Discovering Green, Aqueous Suzuki Coupling Reactions: Synthesis of Ethyl (4-Phenylphenyl)acetate, a Biaryl with Anti-Arthritic Potential

Abstract

Suzuki couplings are powerful chemical reactions commonly employed in academic and industrial research settings to generate functionalized biaryls. We have developed and implemented a discovery-based, microscale experiment for the undergraduate organic chemistry laboratory that explores green Suzuki coupling using water as the primary solvent. This experiment exposes students to the professional responsibilities of a pharmaceutical chemist and promotes a problem-solving approach toward learning green chemistry principles. Specifically, students assume the role of a medicinal chemistry researcher striving to identify the greenest and most cost-effective method out of three proposed synthetic approaches to make ethyl (4-phenylphenyl)acetate. Ethyl (4-phenylphenyl)acetate is a precursor to the drug felbinac and demonstrates promise as a lead compound in the discovery of new nonsteroidal anti-inflammatory drugs for the treatment of arthritis.