Acetonedicarboxylic decarboxylation

Acetonedicarboxylic acid [542-05-2] M 146.1, m 138" (dec), pK 3.10. Crystd from ethyl acetate and stored over P2O5. Decarboxylates in hot water. 

The following synthesis of p ewdopelletierine is of special interest, since it involves only materials and conditions which could occur in plants and is therefore a possible bio-synthesis. Menzies and Robinson showed that when calcium acetonedicarboxylate, glutardialdehyde and methyl-amine are mixed in aqueous solution under specified conditions and the mixture is kept for twenty-four hours, a produet (XX) is formed, which can be decarboxylated to -pelletierine (XXI) and the latter isolated as the picrate, whieh after recrystallisation yields the pure base (m.p. 48-5°), the identity of which can be established by eonversion to the characteristic dipiperonylidene derivative. The course of the synthesis is represented as follows — ... 

A better yield was obtained when, in place of acetone, calcium acetonedicarboxylate was used, the initial product in this case being calcium tropinonedicarboxylate, from which the free dibasic acid is readily isolated and can be decarboxylated by heating in acid solution, yielding tropinone. This idea was taken up in Germany, and a number of processes for the production of tropinone derivatives have been described, mostly in patent literature. According to Willstatter and Pfannenstiel, a yield of... 

Prue (48) investigated the metal ion-catalyzed decarboxylation of the dianion of acetonedicarboxylic acid. He found that while the undissociated acid,... 

The condensation of the sodio derivative of 1,3-diformyl-4-keto-1,2,3,4-tetrahydroquinoline (172) with ethyl acetonedicarboxylate has been reported to give the 5-formyl-9-hydroxy-5,6-dihydrophen-anthridine-8,10-dicarboxylate (173). (However, the material obtained from 173 by hydrolysis, decarboxylation, and dehydrogenation201... 

Ketohendecanedioic acid has been prepared by the reactions described,3 4 by the dialkylation of diethyl acetonedicarboxylate with ethyl 7-iodobutyrate in the presence of sodium ethoxide followed by hydrolysis and decarboxylation,2 5 and by the permanganate oxidation of 6-(l -cyclohexenyl)-l-hexene.6 The present method is a simplification of the procedure originally described by Sauer.3 This method is practical for the preparation of symmetrical keto dibasic acids and esters.7... 

A simpler and more versatile route to comparably functionalized bicyclooctanes has been developed more recently by Weiss and his co-workers.174-176 Specifically, the reaction of 1,2-dicarbonyl compounds with dimethyl 3-ketoglutarate (dimethyl acetonedicarboxylate) in aqueous solution at pH 5, or preferably in a citrate-phosphate buffer, followed by hydrolytic decarboxylation, affords 117 in good... 

This disconnection led to the C3 synthon 48 (and hence to its already familiar synthetic equivalent 44) and C9 amino dialdehyde 47. The Michael addition of malonic ester to acrolein was employed for the synthesis of the key starting material 49. The Claisen ester condensation of the latter followed by decarboxylation and reductive aminolysis led to the preparation of amino-bis-acetal 47a. The respective amino dialdehyde 47, generated in situ by a controlled hydrolysis of the acetal groups of 47a, reacted smoothly with acetonedicarboxylic diester and gave the required adduct 46 in a good yield and nearly complete stereoselectivity. 

Some of the earliest kinetic studies on metal ion-promoted reactions were carried out on metal ion-promoted decarboxylations of j8-oxo acids. The literature on this topic up to about 1974 has been reviewed. Much of the work has centred on oxaloacetic acid (HO2CCOCH2CO2H = H20xac) and its derivatives, a,a-dimethyl oxaloacetic acid and fluorooxaloacetic acid. Studies have also been made with acetonedicarboxylic acid (3-oxoglutaric acid), " dihydroxyfumaric acid, dihydroxytartaric acid, acetosuccinic acid, oxalosuccinic acid and 2-oxalopropionic acid (Figure 6). The decarboxylation of )3-oxo acids is of considerable biological importance, and in a number of cases metalloenzymes are involved. Similarities in the enzymatic and chemical processes stimulated early interest in these reactions as models for the enzymatic systems. 

