I 2/CuO-catalyzed tandem cyclization strategy for one-pot synthesis of substituted 2-aminothiozole from easily available aromatic ketones/a ,b -unsaturated ketones and thiourea
Yan-Ping Zhu,Jing-Jing Yuan,Qin Zhao,Mi Lian,Qing-He Gao,Mei-Cai Liu,Yan Yang,An-Xin Wu *
Key Laboratory of Pesticide &Chemical Biology,Ministry of Education,Central China Normal University,Wuhan 430079,China
a r t i c l e i n f o
Received 18July 2011
Received in revised form 15October 2011Accepted 21October 2011
Available online 28October 2011Keywords:
2-Aminothiazole One-pot reaction Tandem cyclization
a -Halogenation ketones I 2/CuO
a b s t r a c t
A concise and ef ?cient one-pot process from easily available methyl ketones/unsaturated methyl ketones and thiourea was developed for the synthesis of 2-aminothiazoles under the media of I 2/CuO.The method can highly stereoselectivity obtain the E-isomers of 4-ethenyl-2-aminothiazoles (5a e f ).All these target molecules were characterized by NMR,HRMS and IR spectra.Furthermore,the target compounds 3c and 5b were further determined by X-ray crystallographic analysis.
Ó2011Elsevier Ltd.All rights reserved.
Thiazole as useful structural element plays an important role in nature and has broad applications in the ?eld of agriculture and medicinal chemistry.1Thiazole ring is a main structural motif of many natural compounds such as vitamin B1(thiamine),penicillin and carboxylase.
Moreover 2-aminothiazoles as important precursors have been employed in the preparation of different important drugs required for the treatment of allergies,hypertension,in ?ammation,schizophrenia,bacterial,and HIV infections.2Therefore,much at-tention has been paid to the synthesis of 2-aminothiazoles,for which the general approaches include condensation of a -bro-moketone with thiourea,3the reaction of a -thiocyanato carbonyl compounds with aromatic or aliphatic aminehydrochlorides,4treatment of stylene and thiourea with NBS 5and condensation of aromatic ketone and thiourea with solid supported catalyst or heterogeneous catalyst.6
In recent years,tandem,multicomponent,and one-pot re-actions have attracted much attention as powerful and useful synthetic tools in synthetic chemistry and drug discovery.These reactions,by virtue of their atom-economy,reducing the number of
operations,and saving reagents,energy,time,and labour,have been used in many chemical transformations.7
In our previous studies,we proposed a novel method for the synthesis of a -iodo ketones and a ,b -unsaturated a 0-iodo ketones (Scheme 1)on the basis of aromatic ketones and a ,b -unsaturated ketones under the media of I 2/CuO.8Moreover,a -halogenation ketones as important precursors have been employed in the preparation of various heterocycles.9Therefore,we considered the possibility of catalyzing aromatic ketones in situ obtained a -iodo ketones,which can react with thiourea in one-pot to afford 2-aminothiazole under the media of I 2/CuO.If successful,this would simplify the synthetic steps,and develop a novel synthetic method for the synthesis of 2-amino-4-arylthiazole and 2-amino-4-ethenylthiazole derivatives.
Herein,we present a concise,rapid and ef ?cient method for preparation of substituted 2-aminothiazole from easily available aromatic ketones and thiourea.In addition,this method can also synthesize 2-amino-4-ethenylthiazole derivatives ef ?
Scheme 1.Synthesis of a -iodo ketones and a ,b -unsaturated a 0-iodo ketones on the basis of aromatic ketones and a ,b -unsaturated ketones under the media of I 2/CuO.
*Corresponding author.Tel./fax:þ86(0)2767867773;e-mail address:chwuax@http://doc.xuehai.net (A.-X.
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0040-4020/$e see front matter Ó2011Elsevier Ltd.All rights reserved.doi:10.1016/j.tet.2011.10.074
Tetrahedron 68(2012)173e 178