Fast and high-yield microreactor syntheses of ortho-substituted [(18)F]fluoroarenes from reactions of [(18)F]fluoride ion with diaryliodonium salts.

A microreactor was applied to produce ortho-substituted [18F]fluoroarenes from the reactions of cyclotron-produced [18F]fluoride ion (t1/2 = 109.7 min) with diaryliodonium salts. The microreactor provided a very convenient means for running sequential reactions rapidly with small amounts of reagents under well-controlled conditions, thereby allowing reaction kinetics to be followed and Arrhenius activation energies (Ea) to be measured. Prepared symmetrical iodonium chlorides (Ar2I+Cl−) rapidly (<4 min) gave moderate (Ar = 2-MeOC6H4, 51%) to high (Ar = Ph or 2-MeC6H4, 85%) decay-corrected radiochemical yields (RCYs) of a single radioactive product (Ar18F). Reaction velocity with respect to Ar group was 2-MeOC6H4 < Ph < 2-MeC6H4. Activation energies were in the range 18−28 kcal/mol. Prepared unsymmetrical salts (e.g., 2-RC6H4I+2′-R′C6H4X−; X = Cl or OTs) also rapidly gave two products (2-RC6H418F and 2-R′C6H418F) in generally high total RCYs (79−93%). Selectivity for product [18F]fluoroarene was controlled ...