Etherification via Aromatic Substitution on 1,3-Disubstituted Benzene Derivatives

In this study, we developed a method for etherification via aromatic substitution at the ipso-position of an electron-withdrawing group (EWG) that exists at the meta-position of another EWG. To heighten the reactivity of the substitution reaction, we added a t-BuOK solution in tetrahydrofuran (THF) to a mixture of an aromatic substrate, an alcoholic nucleophile, and 18-crown-6-ether in dimethylformamide (DMF), which proved to be a particularly effective sequence. Under the conditions we established, aromatic substrates that are difficult to use for substitution reactions such as aryl fluorides activated with either a bromide or a chloride substituent were aptly converted to corresponding ether products at 25 degrees C. This reaction would potentially be useful to link an alcohol to an additional functional group through further chemical transformations via the use of a residual bromide or chloride substituent.

Automated summary

In this study, a method for etherification via aromatic substitution between two EWGs was developed. Under specific conditions, the conversion of challenging aromatic substrates to ether products was achieved successfully.