Esterification, of cyanoacetic acid

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. 

Ethyl cyanoacetate has been prepared by the action of potassium cyanide on ethyl chloroacetate,1 and by the esterification of cyanoacetic acid.2... 

Esterification, of cyanoacetic acid, 41, 5 of gluconolactone, 41, 79 of tetraacetylgluconic acid, 41, 80 of a-d-unsaturated acids, 41, 62 preparation of sec-butyl crotonate by, 41, 60... 

Dicyanomethane or Malononitrile (called Malonsaure-dinitril, Malonitril or Methylen-cyanid in Ger), NC.CH2.CN mw 66.06, N 42.41% col crysts, mp 31.6-32.4 , bp 108-09° at 17mm press, cryst d I.I9I at 20°, liq d 1.0494 at 35° nj. 1.4139 at 34.2° prepd by esterification of cyanoacetic acid, and treatment of the ester with NH3 which leads to cyanoacetamide which, on reaction with phosphorous oxychloride or pentachloride, gives Dicyanomethane (Ref 1)... 

Derivation Esterification of cyanoacetic acid with ethanol reaction of an alkali cyanide and chloroa-cetic ethyl ester. 

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). 

The method described differs from that given in Org. Syn. 3, 53 mainly in the use of hydrochloric acid in place of sulfuric acid, in the liberation of the cyanoacetic acid from the sodium salt and in the simplified esterification process. These are slight but very important differences and make the procedure much easier to carry out in the laboratory. Moreover, the yields are higher. 

Ethyl Cyanoacetate. Cyaitoacetic acid ethyl estert cyanoacetic ester ethyl cyanoethanoate malonic acid ethyl ester nitrile. CsH,N02 mol wt 113.12. C 53.09%. H 6.24%, N 12.39%, O 28.29%. CNCH2COOC2HS. Made by the interaction of sodium cyanide and chloroacetic acid and subsequent esterification of the cyanoacetic acid formed Kob -ler, Allen. Org. Syn. 3, 53 (1923) Inglis, ibid. 8, 74 (1928). 

Mechanism. The nitrile function (or cyano moiety) in cyanoacetic acid tmdei oes hydrolysis to result into the formation of a carboxylic group i.e., malonic acid, which upon esterification with EtOH forms the corresponding diethylmalonate. 

The potential benefits of the combined use of these clay catalysts are highlighted in the synthesis of epoxynitrile from cyanoacetic acid as a starting material. The synthesis of epoxynitrile occurs via a four step reaction that requires sequential acid and base catalyses through esterification (65) (i), deacetalization, an aldol reaction(ii), and epoxidation (66) (iii) (Fig. 17). If Pd/HT is employed... 

Eligh yields of esters are obtained from both acid-sensitive (cyanoacetic acid) and base-sensitive carboxylic acids (3-phenyl-propionic acid and trichloroacetic acid) and, in these latter cases, use of 4-(dimethylamino)pyridinium chlorosulfite chloride is much more effective than use of thionyl chloride alone. The esterification process has been claimed to be independent of the steric environment of the carboxyl function, though this reagent may be of more limited value with heavily substituted benzoic acids. Carboxyl activation, in the presence of a primary amine, leads to the corresponding amide in excellent yield (eq 2). In both the esterification and amidation processes and the oxime dehydration reaction discussed below, recovery of DMAP is straightforward. 

Disubstituted-1,3,2-dioxaborinanes, 4.5, are structurally similar to 2,5-disubsti-tuted-1,3-dioxanes but without the complication of cis-/fra s-isomerism the creation of the dioxaborinane ring is achieved by esterification of a 2-substituted-propan-1,3-diol with an arylboronic acid [62, 63]. For compounds of this type with a 5-aryl substituent, 2-arylpropan-l,3-diols are required and are prepared by coupling the ethyl cyanoacetate anion and a 4-substitut-ed-phenyl bromide or iodide [62] and the 5-alkyl-substituted-1,3,2-dioxaborinanes [63] are obtained from 2-alkylpropan-1,3-diols (4.1). 

R = H). The subsequent condensation of this ketone with ethyl cyanoacetate, sodium cyanide and acrylonitrile led to a trinitrile the hydrolysis and esterification of which gave the triester (325, R = H). Cyclization of the latter led to the tricyclic keto acid (328 R = H) the treatment of which with acids caused the closure of ring C with the formation of the tetracyclic acid (327 R = H). Hydrogenation of the A -bond gave a derivative of... 

A variant in the production of an intermediate in the Robinson synthesis, the tricyclic ABC diketone (18), was developed by Banerjee and co-workers [635, 636] (Scheme 58). The triester (22) was obtained from a-ethoxycarbonylcyclohexanone (21) by the Michael reaction with methyl acrylate, alkaline cleavage, and esterification, and it was then cyclized by Dieckmann s method with subsequent bromination and dehydrogenation to give the unsaturated keto diester (23). The addition of cyanoacetic ester gave compound (26) from which the keto triester (25) was obtained by methylation, acid hydrolysis, and esterification. The latter, by Dieck-mann cyclization and hydrolysis, gave the BC fragment (24). Selective ketalization, reduction, and hydrolysis of the ketal led to the hydroxy-ketone (27). The trans-B/C linkage present in it required the protection... 

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. 

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