Malononitrile, Knoevenagel reaction

The Knoevenagel reaction between o-hydroxyaryl aldehydes and ketones and substituted acetonitriles affords high yields of 3-substituted coumarins in aqueous alkaline media <96H(43)1257>, whilst 4-hydroxycoumarins have been elaborated to pyrano [3,2-c]benzopyran-5-ones by reaction with aromatic aldehydes and malononitiile <96P148>. The imine (10) resulting from the complex reaction of o-hydroxyacetophenone with malononitrile undergoes a 1,5-tautomeric shift in solution <96JCS(P1)1067>. 

A weak base such as glycine added to [HMIMjPFg has also been reported to catalyze a Knoevenagel reaction of malononitrile and benzaldehyde 110). A KOH-treated [BMIMjPFg also provides a suitable medium for the Corey-Chaykovsky epoxidation of enones and cyclopropanation of aldehydes using trimethyl sulfonium iodide (///). 

An organic base in an ionic liquid was also found to be effective for a Knoevenagel reaction. Glycine was added to the ionic liquid [HMIMjPFs as the base catalyst. The reaction proceeded at room temperature in air without the need for rigorous drying of the ionic liquid. Glycine and the reactants malononitrile and benzaldehyde dissolved readily in the ionic liquid. The product was extracted from the ionic liquid phase with an immiscible co-solvent, toluene 110). 

Salicylaldehydes and some o-hydroxyaryl ketones react with Meldrum s acid to give coumarin-3-carboxylic acids <03TL1755>. 3-Cyanocoumarins, and thus the 3-carboxylic acids, are available in high yield from a Knoevenagel reaction between salicylaldehydes and malononitrile in water <0382331>. 3-Chlorocoumarins result from the cathodic reduction of trichloroacetyl esters of o-hydroxyacetophenones <03T9161>. 

The Knoevenagel reaction of 234 with malononitrile (EtOH, piperidine) afforded the dicyanovinylthiophene derivatives 469 (Equation 56) <1997TL6107>. 

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). ... 

The Knoevenagel reaction (Scheme 6.20) involves the reaction of aromatic aldehydes with a variety of molecules CH2XY. The groups X and Y may be the same or different, but are invariably electron withdrawing, so creating an activated methylene group from which the carbanion CHXY is produced. The reaction is usually carried out in pyridine solution, with piperidine as the basic catalyst. The reactions of benzaldehyde with propane-1,3-dinitrile [malononitrile, CH2(CN)2] and diethyl propane-1,3-dioate [diethyl malonate, CH.,(CO,Et)2] are illustrative. In both cases, manipulation of the CH=CX2 group in the product allows the synthesis of other compounds. 

Alkali and alkaline earth carbonates catalyzed the Knoevenagel reaction (6.22) of benzaldehyde with malononitrile.73... 

Choudary et al. have investigated the Knoevenagel reaction by use of diamine-functionalized MCM-41 [47]. This grafted material was effective in the condensation of several aldehydes with both ethyl cyanoacetate and with malononitrile. In-... 

Knoevenagel reaction. As surrogate for benzaldehyde in the condensation with active methylene compounds, the benzenesulfonimine is superior. In the presence of EtjN in chloroform the reaction with, inter alia, /8-diketones, )3-keto esters, a-sulfonyl ketones, a-nitro esters, and malononitrile proceeds at room temperature. 

Though the Knoevenagel reaction may be considered to be typical for malononitrile [MDN, CH2(CN)2, 10] this unique CH-acidic synthon has been used in numerous different reactions. A number of reviews has been published on MDN. The most comprehensive ones are listed below ... 

The Knoevenagel reaction has been carried out between aldehydes and acetonitrile in water. Thus, salicylaldehydes react with malononitrile at room temperature in the heterogeneous aqueous alkaline medium to give... 

