Ethyl cyanoacetate, condensation with

Ethyl cyanoacetate condenses with ketones and ammonia in absolute ethanol at 0-5° to give 44-73% yields of cyclic dicyanoimides. Endocyclic ketones may be used, giving imides in which the two radicals are p>art of an alicyclic ring. The imides are hydrolyzed and decarboxylated in almost theoretical yields to yS,/S-disubstituted glutaric acids. A similar reaction takes place between aldehydes or ketones and cyanoacetamide, NCCHjCONHj, in the presence of piperidine or potassium hydroxide. When aldehydes are used, the condensation products are dicyanoamides, RCH[CH(CN)CONHj]j, rather than cyclic imides. 

Another recent example is the condensation of ethyl cyanoacetate 709 with 2equiv of trifluoroacetonitrile in the presence of potassium / -tZ-butoxide to give 5-cyano-2,6-bis(trifluoromethyl)-4(3/7)-pyrimidinone 710 in 84% yield <2004SC903>. 

The condensation of active methylene compounds such as malononitrile, ethyl cyanoacetate, etc., with phenyl isocyanate followed by alkylation and cyclization gives 3-aminothiophenes 304 (Scheme 51) <2003T1557>. Dihydrothienopyrimidine-4(/7T)ones 306 are prepared by the reaction of 305 with a-halo ketones <2006HAC104>. 

Choudary et al. have investigated the Knoevenagel reaction by use of diamine-functionalized MCM-41 [47]. This grafted material was effective in the condensation of several aldehydes with both ethyl cyanoacetate and with malononitrile. In-... 

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). 

Ethyl M-butylcyanoacetate has been prepared by alkylation of the sodium enolate of ethyl cyanoacetate with butyl bromide and by condensation of capronitrile with ethyl carbonate, in addition to the method given above. ... 

Functionalized 5-alkoxymethyl- and 5-phenoxymethyl-2(5//)-furanones 44-46 were obtained starting from 3-alkoxy- and 3-phenoxy-2-hydroxy ketones 40 (98T1801). Condensation of the hydroxy ketones 40 with a slight excess of diethyl malonate 41 (Z = COOMe R = Me), ethyl cyanoacetate 42 (Z = CN R = Me),... 

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). ... 

Alkyl uracyls have been known for some time to act as diuretic agents in experimental animals. The toxicity of these agents precluded their use in the clinic. Appropriate modification of the molecule did, however, yield diuretic agents with application in man. Reaction of allylamine with ethyl isocyanate affords the urea, 89 (the same product can of course be obtained from the same reagents with reversed functionality). Condensation with ethyl cyanoacetate affords aminotetradine (90). In... 

An early application of this reaction to the preparation of barbiturates starts by the condensation of the ketone, I21, with ethyl cyanoacetate by Knoevenagel condensation. Alkylation of the product (122) with ethyl bromide by means of sodium ethoxide affords 123. Condensation of this intermediate with guanidine in the presence of sodium ethoxide gives the diimino analog of a barbiturate (124). Hydrolysis affords vinbarbital (111). > ... 

Thus, the condensation product of cyclohexanone and ethyl cyanoacetate (125) affords the intermediate (126) for the synthesis of cyclobarbital (112) on alkylation with ethyl bromide. The condensation product of cycloheptanone (127) affords the starting... 

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). 

The synthesis of pyrido[2,3-d]pyrimidin-7(8H)-ones has also been achieved by a microwave-assisted MCR [87-89] that is based on the Victory reaction of 6-oxotetrahydropyridine-3-carbonitrile 57, obtained by reaction of an Q ,/3-unsaturated ester 56 and malonitrile 47 (Z = CN). The one-pot cyclo condensation of 56, amidines 58 and methylene active nitriles 47, either malonitrile or ethyl cyanoacetate, at 100 °C for benzamidine or 140 °C for reactions with guanidine, in methanol in the presence of a catalytic amount of sodium methoxide gave 4-oxo-60 or 4-aminopyridopyrimidines 59, respectively, in only 10 min in a single-mode microwave reactor [87,88]... 

Imino ethers and, in particular, lactim ethers [141] such as O-ethylpyrrolidone 384a [142] or O-trimethylsilylcaprolactam 384b, which is formed, in equilibrium with N-trimethylsilylcaprolactam, on treatment of caprolactam with HMDS 2, condense readily with activated methylene compounds such as methyl or ethyl cyanoacetate to the y9-enamino esters 385 a and 385 b [140] whereas O-alkylureas such as 2-methoxyimidazoline 386 [143-146] afford products such as 387. 

A distantly related acid with a more highly functionalized ring shows choleretic rather than antiinflammatory activity. That is, the compound is useful in those conditions in which the flow of bile is to be increased. Construction of the thiazolone ring is accomplished by a method analogous to that used above to build the thiazole ring. Thus, condensation of ethyl mercaptoacetate with ethyl cyanoacetate leads to the thiazolinone (203) an intermediate such as 202, involving addition of mercaptide to the nitrile function, can be reasonably invoked. 

Ethylbenzoic acid was converted to the acid chloride, which was treated with AICI3 and benzene to give 4-ethylbenzophenone in 90% yield overall. Condensation with ethyl cyanoacetate afforded ethyl 4-ethyl-a-cyano-B-phenylcinnamate as an essentially 50/50 mixture of the Z- and E-isomers. The yield of the condensation was highly sensitive to reaction conditions, and was optimized at 75% with portionwise addition of the ammonium acetate catalyst. Bromination and dehydrobromination as described earlier then completed the preparation. The overall yield of ethyl 4-vinyl-a-cyano-p-phenylcinnamate was 20%. 

Condensation of l,3-diphenylpyrazol-5-one 429 with ethyl cyanoacetate 430 in the presence of piperidine gave the pyrazolopyranone 431, which was condensed with phenylhydrazine to give the bispyrazolopyran 432 (Scheme 33) <1996EJC83>. 

Cyclobutanedicarboxylic acid has been prepared by hydrolysis of the ethyl ester,1 or of the half nitrile, 1-cyano-l-car-boxycyclobutane.2 The ethyl ester has been prepared by condensation of ethyl malonate with trimethylene bromide1 or chloro-bromide.3 The half nitrile has been prepared by condensation of trimethylene bromide with ethyl cyanoacetate followed by hydrolysis of the ester to the acid.2... 

The one-step condensation to convert 2-butanone, ethyl cyano-acetate, and hydrocyanic acid to ethyl 2,3-dicyano-3-methyl-pentanoate is a modification of the procedure described by Smith and Horowitz 6 in which pyridine acetate was employed as the catalyst. Higson and Thorp 6 employed a two-step procedure in which butanone was converted to its cyanohydrin, which in turn was condensed with ethyl cyanoacetate. 

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