Synthesis and Antimicrobial Activity of 5-Imidazolinone Derivatives

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Desai et al. [14] have synthesized 4-benzylidene-2-phenyloxazole-5-one based on the methods descried in the literature which is a special type of Perkin condensation in which reaction between aldehyde and benzoylglycine proceeds first followed by ring closer.It is observed that aldehyde condenses under the influence of a base with the reactive methylene group in the azalactone which is formed by the dehydration of benzoylglycine, when the latter reacts with Ac 2 O in presence of sodium acetate.In view of these observations, we have synthesized imidazol-5-ones (Scheme I, Table 1).

Pyridine
Where, R = Cl and R' = H (5a-o) Where, R = Cl and R' = Cl (6a-m) Where, Ar= Different aryl groups Other compounds of the series were prepared by using a similar method and their physical data are recorded in Table 1.
The reaction mixture was refluxed on a sand bath for 6 h (Scheme I).The mixture was poured into ice-cold water and then required amount of con.hydrochloric acid was added to neutralize the reaction mixture.The solid obtained was left overnight, filtered and washed with water.The product was dried and recrystallized from ethanol (99%).
Antibacterial activity was carried out by broth dilution method [21] .The strains used for the activity were procured from Institute of Microbial Technology, Chandigarh.The compounds 4a-q, 5a-o and 6a-m were screened for their antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Staphylococcous pyogenes at concentrations of 1000, 500, 200, 100, 50, 25, 12.5 µg/ml respectively (Table 2).Same compounds were tested for antifungal activity against C. albicans, A. niger and A. clavatus at concentrations of 1000, 500, 200, and 100 µg/ml respectively (Table 2).The results are recorded in the form of primary and secondary screening.
The synthesized compounds found to be active in the primary screening were further tested in a second set of dilution against all microorganisms.The compounds found active in primary screening were similarly diluted to obtain 100, 50, 25 μg/ml concentrations.Ten microlitres suspensions from each well were further inoculated on appropriate media and growth was noted after 24 and 48 h.The lowest concentration, which showed no growth after spot subculture was considered as MBC/MFC for each drug.The highest dilution showing at least 99% inhibition was taken as MBC/MFC.The result Gentamycin is used as standard for antibacterial activity which showed (0.05, 0.25, 0.5 and 1 μg/ml) MBC against E. coli, S. aureus, S. pyogenus and P. aeruginosa respectively.K nystatin was used as the standard for antifungal activity which showed 100 µg/ml MFC against fungi, used for the antifungal activity.*All the compounds were tested for the antibacterial and antifungal activities but data of active compounds have been reported as present protocol of this test is affected by the size of the inoculums.The test mixture should contain 10 8 organisms/ml.For antibacterial activity, in present protocol 50 µg/ml is considered as active as compared to the standard drug gentamycin.For antifungal activity, 100 µg/ml is considered as active as compared to standard nystatin.Compounds 4a, 4b, 4i, 4j, 4k, 4q and 5e are active on E. coli where as 4b and 5e are active on P. aeruginosa.Compound 4k is active on S. aureus and 6m is also active on S. pyogens.Compounds 4f, 5b, 6f, 6l, and 6m are active on fungi strains.On the basis of biological activity results, it may be concluded that the introduction of OH, OCH 3 , NO 2 , Cl and Br groups to the heterocyclic frame work enhanced antibacterial and antifungal activities.

: Synthetic pathway for synthesis of 5-imidazolone derivatives acid
was added to neutralize the reaction mixture.The progress of the reaction and the purity of compounds were routinely checked on TLC.The solid obtained was left overnight, filtered and washed with water.The product was dried and recrystallized from ethanol (99%).m.p.195° Yield 53% anal.found: C, 57.06; N, 5.98; calc for C 22 H 12 Cl 4 N 2 O: C, 57.17; N, 6.06%.