Aldehydes Knoevenagel condensation

Keywords active methylene compound, aldehyde, Knoevenagel condensation, ZnCl2, styrene... 

Keywords cyanoacetamide, malodinitril, methyl cyanoacetate, aromatic aldehyde, Knoevenagel condensation, solid-solid reaction, base catalysis, melt reaction, uncatalyzed, cinnamamide, cinnamonitril, methyl cinnamate... 

Keywords dimedone, aromatic aldehyde, Knoevenagel condensation, Michael addition, uncatalyzed... 

The term Knoevenagel Condensation was originally applied to the base-catalysed condensation of the carbonyl ( CO) group of aldehydes and ketones with the reactive methylene group of malonic acid, with loss of w ater ... 

An example of an intermolecular aldol type condensation, which works only under acidic catalysis is the Knoevenagel condensation of a sterically hindered aldehyde group in a formyl-porphyrin with a malonic ester (J.-H. Fuhrhop, 1976). Self-condensations of the components do not occur, because the ester groups of malonic esters are not electrophilic enough, and because the porphyrin-carboxaldehyde cannot form enolates. 

Reactions. The chemical properties of cyanoacetates ate quite similar to those of the malonates. The carbonyl activity of the ester function is increased by the cyano group s tendency to withdraw electrons. Therefore, amidation with ammonia [7664-41-7] to cyanoacetamide [107-91-5] (55) or with urea to cyanoacetylurea [448-98-2] (56) proceeds very easily. An interesting reaction of cyanoacetic acid is the Knoevenagel condensation with aldehydes followed by decarboxylation which leads to substituted acrylonitriles (57) such as (29), or with ketones followed by decarboxylation with a shift of the double bond to give P,y-unsaturated nitriles (58) such as (30) when cyclohexanone [108-94-1] is used. 

The first step in the Gewald reaction is a Knoevenagel condensation of an activated nitrile with a ketone or aldehyde to produce an acrylonitrile 8, which is then thiolated at the methylene position with elemental sulfur. The sulfurated compound 9 initially decays... 

The initial step of the Hantzsch synthesis is likely to be a Knoevenagel condensation reaction of aldehyde 2 and /3-ketoester 1 to give the a ,/3-unsaturated ketoester 6 ... 

The cyano-substituted five-ring oligomers were formed in good yields in a Knoe-venagel condensation between an aldehyde and a cyanomethyl-substituted compound, according to a procedure previously reported by Greenham el at. [6. The Knoevenagel condensation needs careful control of reaction conditions in order to... 

TABLE 23. Knoevenagel condensation of a-sulphinylacetates 435a and a-ketosulphoxides 435b with aldehydes... 

As the name implies, the first step of this domino process consists of a Knoevenagel condensation of an aldehyde or a ketone 2-742 with a 1,3-dicarbonyl compound 2-743 in the presence of catalytic amounts of a weak base such as ethylene diammonium diacetate (EDDA) or piperidinium acetate (Scheme 2.163). In the reaction, a 1,3-oxabutadiene 2-744 is formed as intermediate, which undergoes an inter- or an intramolecular hetero-Diels-Alder reaction either with an enol ether or an alkene to give a dihydropyran 2-745. 

Other valuable substrates for the domino Knoevenagel/hetero-Diels-Alder reaction are chiral oxathiolanes such as 2-778, which are easily accessible by condensation of 2-thioacetic acid and a ketone in the presence ofpTsOH, followed by oxidation with hydrogen peroxide [390]. As described by Tietze and coworkers, the Knoevenagel condensation of 2-778 with aldehydes as 2-777 can be performed in... 

Song A, Wang X, Lam KS (2003) A convenient synthesis of coumarin-3-carboxylic acids via Knoevenagel condensation of Meldrum s acid with ortho-hydroxyaryl aldehydes or ketones. Tetrahedron Lett 44 1755-1758... 

TiIV compounds also work well at promoting cross-aldol reactions between two different aldehydes and/or ketones without prior activation or protection (Scheme 19).74 Claisen condensation and Knoevenagel condensation are promoted by TiX4, an amine, and trimethylsilyl triflate.75-77... 

Both natural and non-natural compounds with a 2ff,5ff-pyrano[4,3-fc]pyran-5-one skeleton are of interest in medicinal chemistry. Several natural products, such as the pyripyropenes, incorporate this bicyclic ring system. The group of Beifuss has described an efficient microwave-promoted domino synthesis of the 2ff,5H-pyr-ano[4,3-fo]pyran-5-one skeleton by condensation of a,/3-unsaturated aldehydes with 4-hydroxy-6-methyl-2]-f-pyran-2-one (Scheme 6.244) [428]. It is assumed that in the presence of an amino acid catalyst a Knoevenagel condensation occurs first, which is then followed by a 6jr-electron electrocyclization to the pyran ring. While the conventional thermal protocol required a reaction time of up to 25 h (refluxing ethyl... 

In a dedicated combinatorial approach, Strohmeier and Kappe have reported the rapid parallel synthesis of polymer-bound enones [33]. This approach involved a two-step protocol utilizing initial high-speed acetoacetylation of Wang resin with a selection of common /i-ketoesters (Scheme 7.13) and subsequent microwave-mediated Knoevenagel condensations with a set of 13 different aldehydes (see Section 7.3.6). 

Knoevenagel condensation reaction of creatinine with aldehydes occurs rapidly under solvent-free reaction conditions at 160-170 °C using focused microwave irradiation (Scheme 6.18) [66],... 

Scheme 6.18 Knoevenagel condensation reaction of creatinine with aldehydes.

The first use of room temperature ionic liquids as potential novel soluble phases for combinatorial synthesis has recently been described. As model reaction the Knoevenagel condensation of salicyl aldehyde grafted on to an imidazolium-derived ionic liquid was studied under the action of microwave irradiation (Scheme 12.19) [66]. Reactions were performed without additional solvent in the presence of a basic catalyst, utilizing microwave irradiation in a designated monomode microwave reac-... 

Knoevenagel condensation of diethyl malonate or related compounds with a,fi-unsaturated aldehydes and ketones results in diene esters (equation 40)78. This condensation reaction has been used to extend the polyene chain length of vitamin A related compounds (equations 4179 and 4280). 

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