In multicomponent coupling reaction, three or more components react in a single flask to produce a single product and is often used in drug discovery research. For example, a biologically active quinazolinone derivative can be synthesized by adding an oxidant to three components (isatoic anhydride, benzaldehyde, and amine) in an organic solvent. However, since it requires a large amount of highly toxic oxidants and the preparation of benzaldehyde from alcohol, the development of a catalytic synthesis method with less environmental impact is warranted.
The group has succeeded in developing a new environmentally-friendly, multi-component coupling reaction for the synthesis of quinazolinones using water as a solvent and a water-soluble palladium catalyst. By adding a palladium catalyst to the above-mentioned three components using water as the solvent, benzyl alcohol, which has low reactivity, can be used directly in the multicomponent coupling reaction, enabling more efficient synthesis of quinazolinone derivatives.
Advanced Synthesis & Catalysis (June 23, 2021)
Title of paper
Direct Use of Benzylic Alcohols for Multicomponent Synthesis of 2-Aryl Quinazolinones Utilizing the π-Benzylpalladium(II) System in Water
Hidemasa Hikawa*, Taku Nakayama, Makiko Takahashi, Shoko Kikkawa and Isao Azumaya* (*Responsible Author)