1.2.4- Triazoles 1.2.4- triazepines

Triphenyl-2//-l,2,4-triazepine rearranges in refluxing mcsitylene to the 1,2,4-triazole 1 other products are 3,4,5-triphcnylpyrazole and 3,4-diphenylpyrazole.337... 

An interesting feature of this reaction is that the N-amino group does not take part in the cyclization. This is also observed in other cases. Thus, cyanogenbromide and 4-amino-3-(o-aminophenyl)-5-triazoles (216) give the condensed 7V-aminotriazoles (217), whereas the reaction of 216 with orz/io-esters proceeds with participation of both amino groups and results in triazepine 218 (73TL1643). 

The reaction of the l-acylamino-2-methylthio-l,4-dihydropyrimidines (85) with 80% hydrazine in acetic acid resulted in ring enlargement with loss of methanethiol to give the 1,2,4-triazolo[4,3-/]-1,2,4-triazepines (86) (30-85% yields), probably via the mechanism indicated in Scheme 13 <90ZC9l>. The hydrazone derivative, derived from the 1,2,4-triazole (87), was also cyclized (70% yield) to the l,2,4-triazolo[3,2-c]-l,2,4-triazepine (88) <82KGSlil3>. 

Ring closure reactions of a 4-hydrazino[l]benzofuro[2,3- /]pyridazine, derived from naturally occurring rotenone, yielded [l]benzofuro[2,3-d]pyridazines fused with 1,2,4-triazole, 1,2,4-triazine, and 1,2,4-triazepine derivatives <01JHC1097>. 

In an effort to synthesize fused 7/5 heterocyclic ring system to obtain boosted bioactivity, Gupta et al. [102] condensed two heterocyclic systems, triazole and triazepine, into a single framework by the cyclocondensation of 5-aryl-3,4-diamino-l,2,4-triazoles with p-chlorocinnamaldehydes in the presence of catalytic amount of p-TsOH in DMF xmder microwave irradiation (also conventional oil bath heating) to afford 3,6-diaryl-5H-[l,2,4] triazolo[4,3-fc]-l,2,4-triazepines (103). Both the heterocyclic motifs (triazepine and triazole) are well-known core units of several drugs and bioactive compoxmds (Scheme 34). 

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