Regiospecific syntheses of the monomethylated 3-phenyldihydro-1,2,4-triazin-6(1H)-ones

Unambiguous syntheses of four unreported monomethylated derivatives of 3-phenyldihydro-1,2,4-triazin-6(1H)-ones, namely, the 1-methyl (2), 2-methyl (3), 4-methyl (4) and the imidic O-methyl derivative (5), are described. Regioselectivity was achieved for the synthesis of (2) by addition of ethyl glycinate to the 1,3-dipolar nitrile imine derived from N-methylbenzohydrazonoyl bromide hydrobromide (8). The key step for the synthesis of (3) was addition of benzyl 3-methylcarbazate (14) to ethyl N-[chloro(phenyl)methylene]glycinate (15b). The 4-methyl compound (4) was prepared by cycloaddition of ethyl N-(thiobenzoyl)sarcosinate (21) with hydrazine hydrate, and the O-methyl compound (5) was prepared by reaction of sodium methoxide with 6-chloro-3-phenyl-4,5-dihydro-1,2,4-triazine (23).