Cyanoacetic ester synthesis

Related and equally important reactions are the acetoacetic ester synthesis and the cyanoacetic ester synthesis Here too the initial snbstitnted product can be hydrolyzed and decarboxylated, to yield a ketone 11 (i.e. a substituted acetone) from acetoacetic ester 10, and a snbstitnted acetonitrile 14 from cyanoacetic ester 13 respectively. Fnrthermore a snbstitnted acetoacetic ester can be cleaved into a substituted acetic ester 12 and acetate by treatment with strong alkali ... 

Simple saturated nitriles are seldom prepared by the decarboxylation of cyano acids derived from the cyanoacetic ester synthesis (cf. method 265). However, difunctional compounds are frequently obtained by this route, as in the preparation of a-methyl-y-phenoxybutyronitrile from /3-phenoxy-ethyl bromide and ethyl methylcyanoacetate (52% over-all). ... 

Cyano acetals, preparation, 598 Cyanoacetic ester condensation, 608 Cyanoacetic ester synthesis, 429, 601 Cyano acids, esterification, 481 preparation, 593, 607, 608 preparations listed in table 74, 622 a-Cyano acids, decarboxylation, 429, 601... 

Hydrolysis and Decarboxylation of a-Cyano Acids (Cyanoacetic Ester Synthesis)... 

The cyanoacetic ester synthesis with ethylene bromide is preferred to the malonic ester synthesis for the preparation of cyclopropanecarboxylic acid. ... 

The cyanoacetic ester synthesis of certain alicyclic compounds is preferred to the malonic ester synthesis. Thus, cyclopropane-1,1-cyano-carboxylate is readily obtained by the condensation of ethylene bromide and ethyl cyanoacetate in the presence of two equivalents of sodium ethoxide (76%). A second procedure for synthesizing alicyclic compounds consists in treating a,a -dibromodicarboxylic esters with alcoholic cyanide, whereby simultaneous replacement and ring closure occurs. ... 

Other examples of the reaction are the cyanoacetic ester synthesis, in which Z is COOEt and Z is CN (as in the malonic ester synthesis, the product here can be hydrolyzed and decarboxylated), and the Sorensen method of amino acid synthesis, in which... 

The most convenient synthesis of 6-hydroxy-2-pyridones is by the condensation of a P-ketoester, eg, ethyl acetoacetate, with an active methylene compound, eg, malonic ester, cyanoacetic ester, and an amine. The amine can be omitted if an acetamide is used and in some cases this modification results in a higher yield. 

A major type of reaction in this class is the cyclization of 4-amino- or 4-halo-pyrimidines carrying 5-cyanoethyl or 5-ethoxycarbonylethyl groups, which cyclize to 7-amino or 7-oxo derivatives of 5,6-dihydropyrido[2,3- f]pyrimidine, e.g. (131)->(63). The intermediates may sometimes be prepared by reaction of 4(6)-aminopyrimidines with acrylonitrile, or even via a pyrimidine ring synthesis from an amidine and a cyanoacetic ester or malononitrile derivative, e.g. (132) -> (133) (7lJOC2 85, 72BCJ1127). 

The Gewald aminothiophene synthesis involves the condensation of aldehydes, ketones, or 1,3-dicarbonyl compounds 1 with activated nitriles such as malononitrile or cyanoacetic esters 2 and elemental sulfur in the presence of an amine to afford the corresponding 2-aminothiophene 3. ... 

The Guareschi-Thorpe pyridine synthesis is closely related to the Hantzsch protocol. The primary point of difference lies in the use of cyanoacetic esters. This modification assembles pyridine 23 by the condensation of acetoacetic esters 21 with cyanoacetic esters 22 in the presence of ammonia. A second variation of this method involves reaction of cyanoacetic ester 22 with P-diketone 24 in the presence of ammonia to generate the 2-hydroxypyridine 25. 

Guareschi imides are useful synthetic intermediates. They are formed from a ketone reacting with two equivalents of the cyanoacetic esters and ammonia. This transformation is illustrated in the formation of 4,4-dimethylcyclopentenone 30.The synthesis was initiated with the Guareschi reaction of 3-pentanone 27 with 28 to generate imide 29. This product was hydrolyzed to the diacid and esterified. Cyclization of the diester via acyloin condensation followed by hydrolysis and dehydration afforded the desired target 30. 

In addition to /3-diketones, /3-ketoacids and /3-ketoesters, cyanoacetic ester and related compounds are suitable starting materials. The arylhydrazones 4 thus obtained are of great importance as starting materials for the Fischer indole synthesis, as well as for the preparation of other iV-heterocycles. ... 

