“Guanidine hydrochloride assisted one-pot synthesis of 2-amino-4,6-disubstituted-3-cyanopyridine derivatives: a sustainable and greener strategy with catalyst recyclability”

Here, we highlight an efficient and novel approach for the one-pot multicomponent synthesis of 2-amino-4,6-disubstituted-3-cyanopyridine derivatives through the cyclo-condensation of substituted aromatic aldehydes, ammonium acetate, malononitrile, and aryl ketones under neat conditions. The current protocol offers several key advantages, including short reaction times (approximately 0.55 hours), high yields (up to 96%), mild reaction conditions (80 °C), broad substrate scope, catalyst recyclability, and a simple isolation procedure. The reported method harnesses the catalytic potential of guanidine hydrochloride, serving as a highly effective organo-catalyst, which exhibits exceptional mildness and catalytic activity, facilitating the reaction with high yield. Furthermore, green chemistry metrics such as Eco-Scale (95), E-Factor (0.29), and Process Mass Intensity (1.60) were employed to evaluate the environmental impact of the process.

Graphical abstract