Researchers at the Tokyo University of Science have developed a novel approach for synthesizing o-bromobenzenethiol equivalents, unlocking new possibilities for creating organosulfur compounds with diverse applications.
Organosulfur skeletons are crucial components in pharmaceuticals, electronics and other fields. Synthesizing organosulfur skeletons requires o-bromobenzenethiols. However, producing o-bromobenzenethiols has faced challenges due to issues like oxidation and highly reactive intermediates.
The new study, published in Organic Letters on May 10, details a method for synthesizing stable o-bromobenzenethiol equivalents called aryl xanthates through the bromothiolation of aryne intermediates.
“We developed a method for synthesizing stable o-bromobenzenethiol equivalents by bromothiolation of aryne intermediates with an appropriate hydrogen sulfide equivalent and an electrophilic brominating reagent, resulting in controlled reactivity at the sulfur atom which prevents subsequent additions with aryne intermediates,” explains Suguru Yoshida, associate professor in the department of biological science and technology at Tokyo University of Science.
The researchers utilized potassium xanthate instead of hydrogen sulfide, owing to its better reactivity in aryne reactions and pentafluorophenyl bromide as an electrophilic brominating reagent.This combination allowed them to efficiently produce complex o-bromobenzenethiol equivalents called aryl xanthates. Notably, this method demonstrated good tolerance for various chemical groups and prevented the formation of unwanted products. Using aryl xanthates, the researchers prepared diverse highly functionalized organosulfur compounds, such as phenothiazines and thianthrenes, utilizing simple protocols without any foul odor, thanks to the high stability of the compounds.
“With our method, it is now possible to synthesize sulfur-containing compounds with complex structures that are difficult to achieve using conventional methods,” Yoshida said. “It can enable the development of novel organosulfur compounds that could lead to the discovery of new drugs, eco-friendly agrochemicals for sustainable agriculture, advanced materials, and organic electronics.”
The study opens up new avenues for synthesizing organosulfur compounds with applications across many domains. This includes the ability to significantly reduce the number of steps in the synthesis of multi substituted organosulfurs, which could contribute toward drug discovery in pharmaceutical sciences.
Further research expanding the scope and applications is currently underway in Yoshida's laboratory.
