Fluoroheteroaromatic

Several fivc-mcmbered-ring fluoroheteroaromatics, such as 4-fluoroimidazoles/ 4f° 2-fluoroimidazoles (e.g., 21),66 and 3-, 4- and 5-fluoropyrazoles,6 have been synthesized in 10-39 % yield via the Balz Schiemann reaction by photochemical irradiation of the corresponding diazonium salts in tetrafluoroboric acid solution (see Vol. ElOa, p 719ff). 

In order to evaluate fluoroheteroaromatic compounds as intracellular pH probes, R.A.J. Smith and co-workers prepared monofunctionalized polymethylated pyridines. To this end, radical Minisci-type substitution reactions were used on substituted pyridines. Reaction of hydroxymethyl radicals with A/-methoxy 2,4- and 2,6-dimethylpyridinium salts gave 2,4,6-substituted hydroxymethylpyridines. Similar reactions with 2,3,5,6-tetramethylpyridine and derivatives failed, but substitution at the 4-position could be achieved using a carbamoyl radical to yield 2,3,5,6-tetramethyl isonicotinamide, which suggested that steric and reactivity restrictions can be overcome by appropriate choice of the reactive radical intermediate. 

---