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.