Organosulfur compounds, which are organic compounds containing sulfur, are important in various fields such as pharmaceuticals, biomedical imaging, agriculture, and electronics. Compounds like phenothiazine, thianthrene, and thienothiophene, which contain organosulfur skeletons, play key roles in these areas. The use of o-bromobenzenethiols as a key component in synthesizing these compounds has been developed due to the high reactivity of the thiol and bromine moieties in these compounds.
Traditional methods for producing o-bromobenzenethiols involve adding bromine to aniline and using diazonium intermediates to add sulfur. However, this process has challenges such as selective bromine addition at the ortho position, difficulties with certain chemical groups, and the tendency of o-bromobenzenethiols to easily oxidize in air, releasing unpleasant odors. Recently, a new method has been discovered to synthesize complex aromatic compounds by selectively adding molecules to aryne intermediates, but creating o-bromobenzenethiols through this process has been difficult due to the reactivity of sulfur-containing compounds.
To address this challenge, Associate Professor Suguru Yoshida and Mr. Shinya Tabata at Tokyo University of Science developed a new method for synthesizing stable o-bromobenzenethiol equivalents. By bromothiolation of aryne intermediates with an appropriate hydrogen sulfide equivalent and electrophilic brominating reagent, they were able to control reactivity at the sulfur atom and prevent subsequent additions with aryne intermediates. This method, utilizing potassium xanthate and pentafluorophenyl bromide, allowed for the efficient production of complex o-bromobenzenethiol equivalents called aryl xanthates.
The use of aryl xanthates in this method demonstrated good tolerance for various chemical groups and prevented the formation of unwanted products. With this approach, the researchers were able to prepare diverse highly functionalized organosulfur compounds such as phenothiazines and thianthrenes using simple protocols without any foul odor. The versatility of this method enables the synthesis of a wide variety of organosulfur compounds with highly fused organosulfur skeletons and has the potential to streamline the synthesis of multi-substituted organosulfurs for drug discovery.
The new method developed by Prof. Yoshida and Mr. Tabata opens up possibilities for synthesizing novel organosulfur compounds with complex structures that were difficult to achieve using traditional methods. This could lead to the discovery of new drugs, eco-friendly agrochemicals for sustainable agriculture, advanced materials, and organic electronics. Further studies are underway to expand the scope and applications of this method for synthesizing bioactive organosulfur compounds in their laboratory, highlighting the potential impact of this research on various fields.
