Studies On The Synthesis Of Benzothiazoles And Diaromatic Ethers With Free-transition Metals

Using simple and easily available starting materials to synthesize natural products and drug molecules is a very important synthesis strategy.Nitrogen and sulfur compounds,thiazole and its derivatives,as an important class of aromatic heterocyclic compounds,are widely present in medical drugs and agrochemicals.Such compounds usually show significant drug activity,including anti-cancer,anti-HIV,treatment of diabetes and so on.The commonly used synthesis method of thiazole compounds is prepared by condensation reaction of 2-aminothiophenol with carboxylic acid or aldehyde compounds,but 2-aminothiophenol is unstable and easily oxidized by air,and there are few commercial substrates.Another method is to use o-halogen aniline and organic sulfur reagent to form thioamide and then form a ring.This method requires the use of malodorous Lawson's reagent,and the ketone,ester and amide part of the substrate cannot be converted.In addition,diaryl ethers and their derivatives are widely present in natural products and drug molecules.These drug molecules exhibit excellent anticancer activity and are also widely used in the field of polymer materials.The traditional synthesis method of diaryl ether compounds is the Ullman synthesis method,but the method is harsh and the yield is average.In response to these problems,we have carried out research on the synthesis of 2-substituted thiazoles and their derivatives without transition metal catalysis and the methods of inorganic bases to promote the synthesis of cyano-substituted aromatic ethers from oxime ethers and phenols / alcohols.The specific research contents are as follows:1?Developed a method to synthesize multi-substituted thiazole from simple starting materials through multi-component reaction.Under the condition of no transition metals,inexpensive and easily available ketones,aldehydes and their derivatives,inorganic ammonium salts and elemental sulfur "one-pot" four-component self-assembly synthesis of thiazole ring,with multiple to moderate yields to obtain multiple substitutions Thiazole derivatives.In this reaction,inorganic ammonium salts and elemental sulfur as heteroatom sources participate in the ring formation,which provides a new way for the construction of nitrogen-containing sulfur-containing heterocycles.2?A method for the direct dehydrogenation and aromatization of tetrahydrobenzoxazole and nitrogen-containing heterocyclic compounds under the condition of non-metallic catalyst participation was developed.Elemental iodine is used as a catalyst,and oxygen is used as a green oxidant.A series of aromatic heterocyclic compounds can be obtained with simple to moderate yields under simple conditions.The method realizes the dehydroaromatization reaction under the condition that no transition metal catalyst participates,and provides a new synthetic route for benzothiazole and azacyclic aromatic hydrocarbons.3?A class of oxime ethers and phenol/alcohols have been developed to synthesize cyano-substituted aromatic ethers without the involvement of transition metal catalysts.The method uses cesium carbonate as a promoter,and the reaction obtains diaryl ether compounds through a series of processes such as oxime ester conversion and nitro desorption.The reaction has broad functional group tolerance and good yield.At the same time,such aryl groups containing substituted aryl ethers can further form a ring,which provides a new way for the construction of heterocyclic compounds.