Diethyl malonate. acidity

Zinc ethyl iodide and diethyl malonate yield ethyl-diethyl malon-ate and some diethyl ester of diethyl malonic acid. ... 

Dieckmann cyclization of, 835 Diethyl malonate acidity of, 842 barbiturates from, 845-846 enolate... 

Tetrone derivative (331) is one of the products of decomposition of (330) which takes place when this reactive intermediate is generated in situ and then the solution is left at room temperature. Diethyl malonic acid and pyrazole derivative (332) are additional products of this decomposition. Pyrazole derivative (332) treated with acetic anhydride provides tetrone derivative (331) <69JOC3l8l>. Species (334), similar to (330), is supposed to be an intermediate in the treatment of chloro-pyrazolinone (333) with a base leading to a mixture of corresponding bimanes (185) and (335)... 

Ethyl isopentyl ester of diethyl malonic acid... 

It is prepared by the interaction of diethyl ester of ethyl malonic acid and iso-pentyl chloride in the presence of sodium metal, when ethyl is isopentyl ester of diethyl malonic acid is obtained as an intermediate compound. This on condensation with urea in the presence of sodium ethoxide results into the formation of amobarbital. 

In this way it was possible to isolate methyl-acrylic acid by the electrolysis of ethyl-potassium dimethyl-malonate, and ethyl-crotonic acid by electrolyzing a solution of the ethyl-potassium salt of diethyl-malonic acid. On the electrolysis of sebacic acid the ethyl ester of an unsaturated acid, CHj CH(CH,),.COOH, was formed. 

On the other hand, an acid enhancing effect through space, independent of the covalent bond linkages, may also contribute to the increased acidity of a carboxylate function. Again, electrostatic effects through space are referred to as field effects. An illustration of these is seen in the consideration of the dissociation behavior of malonic and diethyl malonic acid. The ratio of the two dissociation constants (Ki and K2) in aqueous solution is in the former case 700, in the latter case, 120,000. 

C11H20O4 2,2-diethyl-malonic acid diethyl ester 77-25-8... 

The crude product is evaporated to dryness and then heated with a mixture of ethanol and sulphuric acid the cyano group is thus hydrolysed giving malonic acid, which then undergoes esterification to give diethyl malonate. 

It is now applied more widely to include malonic acid derivatives, such as diethyl monoethyl-malonate, ethyl cyanacetate, etc. Various amines may be used as catalysts, and usually the most effective is piperidine (hexahydro-pyridine) a mixture of piperidine and pyridine, or pyridine alone, is also often used. 

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. 

The solution containing mineral acid should not be heated above 50-60 or diethyl malonate will be formed. 

Ethyl cyanoacetate (Section 111,131) is sometimes preferable to diethyl malonate for the synthesis of acids. It forms a sodio derivative with sodium ethoxide ... 

Malonic acid may be prepared from chloroacetic acid by the following series of reactions (compare Diethyl Malonate, Section 111,153) —... 

The properties of diethyl malonate that make the malonic ester synthesis a useful procedure are the same as those responsible for the synthetic value of ethyl acetoacetate The hydrogens at C 2 of diethyl malonate are relatively acidic and one is readily removed on treatment with sodium ethoxide... 

We see that a secondary alkyl halide is needed as the alkylating agent The anion of diethyl malonate is a weaker base than ethoxide ion and reacts with secondary alkyl halides by substitution rather than elimination Thus the synthesis of 3 methylpentanoic acid begins with the alkylation of the anion of diethyl mal onate by 2 bromobutane... 

As actually carried out and reported in the chemical literature diethyl malonate has been alkylated with 2 bromobutane in 83-84% yield and the product of that reaction converted to 3 methylpentanoic acid by saponification acidification and decarboxylatlon in 62-65% yield j... 

Diethyl malonate has uses other than m the synthesis of carboxylic acids One particu larly valuable application lies m the preparation of barbituric acid by nucleophilic acyl substitution with urea... 

These compounds are prepared m a manner analogous to that of barbituric acid itself Diethyl malonate is alkylated twice then treated with urea... 

