Malononitrile, purification

Malononitrile, purification of, 48, 3 reaction with sodium nitrite and acetic acid, 48,1... 

Less common are literature examples in which mechanochemical reaction was carried out at elevated temperature. Naimi-Jamal reported the heating of double-walled ball-mill beaker equipped with fittings for circulating water at 96°C (boiling water as circulant) [45]. One-pot solvent-free synthesis of pyrano[2,3-d]pyrimidine-2,4(lFf,3F0-diones 154 was achieved by simply ball milling a stioichiometric mixture of an aromatic aldehyde, malononitrile, and barbituric acid, without addition of solvent and catalyst (Scheme 2.53). Quantitative yields were obtained (Table 2.47) and products generally did not require purification, the solid products were just dried at 80°C in vacuum and recrystaUized, if necessary. Reaction presumably takes place by initial Knoevenagel condensation of aromatic aldehyde with malononitrile to afford the intermediate Michael acceptor, which subsequently reacts with barbituric acid. Tautomerization of Michael adduct is followed by intramolecular cyclocondensation and another tautomerization to afford pyrano[2,3-d]pyrimidine-2,4(177,37f)-diones 154. 

Milling of equimolar amounts of ninhydrin and malononitrile (Retsch MM 2000 mill, stainless steel vial 10 mL, two 12 mm balls) produced after Ih Knoevenagel product 155 in quantitative yield (Scheme 2.54) [46]. After reaction completed, product did not need any purification. Solution reaction conditions are in variance with solvent-free method which does not require any catalyst. Metwally has shown that heating of ninhydrin and malononitrile in solution (EtOH/AcOH) yielded entirely different product 156, via initial condensation of two molecules of malononitrile. Manual grinding in mortar afforded after 30min products in considerably lower yields. 

In a 5 mL glass test tube, a mixture of an aldehyde (1 1 equiv), malononitrile (2 1 equiv), triethylphosphite (3 1.5 equiv), and the catalyst (0.1 equiv) was stirred at room temperature for 25 min under ultrastmic irradiation. After completion of the reaction (monitored by TLC), the mixture was dissolved in ethyl acetate and filtered to separate the catalyst. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to obtain the crude product, followed by purification by crystallization technique to furnish pure P-phosphonomalononitrile 4 with good yield (58-97%). All products were characterized on the basis of detailed spectral studies, and from comparisons of physical and spectral data with those of authentic samples reported in literature. The catalyst as filtered out was subsequently washed with ethyl acetate, dried, and reused several times under same reaction conditions. 

A variety of substituted 2-amino -aryl-4H-benzo[/f]chromene derivatives were synthesized from one-pot multicomponent reaction of aromatic aldehydes, malononitrile, and 1-naphthol in aqueous media. In 2004, Maggi and coworkers [79] explored the use of basic alumina as a useful heterogeneous and reusable catalyst for the synthesis of 2-amino-4H-chromenes (8) from the reaction of these substrates in water under reflux condition (Scheme 3). Only a-naphthol was found to be capable of xmdergoing this reaction as an activated phenol although, the easy purification of products simply by crystallization, the use of water as solvent, and of y-alumina as a heterogeneous and reusable catalyst suggest good prospect for the industrial applicability of this process. A simple, clean, and environmentally... 

In their report, Khurana and his group [81] also showed that DBU (10mol%) can effectively catalyze the three-component cyclocondensation reaction between aromatic aldehydes, malononitrile or ethyl 2-cyanoacetate, and 2-hydroxynaphthalene-l,4-dione in aqueous medium under reflux to afford 2-amino-4H-benzo[ ] chromenes (10). A series of diversely substituted 2-amino-4-aryl-5,10-dioxo-5,10-dihydro-4ff-benzo[g]chromene-3-carbonitriles and ethyl-2-amino-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo[j]chromene-3-carboxylates were synthesized using this protocol in excellent yields (Scheme 5). The reactions were claimed to be remarkably clean, and no chromatographic purification was required. 

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