In this study, we undertook the synthesis and characterization of four novel pyrazine derivatives: 'Acetyl Pyrazine 2-Carboxylate', 'Acetic acid; Pyrazine 2-Carboxylic acid', '2- {[trimethylsilyl)oxy]methyl}pyrazine', and '(Pyrazine-2-yl)methyl 4-methylbenzene-1-sulfonate' via a two-step reaction scheme (Scheme 1 and Scheme 2). The structures of these compounds were confirmed through spectroscopic methods, including IR, NMR, and mass spectroscopy.The compounds demonstrated good yield percentages ranging from 68% to 85%. The melting and boiling points were within expected ranges, further confirming the successful synthesis. The synthesized compounds were also evaluated for their antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). 'Acetyl Pyrazine 2-Carboxylate' showed the greatest zone of inhibition against S. aureus (18mm) and E. coli (14mm). The other compounds also exhibited significant antibacterial activity, suggesting that the pyrazine core might have contributed to their inhibitory effect. This study, therefore, establishes the synthesis route for these pyrazine derivatives and showcases their potential as anti-bacterial agents. The structural variation and the related differences in the antibacterial activity among the compounds.