Hemachander, R (2012) Synthesis, Spectral Analysis and Biological Evaluation of Some Novel Fluorobenzothiazole Incorporated 1, 3, 4 –Thiadiazole. Masters thesis, Adhiparasakthi College of Pharmacy, Melmaruvathur.
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Abstract
The study to developing potential therapeutic agents and studying their chemistry we undertook the synthesis of biologically active fluorobenzothiazole incorporated with 1,3,4 - thiadiazole compounds for anti-bacterial and anti-inflammatory activity with minimum toxic levels. In recent year attention has increasingly been given to the synthesis compounds with combination of two heterocyclic nucleuses. In order to expand this we synthesized compounds which contains benzothiazole and 1,3,4 thiadiazole nucleuses. Individually benzothiazole and 1,3,4 thiadiazole nucleuses possess numerous biological activities as documented in literature. Hence this versatile biological significance inspired us to synthesize the compounds which contain combination of these two moieties in hope of getting molecules with biodynamic potentials. Fluorine has become an essential tool in drug discovery, including fluorine atom in potential medicines can have a variety of dramatic effects on the molecular properties perhaps making them more selective, increasing efficacy. Hence the 3-chloro, 4-fluoro aniline was selected as starting molecule to synthesize fluorobenzothiazole incorporated with 1,3,4 – thiadiazole. 3-chloro 4-fluoro-aniline reacted with potassium thiocynate in the presence of glacial acetic acid and bromine at 0° C to give the corresponding 2-amino-6-fluoro-7- chloro-(1,3)- benzothiazole, which further reacts with hydrazine hydrade, ammonia, carbon disulphide, sodium chloroacetate in the presence of ethanol to form 2- thiosemicarbazide substituted 6-fluoro-7-chloro-(1,3)-benzothiazole. The third step involves acyclation of 2-thiosemicarbazide followed by dehydrative cyclization using phosphorous oxy chloride to form 1,3,4 thiadiazole moiety, in this step different aromatic acids were also substituted. Then the 1,3,4 thiadiazole substituted compound was treated with ortho and para nitro anilines, in the presence of DMF to obtain different fluorobenzothiazole incorporated 1,3,4 thiadiazole compounds. The purity of the synthesized compounds was checked by thin layer chromatography (Rf) and determining melting point. The structure of the synthesized compounds were established by spectral (IR, 1H NMR and Mass) analysis data. In SH1, the NH band at 3228 cm-1 and NH proton signal δ 4.0 of 2-amino benzothiazole in IR and 1H NMR spectrum respectively confirmed the formation of benzothiazole nucleus. In SH2, three protons singlet at δ 2.0 and one proton singlet at δ 4.0 confirmed the formation of thiosemicarbazide group. In the compounds SH3, SH4, SH5 C = N band (1653 – 1632 cm-1) and C – S band (645 - 642 cm-1) of IR spectrum conforms the formation of 1,3,4 thiadiazole nucleus. In SH3, two doublets at δ 6.3 and one doublet proton at δ 7.4 indicates the formation of furan ring. In SH4, three doublet protons at δ 8.85, δ 7.97, δ7.44 and one singlet proton at δ 8.81 conforms the formation of an aromatic nucleus. In the case of SH5, two triplets at δ 6.97, 6.68 and two doublet at δ 7.23, 6.52 indicates the formation of an aromatic nucleus. The presence of nitro group in SH6-SH11 was ascertained from strong bands at (1584 -1510 cm-1) and (1365-1335 cm-1) corresponding to asymmetric and symmetric O=N=O stretching respectively. The C – Cl stretching band which appeared at SH1- SH5 at (809 – 683cm-1) was disappeared in SH6-SH11. Instead, C – N stretching band appeared at (1346.02-1255.90cm-1) in SH6-SH11 indicated the attachment of ortho nitro aniline (or) and para nitro aniline group. In compounds SH6, SH8, SH10, two doublet for 2 protons (δ 8.20, δ 7.17- δ7.46) and two triplet protons at (δ 7.68, δ 7.60) confirmed the presence of nitro group at ortho position in the aromatic ring. In compounds SH7, SH9. SH11 two 143 doublet protons at (δ 7.26- δ 7.34, δ 8.03 - δ 8.04) confirmed the presence of nitro group at para position in aromatic ring. In the Mass spectrum, synthesized compounds produced (M+) Molecular ion peaks at 351.12, 362.21, 376.16, 454.45, 454.45, 463.48, 463.48, 479.51 and 479.51 values for SH3, SH4, SH5,SH6, SH7, SH8, SH9, SH10,and SH11 respectively, corresponds to their molecular formulas. The predicted chemical structure of titled compounds was further supported by the fragmentation peaks. All the compounds showed very good antibacterial and antifungal activity even at less concentration. From the data, it is evident that the compound SH6 and SH8 was the most potent candidate against Micrococcus leutus and Proteus vulgaris in the anti-bacterial studies and compound SH11 was the much potent candidate against Aspergillus flavus in the antifungal studies. Since a fewer species have been used in this study, it was warranted to screen these compounds with varied species and resistant strains. The anti-inflammatory activity confirmed that the test compound SH11 showed superior activity in the inhibition of oedema than SH8. However, both the test compounds were found to less activity than the standard drug. These results suggest that the tested compounds of fluorobenzothiazole incorporated with 1,3,4 thiadiazole have excellent scope for further development as commercial antimicrobial and anti-inflammatory agents. Further experiments were needed to elucidate their exact mechanism of activity.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Synthesis; Spectral Analysis; Biological Evaluation; Novel Fluorobenzothiazole; 1, 3, 4 –Thiadiazole; ortho nitro anilin |
| Subjects: | PHARMACY > Pharmaceutical Chemistry |
| Depositing User: | Ravindran C |
| Date Deposited: | 17 Aug 2017 06:25 |
| Last Modified: | 17 Aug 2017 06:25 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/2652 |
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