Aqueous 1,3-dicarbonyl compounds

Scheme 3b). It is instructive at this point to reiterate that the furan nucleus can be used in synthesis as a progenitor for a 1,4-dicarbonyl. Whereas the action of aqueous acid on a furan is known to provide direct access to a 1,4-dicarbonyl compound, exposure of a furan to an alcohol and an acid catalyst should result in the formation of a 1,4-diketal. Indeed, when a solution of intermediate 15 in benzene is treated with excess ethylene glycol, a catalytic amount of / ara-toluenesulfonic acid, and a trace of hydroquinone at reflux, bisethylene ketal 14 is formed in a yield of 71 %. The azeotropic removal of water provides a driving force for the ketalization reaction, and the presence of a trace of hydroquinone suppresses the formation of polymeric material. Through a Finkelstein reaction,14 the action of sodium iodide on primary bromide 14 results in the formation of primary iodide 23, a substance which is then treated, in crude form, with triphenylphosphine to give crystalline phosphonium iodide 24 in a yield of 93 % from 14.

A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

This possible mechanism should be evaluated in relation to the catalysts. If the catalytic action is to be ascribed to the acid character of the catalysts, the condensation under consideration may differ from the ordinary aldol condensation, which is catalyzed preferentially by basic agents. Nevertheless, many condensations of the aldol type are effected with the aid of acidic reagents. Moreover, the condensation of sugars with dicarbonyl compounds has been carried out in aqueous alcoholic media which are non-acidic hence, there also exists the possibility of a mechanism catalyzed simultaneously by acid and by base, somewhat like that suggested by Lowry46 in another connection. A transition state with an amphiprotic structure has been postulated. Its formation can be catalyzed by either acids or bases. 

The p-dicarbonyl compound (10 mmol) in CH,C12 is added, with stirring, to TBA-HS04 (3.4 g, 10 mmol) in aqueous NaOH (2M, 10 ml) at 20°C. The acid chloride (10 mmol) is added dropwise over ca. 2 min and the mixture is stirred for a further 1 h. The aqueous phase is separated, extracted with CH,CI, (10 ml), and the combined organic solutions are washed with H,0 (2x10 ml), dried (MgS04), and evaporated. Et,0 (25 ml) is added to the residue, the solution is filtered, and evaporated to yield the enol esters. 

The dicarbonyl compound (10 mmol) in CH,Cl, (25 ml) is added with stirring toTBA-HS04 (0.68 g, 2 mmol) in aqueous NaOH (2N, 10 ml) at room temperature. Diethyl phos-phorochloridate or phosphorochloridothionate (10 mmol) is added dropwise over ca. 

Alkylation of P-dicarbonyl compounds and p-keto esters occurs preferentially on the carbon atom, whereas acylation produces the 0-acyl derivatives (see Chapter 3). There are indications that C- and 0-alkylated products are produced with simple haloalkanes and benzyl halides, but only C-alkylated derivatives are formed with propargyl and allyl halides [e.g. 90]. Di-C-alkylation frequently occurs and it has been reported that the use of tetra-alkylammonium 2-oxopyrrolidinyl salts are more effective catalysts (in place of aqueous sodium hydroxide and quaternary ammonium salt) for selective (-90%) mono-C-alkylation of p-dicarbonyl compounds [91]. 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

Aldoses generally undergo benzilic acid-type rearrangements to produce saccharinic acids, as well as reverse aldol (retro-aldol) reactions with j3-elimination, to afford a-dicarbonyl compounds. The products of these reactions are in considerable evidence at elevated temperatures. The conversions of ketoses and alduronic acids, however, are also of definite interest and will be emphasized as well. Furthermore, aldoses undergo anomerization and aldose-ketose isomerization (the Lobry de Bruyn-Alberda van Ekenstein transformation ) in aqueous base. However, both of these isomerizations are more appropriately studied at room temperature, and will be considered only in the context of other mechanisms. 

Although the acidity of Meldrum s acid is quite similar to that of barbituric acids, the same reaction conducted with this dicarbonylic compound in aqueous medium gave a complex mixture instead of the expected adduct [107]. The reaction... 

Faust, B. C., K. Powell, C. J. Rao, and C. Anastasio, Aqueous-Phase Photolysis of Biacetyl (an a-Dicarbonyl Compound) A Sink for Biacetyl and a Source of Acetic Acid, Peroxyacetic Acid, Hydrogen Peroxide, and the Highly Oxidizing Acetylperoxyl Radical in Aqueous Aerosols, Fogs, and Clouds, Atmos. Environ., 31, 497-510 (1997). 

The dehydration reactions initiated by eliminating a hydroxyl group from an enediol are discussed in the present article. The products (usually dicarbonyl compounds) of these eliminations are normally transient intermediates, and undergo further reaction. The final products formed are determined by the carbohydrate reacting, the conditions of reaction, and the character of the medium. Except for a Section on analytical methods (see p. 218), the subject matter is restricted to aqueous acids and bases. The presence of compounds other than the carbohydrate under study has only been considered where it has helped to elucidate the mechanism involved. The approach here is critical and interpretative, with emphasis on mechanism. An attempt has been made to demonstrate how similar reactions can logically lead to the various products from different carbohydrates a number of speculative mechanisms are proposed. It is hoped that this treatment will emphasize the broad functions of these reactions, an importance that is not fully recognized. No claim is made for a complete coverage of the literature instead, discussion of results in the articles that best illustrate the principles involved has been included. 

