Background: 1,2,4-Triazine is a prominent structural core system present in numerous natural and
synthetic biologically active compounds. The existing synthetic methodologies have mostly focused on 3,6-
disubstituted-1,2,4-triazines and 3,5,6-trisubstituted-1,2,4-triazines. However, until now only a few methods have
been developed for making 3,5-disubstituted-1,2,4-triazines.
Objective: The primary objective of the study was to find an efficient and simple way to construct 3,5-
Method: The arylethene (0.24 mmol), I2
(0.22 mmol), IBX(0.24mmol.) and DMSO (2 mL) were added to a
round-bottomed flask equipped with a magnetic stirring bar. The reaction mixture was agitated at 110°C under air
for 3h, then amidrazone (0.2 mmol) was added to the mixture and the reaction continued at 110°C for another
1.5h. Afterwards, water (20mL) was added and the reaction mixture was extracted with ethyl acetate (3 × 50mL).
The organic phases was combined and concentrated under reduced pressure to distill ethyl acetate. The residue
was further purified by column chromatography on a silica gel column with petroleum / ethyl acetate (5:1) as eluent
to obtain the desired products.
Results: We developed an operationally simple way of regioselectively synthesizing 3,5-disubstituted-1,2,4-
triazines by a coupled domino strategy with terminal aryl alkenes and amidrazones in one-pot. The overall process
involves three different reactions: iodination, Kornblum oxidation and condensation.
Conclusion: The strategies exhibit high performance with moderate to high yields, using simple and readily
available terminal aryl alkenes and amidrazones, representing a powerful tool for the formation of potentially
biologically active derivatives.