Synthesis and Tuberculostatic Activity of Novel 1,2,4-Triazoles Obtained from Heterocyclic Carbohydrazides

The novel 1,2,4-triazole derivatives have been synthesized by a few different pathways.Heterocyclic carbohydrazides were used to obtain monoesters of hydrazine acids (1-6), thiosemicarbazide derivatives (7-17), and finaly 1,2,4-triazole-5-thiones (18-38).Carbohydrazides were also cyclized with methyl carbamodithioates in the presence of DBU giving 1,2,4-triazole-5-thiones (18, 19, 39-47).Two of final products (39, 40) were undergone alkylation in alkaline solution to appropriate sulfides (48-53).Then methylsulfides (48, 49) were oxidized with peroxyacetic acid to sulfoxides (54, 55).The obtained compounds were tested in vitro towards Mycobacterium tuberculosis.indicated that 1,2,4-triazole derivatives exhibit wide range of biological activity, inclusive tuberculostatic action.These observations prompted us to synthesize some new 1,2,4-triazole-5-thiones substituted in C-3 position with heterocyclic rings of 2-, 3-, 4-pyridine, 3-, 4-pyridine-N-oxide, 3-pyrazine-N-oxide, 2-pyrimidine, and 2-quinoline.Additionally, performed syntheses led to gain derivatives bearing among others cycloalkylamine substituents in N-4 position.Only two reports on that class of compounds have appeared up till now. 9,10 RESULTS AND DISCUSSIONIn this work, we investigate and compare few pathways of 1,2,4-triazole-5-thiones synthesis.The starting heterocyclic carbohydrazides and carbomethylhydrazides were obtained from methyl esters of carboxylic acids in a result of typical reactions described in the literature. 11,12Carbohydrazides under treatment of CS 2 and dimethyl sulfate in ethanol -aqueous solution and of lye excess gave hydrazinecarbodithioic acid methyl esters (1-3) (Scheme 1).