Novel Synthesis and Antimicrobial Evaluation of Some New Cyclic Ketones

A series of 5-oxohexannitrile derivatives IIa-d was prepared by reaction of acrylonitrile with ketones Ia-d. On the other hand, semicarbazone derivatives IVa-d were obtained upon reaction of IIa-d with semicarbazide. Hydrolysis and esterification in one step reaction of δ-ketonitrile IIa-d resulted in the formation of the corresponding δ-ketoesters Va-d. The δ-ketoesters Va-d is readily cyclized to the corresponding cyclohexan-1,3-diones VIa-d when heated with alcoholic sodium methoxide. Moreover, coupling of VIa, VIb and VId with aryl diazonium chloride afforded the corresponding 2-(aryl diazenyl) derivatives VIIa-f, respectively. Furthermore, bis-(2,6-diketo-3-phenylcyclohexyl)methane VIII was synthesized by condensing VIa with benzaldehyde. Bromination of VId in dilute acetic acid afforded the corresponding bromo derivative IX. Heating of cyclohexanone-2-methyl propionate in alcoholic sodium methoxide afforded bicycle[1,3,3]nonan-2,9-dione X. These compounds were characterized by analytical and spectral analyses and screened for their antibacterial activity against Gram-possitive bacteria and Gram-negative bacteria. The synthesized compounds (VIIa-f)-X showed significant antibacterial activity against P. Aeruginosa (MIC 0.30-0.45 μg/mL), S. Aureus (MIC 0.25-0.45 μg/mL) and B. Subtilis (MIC 0.20-0.45 μg/mL) and exhibited moderate antibacterial activity against E. Coli (MIC 0.30-0.45 μg/mL) compared with the standard drug Ciprofloxacin.