Base-Promoted Synthesis Of Isothiourea Derivatives Or The Relevant Cyclization Products Using Anilines As Starting Material

This paper mainly focuses on the synthesis of S-allylation or S-benzylation isothioureas using aniline as starting materials,and one-pot selective synthesis of2-aminobenzoxazoles and 2-mercaptobenzoxazoles by usingo-aminophenol and disulfide compounds as starting materials through ortho-hydroxy-arylthiourea intermediate.These compounds have been widely used in the field of biomedicine and materials due to their potential biological activities,so it is of great significance to study their synthetic methods.The research details are as follows:1.S-Allylation or S-benzylation of arylthioureas.A series of S-allylation or S-benzylation of aryl-isothiourea derivatives were obtained taking arylthioureas as substrate,allylbromide,allylchoride,benzylbromide and benzylchoride as allyllation reagents.With the addition of Na H,the reaction was performed well in DMSO at room temperature,and was finished within 2 hours.Furthermore,the base and base loading,as well as the substrate molar ratio were studied to get the optimal condition.Under the optimal condition,a total of 19 isothioureas were obtained and identified by necessary spectra characterizations.This method has the advantages of no catalyst,mild reaction conditions,easy opration,excellent yield,providing a practicalmethod for the synthesis of isothiourea derivatives.2.Copper catalysted one-pot synthesis of 2-aminobenzoxazole derivatives.Taking o-aminophenol and phenyl dimethylcarbamodithioate as starting materials,the optimal reaction conditions wereobtainedby the screening of solvent,base,base loading,substrate molar ratio,catalysts,catalyst loading and the reaction temperature.Under the optimal conditions(Cu I as catalyst,Na H as base,DMF as solvent,110 o C for 10 h),13 N-substituted benzoxazoles were synthesized and all the products were identified by necessary spectra characterizations.This reaction has advantages of economy and utility by using cheap transition metal salt as catalyst,good adaptability of substrates.It could be applied in large scale synthesis.The protocol provides a new synthetic route for some important pharmaceutically active compounds which contains benzoxazole unit.3.Synthesis of 2-mercaptobenzoxazoles by metal-free condition.Taking o-aminophenol and disulfide tetramethylthiuram as starting materials,the optimal condition was obtained by the screening of substrate molar ratio,base,base loading,solvent and reaction temperature.Under the optimal conditions,a series of 11 substituted 2-mercaptobenzoxazoles(55-80%)were obtained.All products were identified by necessary spectral characterizations.This method is simple to handle,and has the advantages of no catalyst or ligand loading,providing a new synthetic method for some potential pharmaceutically active2-mercaptobenzoxazole derivatives.