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

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, ¹H NMR, ¹³C 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 IC₅₀ 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.