The imidazoles formed in the reaction of aqueous ammonia with other a-hydroxycarbonyl compounds, for example, the triose DL-glyceraldehyde, and such a-dicarbonyl compounds as 3-deoxy-D-glycero-pentosulose (59), and the 3,6-dideoxy-L-erythro-, D-arabino-, and 3-deoxy-D-erytforo-hexosuloses (60, 61, and 62), respectively, are summarized in Table VIII for reactions in which formaldehyde was added, and in Table IX for reactions in which it was not added. 

This benzilic acid type of rearrangement is the result of the action of alkali on the dicarbonyl compound, and is accelerated by calcium ions. The formation of saccharinic acids by the action of aqueous alkali on sugars is very well known 82,84,92 however, if ammonia is present, very little8 or no production of saccharinic acid has been reported. The reaction of the intermediate carbonyl compounds with ammonia is faster than the benzilic acid type of rearrangement to give saccharinic acid, and, hence, substituted imidazoles are formed, as illustrated in Scheme 9. 

Much more studied is the reaction of /8-dicarbonyl compounds with 2-amino-2-deoxyaldoses in particular, with 2-amino-2-deoxy-D-glu-cose (55), both in neutral and alkaline medium. In neutral methanol or aqueous acetone, 2-amino-2-deoxy-D-glucose reacts with 2,4-pen-tanedione to give52 54 3-acetyl-2-methyl-5-(D-arabino-tetrahydroxy-butyl)pyrrole (56a), and, with ethyl acetoacetate,55 the pyrrole 56b. Similar (tetrahydroxybutyl)pyrroles have been prepared from other /3-keto esters, such as ethyl 3-oxohexanoate, ethyl thiolacetoacetate, and diethyl 3-oxopentanedioate.53,56,56a... 

Although pyridones are usually resistant to alkali, pyrone rings are often easily opened. Pyran-2-ones are reversibly ring-opened by aqueous alkali to acid anions (222). Hydroxide ions convert coumarins (223) reversibly into salts of coumarinic acids (224) which can be converted into the trans isomers (225), and chromones (226) into 3-dicarbonyl compounds (227). 

Monosaccharides react with a variety of 1,3-dicarbonyl compounds in the presence of zinc chloride in ethanolic or aqueous solution to yield substituted furans (Scheme 69) (56MI31200). The reaction of ethyl acetoacetate with D-glucose and D-mannose yielded the trisubstituted furan (252) in 20% yield, while D-fructose under similar conditions yielded (253 7%). These products have been used for the synthesis of dehydromuscarones (63HCA1259). Oxidation of the tetrahydroxybutyl side chains with lead tetraacetate gives the aldehyde, which can be converted to the corresponding acid with alkaline silver oxide. 

Hinsburg first reported that various a-dicarbonyl compounds (256) condensed with thiodiglycolic esters in the presence of alcoholic sodium ethoxide to give various substituted thiophene-2,5-dicarboxylic esters (257). R1 and R2 in (256) could be H, OH, alkyl, OR, aryl or carboxyl groups o-quinones will also condense. If the condensation is carried out in aqueous alcohol, as is the case when glyoxal (256 R1 = R2 = H) is used, the thiophene-2,5-dicarboxylic acid is isolated directly. Pyruvic acid gives the half-ester of (257 R1 = Me, R2 = OH). The earlier work has been reviewed (52HC(3)l). 

Most known monocyclic 1,2,3-triazines and 1,2,3-benzotriazines are stable at room temperature. No detailed study of the stability of monocyclic 1,2,3-triazines towards water, aqueous acids or bases has been published, but one can assume from the reaction conditions used in the preparation of monocyclic 1,2,3-triazines, by oxidation of (V-aminopyrazoIes, that they are stable to water, aqueous acids or bases at room temperature, at least for a short time. Treatment of triaryl-1,2,3-triazines with aqueous hydrochloric acid at higher temperatures leads to hydrolysis of the ring and formation of 1,3-dicarbonyl compounds (Scheme 3) (60TL(13)19,76UP21800). 

The conversion of the substituted 1,3-dicarbonyl compound into homophthalic acid is remarkably facile loss of the acetyl group by a retro-Claisen condensation and hydrolysis of the ester group are complete in a few minutes in aqueous sodium hydroxide. The overall synthesis of homophthalic acids from o-bromobenzoic acids occurs in high yield and provides an attractive route. 

The conjugate addition of carbonyl anions catalysed by thiazolium salts (via umpol-ung) that is fully operative under neutral aqueous conditions has been accomplished. The combination of a-keto carboxylates (157) and thiazolium-derived zwitterions (e.g. 160) in a buffered protic environment (pH 7.2) generates reactive carbonyl anions that readily undergo conjugate additions to substituted o /3-unsaturated 2-acylimidazoles (158) to produce (159). The scope of the reaction has been examined and found to accommodate various a-keto carboxylates and /3-aryl-substituted unsaturated 2-acylimidazoles. The optimum precatalyst for this process is the commercially available thiazolium salt (160), a simple analogue of thiamine diphosphate. In this process, no benzoin products from carbonyl anion dimerization were observed. The resulting 1,4-dicarbonyl compounds (159) can be efficiently converted into esters and amides by way of activation of the A-methylimidazole ring via alkylation.181... 

A. Hollnagel and L. W. Kroh, 3-Deoxypentosulose an OJ-dicarbonyl compound predominating in nonenzymatic browning of oligosaccharides in aqueous solution, J. Agric. Food Chem., 2002, 50, 1659-1664. 

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