Dual Function of Cyanoacetic Acid under Visible Light and Dark Conditions: Templating and Catalyzing the Formation of Unexplored Pyrimidine Derivatives and Evaluation of their Antibacterial Activity

Abstract

Cyanoacetic acids are developed as efficient substrates for the synthesis of pyrimidine derivatives. Here, we elaborate on the dual role of cyanoacetic acid under both visible-light and dark conditions in the synthesis of pharmaceutically important compounds. In visible light, the in situ product of cyanoacetic acid and aldehydes is involved in photochemically active electron donor-acceptor (EDA) species with an exocyclic imine group of uracil derivatives, which generates biologically relevant fused pyridopyrimidine derivatives. The detailed mechanism inquiry under visible light is supported by various control experiments and theoretical study (TD-DFT). The photocatalyst and additive-free method features excellent functional group tolerance, feasibility under sunlight and facile scalability. Different light parameters, such as photonic voltage, flow rate, and velocity, help further optimize the reaction yield from mg-to-gm scale in product synthesis. On the other hand, in the dark condition, cyanoacetic acid promotes another bis-pyrimidine scaffold as a Brønsted acid. Furthermore, the biological activities of fused pyrimidine derivatives were screened at the preliminary level, and some compounds showed good antibacterial properties. Our approach circumvents the need for hazardous reagents and energy-intensive conditions typically associated with traditional synthetic methods by employing visible light as an energy source.