Synthesis, Characterization, and Biological Assessment of 2‐Methoxynicotinonitrile Derivatives

ABSTRACT

This study presents the formation of 2‐methoxy‐3‐cyanopyridine derivatives 3(a–g) that occurred while attempting to synthesize furo[2,3‐ b ]pyridines. The structures of all newly synthesized compounds were confirmed by IR, ¹ H NMR, ¹³ C NMR, 2D‐NMR, HRMS, and crystal x‐ray structure analysis. In the crystal structure of 3f , the molecules are connected by C―H···N≡C, C―Cl···O―C, and C―S···N≡C interactions to form layers, which are further connected through π···π and Cl···π interactions, consolidating a 3‐dimensional structure. The antioxidant activities of all synthesized compounds were tested in a DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) free radical scavenger assay. Compound 3d displayed the highest level of activity with an IC ₅₀ of 57.47 ± 1.17 µg/mL. Moderate levels of antibacterial activity were found against Escherichia coli , Coagulase‐Negative Staphylococci (CONS), and Streptococcus species. These findings indicate that the 2‐methoxy nicotinonitrile is an adaptable scaffolding to provide both tunable electronic properties and potential antioxidant and antibacterial properties. This new synthetic conversion described here demonstrates a practical method for preparing structurally diverse cyanopyridines and provides a platform for further lead optimization toward future multifunctional bioactive compounds.