The Medicinal Chemistry of Bicyclic Systems Containing a NNN Bond

  • Ghouse U. Baig

Student thesis: Doctoral ThesisDoctor of Philosophy


Synthetic routes to, and properties of, 4-amino and 4(3H)-imino-1,2,3-
benzotriazines are reviewed in detail in the Introduction.

4-(4-Cyanoanilino)-1,2,3-benzotriazine, when boiled in morpholine,
afforded 3-[2-amino-N-(4-cyanopheny1)-benzimidoy1 ]-4-(4-cyanopheny1 imino) - 3,4-dihydro-1 ,2,3-benzotriazine in addition to the major product 2-amino- N2-(4-cya nopheny1)-NENL-oxydi ethylenebenzami dine. The yield of the former product increased when high boiling non-nucleophilic solvents were
employed as the thermolysis medium.

Decomposition of 3-[2-amino-N-(4-cyanopheny] )-benzimidoy1]-4-(4-
cyanophenylimino)-3,4-dihydro-1 ,2,3-benzotriazine in hot acid alone
yielded 4-(4-cyanoanilino)-2-phenylquinazoline, whereas incorporation of
nucleophiles in to the hot acidic media afforded a series of 4-(4-
cyanoanilino)-2-(2-substituted phenyl) quinazolines. These quinazolines
were prepared by an unambiguous route from the appropriate 2-(2-
substituted phenyl)-4-chloroquinazolines and 4-cyanoaniline.

The tetracyclic triazine, 8-(4-cyanopheny1imino)-8H-quinazolino[3,2-c]-
1,2,3-benzotriazine, was prepared by the diazocyclisation of 2-(2-
aminopheny 1 )-4-(4-cyanoanilino)quinazoline.

4-Anilino-1 ,2,3-benzotriazines and their precursor acyclic triazenes
yielded 3-arylquinazolin-4(3H)-ones when heated in formamide.

The chemistry of the antitumour 3-alkylimidazo[5,1-d]-1,2,3,5-tetrazin-
4(3H)-ones is comparable to that of benzotriazin-4(3H)-ones. The former
series yielded 5-(3-alkyltriazen-1-y1)-imidazole-4-carboxamides when
treated with cold aqueous sodium carbonate and afforded 5-aminoimidazole-
4-carboxamide when boiled in water.

Nitration of 8-carbamoy1-3-alkylimidazotetrazinones yielded the
corresponding 8-nitrocarboxamides and reaction with sodium nitrite in
concentrated sulphuric acid yielded the corresponding 8-carboxylic acids.

5-Diazoimidazole-4-carboxamide generated by thermolysis of 8-carbamoy-]3l-
(2-chloroethy1)imidazo[5,1,-d]-1,2,3,5-tetrazin-4(3H)-one in acetic acid
or pyridine was trapped by reactive methylenic ketones, nitriles or esters
to afford imidazo[5,l1-c]-1,2,4-triazines.

Thermolytic decomposition of the 3-alkylimidazotetrazinones in methanol
and ethanol yielded 2-azahypoxanthine and 5-amino-1-carboalkoxyimidazole-
4-carboxamide. In hydrazine hydrate, 3-(2-chloroethy] )imidazotetrazinone
yielded 5-azidoimidazole-4-carboxamide, whereas the 3-alkyl analogues
formed 5-amino-4-carbamoy1] imidazole-1-carbohydrazide.
Date of Award1986
Original languageEnglish


  • Triazene
  • Triazine
  • Imidazotetrazinone
  • Diazotisation
  • Cyclisation

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