Collect. Czech. Chem. Commun. 2005, 70, 51-62

Cyclization of 1-{[(4-Methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetyl}thiosemicarbazides to 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives and Their Pharmacological Properties

Alicja Maliszewska-Guza, Monika Wujeca, Monika Pituchaa, Maria Dobosza,*, Anna Chodkowskab, Ewa Jagiełło-Wójtowiczb, Liliana Mazurc and Anna E. Koziołc

a Department of Organic Chemistry, Faculty of Pharmacy, Medical University, 6 Staszica Str., 20-081 Lublin, Poland
b Department of Toxicology, Medical University, 8 Chodzki Str., 20-093 Lublin, Poland
c Department of Crystallography, Faculty of Chemistry, Maria Curie-Sklodowska University, 20-031 Lublin, Poland


By the reaction of 4-methyl-4H-1,2,4-triazole-3-thiol with ethyl bromoacetate, ethyl [(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetate (1) was obtained. This compound was converted to [(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetohydrazide (2). In the reaction of 2 with isothiocyanates, new thiosemicarbazides 3a-3g were obtained. The cyclization of 3a-3g in 2% aqueous solution of sodium hydroxide led to the formation of 4H-1,2,4-triazole-3(2H)-thione derivatives 4a-4g, whereas the cyclization in acid media led to the formation of 2-amino-1,3,4-thiadiazole derivatives 5a-5g. Molecular structure was confirmed by X-ray structure analysis of 3a, 4g, 5a and 5g. Compounds 4a, 4b and 4g were investigated pharmacologically to determine their effect on the central nervous system (CNS) in mice.

Keywords: 1,2,4-Triazoles; 1,3,4-Thiadiazoles; Thiosemicarbazides; Cyclizations; X-Ray diffraction; Crystal structure determination; Pharmacological screening; Antidepressives.

References: 40 live references.