Dimedone Michael reaction

Amines, thiols, eOH (p. 226), etc., will also add to the 0-carbon atom of 0-unsaturated carbonyl compounds and esters, but the most important reactions of C=C—C=0 systems are in Michael reactions with carbanions reactions in which carbon-carbon bonds are formed. A good example is the synthesis of l,l-dimethylcyclohexan-3,5-dione (dimedone, 100) starting from 2-methylpent-2-ene-4-one (mesityl oxide, 101) and the carbanion 0CH(CO2Et)2 ... 

Frequently the basic conditions used cause the initial Michael adduct to undergo intramolecular transformations, as for example in the synthesis of dimedone (Expt 7.11). This involves a Michael reaction between mesityl oxide and diethyl malonate followed by an internal Claisen ester condensation. 

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. ... 

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. 

Very interesting transformations were observed with dimedone 103b and arylidenethioacetamides 110 (88ZOR460). When the reaction was carried out at ambient temperature, Michael adducts 111 were formed. Compounds 111 can be converted on heating into hydrogenated pyridi-nethiones 112 (in ethanol) or to 2-aminopyran-3-thioamides 113 (in benzene). The formation of the latter ones was found to be reversible. Thus, 113 convert into 112 on heating in ethanol, and yield 2-amino-3-cyanopyr-ans 104 when heated with MN in benzene (Scheme 39). 

Dimedon, 5,5-dimethylcyclohexane-l,3-dione, is prepared by an interesting process discovered by Vorlander. The reaction of 1 mole each of diethyl malonate, mesityl oxide, and sodium ethoxide in absolute ethanol probably involves a Michael addition followed by an intramolecular ester condensation to close the ring to give the diketo ester formulated (procedure of Shriner and Todd. Aqueous potassium... 

The synthesis of alicyclic 1,3-diketones from 7- or 6-keto esters is a well-established reaction. Over SO examples are tabulated in the 1954 chapter in Organic Reactions, and a similar number are tabulated as involving a Michael addition of a diester or keto ester to an unsaturated ketone followed by a Claisen condensation. These latter reactions involve such well-known syntheses as that of dimedone (S,S-di-methylcyclohexane-l,3-dione Scheme 75). 

When aldoximes 309 reacted with dimedone 58 in the presence of ammonium acetate under MWI, they gave acridines 308 in 80 92% yields within 5 min. These reactions may occur through a Michael addition of dimedone 58 to 309 to give the intermediate 310, which on elimination of hydroxylamine gave 313. Then Michael addition between 311 and 312, resulting from dimedone 58 and ammonium acetate, produced 313, which isomerized and cyclodehydrated to give 308 (Scheme 63) (04SC1289). 

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. 

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... 

Scheme 2.35 Domino Michael/cyclisation reaction of dimedone with l-(2-cro-tonoyl)-3,5-dimethylpyrazoles catalysed by an in situ generated (i ,i )-DBFOX-Ph nickel catalyst.

Scheme 4.5 Domino Michael/cyclisation reaction of dimedone with l-(2-crotonoyl)-3,5-dimethylpyrazoles.

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