The Medicinal Chemistry of Bicyclic Systems Containing a NNN Bond


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.

Divisions: College of Health & Life Sciences
Additional Information: Copyright © Baid 1986. G.U. Baig asserts their moral right to be identified as the author of this thesis. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without appropriate permission or acknowledgement. If you have discovered material in Aston Publications Explorer which is unlawful e.g. breaches copyright, (either yours or that of a third party) or any other law, including but not limited to those relating to patent, trademark, confidentiality, data protection, obscenity, defamation, libel, then please read our Takedown Policy and contact the service immediately.
Institution: Aston University
Uncontrolled Keywords: Triazene,Triazine,Imidazotetrazinone,Diazotisation,Cyclisation
Last Modified: 08 Dec 2023 08:18
Date Deposited: 24 Jan 2011 14:33
Completed Date: 1986
Authors: Baig, Ghouse U.

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