Cascade Synthesis of 2‐Cyanoacrylamides through Deacetalization and/or Knoevenagel Condensation followed by Selective Monohydration of Acetals and Aldehydes over Solid Acid Ferrites

A new protocol of cascade synthesis for biologically active 2‐cyanoacrylamides (1) was developed. The reaction proceeds over a novel magnetically retrievable solid‐acid composite of iron oxide, poly(vinylpyrrolidone) and phosphotungstic acid (Fe3O4/PVP–PWA) in AcOH–H2O medium under reflux conditions. This transformation is facilitated through single‐site Brønsted acid catalyzed cascade reactions involving deacetalization and/or Knoevenagel condensation followed by selective monohydration of nitriles starting from acetals (5) and aldehydes (2) with malononitrile (3). A series of aldehydes, dimethyl and diethyl acetals, along with some heterocyclic aldehydes were successfully transformed to 2‐cyanoacrylamides with >95 % yields. TEM images confirmed the coating of the PVP over nanosized Fe3O4. Stereoselective monohydration of 2‐benzylidenemalononitriles (4) to E isomers was demonstrated by NOESY experiments. The catalyst could be efficiently recycled seven times on employment of both acetals and aldehydes as substrates, as a result of its magnetic nature.