Abstract
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.
Keywords: Amidoxime, 1, 2, 4-oxadiazole, Gabriel amine synthesis, urea/thiourea derivatives, microwave irradiation, antimicrobial activities.
Graphical Abstract
[http://dx.doi.org/10.1016/S0014-827X(00)00099-9] [PMID: 11204948]
[http://dx.doi.org/10.1016/S0968-0896(03)00035-X ] [PMID: 12659768]
[http://dx.doi.org/10.1016/j.farmac.2005.08.003] [PMID: 16242685]
[http://dx.doi.org/10.1016/j.bmcl.2009.05.052] [PMID: 19500976]
[http://dx.doi.org/10.1021/jm2013248] [PMID: 22185670]
[http://dx.doi.org/10.1016/j.ejmech.2012.02.002] [PMID: 22365410 ]
[http://dx.doi.org/10.1021/jm501661f] [PMID: 25590813]
[http://dx.doi.org/10.1016/j.tetlet.2007.06.116]
[http://dx.doi.org/10.1016/j.tetlet.2008.06.091]
[http://dx.doi.org/10.5012/bkcs.2014.35.2.513]
[http://dx.doi.org/10.1016/j.dyepig.2013.09.029]
[http://dx.doi.org/10.1007/s11094-006-0017-7]]
[http://dx.doi.org/10.1039/b908937c] [PMID: 19830279]
[http://dx.doi.org/10.1016/bs.aihch.2015.05.001]
[http://dx.doi.org/10.1007/s10593-017-2154-1]
[http://dx.doi.org/10.1021/jo900818h]] [PMID: 19719253]
[http://dx.doi.org/10.1002/slct.201801857]]
[http://dx.doi.org/10.1039/c1ob05682d]] [PMID: 21826294]
[http://dx.doi.org/10.1002/adsc.201601378]]
[http://dx.doi.org/10.1016/S0040-4020(01)00906-1]]
[http://dx.doi.org/10.1016/j.jphotochemrev.2005.07.001]]
[http://dx.doi.org/10.1016/j.tetlet.2006.02.102]]
[http://dx.doi.org/10.1039/c1ob06055d]] [PMID: 21938295]
[http://dx.doi.org/10.1016/j.tetlet.2013.04.101]]
[http://dx.doi.org/10.1080/00397911.2018.1509350]
[http://dx.doi.org/10.1002/jhet.3430]
[http://dx.doi.org/10.1016/j.ejmech.2007.04.010] [PMID: 17583388]
[http://dx.doi.org/10.1016/j.bmc.2009.01.075] [PMID: 19251423]
[http://dx.doi.org/10.1016/j.ejmech.2012.07.020] [PMID: 22884523]
[http://dx.doi.org/10.1016/j.ejmech.2014.03.020] [PMID: 24675135]
[http://dx.doi.org/10.1016/j.ejmech.2014.04.046] [PMID: 24780598]
[http://dx.doi.org/10.1016/j.bmc.2016.04.006] [PMID: 27102161]
[http://dx.doi.org/10.3390/molecules22040535] [PMID: 28350331]
[http://dx.doi.org/10.1016/j.bmcl.2016.11.060] [PMID: 28041832]
[http://dx.doi.org/10.1007/s11094-016-1429-7]
[http://dx.doi.org/10.1055/s-1995-4012]
[http://dx.doi.org/10.1016/j.arabjc.2014.10.025]
[http://dx.doi.org/10.1021/jf803632t] [PMID: 19271709]
[http://dx.doi.org/10.1021/jo00333a004]
[http://dx.doi.org/10.1002/cber.18840170230]
[http://dx.doi.org/10.3998/ark.5550190.0006.705]
[http://dx.doi.org/10.1016/S0040-4039(00)02288-7]
[http://dx.doi.org/10.1002/jhet.5570420434]
[http://dx.doi.org/10.1016/j.tetlet.2007.02.105]
[http://dx.doi.org/10.1016/j.tet.2009.11.063]
[http://dx.doi.org/10.1016/j.ejmech.2011.12.028] [PMID: 22217867]