Details of preparation procedures of synthesized compounds

2-hydroxy-2-phenyl-acetohydrazide (I₁)

Ethyl mandelate (100 mmol, 13.8 mL) was added dropwise to a solution of hydrazine hydrate (100 mmol, 3.2 mL) in ethanol (8 mL) and was refluxed for 4 h. The ethanol was partially removed by vacuum distillation. On cooling the resultant mixture, white needle crystals of 2-hydroxy-2-phenyl-cetohydrazide began to separate. It was collected, filtered, and recrystallized from ethanol.

Diacyl hydrazide intermediates

A solution of the 4-chloro benzoyl chloride (2 mmol, 350 mg) or 4-nitro-benzoyl chloride (2 mmol, 370 mg) in tetrahydrofuran (THF) (3 mL) was added dropwise to the mixture of 2-hydroxy-2-phenyl-acetohydrazide (2 mmol, 330 mg) and THF (5 mL) over 1 h, while stirring at 0 °C. The reaction mixture was stirred for 3 h at room temperature. The solvent was removed in vacuum to furnish a semisolid material which was washed with saturated aqueous NaHCO₃ solution then extracted with ethyl acetate. The organic layer was evaporated to afford the intermediate.

2,5-disubstituted 1,3,4-oxadiazoles (F₁ and F₂)

A mixture of obtained diacyl hydrazide of 4-chloro benzoyl chloride (0.66 mmol, 200 mg) or 4-nitro-benzoyl chloride (0.67 mmol, 200 mg) and POCl₃ (4 mL) was refluxed for 2-3 h. After cooling to room temperature, the reaction mixture was gradually poured into crushed ice with stirring. The aqueous layer was extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate, and finally distilled under reduced pressure to remove the solvent. The resulting solid was recrystallized using ethanol to give the target compounds.

2-(Chloro(phenyl)methyl)-5-(furan-2-yl)-1,3,4-oxadiazole (F₃)

A mixture of 2-hydroxy-2-phenyl-acetohydrazide (6 mmol, 990 mg) and the furan-2-carboxylic acid (5 mmol, 560 mg) in POCl₃ (4 mL) was heated to 70 °C for about 3 h on water bath. The progress of the reaction was monitored on TLC. The reaction mixture was poured into crushed ice with stirring. The resultant solid was collected, washed with water, and purified by column chromatography chloroform:methanol 19:1 to afford an orange powder (40% yield).

2-Hydroxy-N’-5-nitrofuran-2-yl) methylene)-2-phenylacetohydrazide (I₂)

To a stirred solution of 2-hydroxy-2-phenyl-acetohydrazide (1 mmol, 160 mg) and 5-nitrofuraldehyde (1 mmol, 140 mg) in ethanol, glacial acetic acid (0.2 mL) was added dropwise.

The resulting mixture was refluxed for 5 h, after which the solution was poured into ice water. The precipitate was collected by filtration and dried under reduced pressure to give hydrazone intermediate as brown solid (89% yield).

1-(5-(Hydroxy (phenyl) methyl)-2-(5-nitrofuran-2-yl)-1,3,4-oxadiazole-3(2H)-yl)ethanone (F₄)

5-Nitrofuran derivative of oxadiazole was synthesized by addition of acetic anhydride (2 mL) to hydrazone (0.34 mmol, 100 mg), and the resulting solution was refluxed for 1 h. The reaction mixture was poured into ice water, and the resulting solid was filtered, washed with water, and purified by PTLC to obtain a yellow powder, (54% yield).