Novel Synthesis of 1,3,4‐Thiadiazine Derivatives and Their Cycloaddition Reactions

Abstract

4-Phenyl-3-thiosemicarbazide 1 reacted with the alpha-halocarbonyl compounds 2a, b to give the thiosemicarbazone derivatives 3a, b. The latter compounds underwent cyclization to the 1,3,4-thiadiazine derivatives 4a, b which underwent [2 + 4] cycloaddition reactions to give the 4H-thiopyran derivatives 7a, b. The chemistry of these thiopyrans was studied. Some of the fused derivatives among them compounds 20a, 20b, 21a, 21b allowed good mycelial growth and sporulation by the two fungi. This indicates that the two fungi can use the N-containing heterocyclic ring as a nitrogen source.

Convenient synthesis and X-ray determination of 2-amino-6H-1,3,4-thiadiazin-3-ium bromides endowed with antiproliferative activity

“… 37 Several methods synthesized 1,3,4-thiadiazine, including interactions between thiosemicarbazides and α-halo ketones in different solvents. 38,39 However, Aly et al 40 demonstrated the one-pot synthesis of 2-ylidenehydrazonothiazoles from the reaction of 4-substituted thiosemicarbazides, ketones, and phenacyl bromide, and they proposed that the product was obtained through the formation of the hydrazinylthiazole intermediate, which contradicted the findings of Pfeiffer et al 41 …”

“…37 Several methods synthesized 1,3,4-thiadiazine, including interactions between thiosemicarbazides and a-halo ketones in different solvents. 38,39 However, Aly et al 40 demonstrated the one-pot synthesis of 2-ylidenehydrazonothiazoles from the reaction of 4-substituted thiosemicarbazides, ketones, and phenacyl bromide, and they proposed that the product was obtained through the formation of the hydrazinylthiazole intermediate, which contradicted the ndings of Pfeiffer et al 41 In light of the previous data on the multitargeted inhibitory action of 1,3,4-thiadiazine derivatives and our ongoing efforts to develop multitargeted anti-cancer agents, 6,7,19,[42][43][44] this investigation focuses on the synthesis of new 1,3,4-thiadiazine derivatives (9a-g, Fig. 1) as multitargeted antiproliferative agents.…”