Yokesh Kumar, M (2012) Synthesis and Biological Activity of Novel 2, 5- Disubstituted Benzimidazole Derivatives. Masters thesis, Adhiparasakthi College of Pharmacy, Melmaruvathur.
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Abstract
The study of Synthesize 2-substituted benzimidazole derivatives by both conventional and microwave method and compare the yield. Further the study will extended to introduce substitution on 5th position, and to screen the newly synthesized compounds for their anti-bacterial and anti-fungal activity. PLAN OF THE WORK: Synthesis of 2-subsituted benzimidazole derivatives by conventional Method. Synthesis of 2-subsituted benzimidazole derivatives by Microwave Method and Synthesis of 5-nitro 2-subsituted benzimidazole derivatives. In recent year attention has increasingly been given to the synthesis of benzimidazole derivatives as a source of new anti-microbial agents. The synthesis of novel benzimidazole derivatives remain a main focus of medicinal research. In order to expand the group of benzimidazole derivatives, we synthesized several new benzimidaole ring containing compounds. The O-phenylene diamine reacted with appropriate carboxylic acid under harsh dehydrating reaction condition to give the corresponding benzimidazole in good yield by Phillips reaction. The same was repeated by using microwave irradiation to give the corresponding benzimidazole in excellent yields. Then, a series of 5- nitro substituted benzimidazole derivatives were synthesized using nitration reaction by using Conc. HNO3 and Conc. H2SO4. Then 5-nitro substituted benzimidazoles were reduced by using a mixture of Zn/NaOH to give 5-amino substituted benzimidazoles. The purity of the synthesized compounds were checked by performing TLC (Rf) and determining melting points. Since our titled compounds were known to possess anti-microbial activity, the synthesized compounds were screened for their anti-bacterial and anti-fungal activity. The structure of the synthesized compounds were establ ished by spectral (IR, 1H NMR and Mass) analysis data. The NH band (3463-3114 cm-1) and NH proton signal (5.0 ppm) of 2-substituted benzimidazole in IR and 1H NMR spectrum respectively in the synthesized compounds, (SY1-SY5) confirmed the formation of benzimidazole nucleus. In SY1, 1H NMR spectrum showed a 2 proton singlet at δ 1.5 and δ 3.82 for 3 protons confirmed the presence of methane thiol group. In SY2, multiplet at δ 3.12 for 1 proton and doublet at δ 1.29 for 6 protons indicated the formation of iso-propyl group. In SY3, two triplet at δ 2.55 and 0.96 for 5 protons and two multiplet at δ 1.62 and δ 1.37 for 4 protons indicated the presence of butyl group. In SY4, two multiplet at δ 7.23-7.26 and δ 6.52 for 4 protons and a singlet at δ 4.0 for 2 protons indicated the presence of amino phenyl group. In the case of SY5, two multiplet at δ 8.25 and δ 7.74 for 4 protons indicated the substitution of nitro phenyl group at C2 of benzimidazole nucleus. The presence of nitro group in SY6-SY10 was ascertained from strong bands at 1584 -1532 cm-1 and 1345 cm-1 corresponding to asymmetric and symmetric O=N=O stretch respectively. Further a strong intensity signal at 1231-846 cm-1 was attributed to the C-N stretching for aromatic nitro compounds. Spectrum of SY6-SY10 in the aromatic region indicated that the three chemical environments at δ 8.63, 8.19 and 7.96, instead of two regions which were present in SY1-SY5. The maximal downfield one proton singlet at δ 8.63 was assigned to C-4 proton. The second proton (C-6), ortho to nitro group appeared at δ 8.19 as doublet (J = 4.5 Hz) due to ortho coupling with C-7 proton. The remaining C-7 proton was observed as a one proton doublet at δ 7.96 (J= 8.8 Hz) due to ortho coupling with C-6 proton. The presence of primary amino group in SY11-SY15 was ascertained from strong bands at 3500 cm-1 and 3400 cm-1 corresponding to asymmetric and symmetric H-N-H stretch respectively. Further a strong signal at 1648-1622 cm-1 was attributed to N-H bending for primary amino group. In SY11 – SY15, a singlet at δ 3.48 for 2 protons indicated the presence of primary amino group. In the mass spectrum of the synthesized compounds produced (M+ ) Molecular ion peaks at 179.24, 175.23, 189.25, 224.26, 254.24 values for SY11, SY12, SY13, SY14 and SY15 respectively corresponds to their molecular formulas. The predicted chemical structure of titled compounds was further supported by the fragmentation peaks. All the synthesized compounds exhibited good activity against the studied set of microorganisms. Since a fewer species have been used in this study, it is warranted to screen these compounds with varied species and resistant strains. All the compounds showed very good anti- bacterial and anti-fungal activity even at less concentration. From the data, it is evident that the compound SY15 is a most potent candidate against anti-bacterial studies and compound SY12 is a much potent candidate for anti-fungal studies. Even though, the antimicrobial activity of tested compounds was less than their standard compounds are ciprofloxacin (antibacterial) and ketoconazole (antifungal) in the present study. In future study, it could be increased (or) equalized by altering the number of carbon atoms in side chain (or) introducing aromatic ring (or) substituted aromatic ring (or) heterocyclic ring (or) by introducing double bond in side chain in the 2nd position of benzimidazole nucleus. Further experiments were needed to elucidate their exact mechanism of activity. These results suggest that the tested derivatives of benzimidazoles have excellent scope for further development as commercial anti-bacterial and anti-fungal agents. In future study the activity of the compounds may be manipulated by introducing unsaturation or heterocyclic ring at C2 of benzimidazole.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Synthesis; Biological Activity; Novel 2; Benzimidazole Derivatives; Ciprofloxacin antibacterial; Ketoconazole antifungal |
| Subjects: | PHARMACY > Pharmaceutical Chemistry |
| Depositing User: | Ravindran C |
| Date Deposited: | 17 Aug 2017 07:02 |
| Last Modified: | 17 Aug 2017 07:02 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/2660 |
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