Studies on Pyrazine Derivatives, XLV: Synthesis, Reactions, and Tuberculostatic Activity of N-Methyl-N′-(pyrazine-2-carbonyl)-hydrazinecarbodithioic Acid Methyl Ester

Abstract

Methyldithiocarbonyl derivative 2 of pyrazine-2-carboxylic acid N′-methyl-hydrazide 1 was synthesized by methylation of CS₂ adduct. Benzylamine caused the decomposition of compound 2 to pyrazine-2-carboxylic acid benzylamide 5 and 1,3-dibenzylthiourea 6. N-methyl-N′-(pyrazine-2-carbonyl)-hydrazinecarbodithioic acid methyl ester 2 were evidenced to cyclize to 3-methyl-5-pyrazin-2-yl-3H-[1, 3, 4]oxadiazole-2-thione 8 in the presence of triethylamine. In the reactions with secondary amines such as morpholine, pyrrolidine and phenylpiperazine pyrazinoyl derivatives (9–11) of thiosemicarbazide were obtained. Hydrazine, methylhydrazine, aminoalcohols, and N-alkylamino-substituted cyclic amines reacted with cyclization to 4-substituted 1,2,4-triazole-3-thiones 12, 13, and 18–22. Synthesized compounds exhibited low tuberculostatic activity in vitro (MIC 50–100 μg/mL).

Keywords:

• 2-methyl-[1,2,4]triazole-3-thione
• 3-methyl-[1,3,4]oxadiazole-2-thione
• methyldithiocarbazate esters
• pyrazine-2-carboxylic acid N′-methyl-hydrazide
• thiosemicarbazides
• tuberculostatic activity