Synthesis of some new fused 1,2,4-triazines and their antimicrobial activity

Abstract

The starting material 4-amino-4H-[1,2,4]triazino[5,6-b]indole-3-thiol 1 was synthesized by refluxing a mixture of isatin and thiocarbohydrazide in glacial acetic acid. Compound 1 reacted with various types of reagents including ammonia, hydrazine hydrate, semicarbazide HCl in various media to give triazino-[5,6-b]indole-3,4-diamine 2, 3-hydrazino-4H-[1,2,4]triazino[5,6-b]indol-4-amine 3 and 3,4-dihydro[1,2,4,5]-tetrazino[6',1':3,4][1,2,4]triazino[5,6-b]indole-2(1H)-one 5, respectively. Reactions of compounds 2 and 3 with ethyl chloroformate in boiling DMF led to 1H-[1,2,4]triazolo[5',1':3,4][1,2,4]triazino[5,6-b]indol-3(4H)-one 4 and compound 5, respectively. Microwave irradiation of compound 1 with maleic anhydride yielded 1-(3-mercapto-4H-[1,2,4]triazino[5,6-b]indol-4-yl)-1H-pyrrole-2,5-dione 6. Reactions of 1 with different aldehydes in EtOH-HCl gave the corresponding Schiff bases. Treatment of substrate 1 with NH4SCN in glacial AcOH yielded N-(3-mercapto-4H-[1,2,4]triazino[5,6-b]indol-4-yl)thiourea 9 and 1H-[1,2,4]triazolo[5',1':3,4][1,2,4]-triazino[5,6-b]indole-3(2H,4H)-thione 10, respectively. Reaction of substrate 1 with phenyl isothiocyanate in refluxing dioxan gave N-(3-mercapto-4H-[1,2,4]triazino[5,6-b]indol-4-yl)-N'-phenylthiourea 11. Its reaction with ethyl cyanoacetate upon refluxing in EtONa/EtOH afforded ethyl (4-amino-4H-[1,2,4]triazino[5,6-b]-indol-3-yl)(cyano)acetate 12, which upon boiling gave ethyl 2-amino-1H-pyrazolo[5',1':3,4][1,2,4]triazino-[5,6-b]indole-3-carboxylate 13. Structures of new compounds were confirmed by elemental analysis and spectroscopic data (IR, 1H and13C NMR). The newly synthesized compounds were subjected to the biological screening, which demonstrated promising results.