Cobalt-Catalyzed One-Pot Three-Component Cascade Annulation for the Synthesis of Highly Functionalized 3,5-Disubstituted-2,6-Dicyanoanilines at Room Temperature.

Abstract

A facile one-step, three-component domino reaction has been established for the efficient synthesis of 3,5-disubstituted-2,6-dicyanoaniline derivatives, utilizing aldehydes in conjunction with aromatic, cyclic, and acyclic ketones, as well as malononitrile. This methodology employs CoCl₂·6H₂O as a catalyst specifically for aromatic and acyclic ketones, whereas a metal-free, base-catalyzed approach is applied for cyclic ketones. The reaction proceeds via a sequential mechanism that encompasses Knoevenagel condensation, Michael addition, and nucleophilic cyclization. Conducted at room temperature, this reaction accommodates both aromatic and aliphatic aldehydes, leveraging inexpensive and readily available substrates, thereby obviating the necessity for costly cocatalysts or ligands. It offers simple conditions, shorter reaction times, high yields, and an atom-economical, eco-friendly one-pot approach. It also provides a broad substrate scope of total 21 compounds, including 14 new compounds. The photo-physical properties, assessed via UV-vis and fluorescence spectroscopy, revealed that some compounds showed red-shifted emissions, indicating their potential as fluorescent probes for bioimaging and as dye candidates for optoelectronic applications such as OLEDs. Gram-scale synthesis confirms its industrial relevance, whereas mechanistic studies, including control experiments and Hammett analysis provide insights into the reaction pathway.