Synthetic Transformation of 4-fluorobenzoic acid to 4-fluorobenzohydrazide Schiff Bases and 1,3,4-Oxadiazole Analogs having DPPH Radical Scavenging Potential

Abstract

Aims: Synthesis of 4-fluorobenzohydrazide Schiff bases and 1,3,4-oxadiazole analogs has DPPH radical scavenging potential. Background: Synthetic antioxidants are widely used because they are effective and cheaper than natural antioxidants. On the basis of the literature survey, this present study is mainly focused on the study of free radical scavenging activity of the Schiff base and oxadiazole motifs. Method: In this research work, Schiff’s base (4a-4g) and 1,3,4-oxadiazole (5a-5g) derivatives based on 4-fluorobenzoic acid were synthesized through multistep reactions. Initially, 4-fluorobenzoic acid was esterified in the presence of sulphuric acid (H2SO4) in ethanol solvent, and then it was reacted with an excess of hydrazine hydrate to obtain the desired 4-fluorobenzohydrazide. Various aromatic aldehydes were reacted with 4-fluorobenzo hydrazide in the presence of catalytic amount of acetic acid to obtain the desired hydrazones. Finally, different substituted hydrazones were cyclized in the presence of iodine and potassium carbonate in DMSO to obtain substituted 1,3,4-oxadiazoles. The progress of all reactions was checked using thin layer chromatography. The compounds were recrystallized from ethanol with good yield. The synthesized compounds were characterized with the help of EI-MS and 1H-NMR spectroscopy. Results: The synthesized Schiff bases (4a-4g) and oxadiazole derivatives (5a-5g) of 4-fluorobenzoic acid demonstrated good free radical scavenging activity. Among the series, Compound 4f (IC50 = 25.57 ± 7.41 µM), showed comparable activity when compared with the standard Vitamin C (IC50 = 19.39 ± 12.57 µM). Similarly Compound 4a (IC50 = 40.90 ± 1.92 µM), 4b (IC50 = 34.77 ± 1.03 µM), 4c (IC50 = 90.2 ± 2.90 µM), 4e (IC50 = 78.62 ± 9.64 µM), 4g (IC50 = 80.65 ± 1.80 µM), 5a (IC50 = 52.67 ± 4.98 µM) and 5f (IC50 = 89.45 ± 9.11 µM) showed moderate anti-oxidant activity. Furthermore compounds, 4d (IC50 = 102.55 ± 10.4 µM), 5b (IC50 = 123.76 ± 12.34 µM), 5d (IC50 = 701.62 ± 1.06 µM), and 5e (IC50 = 102.87 ± 7.98 µM) displayed less significant anti-oxidant potential, while compounds 5c and 5g were found inactive. Conclusion: Schiff’s base (4a-4g) and substituted 1,3,4-oxadiazole (5a-5g) derivatives based on 4-fluorobenzoic acid scaffolds were synthesized using standard pathways. All compounds were structurally characterized through EI-MS and 1H-NMR spectroscopy and evaluated for their in vitro DPPH free radical scavenging activity. In-vitro study reveals that the newly prepared derivatives of 4-fluorobenzoic acid have potent antioxidant potential. Whereas compound 5c and 5g was found inactive, this study has recognized a series of potential molecules as antioxidant agents and is useful in the field of medicinal chemistry.