Article

 

Convenient Synthesis and Biological Activity of 4-Aminomethylene 1-phenylpyrazolidine-3,5-diones

 

Eman A. Ahmed

 

Chemistry Department, Faculty of Science, Sohag University, 82524 Sohag, Egypt. E-mail: abdala_15@yahoo.com. Tel.: +20934601159.

 

Received April 1^st, 2015;
Accepted August 3^rd, 2015.

 

Abstract

Reaction of (Z)-4-((dmethylamino)methylene)-1-phenylpyrazolidine-3,5-dione (1) with different nucleophiles is described. Treatment of enaminone 1 with phenylhydrazine led to 3-oxo-W,2-diphenyl-2,3-dihydro-1H-pyrazole-4-carbohydrazide 7. New enaminone derivatives 2-6 and 12-14 were conveniently obtained in high yields via nucleophilic substitution of the dimethylamino group in enaminone 1 when reacted with o-aminophenol, o-aminothiophenol, ethanolamine, cysteamine hydrochloride, piperidine, morpholine, 2-aminopyridine and glycine. Reaction of enaminone 1 with diaza-nucleophiles, such as hydrazine hydrate, ethylenediamine and o-phenylenediamine, afforded the corresponding bis-enaminones 9-11. Anti-inflammatory and antimicrobial activities of some new products were evaluated. Compounds 1, 2, 4, 7, 12a, and 12b showed high anti-inflammatory activity compared with indomethacin as the reference, while the highest antimicrobial effect was observed in the case of compound 3.

Key words: pyrazolidine-3,5-diones, enaminones, nucleophiles, anti-inflammatory activity, antimicrobial activity.

 

Resumen

Se describe la reacción de (Z)- 1-fenil-4-((dimetilamino) metilen)pirazolidin-3,5-diona (1) con diferentes nucleófilos. El tratamiento de la enaminona 1 con fenilhidrazina condujo a la N', 2-difenil-2,3-dihidro-3-oxo-1H-pirazol-4-carbohidrazida 7. Los nuevos derivados enaminónicos 2-6 y 12-14 se obtuvieron convenientemente en elevados rendimientos vía sustitución nucleofílica del grupo dimetilamino en la enaminona 1 cuando reaccionó con o-aminofenol, o-aminotiofenol, etanolamina, clorhidrato de cisteamina, piperidina, morfolina, 2-aminopiridina y glicina. La reacción de 1 con diaza-nucleófilos, tales como hidrato de hidrazina, etilendiamina y o-fenildiamina, proporcionó las bis-enaminonas correspondientes 9-11. Se evaluó la actividad anti-inflamatoria y antimicrobiana de algunos productos nuevos. Los compuestos 1, 2, 4, 7, 12a y 12b mostraron elevada actividad anti-inflamatoria en comparación a la indometacina como compuesto de referencia, mientras que se observó la más elevada actividad antimicrobiana para el compuesto 3.

Palabras clave: pirazolidin-3,5-dionas, enaminonas, nucleófilos, actividad anti-inflamatoria, actividad antimicrobiana.

 

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