Extensive works have been made of the preparation of six sets of 2-substituted pyrazine 4-oxide and its isomeric new 1-oxide by unambiguous route, and of the reaction between substituted pyrazine mono-N-oxides and a series of halogenation reagents and acylating agents and of nuclear magnetic resonance (NMR), infrared, and ultraviolet spectral investigations in comparison with isomeric N-oxides.An application of NMR spectroscopy for determination of the position of the N-O function in mono-substituted pyrazine N-oxides and the analysis of N-oxidation reaction mixture are described.