The halex reaction is a great way to introduce a fluorine atom in to an aromatic ring, but the reaction often requires high temperatures and or long reaction times if metal fluorides are used. Tetralkylammonium fluorides are a better option due to their higher solubility in the reaction medium, however these salts are often hydrated which significantly reduces the observed nucleophilicity of the fluoride ion.
A method for generating anhydrous Me4NF has been developed by Melanie Sandford and her group working with Dow. The key is to form anhydrous Me4NF in situ and this is achieved by reacting Me4N+ –OAr with Ar’COF. The best combination is where –OAr = 2,6-dimethylphenoxide, and Ar’COF is 4-methoxybenzoyl fluoride.
