Controlled nucleophilic aromatic substitution of hexafluorobenzene using a flow microreactor

• Flow nucleophilic aromatic substitution (S N Ar) of hexafluorobenzene was studied. • For S N Ar reactions of hexafluorobenzene, selective mono-substitution of hexafluorobenzene is difficult to achieve due to the contamination of the di-substituted compounds derived from overreactions. • To solve the technical issues involving the overreactions, the use of continuous flow microreactor seems to be effective due to precise setting of the reaction conditions. • We succeeded in the controlled flow S N Ar reactions of hexafluorobenzene with organolithiums for selective formation of mono-substituted compounds. Nucleophilic aromatic substitution (S N Ar) contributes to creating a variety of useful materials. It is well-known that selective S N Ar reactions of perfluorinated aromatics such as hexafluorobenzene with nucleophiles are difficult to achieve using conventional macro batch systems due to the contamination of the di-substituted products. To take advantage of flow microreactor system, we succeeded in the controlled S N Ar reactions of hexafluorobenzene with organolithiums employing continuous flow reactors.