Decarboxylation cyanoacetate

Geranyl acetoacetate (685) is converted into geranylacetone (686). On the other hand, a mixture of E- and Z-isomers of 688 is obtained from neryl acetoacetate (687). The decarboxylation and allylation of the allyl malonate or cyanoacetate 689 affords the o-allylated acetate or nitriie[447]. The trifluoromethyl ketone 691 is prepared from cinnamyl 4.4,4-trifluoroacetoace-tate (690)[448],... 

The allyl cyanoacetate 731 can be converted into an a, /3-unsaturated nitrile by the decarboxylation-elimination reaction[460], but allyl malonates cannot be converted into unsaturated esters, the protonation and allylation products being formed instead. 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

Hydrogenolysis of the diallyl alkylmalonate 757 with formic acid in boiling dioxane affords the monocarboxylic acid 758. Allyl ethyl malonates are converted into ethyl carboxylates[471]. The malonic allyl ester TV-allylimide 759 undergoes smooth deallylation in refluxing dioxane to give the simple imide 760(472]. The allyl cyanoacetate 761 undergoes smooth decarboxylation to give... 

The physical properties of cyanoacetic acid [372-09-8] and two of its ester derivatives are Hsted ia Table 11 (82). The parent acid is a strong organic acid with a dissociation constant at 25°C of 3.36 x 10. It is prepared by the reaction of chloroacetic acid with sodium cyanide. It is hygroscopic and highly soluble ia alcohols and diethyl ether but iasoluble ia both aromatic and aUphatic hydrocarbons. It undergoes typical nitrile and acid reactions but the presence of the nitrile and the carboxyUc acid on the same carbon cause the hydrogens on C-2 to be readily replaced. The resulting malonic acid derivative decarboxylates to a substituted acrylonitrile ... 

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. 

Reactions. The chemical properties of cyanoacetates ate quite similar to those of the malonates. The carbonyl activity of the ester function is increased by the cyano group s tendency to withdraw electrons. Therefore, amidation with ammonia [7664-41-7] to cyanoacetamide [107-91-5] (55) or with urea to cyanoacetylurea [448-98-2] (56) proceeds very easily. An interesting reaction of cyanoacetic acid is the Knoevenagel condensation with aldehydes followed by decarboxylation which leads to substituted acrylonitriles (57) such as (29), or with ketones followed by decarboxylation with a shift of the double bond to give P,y-unsaturated nitriles (58) such as (30) when cyclohexanone [108-94-1] is used. 

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). ... 

Malonic acid or cyanoacetic acid can also be used as the nucleophile. With malonic acid or cyanoacetic acid as reactants, the products usually undergo decarboxylation. This may occur as a concerted fragmentation of the adduct.214... 

Applications of decarboxylation of metal cyanoacetates are currently restricted to derivatives of tin, lead, and copper. Both copper(I) and copper(II) cyanoacetate lost carbon dioxide in dmf at 50° C and formed cyanomethylcopper(I) (15). In the presence of tertiary phosphines, the copper(I) cyanoacetate reaction was reversible [Eq. (35), R = Ph, Et, Bu,... 

The reversible complexing of carbon dioxide by bis[bis(l,2-diphe-nylphosphino)ethane]iridium(I) chloride, [Ir(dpe)2]Cl, in acetonitrile [Eq. (36)] (48) appears not to involve carboxylation of a cyanomethylir-idium(III) complex or its formation by decarboxylation of the cyanoacetate... 

Studies of the thermal decarboxylation of phenylpropiolates of copper, tin, and lead parallel those of the corresponding cyanoacetate compounds. Copper phenylpropiolate decarboxylated irreversibly in dmf at 35°C and reversibly in the presence of tertiary phosphines in dmf (52). Triorga-iio(phenylethynyl)tin and -lead compounds, R3MC=CPh [M=Sn, R = Ph or Bu (53) M = Pb, R = Ph (5/)], were isolated when the triorganotin or -lead phenylpropiolates, R3M02CC=CPh, were heated in vacuo. Triphenyllead phenylpropiolate also decarboxylated in refluxing toluene (54). 

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. 

Valproic acid, 2-propylvaleric acid (9.4.3), is synthesized by the alkylation of cyanoacetic ester with two moles of propylbromide, to give dipropylcyanoacetic ester (9.4.1). Hydrolysis and decarboxylation of the carbethyoxy group gives dipropylacetonitrile (9.4.2), which is hydrolyzed into valproic acid (9.4.3) [12-15]. 

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 ... 

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