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

• Published in: Inorganic chemistry Vol. 41; no. 6; pp. 1550 - 1557
• Main Authors: Casas, José S, Castaño, María V, Castellano, Eduardo E, Ellena, Javier, García-Tasende, María S, Gato, Ángeles, Sánchez, Agustín, Sanjuán, Luisa M, Sordo, José
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25.03.2002
• Subjects: Amides - chemistry; Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Carrageenan - chemistry; Carrageenan - therapeutic use; Catalysis; Crystallography, X-Ray; Cyclization; Edema - chemically induced; Esters - chemistry; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Pyrazoles - chemistry; Rats; Rats, Sprague-Dawley; Spectrophotometry, Infrared; Structure-Activity Relationship; Thioamides - chemistry; Zinc - chemistry
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/ic0111942

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(TSC x )2] (x = 1, 2, 3), the mother liquors afforded pyrazolonate complexes [ZnL1 2(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 [ZnL2 2(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, [ZnL1 2(H2O)]·2DMSO, and [ZnL2 2(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 [ZnL1 2(H2O)] on rat paw inflammatory edema induced by carrageenan, HL1 showed antiinflammatory activity.