Synthesis, spectral characterization and antihaemostatic activity of 1,2,4-triazoles incorporating 1,2,4-triazine rings

Abstract

A simple and high yielding method for the integration of a 1,2,4-triazole ring with 1,2,4-triazine-5-one (4a-j) has been developed starting from 3-arylsydnones (1a-d). The structures were proved by their spectral data and screened for antihaemostatic activity.

1,2,4-Triazine Chemistry Part I: Orientation of cyclization reactions of functionalized 1,2,4-triazine derivatives

“…These effects at position 6 of 3-hydrazino-5-hydroxy-1,2,4-triazine (1) on the orientation of cyclization to form 1,2,4-triazolo [1,2,4]triazines, was examined by Daunis et al [13]. Thus, when R was an electron attracting group, 1,2,4-triazolo [3,4-c] [1,2,4]triazines (2) were formed in the presence of acidic (HCO2H or AcOH) or neutral [HC(OEt)3 or MeC(EtO)3] media. On the other hand, when R was an electron donating group and the reagent was acidic (HCO2H or AcOH), 1,2,4-triazolo [4,3-b] [1,2,4]triazine derivatives (3) were formed.…”

“…Thus, when R was an electron attracting group, 1,2,4-triazolo [3,4-c] [1,2,4]triazines (2) were formed in the presence of acidic (HCO2H or AcOH) or neutral [HC(OEt)3 or MeC(EtO)3] media. On the other hand, when R was an electron donating group and the reagent was acidic (HCO2H or AcOH), 1,2,4-triazolo [4,3-b] [1,2,4]triazine derivatives (3) were formed. Compound 4 was obtained as by-product with 2 and the amount of 4 increased with long reaction time (Scheme 1).…”

“…Also, hydrazinolysis of 39 using N-acetylhydrazine yielded the 1H-4,5-diphenyl-5H-6-methyl-1,2,4-triazolo [3,4-c] [1,2,4] triazine (40) and not (41) (Scheme 12) [25]. The reaction proceeded through nucleophilic displacement of ethylthio group, followed by cyclization at N-4 and not N-2 atom.…”

“…On the other hand, the reactivity of compound 42 towards both nucleophilic and electrophilic reagents in different medium have been reported [28] where the nucleophilicity increase in order S> O> N. Thus, treatment of 42 with phenacyl bromide in refluxing DMF yielded 1,2,4-triazino [3,4-b] [1,3,4]thiadiazin-4-one (47) while its boiling with glyoxylic acid in DMF followed by careful dehydration with concentrated H2SO4 afforded 1,2,4-triazino [3,4-…”

“…Furthermore, many heterocyclic systems bearing 1,2,4-triazines are found to exhibit remarkable pharmacological effects [1][2][3][4][5]. In search for new anti-HIV and anticancer agents, some additional heterocyclic moieties were incorporated in the 1,2,4-triazine nucleus via the interaction between functionalized 1,2,4-triazines with various nucleophilic and electrophilic reagents in different media [6][7][8][9][10][11][12].…”