Acetonedicarboxylic acid

Fig. 1. Thermal decomposition of citric acid (1) to aconitric acid (2), citraconic acid (3), itaconic acid (4), and oxidation to acetonedicarboxylic acid (5).

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). 

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. 

Sehdpf and Lehmann have effeeted syntheses on this prineiple under varying conditions. Thus, using buffered solutions of glutardialdehyde, raethylamine hydrochloride and acetonedicarboxylic acid, they have obtained yields of 60-72 per cent, of A-pelletierine working at pH 3-7, with smaller, but still important, yields at pH 9-0-13 0. 

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

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. 

The original Robinson synthesis (66) of tropinone (124), which consists of a reaction between succinaldehyde (140), methylamine (141), and the calcium salt of acetonedicarboxylic acid (142), proceeds in low yield (Scheme 2). However, it has the great merit of being the pioneering achievement in the field of biomimetic syntheses of natural products. 

The domino approach is also used by Nature for the synthesis of several alkaloids, the most prominent example being the biosynthesis of tropinone (0-16). In this case, a biomimetic synthesis was developed before the biosynthesis had been disclosed. Shortly after the publication of a more than 20-step synthesis of tropinone by Willstatter [14], Robinson [15] described a domino process (which was later improved by Schopf [16]) using succinaldehyde (0-13), methylamine (0-14) and acetonedicarboxylic acid (0-15) to give tropinone (0-16) in excellent yield without isolating any intermediates (Scheme 0.5). 

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. 

Phenylethyl Alcohol Pyruvic Acid Oxalylacetic Acid Dihydroxytartaric Acid Dihydroxymaleio Add Acetonedicarboxylic Acid (ethyl ester) Muoonio Acid... 

In 1917, Sir Robert Robinson [9] suggested that tropinone (141 could be synthesised in Nature from succinic dialdehyde (151. N-methylamine (161 and acetonedicarboxylic acid (171. or some of their "equivalents", according to a double... 

Take the total amount of succinaldehyde (obtained from 4 of the above syntheses combined) and without further treatment or purification (this had better be 15.5 g of succindialdehyde) put into an Erlenmeyer flask of 4-5 liters capacity. Add 21.6 g of methylamine hydrochloride, 46.7 g of acetonedicarboxylic acid, and enough water to make a total volume of 2 liters. Adjust the pH to 8-10 by slowly adding a saturated solution of disodium phosphate. The condensate of this reaction (allow to set for about 6 days) is extracted with ether, the ethereal solution is dried over sodium sulphate and distilled, the product coming over at 113° at 25 mm of pressure is collected. Upon cooling, 14 g of tropinone crystallizes in the pure state. Tropinone can also be obtained by oxidation of tropine with potassium dichromate, hut I could not find the specifics for this operation. 

Another interesting example is the synthesis of 77-(2-thiazolyl)-nortropinon 121. Stoll and co-authors [175] described the synthesis of this drug-like product via the legendary first total synthetic approach proposed by Robinson in 1917 [176] for the natural alkoloid tropinone, also well known as a good example of biomimetic reaction. In this tandem treatment, 2-aminothiazole was reacted with succinaldehyde and acetonedicarboxylic acid yielding 77-(2-thiazolyl)-nortropinon 121 in moderate yields (Scheme 58). 

Dioxo-8a-methyl-l, 2,3,4,6,7,8,8a-octahydronaphthalene has been obtained through the reaction of 2-methyl-l,3-cyclohexane-dione with acetonedicarboxylic acid and formaldehyde,3 4-diethyl-amino-2-butanone methiodide,3 pyridine and 4-diethylamino-2-butanone,4 triethylamine and 4-diethylamino-2-butanone,5 and by cyclization of 2-methyl-2-(3-oxobutyl)-l,3-cyclohexanedione using either aluminum fer/-butoxide or piperidine phosphate as catalyst.6 7... 

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

Acetonedicarboxylic acid (3-Ketoglutaric acid), HOOCCH. C (Ml I.COOll (1). Mol. 

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