Researchers have developed a chemical reaction that could enable the rapid and safe synthesis of medicines and advanced materials.
Writing in the journal ACS Catalysis, scientists at Chiba University in Japan described the effect of adding a new catalyst to the Friedel−Crafts reaction. The reaction adds substituents to specific positions on aromatic compounds and is already used for the design of organic compounds such as agrochemicals and pharmaceuticals.
In the traditional acid-catalyzed reaction, substituents are added next to the hydroxy group of the phenol ring, resulting in ortho-products. The products are useful, but the utility of the reaction would increase if it could also be used to add substituents opposite the hydroxy group to create para-products.
Other researchers have achieved selective substitution at the para-position for some substrates, but the field has lacked a method for consistently creating para-products via the Friedel−Crafts reaction. The team at Chiba University addressed this unmet need by using a novel enzyme to modify the reaction to favor the generation of para-substituted products.
The chemists applied the method to an orexin antagonist, a class of medicines used in the treatment of sleep disorders. Takayoshi Arai, a professor at Chiba University, explained the significance of the study.
“There has been no general way to achieve a para-selective aza-Friedel−Crafts reaction of phenols until now,” Arai said. “The rapid and safe synthesis method has improved the synthetic efficiency of an orexin antagonist and is expected to contribute to an environmentally benign and sustainable chemistry.”
