New Potential Biologically Active Compounds: Synthesis and Characterization of Urea and Thiourea Derivatives Bearing 1,2,4-oxadiazole Ring

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Author(s): Nevin Arıkan Ölmez*, Faryal Waseer

Journal Name: Current Organic Synthesis

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Background: Urea, thiourea, and 1,2,4-oxadiazole compounds are of great interest due to their different activities such as anti-inflammatory, antiviral, analgesic, fungicidal, herbicidal, diuretic, antihelminthic and antitumor along with antimicrobial activities.

Objective: In this work, we provide a new series of potential biologically active compounds containing both 1,2,4- oxadiazole and urea/thiourea moiety.

Methods: First, 5-chloromethyl-3-aryl-1,2,4-oxadiazoles (3a-j) were synthesized from the reaction of different substituted amidoximes (2a-j) and chloroacetyl chloride in the presence of pyridine by conventional and microwave-assisted methods. In the conventional method, 1,2,4-oxadiazoles were obtained in two steps. Oacylamidoximes obtained in the first step at room temperature was heated in toluene for an average of one hour to obtain 1,2,4-oxadiazoles. The yields varied from 70 to 96 %. 1,2,4-oxadiazoles were obtained under microwave irradiation in a single step in a 90-98 % yield at 160 °C in five minutes. 5-aminomethyl-3-aryl-1,2,4-oxadiazoles (5a-j) were obtained by Gabriel amine synthesis in two step from corresponding 5-chloromethyl-3-aryl-1,2,4- oxadiazoles. Finally, twenty new urea (6a-j) and thiourea (7a-j) compounds bearing oxadiazole ring were synthesized by reacting 5-aminomethyl-3-aryl-1,2,4-oxadiazoles with phenyl isocyanate and isothiocyanate in tetrahydrofuran (THF) at room temperature with average yields (40-70 %).

Results: An efficient and rapid method for the synthesis of 1,2,4-oxadiazoles from the reaction of amidoximes and acyl halides without using any coupling reagent under microwave irradiation has been developed, and twenty new urea/thiourea compounds bearing 1,2,4-oxadiazole ring have been synthesized and characterized.

Conclusion: We have synthesized a new series of urea/thiourea derivatives bearing 1,2,4-oxadiazole ring. Also, a facile synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from amidoximes and acyl chlorides under microwave irradiation was reported. The compounds were characterized using FTIR, 1H NMR, 13C NMR, and elemental analysis techniques

Keywords: Amidoxime, 1, 2, 4-oxadiazole, Gabriel amine synthesis, Urea/Thiourea derivatives, microwave irradiation, 13C NMR.

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(E-pub Ahead of Print)
DOI: 10.2174/1570179417666200417112106
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