4-[5-(2-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]benzohydrazide

Abstract

4-(5-(2-Methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzohydrazide (5) was synthesized by three steps. The synthesis started with 2-methoxybenzohydrazide to form hydrazone (3) which was then cyclized to oxadiazole (4) and finally, treatment of oxadiazole (4) with hydrazine hydrate afforded the final product (5).

Introduction

Benzohydrazides have been reported to possess various biological activities such as antileishmanial [1], antioxidant [2] or antibacterial effects [3]. Benzohydrazides are easily converted into hydrazones by treating with aldehyde or ketone [4]. Benzohydrazones are applicable in mass spectrometry as alternate UV-LDI matrices for the analysis of peptides with significantly low background signals [5]. Recent studies on benzohydrazones also showed that they are potent antileishmanial [6] antioxidant [7,8] antidiabetic [9,10] antibacterial [3] and antifungal [11] agents. Benzohydrazones can be converted into oxadiazole by using cerium ammonium nitrate (CAN) [12], bis(trifluoroacetoxy)iodobenzene [13] or Dess–Martin reagent (DMP) [14]. Literature search showed that oxadiazole carrying a benzoyl hydrazine moiety has not been reported. Therefore, 4-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzohydrazide (5), a new oxadiazole containing a benzoyl hydrazine unit, was obtained as shown in Scheme 1. The product was prepared with satisfactory yield and fully characterized by spectroscopy.

Results and Discussion

We have synthesized (E)-methyl 4-((2-(2-methoxybenzoyl)hydrazinylidene)methyl)benzoate (3) by condensing 2-methoxybenzohydrazide (1) with methyl 4-formylbenzoate (2) [6]. Compound 3 was then cyclized to form methyl 4-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzoate (4) by using DMP [13]. Finally oxadiazole 4 was refluxed with hydrazine hydrate for 6 hours to give 4-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzohydrazide (5) in high yield (Scheme 1).

Experimental

4-(5-(2-Methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzohydrazide

4-(5-(2-Methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzohydrazide (5) was synthesized by mixing compound 4 (0.620 g, 2 mmol) with 2 mL hydrazine hydrate and 10 mL methanol. The mixture was refluxed for 6 h. Excess hydrazine hydrate and solvent were evaporated to afford pure product 5 (94%, yield 0.58 g). M.p. above 250 °C; ¹H-NMR (500 MHz, DMSO-d₆): 10.01 (s, 1H, NH), δ 8.14 (d, 2H, J_2’,3’ = J_6’,5’ = 8.5 Hz, H-2’/H-6’), 8.02 (d, 2H, J_3’,2’ = J_5’,6’ = 8.5 Hz, H-3’/H-5’), 7.97 (dd, 1H, J_3,4 = 6.0, J_3,5 = 2.0 Hz, H-3), 7.64 (ddd, 1H, J_4,3 = 7.5, J_4,5 = 6.5, J_4,6 = 2.0 Hz, H-4), 7.29 (d, 1H, J_6,5 = 8.5, H-6), 7.16 (t, 1H, J_5(6,4) = 8.5, H-5), 4.58 (s, 2H, NH₂), 3.93 (s, 3H, O-CH₃); ¹³C-NMR (125 MHz, DMSO-d₆): δ 165.41, 163.79, 163.59, 158.02, 136.50, 134.22, 130.70, 130.70, 128.48, 128.48, 127.05, 125.98, 121.28, 113.22, 112.45, 56.55; Anal. Calcd for C₁₆H₁₄N₄O₃, C, 61.93; H, 4.55; N, 18.06; Found C, 61.95; H, 4.56; N, 18.04; EI MS m/z 310.