The stereoselective total synthesis of both ( )-corynantheidine (61) (170,171) (alio stereoisomer) and ( )-dihydrocorynantheine (172) (normal stereoisomer) has been elaborated by Szdntay and co-workers. The key intermediate leading to both alkaloids was the alio cyanoacetic ester derivative 315, which was obtained from the previously prepared ketone 312 (173) by the Knoevenagel condensation accompanied by complete epimerization at C-20 and by subsequent stereoselective sodium borohydride reduction. ( )-Corynantheidine was prepared by modification of the cyanoacetate side chain esterification furnished diester 316, which underwent selective lithium aluminum hydride reduction. The resulting sodium enolate of the a-formyl ester was finally methylated to racemic corynantheidine (171). 

Smalley et al. reported the synthesis of the cyano-containing keto ester 98 by reaction of o-azidobenzoyl chloride 97 with cyanoacetic ester in the presence of triethylamine. This keto ester was then heated in acetonitrile for 30 min and gave the ring closed product 99 which was isolated in the fully aromatic tautomeric form 100 <1997S773>. A similar approach to tetrazolo[l,5- ]quinolines has been applied by a Korean research group in this case a reflux of the cyano-azido compound 101 for a longer period was needed in order to accomplish the cyclization to 4-acetoxymethyl-tetrazolo[l,5- ]quinoline 102 <2003JHC1103>. 

For the synthesis of aminotriacetylpyrans 84 a reaction of 3-bromoace-tylacetone 85 with cyanoacetic ester in ethanolic NaOH was employed. Possibly, it proceeds via the formation of acetylacetone dimer 86... 

Malononitrile and cyanoacetamide only give aminopyrans. However, in reaction with cyanoacetic ester 27b aminopyran 233 has been isolated from the mother liquor and also side product 234 from the cooled mixture. Mechanistic considerations have been proved by the isolation of a deace-tylated intermediate (95M615). Similar transformations occur in the synthesis of spiropyrans 235 from benzothiazole 236 (97G605) (Scheme 90). 

Ingold, C. K. Powell, W. J. Experiments on the synthesis of the polyacetic acids of methane. Part II. Some abnormal condensations of malonic and cyanoacetic esters with haloge-nated methanes./. Chem. Soc. 1921, 119, 1222-1229. 

Cuprous cyanide, 4, 69 Cuprous Hydroxide, 7, 30 Cuprous oxide, 6, 6 7, 33 Cyanoacetic acid, 7, 22 Cyanoacetic ester (ethyl), 7, 21 Cyanohydrin Synthesis, 6, 58 a-CYANO-/3-PlIENYLACRYLIC ACID, 7, 20, 21... 

Controlled, stepwise dialkylation may be performed as exemplified in equation 73, which shows a typical malonic ester synthesis including hydrolysis and decarboxylation to give an a,a-dialkylated acid. Acetoacetic ester synthesis and cyanoacetic ester syntheses give ketones (CH3COCHRR ) and nitriles (RR CHCN), respectively. 

Several specialized cyclization strategies should not be dismissed. A novel rhodium acetate-mediated cyclization was employed for the first synthesis of 3-methyl-4,6-diphenylfuro[3,4-tf]is-oxazole (9) from the 5-(a-diazobenzyl)isoxazole (185) (Equation (56)). The reactive intermediate is believed to be a carbenoid species <9iCB248i>. Another strategy exploits the reactivity of 4-halo-pyrazol-5-ones (e.g., 186) with stabilized anions (e.g., cyanoacetate esters and nitriles) to afford the 4-cyanofuro[2,3-c]pyrazol-5-ones (187) and 5-aminofuro[2,3-c]pyrazoles (188) (Scheme 30) <84H(22)2523>. Also of interest is the trichloroacetonitrile cyclization of aminopyrazole ketones (189) to the pyrrolo[2,3-c]pyrazoles (190) (Equation (57)) <86S74>. The generality of this cyclization is not known. 

The promising analgesic activity of 3-hydroxy-17-methylmorphinan stimulated Schnider and Hellerbach(11,12) to seek a commercial synthesis of it via 8. Bromoacetic ester reacted with cyclohexanone to give 10, which was converted rather laboriously to 8 (Scheme 3.2), Cyanoacetic ester afforded a more fluent route by way of cyclohexenylacetonitrile (11). In the presence of... 

A convenient procedure has been developed for the synthesis of cyano ester is prepared and treated with hydrogen cyanide in a single operation. For this purpose, a hot mixture of the carbonyl compound, cyanoacetic ester, and pyridyl acetate s treated with ethanol and potassium cyanide. 

Few acids have been prepared by this method. It is important in the preparation of diisopropylacetic acid, which is made with difficulty by the malonic ester synthesis. Ethyl cyanoacetate is readily alkylated ... 

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