Ethyl cyanoacetate, acidity

Beilstein Handbook Reference) Acetic acid, cyano-, ethyl ester AI3-19027 BRN 0605871 Cyanacetate ethyle Cyanoacetic acid ethyl ester Cyanoacetic ester EINECS 203-309-0 Estere cianoacetico Ethyl cyanacetate Ethyl cyanoacetate Ethyl cyanoethanoate Ethylester kyseliny kyanoctove HSDB 2769 Malonic acid ethyl ester nitrile NSC 8844 UN2666 USAF KF-25. Liquid mp = -22.5° bp = 205° d = 1.0654 very soluble in EtOH, Et20. 

Ethyl cyanoacetate, a substance of importance in synthetical work, is prepared from chloroacetic acid by the following series of reactions ... 

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

Into a 500 nil. round-bottomed flask, provided with a double surface condenser, place 50 g. (63 ml.) of pure, dry acetone, 50 g. (47 ml.) of ethyl cyanoacetate (Section 111,131) and 0 -5 g. of piperidine. Allow to stand for 60 hours and heat on a water bath for 2 hours. Treat the cold reaction mixture with 100 ml. of ether, wash with dilute hydrochloric acid, then with water, and dry over anhydrous sodium or magnesium sulphate. Distil under diminished pressure and collect the ethyl fsopropylidene cyanoacetate (ethyl a-cyano-pp-dimethylacrylate) at 114-116°/14mm.(l). The yield is 39 g. 

When acetone is condensed with ethyl cyanoacetate in the presence of a solution of anhydrous ammonia in absolute alcohol at —5°, the ammonium salt of the dicyano-imlde (I) is precipitated. Upon dissolving this salt in water and adding excess of concentrated hydrochloric acid, the crystalline dicyano-imide (II) is obtained. Hydrolysis of the last-named with strong sulphuric acid affords p p dimethylglutaric acid (III). 

The preparation of ethyl cyanoacetate proceeds via ethyl chloroacetate and begins with acetic acid Wnte a sequence of reactions descnbmg this synthesis... 

The methyl and ethyl esters of cyanoacetic acid are slightly soluble ia water but are completely miscible ia most common organic solvents including aromatic hydrocarbons. The esters, like the parent acid, are highly reactive, particularly ia reactions involving the central carbon atom however, the esters tend not to decarboxylate. They are prepared by esterification of cyanoacetic acid and are used principally as chemical iatermediates. 

Table 11. Some Physical Properties of Cyanoacetic Acid and Methyl and Ethyl Esters ...

Cyanoacetic acid, NCCH2COOH Methyl ester, NCCH2COOCH3 Ethyl ester, NCCH2COOC2H3... 

Health and Safety Factors. The following toxicities have been reported for cyanoacetic acid oral LD q (rat) 1500 mg/kg subcutaneous LD q (rabbit), 1900 mg/kg and subcutaneous LD q (frog) 1300 mg/kg (29). Eor ethyl cyanoacetate the following toxicities have been reported interperitoneal LD q (mice), 750 mg/kg subcutaneous LD q (rabbits), 1500 mg/kg and subcutaneous LD q (frogs), 4000 mg/kg. 

Physical Properties. The physical properties of cyanoacetic acid [372-09-8] NM7—CH2COOH (28) ate summarized in Table 4. The industrially most important esters ate methyl cyanoacetate [105-34-0] and ethyl cyanoacetate [105-56-6]. Both esters ate miscible with alcohol and ether and immiscible with water. 

Table 4. Physical Properties of Cyanoacetic Acid, Methyl Cyanoacetate, and Ethyl Cyanoacetate...

Property Cyanoacetic acid Methyl cyanoacetate Ethyl cyanoacetate... 

Analytical and Test Methods. Potentiometic titration is an analytical method for cyanoacetic acid. Methyl and ethyl cyanoacetates are usually analyzed by gas chromatography usiag the same equipment as for the malonates but with a higher column and iajector temperatures, namely 150 and 200°C, respectively. 

Health and Safety Factors. Handling of cyanoacetic acid and cyanoacetates do not present any specific danger or health hazard if handled with the usual precautions. Cyanoacetic acid is classified as a moderate irritant (skin irritation, rabbits) and has an LD q (oral, rats) of 1500 mg/kg. Methyl and ethyl cyanoacetate are both classified as slight irritants (skin irritation, rabbits) and have an LD q (oral, rats) of 3062 and 2820 mg/kg, respectively. Transport classification cyanoacetic acid RID/ADR 8 IMDG-Code 8 lATA/ICAO 6.1. Methyl and ethyl cyanoacetate RID/ADR 6.1 IMDG-Code 6.1 lATA/ICAO 6.1. 

D A R A P S K I Amino Acid Synthesis (see Curtius) Amino acid synthesis from ethyl cyanoacetates... 

From ethyl chloroacetate and sodium cyanide, and by esteri-fying cyanoacetic acid. Stephens, J. Soc. Chem. Ind. 43, 313T, 327T (1924). 

A mixture of ethyl cyanoacetate (Note 1) (56.6 g., 0.5 mole), freshly distilled butyraldehyde (43.2 g., 0.6 mole), 1 g. of palladium on carbon (Note 2), and 80 ml. of glacial acetic acid is placed in a 500-ml. bottle suitable for attachment to a low-pressure reduction apparatus. A solution of piperidine (2.0 ml., 0.02 mole) in 20 ml. of glacial acetic acid is added, and the bottle is connected to the reduction apparatus. 

Formal oxidation of pyrrolidine to the succinimide stage affords a series of compounds used as anticonvulsant agents for treatment of seizures in petit mal epilepsy. Knoevnagel condensation of benzaldehyde with ethyl cyanoacetate affords the unsaturated ester, 9. Conjugate addition of cyanide ion leads to the di-nitrile ester (10). Hydrolysis in mineral acid affords the succinic acid (11), presumably by decarboxylation of the intermediate tricarboxyllie acid. Lactamization with methylamine gives phensuximide (12). ... 

Cycloheptanone Cyanoacetic acid methyl ester Ethyl bromide Hydrogen chloride... 

Ethyl thioglycolate and ethyl cyanoacetate are first reacted in the presence of sodium ethylate to give 4-oxo-thiazolidin-2-ylideneacetic acid ethyl ester. That is reacted with diethyl sulfate and then with piperidine to give piprozolin. 

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). 

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