Acetonedicarboxylate, preparation

As an e.xtension of the oxidative carbonylation with alkyl nitrites, malonate can be prepared by the oxidative carbonylation of ketene (583)[524], Also, the acetonedicarboxylate 585 is prepared by the Pd-catalyzed, alkyl nitrite-mediated oxidative carbonylation of diketene (584)[525],... 

Substitutedisoxazole-3,5-dicarboxylic acids have been prepared from ethyl nitroacetate and an aldehyde (63BCJii50). A related reaction leads to diethyl 4-hydroxyisoxazole-3,5-dicarboxylate (334) and involves the reaction of acetonedicarboxylic acid ester (333) with nitrosyl chloride (78JHC1519). 

Blount and Robinson have extended this mode of synthesis to the preparation of iV-methyl/iomogranatonine (XXII) by the use of adipaldehyde, CHO. [CH2]4. CHO. The base, on reduetion with sodium in butyl aleohol, yields A -methyl/mmogranatoline (XXII CO — CHOH), the benzoyl derivative of which possesses marked local anaesthetic aetion. Similarly Blount, by eondensing /3-(o-formylphenyl)propaldehyde, CHO. CgH4. CHj. CHj. CHO, with methylamine and calcium acetonedicarboxylate, has prepared 8 9-benz-d - -feomogranatene-3-one (XXIII), which was reduced to the -alcohol (cf. reduction of tropinone to -tropine) and the latter converted to the benzoyl-derivative (m.p. 98°),... 

Using maleic aldehyde, acetonedicarboxylic acid and methylamine hydrochloride in aqueous solution, in presence of sodium acetate, Iheobrazhenskii, Rubtsov, Dankova and Pavlov have prepared troperume. 

Though the dialdehyde-tropinone synthesis does not succeed when the dialdehyde is replaced by a diketone, Blount and Robinson have shown that 1-methyltropinone (XXXV) can be obtained by the interaction of the keto-aldehyde, laevulinaldehyde. Me. CO. CH. CH. CHO, with methylamine and calcium acetonedicarboxylate, and from this by reduction to 1-methyl- -tropine and benzoylation, 1-methyl tropacocaine (b.p. 210°/15 mm. picrate, m.p. 163-4°) has been prepared. 

Anet et al. ( 04) obtained in 1947 the alkaloids hygrine (191) and kusk-hygrine (192) in a very good yield by treatment of y-methylaminobutyralde-hyde with acetoacetic or acetonedicarboxylic acids at pH 7. The same reaction was later accomplished by Galinovsky et al. (305-307), who prepared the starting aldehyde by partial reduction of 1-methyl-2-pyrroli-done with lithium aluminum hydride. He used acetonedicarboxylic acid for the synthesis of both alkaloids and showed that a mixture of both alkaloids is formed, the composition of which depends on the ratio of components. 

Cocaine has been prepared by a sequence beginning w ith a Mannich reaclion (Problem 23.63) between dimethyl acetonedicarboxylate, an amine, and a dialdehyde. Show the structures of the amine and dialdehyde. 

Even fully substituted aromatic compounds can be prepared utilizing the Mi-chael/Dieckmann strategy. As reported by Covarrubias-Zuniga and coworkers (Scheme 2.32) [67], reaction of the anion of l-allyl-l,3-acetonedicarboxylate (2-138) and the ynal 2-139 afforded the intermediate 2-140 which led to the resorcinol 2-142 with spontaneous aromatization under acidic conditions via 2-141 in an overall yield of 32 %. 2-142 was transformed into mycophenolic acid (2-143) in only a few additional steps [68]. 

The preparation of acetonedicarboxylic acid is described in Org. Syntheses, Coll. Vol. 1,10 (1941). The acid may also be obtained from Chas. Pfizer Company, 630 Flushing Avenue, Brooklyn 6, New York. 

The checkers found that the purification of the pseudopelletierine could be simplified, at least in those preparations in which commercial acetonedicarboxylic acid was used. Thus, the crude product obtained by evaporation to dryness of the methylene chloride extracts can be sublimed directly. Two sublimations give pseudopelletierine of m.p. 62-64°, in 58-62% yield, comparable to the product obtained after the more extended purification procedure described in the text. 

Optically pure 1,3-allenedicarboxylate 110c possessing central and axial chirality was prepared from dimethyl acetonedicarboxylate by incorporation of menthol as a chiral auxiliary [98]. The [4+2]-cycloaddition reaction of 110c with cyclopentadiene in the presence of A1C13 proceeded with high diastereoselectivity to afford adduct 115. 

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... 

Several 4-piperidone syntheses are based on the addition of a primary amine to a divinyl ketone and methods for the preparation of l,2,5-trimethyl-4-piperidone (the precursor of the promedols) and the 2,3-dimethyl analog by this means are shown (Schemes 7.2 and 7.3). 3,5-Dimethyl-4-piperidone is prepared on a similar basis/41 while the 2,6-dimethyl ketone is made either by a Mannich procedure from dimethyl acetonedicarboxylate and acetaldehyde (leading to c-t mixtures)(26) or by catalytic reduction of l,2,6-trimethyl-4(lH)-pyridone (37) and oxidation of the resultant 4-piperidinols, giving a cis product.(58)... 

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. 

The mycotoxin patulin was synthesized via the oxidation of a disubstituted furan in the laboratory of M. Tada. The required 2,3-disubstituted furan was conveniently prepared via the Feist-Benary reaction of acetonedicarboxylic acid dimethyl ester and chloroacetaldehyde in the presence of pyridine. Subsequent functional group modification and oxidation of this furan finally gave the natural product. 

In continuation of extensive synthetic work on alkaloids, Schopf and coworkers have prepared meso-l,3-di-(2-piperidyl)propan-2-one and shown that it is identical with anaferine (15), previously isolated from Withania somnifera.20 Condensation of 2,3,4,5-tetrahydropyridine with acetonedicarboxylic acid at pH 11.5 gives a mixture of the meso- and racemic forms of (15). Their configurations were established by reduction to stereoisomeric mixtures of alcohols. An interesting reaction [(15) —>(16)] was observed when anaferine was distilled at high vacuum. The preparation of (17), a compound related to the piperidine alkaloid anaferine, using a well-travelled reaction sequence, has been reported.21... 

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