Nucleophilic fluorination facilitated by a CsF-CaF₂ packed bed reactor in continuous flow

Area of Science:

• Chemical Engineering
• Organic Synthesis
• Flow Chemistry

Background:

• Continuous flow chemistry offers advantages in safety and efficiency for organic reactions.
• Developing robust and easy-to-handle catalytic systems is crucial for flow chemistry applications.
• Nucleophilic fluorination and trifluoromethylation are important synthetic transformations in organic chemistry.

Purpose of the Study:

• To report a novel, easily prepared, dry, and handleable packed bed reactor.
• To demonstrate the reactor's utility in continuous flow nucleophilic fluorinations.
• To investigate the reactor's adaptability for other key organic transformations and its stability.

Main Methods:

• Preparation of a packed bed reactor by supporting cesium fluoride (CsF) on calcium fluoride (CaF2).
• Utilizing the packed bed reactor for continuous flow nucleophilic fluorination reactions.
• Testing the reactor's performance in silyl-ether deprotection and trifluoromethylation using Ruppert's reagent.

Main Results:

• The CsF/CaF2 packed bed reactor was successfully prepared and demonstrated to be stable and easy to handle.
• The reactor enabled efficient continuous flow nucleophilic fluorinations.
• The system also showed adaptability for silyl-ether deprotection and trifluoromethylation reactions, indicating broad applicability.

Conclusions:

• A simple, stable, and versatile packed bed reactor system has been developed for continuous flow organic synthesis.
• This reactor facilitates key transformations including nucleophilic fluorination, silyl-ether deprotection, and trifluoromethylation.
• The study confirms the reactor's potential for scale-up investigations in flow chemistry.