Keywords Aromatic carbraiyl compounds, malononitrile, ethyl cyanoacetate, modified and activated Mg-Al hydrotalcite (MHT), toluene or DMF, room temperature, condensation, Knoevenagel reaction, substituted alkenes... 

Keywords Ninhydrin, malononitrile, aryl isothiocyanates, primary aliphatic amines, ethanol, triethylamine, room temperature, one-pot multicomponent synthesis, thio-Michael and Knoevenagel reactions, sulfur-nitrogen heterocycles, oxathiaaza[3.3.3]-propellanes, che-moselectivity, regioselectivity... 

Wang and coworkers made a similar approach using isocyanoesters [25]. The reaction was catalyzed by bifunctional tertiary amine-thiourea catalysts and afforded the pyrrolidinyl spirooxindoles in good yields and excellent enantioselectivities but low diastereoselectivities. Later, Yan and coworkers developed a similar reaction involving the three-component cascade reaction of isatin, isocyanoesters, and malononitrile [26]. First, the Knoevenagel reaction between isatin and malononitrile afforded the... 

To evaluate properties of basic catalysts, the Knoevenagel condensation over aluminophosphate oxynitrides was investigated [13]. In this reaction usually catalysed by amines, the solid catalysts function by abstraction of a proton from an acid methylene group, which is followed by nucleophilic attack on the carbonyl by the resultant carbanion, re-protonation of oxygen and elimination of water. The condensation between benzaldehyde and malononitrile is presented below. 

Knoevenagel adduct 239 of oxohomophthalimide 240 with malononitrile 27a in reactions with CH-acids behaves ambiguously (82CPB1215). Reactions of 239 with acetylacetone, ethyl esters of acetoacetic and ben-zoylacetic acids, as well as methyl pyruvate led to the formation of the desired spiropyrans 241. However, benzoylacetone, dibenzoylmethane, cyanacetamide, and oxindole always gave the same 242. Authors explain this feature in terms of a retro-cleavage of adducts of Michael product 239... 

In a one-pot three-component reaction, aromatic aldehydes, malononitrile and 1,3-dicarbonyl compounds react to form 2-amino-5-carboxy-4-aryl-47/-pyran-3-carbonitriles 87. The reaction proceeds by an initial Knoevenagel condensation of malononitrile with the aromatic aldehyde to afford the 2-benzylidenemalononitrile intermediate 88. Michael addition of the activated methylene group forms the 1,5-dicarbonyl equivalent 89, which upon ring closure affords 477-pyrans (Scheme 29) <2004SL871, 1999H(51)1101 >. 

A three-component reaction of aromatic aldehydes, malononitrile and phenols leads to 4-aryl-2-amino-3-cyano-4//-chromenes this reaction can be carried out in aqueous media with improvements in yield and obvious environmental advantages (Scheme 35). The aromatic aldehyde undergoes a Knoevenagel condensation with malononitrile, followed by ortho-alkylation of the phenol and cyclization to form the iminopyran intermediate 114, which isomerizes to the 4//-chrorncncs (Scheme 36) <2003SL2001>. High yields for this three-component reaction can also be achieved in aqueous media when mediated by 7-alumina <2004TL2297> or cetyltrimethylammonium chloride <2001T1395>. 

Selenophene-2-aldehyde takes part in the Hantzsch synthesis [Eq. (I)]108 and reacts readily with ammonia, aromatic amines and diamines,109 hippuric, barbituric, and malonic acids, malononitrile,70 and rhodanine.109 /3-(Selenien-2-yl)acrylic acid has been obtained from selenophene-2-aldehyde by the Perkin reaction and by Knoevenagel condensation with malonic acid.70 Esters of /9-(selenien-2-yl)acrylic acid are easily formed by condensation of the aldehyde... 

Reactions of chrotnene 168 (Scheme 32) with Knoevenagel adducts derived from aldehydes and ethyl cyanoacetate or malononitrile and ammonium acetate yielded, after condensation, libraries of general structure 169 and 170, respectively [69]. 

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