1.2.4- Triazoles thiosemicarbazones

Mercaptotriazoles 133, available from thiosemicarbazones, are versatile starting materials for the preparation of thiazolo[3,2-h][l,2,4]triazoles. Treatment with a-halo ketones (and esters) yields S-alkylated derivatives that are cyclized to 134 either directly or on treatment with acidic catalysts (e.g., P2O5/H3PO4). 

Thiosemicarbazone 4 reacted in a similar manner to give l,2,4-triazole-3-one 5 in good yield (1986JHC881), whereas at lower temperature (40 °C), unexpectedly, 2-methylamino-5-phenyl-l,3,4-thiadiazole 6 was isolated in low yield (Scheme 4). 

The proposed mechanism includes the addition of sulfur monochloride to the N-H bond of semicarbazone or thiosemicarbazone with the formation of an N-S-S-Cl intermediate followed by its cyclization into the triazole or thiadiazole ring with the extrusion of two sulfur atoms and HCl. 

The treatment of the 2-(4-chloromethylthiazol-2-yl)hydrazone of a heteroaromatic aldehyde (196) (formed as an intermediate in the reaction of some thiosemicarbazones with 1,3-dichloroacetone) with acetic anhydride gives rise to 3-hetaryl-substituted 2-acetyl-5-chloromethyl-2,3-dihydro-thiazolo[2,3-c][ 1,2,4]triazoles (197) (Scheme 17) <92JIC596>. 

Chemistry and heterocyclization of thiosemicarbazones. Synthesis of pyrrohdine, thiazole, thiazoline, thiazohdine, pyrazole, thiadiazole, oxa-(hazole, triazole, pyridazine, thiazine, and triazine derivatives and fused heterocycles 12JHC21. 

Reactions.— Recent studies of the nucleophilic reactivity of the thiocarbonyl sulphur atom of thiosemicarbazides have dealt largely with heterocycles containing the thiosemicarbazide or the thiosemicarbazone moiety, and comprise methylation reactions of 3-methyl-l,2,4-triazole-5-thiones and... 

The ability of thiosemicarbazides, thiosemicarbazones, thiocarbohyd-razides, and their selenium analogues to undergo a variety of cyclization reactions has been further exemplified in recent syntheses of derivatives of 1,3,4-thiadiazoles, " 1,3,4-selenadiazoles, - l,3,4-triazole-2-thiones, " quinazoline-2-thiones, l,2,4-triazine-2-thiones, and pyrimido[2, l-b]benzothiazoles. ... 

---