Sodium Cyanoacetate Solution

Manufacture. Cyanoacetic acid and cyanoacetates are iadustrially produced by the same route as the malonates starting from a sodium chloroacetate solution via a sodium cyanoacetate solution. Cyanoacetic acid is obtained by acidification of the sodium cyanoacetate solution followed by organic solvent extraction and evaporation. Cyanoacetates are obtained by acidification of the sodium cyanoacetate solution and subsequent esterification with the water formed being distilled off. Other processes reported ia the Hterature iavolve the oxidation of partially oxidized propionittile [107-12-0] (59). Higher esters of cyanoacetic acid are usually made through transesterification of methyl cyanoacetate ia the presence of alumiaiumisopropoxide [555-31-7] as a catalyst (60). 

Ethyl malonate can be conveniently prepared by neutralising a solution of monochloroacetic acid with sodium bicarbonate, then heating with potassium cyanide to form sodium cyanoacetate ... 

A solution of sodium cyanide [143-33-9] (ca 25%) in water is heated to 65—70°C in a stainless steel reaction vessel. An aqueous solution of sodium chloroacetate [3926-62-3] is then added slowly with stirring. The temperature must not exceed 90°C. Stirring is maintained at this temperature for one hour. Particular care must be taken to ensure that the hydrogen cyanide, which is formed continuously in small amounts, is trapped and neutrali2ed. The solution of sodium cyanoacetate [1071 -36-9] is concentrated by evaporation under vacuum and then transferred to a glass-lined reaction vessel for hydrolysis of the cyano group and esterification. The alcohol and mineral acid (weight ratio 1 2 to 1 3) are introduced in such a manner that the temperature does not rise above 60—80°C. For each mole of ester, ca 1.2 moles of alcohol are added. 

Reaction of melatonin with various aryldiazonium chlorides in ethanolic sodium acetate solution afforded arylazo-melatonin derivatives. Reactions of these products with either malonitrile or ethyl cyanoacetate formed the corresponding ary lam inotriazino[4,3-/z indole scaffolds 60-63 <2005BMC1847>. 

In an initial step, the sodium derivative of ethyl (3-benzoylphenyl) cyanoacetate is prepared as follows (3-benzoylphenyl)acetonitrile (170 9) is dissolved in ethyl carbonate (900 g). There is added, over a period of 2 hours, a sodium ethoxide solution [prepared from sodium (17.7 g) and anhydrous ethanol (400 cc)], the reaction mixture being heated at about 105° to 115°C and ethanol being continuously distilled. A product precipitates. Toluene (500 cc) is added, and then, after distillation of 50 cc of toluene, the product is allowed to cool. Diethyl ether (600 cc) is added and the mixture is stirred for 1 hour. The crystals which form are filtered off and washed with diethyl ether (600 cc) to give the sodium derivative of ethyl (3-benzoylphenyl)cyanoacetate (131 g). 

Colour Test. Dissolve about 0.5 mg in 5 ml of ethanol and add 2 ml of strong ammonia solution and a few drops of ethyl cyanoacetate—violet add 5 ml of sodium hydroxide solution— brown-yellow. The violet colour is destroyed on the addition of acid or on exposure to sunlight. 

By treating a neutral solution of mercuric nitrate with ammonium cyanoacetate, Meves obtained a mercury compound of indefinite composition, Petterson, by adding ammonium cyanoacetate solution, 0 02 mol., to an aqueous solution of mercuric acetate, 0 03 mol., obtained in tw o days a white flocculent precipitate, which split off mercuric oxide w hen treated with sodium carbonate. The following formuhc have been proposed for the substance —... 

Esters of strongly acidic acids such as cyanoacetic acid47b are hydrolysed by 20% sodium hydroxide solution even in the cold esters of dicarboxylic acids such as diethyl malonate62 or 2-methylheptanedioic acid63 are converted in that way into their acid esters. 

In an initial step, the sodium derivative of ethyl (3-ben2oylphenyl)cyanoacetate Is prepared as follows O-benzoylphenyOacetonitrile (170 g) is dissolved in ethyl carbonate (900 g). There is added, over a period of 2 hours, a sodium ethoxide solution [prepared from sodium (17.7 g) and anhydrous ethanol (400 cc)j, the reaction mixture being heated at... 

Preparation from cyanoacetic acid and 2,4-dihydroxy-3-formylpropiophenone in 20% sodium hydroxide solution (59%) [6768]. 

