A-Keto-/?-dicarboxylic----

Wittig-Smiles reaction.l The reaction of a triarylmethylphosphonium halide and a base with an a-keto dicarboxylic acid halide imide such as 1 results in a Wittig reaction followed by a Smiles rearrangement to provide a pyrrolidine dione... 

Oxalacetic acid esters s. a-Keto-/ -dicarboxylic acid esters... 

Oxalacetic acid esters s. a-Keto-/ -dicarboxylic acid esters Oxalic acid as reagent 16, 253 18, 231, 332, 604... 

One of the most actively investigated aspects of enamine chemistry has been the acylation process (i). Initial intensive studies by Hiinig (373-375) showed the ease of preparing a variety of 9-diketones and particularly the synthetic potential of acylated cyclic ketones as intermediates in the preparation of aliphatic keto acids, keto dicarboxylic acids and diketo dicarboxylic acids (376-378). 

Method. The keto acid residue is dissolved in 1.0 ml of 2,4-dinitrophenylhydrazine (prepared by dissolving 500 /rmoles in 100 ml of 2.0 Nhydrochloric acid at 40 °C stable for 2 weeks) and left to stand for 30 min at 30 °C. A minimum of a four-fold molar excess of 2,4-dinitrophenylhydrazine is required for stoichiometric conversion of the keto acid into the hydrazone. The reaction is complete in 5 min for keto monocarboxylic acids, and in ca. 20 min for keto dicarboxylic acids. The hydrazones may be extracted from the reaction mixture with ethyl acetate. An aliquot portion of this solution is subjected to TLC. 

Structures 64 and 65 were proposed in [7] for the product from the condensation of isatin 7 with acetoacetic acid (a P-keto acid). The first must clearly be preferred, since the CH2 group must be more active than CH3 under the conditions of the Pfitzinger reaction. Actually in [21] the structure of the product 64 was proved by its oxidation to the tricarboxylic acid 66, which was also synthesized from the keto dicarboxylic acid 67 and isatin 7. 

As Section IV will be mostly devoted to 2,4-pentanedione, acacH, it is worthwhile to dwell on this well studied species. The rate of interconversion between the keto and the enol form of acacH is rather slow at room temperature , thus they can be simultaneously detected by NMR spectroscopy it has been observed that the lower the polarity of the solvent, the higher the percentage of the enol tautomer . Electron diffraction studies indicate that in the gas phase acacH adopts the enol configuration with a keto/enol ratio of 8/92. More recently, an X-ray analysis of acacH, carried out at 110 showed that it exists as a mixture of the two enol forms 86 and 87, with the enolic hydrogen atom equally distributed over two positions close to the oxygen atoms as in 88. It should be noted that inclusion compounds containing different host molecules show different ratios of acacH in the enol form. For example, acacH exists as a dynamically averaged 1 1 mixture of 86 and 87 in an inclusion complex with l,T-binaphthyl-2,2 -dicarboxylic acid as host , while l,l-bis( >-hydroxyphenyl)cyclohexane and (4R,5R)-trawi-4,5-bis(hydroxydiphenylmethyl)-2,2-dimethyl-l,3-dioxolane include acacH in pure enolic form. ... 

Another dicarboxylic peroxy acid, peroxyphthalic acid, is used for the Baeyer-Villiger reaction of p-diketones and a-keto esters [334]. Besides peroxy acids, ceric ammonium nitrate oxidizes 2-adamantanone to 2-oxa-homoadamantanone in aqueous acetonitrile in 73% yield at 60 °C after 3 h [422]. Tetracyclone (2,3,4,5-tetraphenyl-2,4-cyclopentadien-l-one) is oxidized by ceric ammonium nitrate in aqueous acetonitrile to tetraphenyl-2-pyrone in 77% yield [422]. 

Dihydro-2/7-l,4-selenazine-3,5-dicarboxylic acid (162) is formed via the a-keto acid (161), which is obtained by the the deamination of selenolanthionine (160) with snake venom L-amino acid oxidase (Scheme 38) <90MI 624-01 >. The mono acid (164) is formed from the similar treatment of L-selenolysine (163), but its isomer (165) is the result of replacing the snake venom with diamine oxidase from pea seedlings (Scheme 39) <81MI 624-oi>. 

Condensation of the diamine with a-keto acids (RCOCOjH) " and a-oximino esters [RC(=N0H)C02RM leads to mixtures of isomeric 2-and 3-0X0 compounds. Reaction of the diamine with diethyl acetylene-dicarboxylate gives the 2-oxo ester 9 or the isomeric 3-oxo ester and with cyanogen di-iV-oxide (6—N=C—C=N—O), the dioximino derivative 10 is obtained. 

We saw in Section 19.1 that it is harder to remove a proton from an a-carbon if the electrons are delocalized onto the carbonyl group of an ester rather than onto the carbonyl group of a ketone. For the same reason, a higher temperature is required to decarboxyiate a 8-dicarboxylic acid such as malonic acid than to decarboxyiate a jS-keto acid. 

A keto-ester (3.4 g, 0.01 mol) was added slowly to a mixture of 15 mL concentrated sulfuric acid and 15 mL 85% phosphoric acid at 0-5°C. After standing at room temperature for 3 h, the mixture was poured onto chopped ice. The product separated slowly in crystalline form, which was removed, dried, and recrystallized from benzene-hexane to give 1.8 g diethyl 5,6-dimethoxyindene-2,3-dicarboxylate in a yield of 55%, m.p., 159-160°C. This was the only product obtained under varying cyclization conditions with sulfuric-phosphoric acids. 

Although carboxylic acids can be readily determined by GLC methods, fluorescence labelling with Br-Mmc has nevertheless gained some importance for the sensitive derivatization of fatty acids [461-463] dicarboxylic acids, a-keto acids and other organic acids [460,464], prostaglandins and thromboxanes [465], glucuronides [466], giberellins [467], imides [461,468,469] and phenols [460]. 

For any alkene, hydrogen peroxide may be used as the oxidizing agent and either dimethyl sulfide or zinc and acetic acid may be used as the reducing agent (see Chapter 18, Section 18.4.3). Ozonolysis of a cyclic alkene leads to oxidative cleavage to a diketone, a dialdehyde, a keto-aldehyde, a keto acid, or a dicarboxylic acid. When 1,3-dimethylcyclopentene (67) is treated with ozone and then with zinc and acetic acid, oxidative cleavage leads to keto-aldehyde 68 (2-ethyl-5-oxooctanal). 

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