Aqueous reactions malonic acid

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. 

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

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. 

Beryllium, calcium, boron, and aluminum act in a similar manner. Malonic acid is made from monochloroacetic acid by reaction with potassium cyanide followed by hydrolysis. The acid and the intermediate cyanoacetic acid are used for the synthesis of polymethine dyes, synthetic caffeine, and for the manufacture of diethyl malonate, which is used in the synthesis of barbiturates. Most metals dissolve in aqueous potassium cyanide solutions in the presence of oxygen to form complex cyanides (see Coordination compounds). 

Although heating benzene-1,2-diamine with malonic acid in aqueous hydrochloric acid affords the parent dione 26 (R = H) in 62% yield,277 the method cannot be extended to substituted malonic acids because decarboxylation intervenes however, the reaction of benzene-1,2-diamines with diethyl malonate and its derivatives constitutes a general procedure for the synthesis of l,5-benzodiazepine-2,4-diones 26 selected examples are given.278... 

The Belousov-Zhabotinsky (BZ) reaction involves the oxidation of an organic species such as malonic acid (MA) by an acidified aqueous bromate solution in the presence of a metal ion catalyst such as the Ce(m)/Ce(IV) couple. At excess [MA] the stoichiometiy of the net reaction is... 

Beside this basic method of manufacturing mercury fulminate, which is widely practised, there are alternate processes. Angelico [11] recognized that mercury fulminate is formed by treating a mercury solution in an excess of nitric acid with a concentrated aqueous solution of malonic acid in the presence of a small amount of sodium nitrate. The reaction results in a considerable rise of temperature, C02 evolution and the precipitation of the fulminate (L. W. Jones [12]). 

In a 1-1. round-bottomed flask fitted with a reflux condenser are placed 192 g. (166 ml., 2 moles) of freshly distilled furfural (Note 1), 208 g. (2 moles) of malonic acid (Note 2), and 96 ml. (1.2 moles) of pyridine (Note 3). The flask is heated on a boiling water bath for 2 hours, and the reaction mixture is cooled and diluted with 200 ml. of water. The acid is dissolved by the addition of concentrated aqueous ammonia, the solution is filtered through a fluted filter paper, and the paper is washed with three 80-ml. portions of water. The combined filtrates are acidified with an excess of diluted (1 1) hydrochloric acid with stirring. The mixture is cooled by running water and then allowed to stand in an ice bath for at least 1 hour. The furylacrylic acid is filtered, washed with four 100-ml. portions of water, and dried. The yield of practically colorless needles melting at 141° is 252-254 g. (91-92%). If a purer product is desired, recrystallization is best effected from dilute alcohol (Note 4). On slow cooling of the solution, needles melting at 141° separate. 

In reactions where nitriles are prepared from halogen compounds by double decomposition with alkali cyanide in alcoholic or aqueous alcoholic solution, the latter is usually added in solution or as a powder (cf. Preparations 77,78,79), otherwise the alkali halide which separates forms a coating round the cyanide and hinders further action. If the reaction is performed in aqueous solution, as in the preparation of malonic acid (p. 125), this precaution is not so necessary the alkali halide, when formed, remains in solution. 

The residue then was dissolved in 30 ml of 0.04 M aqueous triethyl-ammonium bicarbonate buffer (pH 7.5), (resulting pH 5.6). It was chromatographed on a DEAE cellulose column (HCOJ form) (3.4 X 15.0 cm), with elution first with 500 ml of water and then with a linear gradient of trimethylammonium bicarbonate at pH 7.2 (0-0.07 M). XXVII was completely resolved from some of XXVIII which was formed under the above reaction conditions. However, it was still contaminated by small amounts of cAMP and ethyl 2-diazo-malonic acid. These impurities were apparently generated from the hydrolysis of some XXVII when the triethylammonium bicarbonate was removed. Pure samples of XXVII were obtained by preparative paper chromatography on either Whatman 40 or 3 MM paper with overnight development with ethanol 0.5 M ammonium acetate, pH 7.0 (5 2, v/v). 

In the first part of the malonic ester synthesis, the a-carbon of the diester is alkylated (Section 19.8). A proton is easily removed from the a-carbon because it is flanked by two ester groups (pK =13). The resulting a-carbanion reacts with an alkyl halide, forming an a-substituted malonic ester. Because alkylation is an Sn2 reaction, it works best with methyl halides and primary alkyl halides (Section 10.2). Heating the a-substituted malonic ester in an acidic aqueous solution hydrolyzes it to an a-substituted malonic acid, which, upon further heating, loses CO2, forming a carboxylic acid with two more carbons than the alkyl halide. 

ZZZ Construction of Pyrimidines. To make use of this reaction for pyrimidine synthesis, a diamino compound, usually urea, thiourea, or guanidine, can be reaeted with the diaeid malonic acid (HOOC-CH2-COOH) (Scheme 4.22) or preferably its diethyl ester. In its simplest form, the reaetion has been used to make barbiturie acid (4.21 see also Chapter 8, section 8.2). Salts can be made from barbiturie aeid with aqueous base this reaction ean be viewed as removing a C-H proton from C-5, or from the corresponding enol (found in stmeture 4.23). 

Figure 1. Oscillatory behavior following an initial induction period in the potentials of a platinum redox electrode and a bromide sensitive electrode in a BZ reaction mixture containing an aqueous solution of bromate, malonic acid, a ceric salt, and sulfuric acid. Reproduced from Field et al. (6). Copyright 1972 American Chemical Society,...

In Chapter 22 (Section 22.7.4), malonate derivatives were easily converted to the corresponding enolate anion, and reaction with alkyl halides or other electrophilic species gave the C3-alkylated product. Indeed, if 102 is treated with sodium metal (or NaH, LDA, etc.), enolate anion 103 is formed it reacts with an alkyl halide such as benzyl bromide (PhCH2Br) to give 104. If 104 is heated with aqueous sodium hydroxide and then treated with aqueous HCI, phthalic acid (35) and the amino acid phenylalanine (57) are formed as the final products. 

Recall from Section 18.4C that hydrolysis of an ester in aqueous sodium hydroxide (saponification) followed by acidification of the reaction mixture with aqueous HCl converts an ester to a carboxylic acid. Also recall from Section 17.9 that j8-ketoacids and j8-dicarboxylic adds (substituted malonic acids) readily undergo decarboxylation (lose CO2) when heated. Both the Claisen and Dieckmann condensations yield esters of j8-ketoacids. The following equations illustrate the results of a Claisen condensation followed by hydrolysis of the ester, acidification, and decarboxylation. 

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