A convenient Synthesis of 3-aryl-5-Hydroxyalkyl-1,2,4-oxadiazoles from a-hydroxy Esters and Amidoximes under Solvent-free Conditions

Abstract

The present study aimed to synthesis and characterization of 3-aryl-5-hydroxyalkyl-1,2,4-oxadiazoles (5a-d, 6a-d, 7a/d, 8a-d and 9a-c). The 3-aryl-5-hydroxyalkyl-1,2,4-oxadiazoles were synthesized by treatment of arylamidoxime 1a-d with a-hydroxy esters for 4 hours without any solvent and in the absence of a base. The reaction was monitored by thin layer chromatography (TLC). The heterocycles 5a-d, 6a-d, 7a/d, 8a-d and 9a-c were obtained in moderate and good yields (16-76%). The minor yield of the product (16-55%) probably due to the steric hindrance. The presences of electron-withdrawing and electron-donating groups attached to the para position of arylamidoximes were well tolerated by the reaction. The products were characterized by IR, 1H and 13C NMR spectroscopy and all compounds were in full agreement with the proposed structure. For instance, IR absorptions at 1593 (C=N) and 1473 cm–1 (C–O) were obtained for 3-phenyl-5-(1-hydroxyethyl)-1,2,4-oxadiazoles (5a). 1H NMR spectra showed absorption of methine proton of C–OH at δ 5.16. Signals of the methyl groups for 5a-d appeared as doublets at 1.69 ppm (J = 6.6 Hz). The characteristic signals for NCO and NCN in 13C NMR at 180.9 and 168.1 ppm further identified oxadiazole moiety in 5a. With respect to compounds 6a-d the 1H NMR spectra showed a triplet at 5.33 ppm (J= 4.5 Hz) for methine proton and a doublet at 3.71 ppm (J=4.5 Hz) for the methylene groups. The compounds 8a-d showed a singlet at 3.76 ppm due to methyl groups of ester groups. Signals of the CH protons for 7ad appeared as singlet at 6.93 and 5.50 ppm. All other proton signals are observed in their usual resonance areas. On the other hand, the compounds 8a-d showed a singlet at 3.76 ppm due to methyl groups of ester groups. Additionally, the in silico study indicated that all synthesized compounds have a low risk of chronic toxicity and can be administered orally.