Halogen exchange reactions aromatic fluorination

Nucleophilic substitution can be employed to introduce fluorine into specific positions within an aromatic ring, and the Halex (halogen exchange) reaction is commonly used in industty. ° Unlike aliphatic reactions, elimination is usually not an issue for aromatic substrates, and as such, strongly basic nucleophilic sources of fluoride can be utilised in the reaction. The reaction works for electron deficient aromatics and is generally carried out... 

Aromatic fluorine for halogen (F-X) exchange reactions (DMSO, 160°C, 20 min) in an [ F]fluoride-cryptand-oxalate system using 4 -halo-acetophe-nones (F, Cl, Br and I) has also been studied. The relative efficacy of the exchange is the following one F-F > F-Cl > F-Br > F-I, the radiochemical yield for the exchange F-F being similar to that of the commonly employed NO2 or +NMej displacements [113]. 

The synthesis of benzyl fluorides from benzyl halides is problematic due to the tendency to undergo Friedel Crafts reactions.The fluorination of benzyl bromide with thallium(l) fluoride gives impure benzyl fluoride and attempts to fluorinate benzyl halides with anti-mony(III) fluoride, silver fluoride, and potassium fluoride were all unsuccessful. Benzyl fluorides with substituents which deactivate the aromatic system towards Friedel-Crafts reactions are successfully obtained through halogen exchange with mercury(II) fluoride (Table... 

FLUORINATION OF AROMATIC COMPOUNDS BY HALOGEN EXCHANGE WITH FLUORIDE ANIONS ("HALEX" REACTION)... 

Halogen exchange with a fluoride anion is one of the two main techniques to introduce a fluorine atom on an aromatic nucleus, which is a useful complement of diazotization of anilines in hydrogen fluoride or thermal decomposition of arenediazonium fluoroborates (Schiemann reaction). It is used on an industrial scale to produce, for example, 2,6-difluorobenzonitrile (the precursor of the insecticide Diflubenzuron) or 2,4-difluoroaniline (the precursor of Diflufenican or other herbicides). 

An alternative approach to the synthesis of l-fluoroisoquinoUnes was accomplished by the nucleophilic aromatic substimtion (SnAt) [12], The chlorine-fluorine exchange reaction (Halex reaction) [13, 14] was effected in 1-chloroisoquinoIines with potassium fluoride to provide l-fluoroisoquinoUnes in high yield (Schane 2). In the case of 1,3-dichloroisoquinoline used as a substrate, 3-chloro-l-fluoroisoquinoline was selectively obtained despite the use of an excess of potassium fluoride. The chemoseleclivity was attributed to the lability of the carbon-halogen bond at the 1-position of the isoquinoline ring. 

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