Three series of 1,2,4-triazin-5(2H)-ones have been synthesized and methylated by a variety of methylating conditions, to investigate the role of substituent effect in directing the site of methylation. The three series investigated were the 3-methylthio-1,2,4-triazin-5(2H)-ones; 3,6-disubstituted-1,2,4-triazin-5(2H)-ones and the 3-amino-1,2,4-triazin-5(2H)-ones. It was established that by increasing the steric hindering capability of the substituent at C3, methylation could be directed to occur on N1, forming new zwitterionic methylation products. In addition to these unique dipolar compounds, methylation was also found to occur on the alternative N2 and N4 annular nitrogens. All methylation isomers were structurally elucidated by 13C n.m.r. spectroscopy, involving the use of both 13C-1H coupled and proton decoupled spectral information.
In addition, the ionization constants of some methylated 3-amino-1,2,4-triazin-5-ones were investigated, with the site of protonation determined by the use of a combination of 13C and natural abundance 15N n.m.r. spectroscopy.