Ball milling for the quantitative and specific solvent-free Knoevenagel condensation + Michael addition cascade in the synthesis of various 2-amino-4-aryl-3-cyano-4H-chromenes without heating†
Ball milling is used as a facile, efficient, cheap, and environmentally friendly procedure for the solvent-free three-component reaction of aromatic aldehydes with malononitrile and dimedone, or 1,3-cyclohexanedione, resorcinol, and α- and β-naphthol. The reactions proceed quantitatively at room temperature by milling stoichiometric mixtures of the reagents in the presence of 10 mol% Na2CO3. This method offers the advantages of short reaction times, low cost, quantitative yields and simple work-up with no need of any organic solvent. It is thus enviro-economic without producing dangerous wastes. The orientation selectivity with β-naphthol and resorcinol is discussed. Existing structural misattributions are pointed out and clarified by 1H NMR spin coupling analysis.