Diaryl ether synthesis in supercritical carbon dioxide in batch and continuous flow modes

Area of Science:

• Organic synthesis
• Green chemistry
• Flow chemistry

Background:

• Diaryl ethers and sulfides are important structural motifs in pharmaceuticals and materials.
• Traditional synthesis methods often involve harsh conditions or toxic reagents.
• Supercritical carbon dioxide (scCO(2)) offers an environmentally benign reaction medium.

Purpose of the Study:

• To develop a high-yielding, batch synthesis of diaryl ethers and sulfides.
• To adapt the synthesis to a continuous flow process using scCO(2).
• To utilize a polymer-supported imidazolium fluoride reagent for efficient fluoride-mediated S(N)Ar reactions.

Main Methods:

• Nucleophilic aromatic substitution (S(N)Ar) reaction.
• Fluoride-mediated synthesis in supercritical carbon dioxide (scCO(2)).
• Batch and fixed-bed continuous flow reactor setups.
• Use of a polymer-supported imidazolium fluoride reagent.

Main Results:

• High yields achieved in batch mode synthesis.
• Successful development of a fixed-bed continuous flow process.
• High conversions demonstrated in the continuous flow system.
• Efficient S(N)Ar reactions mediated by fluoride in scCO(2).

Conclusions:

• A versatile and efficient method for synthesizing diaryl ethers and sulfides has been established.
• The developed continuous flow process offers advantages for scalable and sustainable chemical production.
• The use of scCO(2) and polymer-supported reagents aligns with green chemistry principles.