Diethyl acetonedicarboxylate

The first in this series to be reported was 4-oxoisoxazoline-3,5-dicarboxylic acid diethyl ester, which was formed by the reaction of nitrous acid on diethyl acetonedicarboxylate in 1891. Quilico described a number of syntheses in his 1962 review and the most general include the reaction of hydroxylamine and a-hydroxy-(or acetoxy)- 3-diketones and the conversion of 4-isoxazolediazonium salts to the hydroxy moiety (62HC(17)1, p. 3). Additional syntheses reported were the oxygenation of a 4-boric acid derivative (67JOM(9)l9) and peroxide oxidation of a 4-nitro-2-isoxazoline (Scheme 151) (79ZOR2436). 

All the syntheses of this type give piperid-4-ones or pyrid-4-ones. Errera reported that diethyl acetonedicarboxylate condensed with triethyl orthoformate in hot acetic anhydride, and that treatment of the product with ammonia gave a poor yield of the pyrid-4-one (644) (1898CB1682). It is certain that the intermediate is the di(ethoxyvinyl) ketone (643), so that this is perhaps better classified as a [5 + 1] synthesis, but most developments from this beginning do not involve isolation of intermediates. An arylamine has been used to obtain an A-arylpyrid-4-one (645) (46JA1253). 

Carboni and co-workers have used 1,3-dicarbonyl compounds to cyclize a large variety of aminonaphthyridines (66G1443, 67G1262, 69G677). The use of ethyl acetoacetate on 2-aminonaphthyridines (390) followed by polyphosphoric acid or Dowtherm treatment produces oxopyrimidonaphthyridines (391) which can be rearranged to the isomeric 1,8,9-anthyridines (392). The products obtained from diethyl acetonedicarboxylate are very similar (69G677). 

Among carbon nucleophiles, diethyl malonate gives adducts 377 and 378 malononitrile, even at 20°C, gives an analog of 378 (with R = CN) and diethyl acetonedicarboxylate yields a bridged diketotetracarboxylate. 

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... 

Condensing pyridazin-3-amine 1-oxide with ethyl acetoacetate, ethyl 2-oxocyclopentanecar-boxylate or -hexanecarboxylate, or with diethyl acetonedicarboxylate in the presence of polyphos-phoric acid gives the corresponding pyrido[2,3-c]pyridazin-7(8/T)-one 2-oxides 3 in moderate yield.27 The parent compound, pyrido[2,3-e]pyridazine 2-oxide (4), is prepared in low yield using 1.3,3-triethoxyprop-l -ene.2 7... 

The action of nitric acid on diethyl 3-oxopentane-l, 5-dioate (diethyl acetonedicarboxylate, 1) was stated to yield the peroxide 2, which on reduction with sodium hydrogen sulfite gave the diester 3.31... 

In addition and with reference to earlier work, which describes the synthesis of a bicyclic piperidone, derived from treating diethyl acetonedicarboxylate, an aldehyde and y-aminobutyraldehyde (79), it is possible to synthesize the bispidine derivative 57 with an unsymmetric substitution pattern (see Chart 6)(80). This Ending may be the basis for a whole new series of chiral bispidine ligands. 

Diethyl acetonedicarboxylate can be only mononitrosated when attempting dinitrosation with pentyl nitrite, von Pechmann258 obtained diethyl 4-hy-droxyisooxazole-3,5-dicarboxylate ... 

Two carbon-carbon bonds are cleaved when diethyl acetonedicarboxylate is heated with three times the amount of an amine. Substituted phenethyl-amines thus yield the corresponding ureas.1196... 

Chlorobenzoyl chloride refluxed with diethyl acetonedicarboxylate and trifluoro-acetic acid until HCl-evolution is complete, water added, and heated 15 hrs. ->... 

The sodium salt of diethyl acetonedicarboxylate reacts with aryl isocyanates to give 1-aryl-4,6-dihydroxy-2-pyridones (XU-104)and with phenyl isothiocyanate to give 3-carbethoxy4-hydroxy-2-mercapto-l-phenyl-6-pyridone, Th e compound formed on treatment of XI-104 (R = H) with acetic anhydride has been proposed to be 3,5-diacetyl-4,6-dihydroxy-l-phenyl-2-pyridone. Characterization was based on the infrared spectrum, ... 

Diethyl acetonedicarboxylate added rapidly at 15° to aq. 40%-methylamine followed immediately with cooling during 1 hr. by chloracetone at a rate to keep the temp, below 40° -> ethyl l,4-dimethyl-3-ethoxycarbonylpyrrole-2-acetate. Y 70%. J.R. Carson and S.Wong, J. Med. Chem. 16, 172 (1973). 

The reaction was examined under various conditions and was optimized to yield diethyl acetonedicarboxylate 137 (93% purity) in 72% yield. 

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