Amine‐Based Organocatalysts for the Regioselective Synthesis of Mono‐ and Di(arylethenyl)Nicotinonitriles: Reaction Optimization, Substrate Scope, and Photophysical Study

Abstract

ABSTRACT A highly efficient and amine‐catalyzed method for the regioselective synthesis of mono‐ and di‐styryl nicotinonitrile, has been developed through a one‐pot reaction of 2‐mercapto‐3‐cyano‐4,6‐dimethylpyridine, aromatic aldehydes under mild conditions. A series of organic bases, including piperidine, morpholine, pyrrolidine, diethyl amine, and triethylamine, were screened to optimize catalytic efficiency, along with variations in solvent and reaction time. Among the tested conditions, piperidine in ethanol under reflux provided the highest yield and operational simplicity for delivering mono‐styryl nicotinonitrile, whereas pyrrolidine in methanol acts as the best conditions for synthesis of di‐styryl nicotinonitrile. The optimized protocol tolerates a wide range of aromatic aldehydes bearing both electron‐donating and electron‐withdrawing substituents, affording the desired products in moderate to excellent yields. Moreover, the photophysical properties of some selected products were studied. This method offers a straightforward, metal‐free, and atom‐economical approach to access functionalized nicotinonitrile derivatives with excellent regioselectivity by alteration of the amine catalyst and solvent.