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Synthesis, characterization and biological activity of some new 1,3,4-oxadiazole bearing 2-flouro-4-methoxy phenyl moiety

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Abstract

In the present study a series of new 1,3,4-oxadiazole derivatives containing 2-fluoro-4-methoxy moiety were synthesized. These newly synthesized compounds were characterized by NMR, mass spectral, IR spectral study and also by C, H, N analyses. All the newly synthesized compounds were screened for their antibacterial and antifungal studies. Antimicrobial studies revealed that compounds 4a and 4b showed significant antibacterial activity against Escherichia coli and Pseudomonas aeruginosa Compound 4i showed significant antifungal activity against C. albicans.

Graphical abstract

In the present investigation, a new series of 1,3,4-oxadiazoles bearing 2-flouro 4-methoxy phenyl moiety were synthesized, characterized and their antimicrobial studies were performed. Few of the compounds showed significant antimicrobial activity.

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Introduction

1,3,4-Oxadiazole is a versatile lead molecule for designing potential bioactive agents. The 1,3,4-oxadiazole derivatives have been found to exhibit diverse biological activities such as antimicrobial [1], anti-HIV [1], antitubercular [2], antimalarial [3], analgesic [4], anti-inflammatory [5], anticonvulsant [6], hypoglycemic [7] and other biological properties such as genotoxic studies [8] and lipid peroxidation inhibitor [9].

Used extensively in the symptomatic treatment of rheumatic fever, arthritis [10] (rheumatoid, osteo and Jaundice arthritis), myocardial infarctions and management of primary dysmenorrheal [11]. The major side effects in the use of aryl alkanoic acids is their gastric irritation, which is partly due to the corrosive nature of carboxylic acid group present in them. In order to reduce or mask the side effects of carboxylic moiety we planned to synthesize different 2,5-disubstituted-1,3,4-oxadiazoles (4am) via the condensation of 4-hydroxybenzohydrazide with various aromatic acids in presence of phosphorus oxychloride respectively in the hope of getting potent biodynamic agents and evaluate their antimicrobial activity.

Further fluorine containing molecules showed wide spectrum antimicrobial and biological properties. Keeping in view of these and in continuation of our research on biologically active molecules, we hereby report the synthesis of some novel 1,3,4-oxadiazoles containing 2-fluoro-4-methoxy phenyl containing moieties.

Section snippets

Chemistry

2-Fluoro-4-methoxybenzoic acid was converted into ethyl 2-fluoro-4-methoxybenzoate 2, by the esterification reaction using known procedure [12]. Further this ester was converted into 2-fluoro-4-methoxybenzohydrazide 3, by reacting with hydrazine hydrate in ethanol medium. Title compounds 2-(2-fluoro-4-methoxyphenyl)-5-substituted-1,3,4-oxadiazoles were synthesized by refluxing equimolar mixture of 2-fluoro-4-methoxybenzohydrazide 3, with different aromatic carboxylic acid (am) in phosphorous

Antimicrobial studies

All the newly synthesized oxadiazoles were screened for their antibacterial and antifungal activity. For antibacterial studies microorganisms employed were Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. For antifungal, Candida albicans was used as organism. Both microbial studies were assessed by Minimum Inhibitory Concentration (MIC) by serial dilution method [13]. For this, the compound whose MIC has to be determined is dissolved in serially diluted

Results and discussion

Formation of 2-(2-fluoro-4-methoxyphenyl)-5-substituted-1,3,4-oxadiazoles was confirmed by recording their IR, 1H NMR and mass spectra. IR spectrum of oxadiazole 4a showed absorption at 3097 cm−1 which is due to the aromatic stretching. An absorption band at 1594 cm−1 is due to the Cdouble bondN group, band at 1057 cm−1 is due to stretching of oxadiazole ring and the absorption band appeared at 1093 cm−1 is due to C–F group.

The 1H NMR spectrum of 4a showed multiplet in the region of δ, 8.07–7.00. δ, 8.07 is

Conclusions

A series of novel 2-(2-fluoro-4-methoxyphenyl)-5-substituted-1,3,4-oxadiazoles were synthesized and characterized by 1H NMR, Mass spectrometry and IR studies. All the newly synthesized compounds were screened for their antibacterial and antifungal activity. Among the screened samples, compounds 4a and 4b showed excellent antibacterial activity against E. coli and P. aeruginosa even at low concentration of 3 μg/ml. Compound 4a has 3-bromo-2-methyl phenyl group and 4b has 2,3,4-trifluoro phenyl

Experimental

Melting points were determined by open capillary method and were uncorrected. Elemental analysis was performed on Thermo Finningan FLASH EA 1112 CHN analyzer. The IR spectra (In KBr pellets) were recorded on a Shimadzu FT-IR 157 spectrophotometer. 1H NMR spectra were recorded on a Perkin–Elmer EM 300 MHz spectrometer using TMS as internal standard. Mass spectra were recorded on LC–MS-Aglilent 1100 series with MSD (Ion trap) using 0.1% aqueous TFA in acetonitrile system on C18-BDS column for 10 

Acknowledgements

AMI is thankful to Director, NITK Surathkal, India for providing research facilities and also to Board of Research in Nuclear Sciences, Department of Atomic Energy, Government of India for YOUNG SCIENTIST award. C.B is thankful to Dr. John Kallikat and Premsai Rai. N of Syngene International Ltd. Bangalore, India, for their encouragement.

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