcoholic potassium hydroxide yielded the substituted malonic acid. This on heating furnished acid (193). Its acid chloride in benzene underwenr cyclization with aluminium chloride to yield tetralone (194). It was... 

Previously cyclopropane-1,1-dicarboxylic acid had been prepared2-4 by hydrolysis of the corresponding diester. The preparation of 1,1-dicarboalkoxycyclopropanes by a conventional double alkylation of diethyl malonate with 1,2-dibromoethane was severely complicated by the recovery of unreacted diethylmalonate. This required a rather difficult distillation to separate starting material and product. In fact, many commercially offered lots of cyclopropane diester contain extensive amounts of diethyl malonate. Furthermore, preparation of the diacid required a separate and relatively slow saponification of the diester.5... 

Stronger solid base catalysts can be prepared by grafting guanidine bases to mesoporous silicas. For example, the functionalization of MCM-41 with 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD), as shown in Fig. 2.40, afforded a material (MCM-TBD) that was an effective catalyst for Michael additions with ethylcya-noacetate or diethylmalonate (Fig. 2.41) [136]. 

The synthesis of 10-oxa-l 1-deoxyprostanoids that is of prostanoids with a 7-lactone structure has been reported in the patent literature82 and from a research group from the Research Triangle Institute83. The latter synthesis started with diethyl-2-(3-cyclooctenyl)-malonate 112 which can be prepared according to the literature M, 85) jjy a treating the sodium salt of diethylmalonate with 3-bromocyclooctene or 1,2-dibromocyclooctane. 

The first group93) chose an approach by which the introduction of the upper side chain was achieved by reaction of the optically active epoxide 165 with the sodium derivative of diethylmalonate to the mixture of the isomers 166 and 167. The desired isomer 166 was isolated in 20% yield by chromatography on silica gel. The stereocontrolled opening of the epoxide which had been prepared out of 163 via the mesylate 164 was the prerequisite for the correct configuration of the prostanoid side chains in compound 171. 

The essential requirement in the preparation of diethylmalonic ester and veronal" is that all reagents must be absolutely anhydrous, otherwise the yields will be vanishingly small. All reagents and solutions must therefore be protected from the moisture of the air after drying. 

Two-carbon chain extension at the carboxyl end, mimicking biosynthesis, uses the malonic ester route (102). After reduction of the carboxyl to an alcohol, the readily displaced mesylate is prepared and reacted with sodium diethylmalonate. Saponification and decarboxylation gives the chain extended product in high yield. 

As early as 1974, Hanessian and Pemet [56] demonstrated the use of anion chemistry in the preparation of C-glycosides. As shown in Scheme 7.6, acetobromoglucose was treated with the anions of diethylmalonate and dibenzylmalonate, yielding two distinct C-glycosides. In the case of the dibenzyl analog, debenzylation, followed by treatment with the Meerwein reagent, gave a... 

The 1,3-bisamide 5.7-(m)-dioxo-cyclam (47) is prepared by reaction of 2,3,2-tet with a bisacy-lating reagent, commonly diethylmalonate, and the 1,2-bisamide 2,3-dioxo-cyclam (50) is similarly prepared from 3,2,3-tet by reaction with diethyl oxalate (Scheme 14).54 The (5,12)-(/ra ,y)-dioxo-cyclam (51) is prepared by a 2 + 2 condensation of en with (m)ethylacrylate.55... 

A new route to pyridazine analogues of dihydropyridine calcium antagonists has been devised. Ethyl l,3-dithiolane-2-carboxylate was found to add efficiently, as its lithium salt, to benzylidene derivatives prepared from aryl aldehydes and diethylmalonate or ethyl acetoacetate the dithiolane adducts were readily deprotected using NBS (Scheme 98). The resultant diketo derivatives (121) were cyclized with hydrazine to give either 1,4-dihydropyridazines (122) or l,4,5,6-tetrahydro-6-... 

A mole each of diethyl fnmarate and diethylmalonate reacts together in the presence of freshly prepared sodium ethoxide to result into the formation of ethylpropane-1, 1, 2, 3-tetracarboxylate. In fact, diethylmalonate gets split up as shown above by the dotted line, the double bond in diethyl fnmarate changes into a single covalent bond thereby the residual,... 

C-8 fluorine analogs are prepared from 2,3,4,5-tetrafluorobenzoic acid by the same methodology as previously reported but interestingly diethylmalonate can be replaced by the dilithiodianion of monoethyl malonate to give 12 in a one step process from 11 [22]. 

To a 75 mL solution of NaOEt in absolute ethanol prepared by addition of 4.5 g sodium in absolute ethanol were added 9.0 g benzamidine hydrochloride and 10 g carefully purified methyl a,a-diethylmalonate. The mixture was heated for 5 h at 70°C. The alcohol was partially removed by a current of dry air, and the residue was acidified with a slight excess of cone. HCl. After removal of the precipitated NaCl, the solution was further concentrated on the steam bath. The addition of water caused 5,5-diethyl-2-phenyl-4,6-diketo-tetrahydro-pyrimidine to separate in white needles, in an amount of 3.0 g. The product was further purified by recrystallization from dilute acetic acid. 

Design and Preparation of Radiation Cieavahie Crosslinkers and Solubility Modifiers. In order to achieve the thermal insolubilization of our water soluble films, as outlined in Figure 1, a series of crosslinkers, compounds -c and 6, were initially prepared. Compounds 4a-c were obtained through the saponification and decarboxylation of intermediate bis(diethylmalonate)acetal products, 3a-3c, as... 

Following is an equation for the preparation of barbital from diethyl 2,2-diethylmalonate and urea (barbital, a long-duration hypnotic and sedative, is prescribed under a dozen or more trade names) ... 

Allylic substitution of cinnamyl methylcarbonate with nucleophiles such as ethyl acetoacetate, diethylmalonate and morpholine was catalyzed by a Pd-complex prepared in situ from [Pd(dba)2] and P(C6H4-4-C2H4-C6Fi3)3 (Scheme 51). The substitution products were formed with high rates and good yields at 50°C in a perfluoromethylcyclohexane-THF solvent mixture, and the catalyst could be recycled several times without deterioration (259). 

B-l-Alkynyl-9-BBN compounds prepared [6-8] from the corresponding 1-alkynes and B-MeO-9-BBN, readily undergo addition to aldehydes and ketones, and afford the propargylic alcohols in very high isolated yields (Scheme 6.8) [9]. They are not basic and are safely used in the presence of compounds such as sulfoxides and diethylmalonate. 

Attempts to apply the same approach for preparation of carboxylic acids starting from the 1,4-dioxane-based derivatives failed due to the elimination of acrylonitrile under hydrolysis of the nitrile derivatives. In order to avoid this problem, the 1,4-dioxane derivative of the c/050-dodecab-orate anion was opened with diethylmalonate in the presence of potassium carbonate and the subsequent acidic hydrolysis and decarboxylation gave the carboxylic acid containing one extra methylene group (Figure 24.3) [44]. 

In a different approach to the design of a two-electron redox system, we appended the ferrocene firagment to a tetra-aza macrocode (a further example of an LrX system) the functionalized ligand should incorporate a d metal centre and should promote its redox activity. The tetra-aza macrocycle we have chosen is dioxocyclam, 9. This ligand, which can be prepared throu reaction of diethylmalonate with 2.3.2-tet, on addition of 2 eqmvalents of a strong base incorporates in aqueous solution a Cu ion, with simtdtaneous extrusion of two protons from the two amido groups [19]. 

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