The following sequence of dipositive metal ions shows a decreasing effect on the rate of decarboxylation of oxaloacetic acid Cu(II), Zn(II), Co(II), Ni(II), Mn(II), Cu(II) (91). The rate constants for these decarboxylations approximately parallel the formation constants of the corresponding metal oxalates. A similar result was found in the decarboxylation of acetonedicarboxylic acid in the presence of certain transition metal ions the decarboxylation rates paralleled the formation constants of the metal malonates (170). These parallelisms indicate that the effectiveness of a metal ion in these decarboxylation reactions depends on its ability to chelate with the oxalate ion and the malonate ion, which resemble the transition states of the oxaloacetic and acetonedicarboxylic acids, respectively. 

The synthesis of pyridazine derivatives from hydrazones includes the thermal cyclization of 2-arylhydrazono-3-oxo-5-phenyl-4-pentenenitriles (readily obtained from ethyl cinnamate by condensation with acetonitrile followed by Japp-Klingemann type reactions) to l-aryl-3-cyano-6-phenyl-5,6-dihydro-4(l//)-pyridazinones (Scheme 85) <86JHC93>, and base-induced cyclization of a hydrazone of a 4-chloro-l-arylbutan-l-one to prepare a 2,3,4,5-tetrahydropyridazine (Scheme 85) <88JHC1543>. An earlier route to 6-carboxy-5-hydroxy-2-phenyl-3(2//)-pyridazinone via condensation of benzenediazonium chloride and dimethyl acetonedicarboxylate has been adapted to give a series of aryl derivatives either as esters (by thermal cyclization) or as acids (by cyclization with hydroxide). Both cyclizations proceed in high overall yield (Scheme 86) and decarboxylation of the acids also proceeds in high yield <89JHC169>. 

It should also be noted that decarboxylation of / -oxo acids is subject to specific catalysis by primary amines as well as to general catalysis. For example, the very smooth decarboxylation of 2,2-dimethylacetoacetic acid in water is uninfluenced by addition of a secondary or tertiary amine but its rate is increased by a factor of 10 on addition of aniline. The explanation lies in the fact that primary amines can react to form / -imino acids, whose imino-nitro-gen atom, being considerably more strongly basic than the ketonic oxygen atom, causes almost complete transfer of the proton from the carboxyl group, and it is this transfer that initiates the decomposition. A further example is the violent decomposition to acetone and carbon dioxide that occurs when a small amount of aniline is added to acetonedicarboxylic acid. 

Indeed, Robinson s initial experiments demonstrated tropinone could be prepared in a single step, albeit in low yield, via condensation of succindialdehyde, with acetone and methyl amine in aqueous solution. Further work by Robinson demonstrated the replacement of acetone by a salt of acetonedicarboxylic acid or ethyl acetonediarboxylate gave some improvement in yield after decarboxylation. As previously mentioned, a critical contribution to this process was Schdpf s demonstration of greatly improved yields under buffered or physiological conditions. ... 

If benzoylacetyl-CoA, an intermediate in the p-oxidation of cinnamic acid [30], instead of acetonedicarboxylic acid bisCoA ester participates in the Mannich reaction with imine 41, (S)-l-phenyl-2-(piperidin-2-yl)ethanone 49 is formed after subsequent hydrolysis and decarboxylation. Then, intermediate 49 either is reduced selectively to sedamine (50) after methylation of the secondary amine or is oxidized to the corresponding imine 51, which yields di-norlobelanine (52) upon reaction with a second equivalent benzoylacetyl-CoA. 

Mataka s synthetic approach to stacked arene-fused bicyclo[4.4.1]undecanes is illustrated for the benzo-fused compound in Fig. 34a [148]. Briefly, dimethyl 1,3-acetonedicarboxylate is alkylated with two equivalents of a 1,2-bis(bromomethyl) arene (l,2-bis(bromomethyl)benzene in this case) to form the bicycloundecane core. Saponification followed by thermal decarboxylation removes the ester groups. Finally, ketalization affords the stacked compound. Variation of thebis(bromomethyl) arene, and stepwise alkylation with two different bis(bromomethyl)arenes, as shown in Fig. 34b, allows for the synthesis of a series of symmetric and unsymmetric compounds, as illustrated by the examples shown in Fig. 34c. 

Knoblock s smdy began with the preparation of the bisthieno-fused bicy-clo[4.4.1]undecanone by alkylation of dimethyl 1,3-acetonedicarboxylate with 3,4-bis(bromomethyl)thiophene followed by saponification, decarboxylation, and... 

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