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/thiouprea moiety.
Materials and Methods:
Firstly, 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. O-acylamidoximes obtained in the first step at room temperature were 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 steps 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 and Discussions:
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
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.
Cover Picture: Biologically Active Compounds through Catalysis: Efficient Synthesis ofN-(Heteroarylcarbonyl)-N′-(arylalkyl)piperazines (Chem. Eur. J. 3/2004)
