Metal-Induced Cyclization of Thiosemicarbazones Derived from β-Keto Amides and β-Keto Esters: Open-Chain and Cyclized Ligands in Zinc(II) Complexes

The reactions of Zn(OAc)2 with acetoacetanilide, methyl acetoacetate, o-acetoacetanisidide, and ethyl 2-methylacetoacetate thiosemicarbazones (HTSC1, HTSC2, HTSC3, and HTSC4, respectively) were explored in methanol.
With HTSC1, HTSC2, and HTSC3, following isolation of the corresponding zinc(II) thiosemicarbazonates [Zn(TSCx)2]
(x = 1, 2, 3), the mother liquors afforded pyrazolonate complexes [ZnL12(H2O)] (HL1 = 2,5-dihydro-3-methyl-5-oxo-1H-pyrazole-1-carbothioamide) that had been formed by cyclization of the corresponding TSC-. The reaction
of HTSC4 with zinc(II) acetate gave only the pyrazolonate complex [ZnL22(H2O)] (HL2 = 2,5-dihydro-3,4-dimethyl-5-oxo-1H-pyrazole-1-carbothioamide). All compounds were studied by IR and NMR spectroscopy, and HTSC3,
[Zn(TSC3)2]·DMSO, [ZnL12(H2O)]·2DMSO, and [ZnL22(H2O)]·2DMSO were also studied by X-ray diffractometry,
giving a thorough picture of the cyclization process. In preliminary tests of the effects of HL1 and [ZnL12(H2O)] on
rat paw inflammatory edema induced by carrageenan, HL1 showed antiinflammatory activity.