Synthesis and antimicrobial activity of some new imidazolinone derivatives containing benzimidazole

In this study some new o-benzimidazol-2'-yl-benzamido-p'-benzamido-2-phenyl-4-substituted phenyl-5-oxo-Imidazolines 3a-3j were synthesized . To synthesized target molecules we used various substituted oxazolone derivatives, synthesized from substituted benzaldehyde with hippuric acid. Substituted oxazolones 2a-2j were reacted with carbohydrazide derivative of benzimidazole 1 in presence of pyridine as base to obtained substituted imidazolinone derivatives. All synthesized compounds were characterized by IR, 1 H NMR, elemental analysis and further supported by mass spectroscopy. All synthesized compounds were screened for their antimicrobial activity against gram positive and gram negative bacteria which showed moderate to good activity. All compounds showing good to moderate active against fungal strain as compare to standard drug.


EXPERIMENTAL
All chemicals and solvents were purchased from Spectrochem Pvt Ltd., Mumbai of AR grade and were used without further purification. Melting points were taken in open capillary method and are uncorrected. IR spectra were recorded on FTIR-8400 spectrophotometer (Shimadzu, Kyoto, Japan), using DRS prob. KBr pallet. 1 H-NMR spectra of the synthesized compounds were recorded on a Bruker-Avance-II (400 MHz) DMSO-d 6 solvent. Chemical shifts are expressed in δ ppm downfield from TMS as an internal standard. Mass spectra were determined using direct inlet probe on a GCMS-QP 2010 mass spectrometer (Shimadzu, Kyoto, Japan). Physical constants of the synthesized compounds 3a-3j are shown in Table 1.
Step 2: A mixture of o-benzoylene 2-1-benzimidazole (1 mmol) and benzocaine (1 mmol) were refluxed for 4-5 hours in DMF at 150 °C. Completion of reaction was monitored by TLC. Pour the reaction in chilled water and filter out the precipitate of crude product. Dry in vacuo. Crystalline from DMSO to obtained analytical grade pure 2-o-(4'-carbethoxyphenyl amino carbonyl phenyl) benzimidazole. Yield 85 %.

3. General procedure for the synthesis of o-benzimidazol-2'-yl-benzamido-p'benzamido-2-substituted phenyl-4-substituted phenyl-5-oxo-Imidazolines (3a-j)
A mixture of compound 1 (1 mmol) and substituted compound 2a-2j (1 mmol) was placed in a round bottom flask and 10 ml of pyridine were added to it. The reaction mixture was refluxed in oil bath (Scheme III). The progress of the reaction was checked by TLC. After completion of the reaction, reaction mass was poured into ice-cold water and then a required amount of conc. 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 DMSO.

ANTIMICROBIAL ACTIVITY
The MICs of synthesized compounds were carried out by broth micro dilution method as described by Rattan 26]. Antibacterial activity was screened against two gram positive (Bacillus megaterium, Streptococcus citreus) and two gram negative (Escherichia coli, Salmonella typhosa) bacteria. Ampicillin, norfloxacacin and chloramphenicol were used as a standard antibacterial agent.
Antifungal activity was screened against Aspergillus Niger. Greseofulvin was used as a standard antifungal agent. The obtained results for compounds 3a-3j are recorded in Table 2.
International Letters of Chemistry, Physics and Astronomy Vol. 29

CONCLUSION
In present report, we synthesized new carbohydrazide derivative of benzimidazole from very cheap starting material. Synthesis of some new imidazolinone derivatives (3a-3j) were carried out by reaction of carbohydrazide 1 with substituted oxazolone derivatives (2a-2j).

ILCPA Volume 29
All synthesized compounds were obtained in good to moderate yield. The synthesized compounds were characterized by 1 H NMR, Mass and IR spectroscopy and the obtained results are showing good agreement with the synthesized structures. From the results of antimicrobial data, compounds 3j containing 4-Br group is most active for antimicrobial activity as compared to others.