Dimedone Knoevenagel reaction

The Knoevenagel reaction between benzaldehydes 22 and malononitrile or ethyl cyanoacetate 74 followed by condensation of the resulting ot,p-unsatu-rated nitriles 75 with dimedone (76) was performed in the presence of SiO2-(CH2)3-NEt2 (Scheme 3.22). ... 

Interestingly enough, a closely related protocol was successfully proposed for the synthesis of spirooxindoles-containing tetrahydrochromene skeletons when aromatic aldehydes were switched for isatin derivatives. This high-yielded reaction was performed with dimedone, 4-hydroxycoumarin, or barbituric acids in water using triethylbenzylammonium chloride (TEBA) as catalyst (Scheme 36) [125]. A Knoevenagel condensation occurred first between isatin and malonitrile derivative, followed by Michael addition of 1,3-dicarbonyl substrates and cyclization to the cyano moiety. 

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. ... 

The stoichiometric reaction of aromatic aldehydes with Meldrum s acid at 50°C gave an intermediate melt from which products 139 crystallized quantitatively at the reaction temperature (Scheme 2.47). These Knoevenagel condensations were termed melt reactions with direct crystallization. Similar condensation with dimedone 140 afforded a cascade reaction starting with Knoevenagel condensation, which was followed by elimination and subsequent Michael addition (Scheme 2.48). Unlike the solution synthesis, yields are superior and no wastes was produced. 

A domino Knoevenagel/hetero-DA reaction of 2-formyl-4-phenyl ( )-2-phenylethenesulfonates 133 with dimedone 33a or N,N-dimethylbarbituric acid in water was reported by Ghandi and coworkers [77] (Scheme 12.53). The optimized conditions showed that performing the reaction in water without using any catalyst gave the best result. Subsequently, a series of hexahydrochromenes and... 

The reaction of dimedone-derived enamines 110, methyl (2-cyano)acetate 109, and formaldehyde 72 mediated by lithium perchlorate led to the formation of a Knoevenagel/ enamine-Michael addition product (Scheme 13.33) [52], This could be cyclized in a one-pot procedure with substoi-chiometric amounts of triphenyl phosphine to provide... 

The lactic acid catalyzed three-component reactions leading to the 1,4-dihydropyridine ring formation were successfully carried out in ethyl lactate [154]. The reaction of 4-aminocoumarin and aromatic aldehydes was equally effective with 1,3-indandione or dimedone as the third component providing fused compounds 177 and 178 (Scheme 107). The X-ray crystallographic study was performed with 178 (Ar = Ph) to confirm the structure. The same products 177 and 178 were obtained when these reactions were performed in two steps Knoevenagel condensation of 1,3-indandione or dimedone with benzaldehyde and then reaction of the product with 4-aminocoumarin... 

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