Study On The Synthesis Of Disulfides Tethered Pyrroles Based On Thioamides

Pyrroles are the most important components of nitrogen-containing heterocyclic compounds and exist in a wide range of natural bioactive molecules.They are the core of many complex macrocycles.Pyrrole derivatives have many biological activities,such as antibacterial,anti-inflammatory,anti-oxidation and anti-tumor.They are also widely used in materials,as a chemical sensor for laser manufacturing and image diagnosis.Disulfides are widely found in nature and show high biological properties,such as anti-bacterial,antifungal and anti-cancer,which are the important components of anticancer drug intermediates.In the industry,disulfides are used for the preparation of rubber and elastomer pre-vulcanizing agents,which are the important intermediates of synthesizing sulfur oxy and sulfinyl compounds.?-Ketothioamides are versatile synthons for building heterocyclic compounds.They have five reaction sites,two nucleophilic centers on sulfur and nitrogen atom,carbonyl and thiocarbonyl two electrophilic centers,?-carbon atom can act as a potential nucleophile center or Michael addition donor.Based on the above properties,?-ketothioamides can react with dielectrophiles,dinucleophilic,and reagents that have both nucleophilic and electrophilic sites.A novel strategy for 33 kinds of disulfides tethered pyrroles from?-ketothioamides and ethyl cyanoacetate with Na₂CO₃ was set up,one step to build a new C-C,C-N,S-S bonds,oxygen was both used as free radical source and oxidant.Based on the above reaction,the reaction mechanism was explored in detail,and the following control experiments were performed:adding free radical trapping agent,under oxygen atmosphere,nitrogen protection,and proposed a free radical mechanism.The structures of all the target compounds were confirmed by IR,¹H NMR,¹³C NMR and HRMS.The structures of target compounds have been confirmed by the X-ray single crystal diffraction analysis of compound 3aa.