An Efficient Synthesis of New 2-Aryl-5-phenylazenyl-1,3,4-oxadiazole Derivatives from N,N'-Diarylcarbonohydrazides

Abstract

A series of new 1,3,4-oxadiazoles conjugated to aromatic substituents by an azo linker was synthesized in a four-step reaction sequence, involving cyclodehydration of a N,N'-diacylhydrazine fragment and dehydrogenation of the neighboring hydrazine fragment of the intermediate N,N'-diarylcarbonohydrazide.

Key words

1,3,4-oxadiazoles - azo compounds - heterocycles - cyclodehydration - dehydrogenation

• References

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• 41 Representative Procedures N'-[(2-Phenylhydrazinyl)carbonyl]benzohydrazide (5a) Sodium hydrogen carbonate (2.1 g, 0.03 mol) was dissolved in water (60 mL) and N-phenylcarbonohydrazide (3, 4 g, 0.02 mol) was added with vigorous stirring. Then, benzoyl chloride (4a, 2.9 ml 0.03 mol) dissolved in toluene (14 mL) was added dropwise to the resultant slurry and the precipitate was stirred at room temperature for 24 h. The viscous mass was cooled in an ice bath and filtered. The product was treated with diethyl ether, triturated, and dried. The solid was crystallized from a mixture of ethanol and acetic acid (3:1 v/v) to give pure N'-[(2-phenylhydrazinyl)carbonyl]benzohydrazide. White solid (2.97 g, 55% yield). Mp 204–206 °C. IR (ATR): ν = 3325, 3219, 3057, 2162, 1683, 1632, 1601, 1576, 1521, 1485, 1442, 1418, 1333, 1315, 1304, 1257, 1217, 1175, 1152, 1090, 1074, 1026, 974, 899, 812, 750, 687 cm^–1. ¹H NMR (400 MHz, DMSO): δ = 6.72 (t, J = 7.2 Hz, 1 H), 6.81 (d, J = 8.0 Hz, 2 H), 7.16 (t, J = 8.2 Hz, 2 H), 7.48 (t, J = 7.6 Hz, 2 H), 7.55 (t, J = 7.2 Hz, 1 H), 7.61 (s, 1 H), 7.90 (d, J = 6.8 Hz, 2 H), 8.36 (s, 2 H), 10.13 (s, 1 H) ppm. ¹³C NMR (100 MHz, DMSO): δ = 112.5, 118.6, 127.5, 128.2, 128.5, 131.5, 132.8, 149.6, 158.8, 166.1 ppm. UV-VIS: λ_max (MeOH) 275.5 nm (ε·10^–3 4.76 cm^–1M^–1), λ_max (MeOH) 231.0 nm (ε·10^–3 27.35 cm^–1M^–1), λ_max (MeOH) 202.0 nm (ε·10^–3 46.43 cm^–1M^–1). Anal. Calcd for C₁₄H₁₄N₄O₂: C, 62.21; H, 5.22; N, 20.73. Found: C, 62.22; H, 5.20; N, 20.75. HRMS calcd for (C₁₄H₁₄N₄O₂ + H⁺): 271.1190; found: 271.1188. 2-Phenyl-5-phenyldiazenyl-1,3,4-oxadiazole (6a) N'-[(2-Phenylhydrazinyl)carbonyl]benzohydrazide (5a, 0.01 mol) was heated with phosphorus oxychloride (19 mL) for 3 h, the course of the reaction being monitored by TLC. The resulting dark brown mixture was concentrated with a rotary evaporator. Then, distilled water (100 mL) was poured into the flask, ice cubes were added and the mixture stirred, resulting in a dark precipitate. The mixture was left over night in a refrigerator and then filtered. The resulting solid was purified by column chromatography with chloroform/ethyl acetate (5:1 v/v) as the eluent to give pure 2-phenyl-5-phenylazenyl-1,3,4-oxadiazole. Red solid (1.4 g, 56% yield). Mp 139–140 °C. IR (ATR): ν = 2921, 2161, 1968, 1694, 1603, 1585, 1540, 1509, 1478, 1461, 1449, 1422, 1330, 1318, 1307, 1245, 1220, 1203, 1151, 1096, 1071, 1017, 975, 959, 928, 773, 721, 702, 688, 679 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.54–7.64 (m, 6 H), 8.11 (dd, J ₁ =7.6 Hz, J ₂ = 0.8 Hz, 2 H), 8.22 (dd, J ₁ =8.4 Hz, J ₂ =1.6 Hz, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 123.2, 124.4, 127.6, 128.8, 129.0, 129.2, 129.6, 132.7, 134.4, 152.8, 164.5 ppm. UV-VIS: λ_max (MeOH) 348.0 nm (ε·10^–3 5.97 cm^–1M^–1), λ_max (MeOH) 261.5 nm (ε·10^–3 8.33 cm^–1M^–1), λ_max (MeOH) 202.0 nm (ε·10^–3 18.16 cm^–1M^–1). Anal. Calcd for C₁₄H₁₀N₄O: C, 67.19; H, 4.03; N, 22.39. Found: C, 67.15; H, 4.01; N, 22.37. HRMS calcd for (C₁₄H₁₀N₄O + H⁺): 250.0927; found: 250.0923.