Then, ethyl methyl(3-benzoylphenyl)cyanoacetate employed as an intermediate material is prepared as follows The sodium derivative of ethyl (3-benzoylphenyl)cyanoacetate (131 g) is dissolved in anhydrous ethanol (2 liters). Methyl iodide (236 g) is added and the mixture is heated under reflux for 22 hours, and then concentrated to dryness under reduced pressure (10 mm Hg). The residue is taken up in methylene chloride (900 cc) and water (500 cc) and acidified with 4N hydrochloric acid (10 cc). The methylene chloride solution is decanted, washed with water (400 cc) and dried over anhydrous sodium sulfate. The methylene chloride solution is filtered through a column containing alumina (1,500 g). Elution is effected with methylene chloride (6 liters), and the solvent is evaporated under reduced pressure (10 mm Hg) to give ethyl methyl(3-benzoylphenyl)cyano-acetate (48 g) in the form of an oil. 

On evaporating the alcoholic solution under reduced pressure from a water bath held at 50-60° (Note 6) the residue weighs about 540 g. A mixture of 600 cc. of absolute alcohol and 10 cc. of concentrated sulfuric acid (Note 7) is then added. The mixture is then heated on the water bath under a reflux condenser for three hours. The excess of alcohol and some of the water formed are removed by distillation under reduced pressure and the residue again heated for two hours with 300 cc. of absolute alcohol and an additional 4 cc. of concentrated sulfuric acid. The alcohol is removed by distillation under reduced pressure, and when the ester has cooled to room temperature, the sulfuric acid is neutralized with a concentrated solution of sodium carbonate the ester (upper layer) is separated, and the aqueous solution extracted with ether, or preferably benzene about one-tenth of the yield is in the extract. The combined products are placed in a i-l. distilling flask and distilled under reduced pressure after the solvent and alcohol and water have been removed. The ester is collected at 94-990, chiefly at 97-98°/x6 mm. (Note 8). The yield of a product analyzing about 97-98 per cent ethyl cyanoacetate amounts to 474-492 g. (77-80 per cent of the theoretical amount) (Note 9). 

C with a solution of 16 g of sodium nitrite in 40 ml of water. To this solution was added a solution of 8.5 g of cyanoacetic acid in 100 ml of water cooled to 0 °C. The resulting solution was neutralized with 200 ml of a 20% solution of sodium hydroxide when an intense red color formed. The formazan was precipitated with 10% hydrochloric acid, filtered, and air dried. The crude formazan was recrystallized from 400 ml of ethanol to yield 9.5 g (40%) of golden platelets mp 158 °C. 

The submitters prepared o-chlorohydrocinnamonitrile by the following procedure. Ethyl cyanoacetate (3040 g., 27 moles) was added to a solution of 140 g. (6.1 g. atoms) of sodium in 4 1. of absolute ethanol, followed by 970 g. (6 moles) of o.a-dichloro-toluene (Eastman Organic Chemicals), to afford 890 g. (63%) of ethyl 2-(o-chlorobenzyl)cyanoacetate,2 b.p. 117-123° (0.03 mm.). Hydrolysis of this material in 2 1. of 10% aqueous sodium hydroxide at room temperature gave a quantitative yield (790 g.) of 2-(o-chlorobenzyl)cyanoacetic acid, m.p. 129-132° without recrystallization. Decarboxylation of 750 g. of the acid in 750 ml. 

The reaction of 2-mercapto-4-(2, 4 -dichlorophenyl)-5-cyanopyrimidin-6(l//)one 421 (obtained by stirring ethyl cyanoacetate and thiourea with 2,4-dichlorobenzaldehyde in sodium ethylate at room temperature, in 70% yield), with a solution of monochloroacetic acid and />-cholorobenzaldehyde in glacial acetic acid, in the presence of sodium acetate, affords 2-[(/>-chlorophenyl)methylene]-6-cyano-7-(2, 4 -dichlorophenyl)thiazolo[3,2-tf]pyrimidin-3,5-dione 422. Finally, the reaction of compound 422 with hydrazine hydrate converts it into product 423 (Scheme 49) < 1996PS( 116)39>. 

Ethyl (6-Methoxy-l,2-naphthoquinonyl-6) Cyanoacetate. The above naphthoquinone (21.7 g) is added to a solution of 500 cc of ethanol and 14 cc of ethyl cyanoacetate, followed by the addition of 32 cc triethylamine. A deep purple color will develop and the mixture should be swirled for 4 min to dissolve the quinone completely. A solution of 75.9 g of potassium ferricyanide in 320 cc of water is then added to the solution, causing a thick dark complex to form and separate. Redissolve by adding a soluhon of 24 g of sodium carbonate in 1,600 cc of water. Swirl or stir and filter through diatomaceous filter aid. Acidify the filtrate with 100 cc of 6 M sulfuric acid to precipitate 34.8 g of red-orange powder, which is oven dried at 70°. Reciystallize from ethyl acetate to get 19.3 g, mp 157-158.5°. The remaining filtrate is evaporated to a small bulk and reciystallization from ethyl acetate gives an additional 2.8 g of product. 

Extraction of the aqueous solution removes ethyl cyanoacetate from the aqueous solution of the sodium bisulfite addition product of ethyl (l-ethylpropylidene)-cyanoacetate. 

---