Synthesis methods of 1,2,4-triazole-3-thiones: review

1,2,4-Triazole-containing compounds are unique heterocyclic compounds present in an array of pharmaceuticals and biologically important compounds used in drug-discovery studies against cancer cells, microbes, and various types of diseases in the human body. The aim of the study was to analyze in detail and combine the available literature materials to study the reactions associated with the formation of different classes of derivatives of 1,2,4-triazole-3-thione and to study their physical-chemical properties. Various innovative methods have been proposed and explored for synthesizing different classes of 1,2,4-triazole compounds, each with distinct applications and potential medicinal benefits. When analyzing the outcomes of studies aimed at obtaining new 1,2,4-triazole-3-thiones, it’s crucial to recognize the multiple stages involved in their synthesis. These stages typically include the esterification of carboxylic acids, hydrazinolysis, the formation of carbothioamides, and thiones through alkaline cyclization. Subsequently, reactions involving the S-function are conducted, leading to the formation of various classes of derivatives of 1,2,4-triazole. The study by a team of scientists introduced a novel method for synthesizing imidazolyl- and imidazole-1,2,4-triazoles, targeting the design of safer analgesic and anti-inflammatory agents. Moreover, researchers have successfully synthesized derivatives of 3-[2-(5-thio-4-aryl-4H-1,2,4-triazole-3-yl)ethyl]quinoxalin-2(1H)-one, N-(3-thio-5-aryl-[1,2,4]triazole-4-yl)acylamides, 5-alkylthio-4-amino-3-(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-thiomethyl)-1,2,4-triazole and 3-(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-thiomethyl)-6-aryl-5,6-dihydrogen-1,2,4-triazole-[3,4-b]-1,3,4-thiadiazole, 5,5’-(alkyldiyl-bis(sulfandiyl))bis(N-(arylidene)-3-thiophen-2-ylmethyl)-4H-1,2,4-triazole-4-amines, 3-(arylsulfonyl)-4-phenyl-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole, expanding the scope of 1,2,4-triazole-based, compounds with potential pharmacological activities. Furthermore, the synthesis of molecules containing two 1,2,4-triazole and two benzole rings has gained traction, offering new avenues for drug development. Mannich bases were synthesized from the corresponding thiones through a reaction with N-methylpiperazine or N-phenylpiperazine in dimethylformamide in the presence of formaldehyde. Additionally, the synthesis of salts derived from 1,2,4-triazole highlights its importance in pharmaceutical formulations, with studies focusing on both organic and inorganic salts for potential therapeutic applications. Conclusions. The analysis of the above-mentioned publications indicates that the search for new biologically active compounds among derivatives of 1,2,4-triazole-3-thiones is promising. Many 1,2,4-triazole-3-thiones exhibit a wide spectrum of biological activity with little toxicity.