Study Of Benzothiazole And Its Derivatives C-S Bond Formation In Superbase System

Many extensive researches have been reported since the "superbase media" was proposed for the first time in the seventies of the last century. The "superbase" system’s concept:A mixture system formed by the Lewis bases or a strong ionic alkali metal cation in the weak anion system. The Superbase system has been widely used in a number of areas of the metal organic chemistry and physical organic chemistry.C-S bond formation has been proved a very critical step in the synthesis of many compounds of biological activity, pesticides, pharmaceuticals and materials. In these sulfur containing compounds, more and more2-S-substituted benzothiazoles have been designed and successfully synthesized for pharmacological activity and biological evaluation. Because1,3-benzothiazoles have a particular framework, therefore, it is widely used in pharmacologically active agents and natural products, particularly noteworthy is that2-sulfur-substituted benzothiazole and its derivatives have specific biological activity, many drugs have been widely used in the pharmaceutical and pesticide industry because they have the core heterocycle framework.2-(phenylthio)-aniline is also a compound which has a special framework, showing specific biological and pharmacological properties, various amine-substituted aryl sulfides were widely used in different kinds of pharmaceutical compounds, they have the activities of anti-fungal, anti-cancer, anti-inflammatory, anti-tumor, anti-depressants and anti-viral.2-(phenylthio)-formanilide and its derivatives have been found have the activities of anti-inflammatory, anti-allergic and anti-arrhythmic. A increasing number of formanilides have been designed and synthesized for more extensive medical research.1. Study of cuprous iodide catalyzed benzothiazoles C-H activation and C-S formation reactions in superbase system.Our group found that iodobenzene and sulfur powder could generate diphenyl disulfide in superbase system, so we designed a new path to synthesis2-(phenylthio)-benzothiazole and its derivatives, the experimental procedure was that cuprous iodide catalyzed benzothiazoles C-H activation and C-S bond coupling with the diphenyl disulfide which generated by sulfur powder and iodobenzene in KOH/DMSO superbase system under oxygen condition in the130℃oil bath. The method used the generated diphenyl sulfide and avoided using the toxic reagents like thiophenol which would be used in conventional synthetic methods, it is environment friendly and more safety.2. Study of cuprous iodide Catalyzed Direct Ring-Opening Arylation of Benzazoles with Aryl Iodides in KOH/DMSO superbase system.In the second part, we continue the research of the C-S bond formation in superbase system. In our research we found that benzothiazole will have a ring-opening reaction if there has trace water in the KOH/DMSO superbase system and the amino-containing intermediate would coupling with iodobenzenes to form a C-S bond in the presence of cuprous iodide. Therefore, we have developed a novel path to synthesis2-(phenylthio)-aniline compounds by using benzothiazole and iodobenzenes in superbase system, and it has an excellent yield, the best yield of16examples could up to99%.3. Synthesis of2-(phenylthio)-formanilide compounds in superbase systemIn the third part, we found that in the KOH/DMSO superbase system benzothiazoles and iodobenzenes could be catalyzed by cuprous iodide to form2-(phenylthio)-formanilide in the100℃oil bath under anhydrous anaerobic environment, but the yield was not good, in the process of condition optimization, we found the t-BuOK/DMSO superbase system was more suitable for this reaction, the yield has greatly enhanced. Because2-(phenylthio)-formanilide is a new compound, we analysis its structure by NMR, LC-MS and X-ray diffraction method, and we verify that it has enolic tautomeric structure. Therefore, we have developed a new method to synthesis2-(phenylthio)-formanilide and its derivatives.