Metal-induced cyclization of thiosemicarbazones derived from beta-keto amides and beta-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 (HTSC(1), HTSC(2), HTSC(3), and HTSC(4), respectively) were explored in methanol. With HTSC(1), HTSC(2), and HTSC(3), following isolation of the corresponding zinc(II) thiosemicarbazonates [Zn(TSC(x))(2)] (x = 1, 2, 3), the mother liquors afforded pyrazolonate complexes [ZnL(1)(2)(H(2)O)] (HL(1) = 2,5-dihydro-3-methyl-5-oxo-1H-pyrazole-1-carbothioamide) that had been formed by cyclization of the corresponding TSC(-). The reaction of HTSC(4) with zinc(II) acetate gave only the pyrazolonate complex [ZnL(2)(2)(H(2)O)] (HL(2) = 2,5-dihydro-3,4-dimethyl-5-oxo-1H-pyrazole-1-carbothioamide). All compounds were studied by IR and NMR spectroscopy, and HTSC(3), [Zn(TSC(3))(2)] x DMSO, [ZnL(1)(2)(H(2)O)] x 2DMSO, and [ZnL(2)(2)(H(2)O)] x 2DMSO were also studied by X-ray diffractometry, giving a thorough picture of the cyclization process. In preliminary tests of the effects of HL(1) and [ZnL(1)(2)(H(2)O)] on rat paw inflammatory edema induced by carrageenan, HL(1) showed antiinflammatory activity.
Casas
José S
JS
Departamento de Química Inorgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Galicia, Spain. qiscasas@usc.es
Castaño
María V
MV
Castellano
Eduardo E
EE
Ellena
Javier
J
García-Tasende
María S
MS
Gato
Angeles
A
Sánchez
Agustín
A
Sanjuán
Luisa M
LM
Sordo
José
J
D000577:Amides / Q000737:chemistry*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000627:therapeutic use; D002351:Carrageenan / Q000737:chemistry* / Q000627:therapeutic use; D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D004487:Edema / Q000139:chemically induced; D004952:Esters / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
C453659:2,5-dihydro-3-methyl-5-oxo-1H-pyrazole-1-carbothioamide; D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004952:Esters; D009942:Organometallic Compounds; D011720:Pyrazoles; D013854:Thioamides; D002351:Carrageenan; D015032:Zinc