Aldehydes condensation with diketones

The carbanions derived from acylthiophenes have been condensed with aldehydes,and, through the Claisen condensation with esters, thienylsubstituted -diketones have been obtained. 2-Thenoyl trifluoroacetone, first prepared by Reid and Calvin through the Claisen condensation of 2-acetylthiophene with ethyl trifluoracetate, has become an extremely useful chelating agent for the extraction of numerous elements from strongly acidic solutions, The tautomeric form which dominates in aqueous solution is the ketone hy-drate. Other thiophenes have also proved useful for analytical purposes. ... 

Aldehydes can be condensed with 1,3-diketones to give vinylic diketones 39 (X = H) and /V-bromsuccinimide converts these into the bromides 39 (X = Br) which supply furans 40 when heated. Yields are poor if the product carries no 5-substituent.101... 

Ketols can also be formed enzymatically by cleavage of an aldehyde (step a, Fig. 14-3) followed by condensation with a second aldehyde (step c, in reverse). An enzyme utilizing these steps is transketolase (Eq. 17-15),132b which is essential in the pentose phosphate pathways of metabolism and in photosynthesis. a-Diketones can be cleaved (step d) to a carboxylic acid plus active aldehyde, which can react either via a or c in reverse. These and other combinations of steps are often observed as side reactions of such enzymes as pyruvate decarboxylase. A related thiamin-dependent reaction is that of pyruvate and acetyl-CoA to give the a-diketone, diacetyl, CH3COCOCH3.133 The reaction can be viewed as a displacement of the CoA anion from acetyl-CoA by attack of thiamin-bound active acetaldehyde derived from pyruvate (reverse of step d, Fig. 14-3 with release of CoA). 

The enol content of simple ketones is much lower than that of /1-ketoesters or /3-diketones. For a number of electrophiles it is often too low. Hence, functionalizations with the respective electrophile via the enol form do not succeed in these cases. This problem can be managed, though, by converting the ketone (Formula A in Figure 12.16) into an enamine D with the aid of a condensation with a secondary amine that is in line with Figure 9.29 and the mechanism given there. Enamines are common synthetic equivalents for ketonic and aldehyde enols. 

In the case of 1,3-dicarbonyl compounds, the solvent frequently interferes with the coupling reaction. So with diethyl sodio malonate in ethanol [212b], methanol [212b], dimethylacetamide [212b], or HMPTA [216], besides the dimer and the trimer, the compounds LIXa-c are obtained. They are presumably formed by oxidation of the solvent to the aldehyde and its condensation with the active methylene compound. No dimer was detected in the oxidation of sodio acetoacetate in ethanol, with the major product being LX [217]. Anodic oxidation of cyclic 1,3-diketones in aqueous methanolic sodium hydroxide does not yield the dimer but product LXI, formed by condensation of the starting compound with formaldehyde [218]. 

For the synthesis of (69), the enol ether (71) from the indanone (70) was carboxylated with COa-n-butyl-Iithium in THF at —70 C to yield (72). The methyl ester (73) was converted into (75) via the maleic anhydride adduct (74), essentially as described in earlier work. Lithium aluminium hydride reduction followed by oxidation with dicyclohexylcarbodi-imide afforded the aldehyde (76). This was condensed with excess (77) to yield a mixture of the diastereomers (78). Oxidation with chromium trioxide-pyridine in methylene dichloride gave (79), which could be converted into the diketone (80) by treatment with excess benzenesulphonylazide. The diketo-lactam (81) was prepared from (80) as described for the synthesis of the analogous intermediate used in the synthesis of napelline. Reduction of (81) with lithium tri-t butoxyaluminohydride gave the desired dihydroxy-lactam (82). Methylation of (82) with methyl iodide-sodium hydride gave (83). Reduction of this lactam to the amine (84) with lithium aluminium hydride, followed by oxidation with potassium permanganate in acetic acid, gave (69). 

Several complementary reactions, such as the Hantzsch, the Krohnke, and the Chichibabin, lead to tpy in which the central pyridine ring is built up in a condensation process.2 These reactions lend themselves well to the formation of 4 -substituted derivatives. The basic ingredient is acetylpyridine, which provides the two distal rings of tpy, as well as C2, C3, C5, and C6 of the central ring. C4 originates from an aldehyde which is generally aromatic. In the example in Scheme 2, an intermediate 1,5-diketone condenses with a nitrogen source, often ammonium acetate, to provide the final tpy. Table 1 summarizes some tpy derivatives which have been prepared by similar condensation approaches. 

The Knoevenagel condensation with 1,3-dicaibonyls followed by a Michael reaction of a second molecule of the methylene compound, with or without addition of an amine or ammonia, may be used for the qualitative and quantitative determination of aldehydes even in the presence of ketones. Thus, cyclic 3-diketones such as dimedone (59) react with aldehydes but not with ketones in the absence of a catalyst. For the characterization the bis(2,6-dioxo-4,4-dimethylcyclohexyl)methanes (67) or the 4,6-dioxo-2,2,8,8-tetramethyl-l,2,3,4,5,6,7,8-octahydro-9F/-xanthene (68) may used. ... 

Halo-substituted diaminopyrazines have been successfully condensed with diethyl oxalate and with diacetyl to give pyrazino[2,3-h]pyrazines. 2,3-Diamino-5,6-dimethylpyrazines have been reacted with a large number of diaryl a-diketones and aryl a-keto aldehydes to give aryl-substituted derivatives of the heterocycle. 

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