Synthesis and evaluation of antibacterial activities of some important bridge-head nitrogenous heterocyclic compounds

Abstract EN

The key intermediates in the present study to synthesize the title bridge-head nitrogen heterocycle compounds were N-substituted semicarbazides 2 (a-c), which prepared by hydrazinolysis of the ethyl substituted carbamates 1 (a-c) with hydrazine hydrate.

These carbamates were prepared by the reaction of proper amines and ethylchloroformate.

The reaction of these semicarbazides with ethanolic solution of carbon disulfide under strong basic conditions at room temperature, followed by acidification resulted in the formation of the corresponding potassium (2-arylcarbamoyl) hydrazine carbodithioate 3 (ac), while refluxing the ethanolic solution for three hours afforded 5- (arylamino) -1, 3, 4- oxadiazole -2- thioles 4 (a-c).

The potassium salts 3 (a-c) were cyclized with hydrazine hydrate to 4- amino -5- arylamino -1, 2, 4-triazole -3- thiones (thioles) 5 (a-c).

Compounds 5 (a-c) were excellent precursors for 3- (arylamino)-[1, 2, 4] triazolo [3, 4- b] [1, 3, 4] thiadiazoles 6 (a-c) by dehydrative ring closure of the proper triazole with formic acid in benzene in presence of phosphorous oxychloride or using microwave irradiation technique.

Also, refluxing of the proper triazoles with carbon disulfide under basic conditions afforded 3-(arylamino)-[1, 2, 4] triazolo [3, 4-b] [1, 3, 4] thiadiazole -6- thiones 7 (a-c).

Finally 4- amino -3- (4-(5-(4-amino-5-thioxo-4, 5-dihydro-1H-1, 2, 4-triazol -3- ylamino)-1,3,4-thiadiazol- 2-yl) phenylamino)-1H-1, 2, 4-triazole-5 (4H)-thione 5 (d) were synthesized by the same procedures that were followed to synthesize its analogs starting from 5- (4-aminophenyl)- 1, 3, 4-thiadiazole -2- amine and duplicated all the scales of the reactants.

The structures of these compounds were confirmed by their physical properties in addition to the IR, UV and NMR spectra.

All synthesized compounds were tested for their in vitro growth inhibitory activity against a panel of standard strains of pathogenic microorganism including bacteria Staphylococcus, Streptococcus and Salmonella.

All these compounds were practically inactive against the tested microorganisms.