Most of the reactions of ester enolates described so far have centered on stabilized eno lates derived from 1 3 dicarbonyl compounds such as diethyl malonate and ethyl ace toacetate Although the synthetic value of these and related stabilized enolates is clear chemists have long been interested m extending the usefulness of nonstabilized enolates derived from simple esters Consider the deprotonation of an ester as represented by the acid—base reaction... 

Section 21 8 Alkylation of diethyl malonate followed by reaction with urea gives derivatives of barbituric acid called barbiturates, which are useful sleep promoting drugs... 

The most widely used method for the laboratory synthesis of a ammo acids is a modification of the malonic ester synthesis (Section 21 7) The key reagent is diethyl acetamidomalonate a derivative of malonic ester that already has the critical nitrogen substituent m place at the a carbon atom The side chain is introduced by alkylating diethyl acetamidomalonate m the same way as diethyl malonate itself is alkylated... 

Malonic ester synthesis (Section 21 7) Synthetic method for the preparation of carboxylic acids involving alkylation of the enolate of diethyl malonate... 

The physical properties of cyanoacetic acid [372-09-8] and two of its ester derivatives are Hsted ia Table 11 (82). The parent acid is a strong organic acid with a dissociation constant at 25°C of 3.36 x 10. It is prepared by the reaction of chloroacetic acid with sodium cyanide. It is hygroscopic and highly soluble ia alcohols and diethyl ether but iasoluble ia both aromatic and aUphatic hydrocarbons. It undergoes typical nitrile and acid reactions but the presence of the nitrile and the carboxyUc acid on the same carbon cause the hydrogens on C-2 to be readily replaced. The resulting malonic acid derivative decarboxylates to a substituted acrylonitrile ... 

Tribromoacetic acid [75-96-7] (Br CCOOH), mol wt 296.74, C2HBr302, mp 135°C bp 245°C (decomposition), is soluble in water, ethyl alcohol, and diethyl ether. This acid is relatively unstable to hydrolytic conditions and can be decomposed to bromoform in boiling water. Tribromoacetic acid can be prepared by the oxidation of bromal [115-17-3] or perbromoethene [79-28-7] with fuming nitric acid and by treating an aqueous solution of malonic acid with bromine. 

Hydrochloric acid [7647-01-0], which is formed as by-product from unreacted chloroacetic acid, is fed into an absorption column. After the addition of acid and alcohol is complete, the mixture is heated at reflux for 6—8 h, whereby the intermediate malonic acid ester monoamide is hydroly2ed to a dialkyl malonate. The pure ester is obtained from the mixture of cmde esters by extraction with ben2ene [71-43-2], toluene [108-88-3], or xylene [1330-20-7]. The organic phase is washed with dilute sodium hydroxide [1310-73-2] to remove small amounts of the monoester. The diester is then separated from solvent by distillation at atmospheric pressure, and the malonic ester obtained by redistillation under vacuum as a colorless Hquid with a minimum assay of 99%. The aqueous phase contains considerable amounts of mineral acid and salts and must be treated before being fed to the waste treatment plant. The process is suitable for both the dimethyl and diethyl esters. The yield based on sodium chloroacetate is 75—85%. Various low molecular mass hydrocarbons, some of them partially chlorinated, are formed as by-products. Although a relatively simple plant is sufficient for the reaction itself, a si2eable investment is required for treatment of the wastewater and exhaust gas. 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

The intense reddish-brown color of the acetylacetone titanium complexes impart a yellow discoloration to white inks. This discoloration is accentuated when the inks are used to print substrates that contain phenol-based antioxidants. The phenoHc compounds react with the organic titanate to form a highly colored titanium phenolate. Replacement of 0.25 to 0.75 moles of acetylacetone with a malonic acid dialkyl ester, such as diethyl malonate, gives a titanium complex that maintains the performance advantages of the acetyl acetone titanium complexes, but which is only slightly yellow in color (505). These complexes still form highly colored titanium phenolates. 

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