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