Fluorodenitration reactions

Fluoroarenes may be prepared by fluorodenitration reactions of activated substrates by reaction with potassium fluoride in sulfolane. Here, it is necessary to add a nitrite trap so that the liberated nitrite ion does not attack the aromatic ring [236]. 

Fluorodenitration of nitroaliphatics has been primarily restricted to polyni tromethanes (Table 9) Side reactions involving potassium nitnte by-product reduce yields of fluoromtromethane The novel use of the adduct of potassium fluoride with hexafluoroacetone in diglyme as a source of fluoride ion for the fluorodenitration of tetranitromethane significantly increases the yield of fluorotn nitromethane [102] (equation 29)... 

Aromatic fluorodenitration was first discovered in the reaction of polychloro-nitrobenzenes with potassium fluoride, when 2,3,5,6-tetrachlorofluorobenzene was prepared in 37% yield from 2,3,5,6-tetrachloronitrobenzene 105] The technique has been adapted to prepare aryl fluorides from other activated nitro aromatics for applications in pharmaceutical and polymer chemistry (equation 31) Fluorodenitration also has been applied to prepare radiolabeled ( F) fluo-roaromatics [74, 106]... 

A characteristic feature of aromatic fluorodenitration is modest yield due to side reactions promoted by potassium nitrite and/or its decomposition product, potassium oxide, with the aryl fluoride or starting material... 

Moderate yields of the 1- (47%) and 4- (51%) fluoro derivatives of benzo[c]cinnoline were obtained by fluorodenitration of the nitro precursors using tetrabutylammonium fluoride. The 2- and 3-fluoro isomers have been made by Schiemann reactions, though yields were only 25 and 35%, respectively (92SC545). 

In comparison with conventional nucleophilic displacement of other groups, such as chlorine, bromine and iodine, fluorodenitration is much faster. Therefore, substitution can be carried out under milder reaction conditions. In particular, lower temperatures allow the synthesis of complex, thermolabile derivatives, e.g. [ F]spiroperidol from its inactive nitro analog using rubidium [ F]fluoride. ... 

F]Fluorodenitration is faster than the isotopic exchange reaction of activated fluorobenzenes with [ F]fluoride and has the advantage of yielding no-carricr-added derivatives. ... 

Anhydrous tetrabutylammonium fluoride (TBAF) has been reported as being a very powerful fluoride source for the preparation of fliioroaromalic derivatives, via fluorodenitration, under mild reaction conditions. In fact, this reagent is not totally anhydrous and water, in less than one molar equivalent, is present together with < 10 mol% of decomposition products that arise during the synthesis of TBAF from commercially available tetrabutylammonium fluoride trihydrate. 

When phthaloyl chloride is employed together with bromo(tetraphenyl)-z -phosphanc, an increase in the fluorodenitration yield is observed. Phthaloyl chloride acts as a trapping agent of potassium nitrite (KNO2), generated during the fluorodenitration process, which is responsible for most of the undesired side reactions. 

A related fluorodenitration was shown to proceed efficiently allowing for transformation of benzyl 5-nitrofuran-2-carboxylate 35 into 5-fluoro derivative 36 in 59 % yield. The reaction did not proceed with methyl or tcrt-butyl esters as well as in the case of free acid or nitrile. Hydrogenolysis of benzyl ester allowed to obtain... 

Kuduk has demonstrated that fluorodenitrations can be carried out using a solution of TBAF in THF which contains approximately 5% water. In some cases they have found that use of commercial TBAF proved deleterious, leading to some of the hydro) product rather than the fluoro. This observation was exploited to obtain hydro)g/pyridine and methojg yridines from nitrop3Tidines using TBAOH and TBAOMe. Merck chemists have optimised such a reaction in the synthesis of a potent bradykinin Bi antagonist (Seheme 15.46). ... 

The formation of aryl fluorides from aryl iodides has been achieved using silver fluoride and a cationic copper reagent. The reaction is likely to involve oxidative addition of the aryl iodide to the copper to give an aryl copper(III) iodide, followed by trans-metalation of silver fluoride forming an aryl copper(III) fluoride, (12). The product is formed after reductive elimination. There has been a theoretical study, using DPT, of the gas-phase fluorodenitration of nitrobenzene. ... 

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