Fluoroarenes with amines

Substitution with amine nucleophiles in the series of chlorotoluene complexes showed that the substitution is direct no cine or tele substitution was observed.75 The analogous [(fluoroarene)FeCp]+ complexes are known, but less well developed. Kinetic studies show that the fluoro derivatives are more reactive compared to the chloro analogs.47... 

Milner (1992) recently described a novel and versatile modification of the Balz-Schiemann reaction. The amine is diazotized with solid nitrosonium tetrafluoro-borate in CH2C12 and, without isolation, the diazonium salt is heated and yields the fluoroarene in good yield. The method is also applicable to aniline derivatives bearing carboxy and hydroxy substituents, compounds which give poor yields in the classical procedure. 

ArNHj remains (as it is a weak base), but the concentration is low enough to prevent as yet undiazotised amine undergoing a coupling reaction with the first formed ArNj (c/. p. 147). Aromatic diazonium chlorides, sulphates, nitrates, etc., are reasonably stable in aqueous solution at room temperature or below, but cannot readily be isolated without decomposition. Fluoroborates, ArN2 BF4 , are more stable cf. stabilising effect of BF on other ion pairs, p. 136) and can be isolated in the dry solid state thermolysis of the dry solid is an important preparative method for fluoroarenes ... 

The decomposition of arenediazonium tetrafluoroborates in the resulting fluoroarene as solvent has also been utilized.179 This method is very fruitful in the synthesis of fluorobenzene (96% yield) or fluorotoluenes (85-88% yield for the three isomers) but fails with substrates such as anisolediazonium tetrafluoroborates which probably arylate the reactive fluoroaromatic solvent. In contrast, perfluorinated tertiary amines (EF-L 174, F-C 40), perfluorinated alkyl tetrahydropyran (EF-L 102), perfluorodecahydronaphthalene (Flutec PP7) or other per-fluorocycloalkanes (Flutec s) are claimed to be the best media for fluorodediazoniation of all types of diazonium tetrafluoroborates.224 These media seem to be more efficient, at least in the synthesis of 1,2-difluorobenzene, than silicone oil which has also been claimed to improve fluorodediazoniation.225... 

Fluoroarene-Cr(CO)2L complexes 33p [L = CO, PPh3, P(OPh)3, P(pyrrolyl)3, P(pyrolyl)2 (NMeBn)], where L is a potential linker ligand for solid-phase synthesis, have been evaluated with regard to the rates of nucleophilic substitution by amines [35]. The preparative and kinetic results indicate that SNAr reactions on tris(pyrrolyl)phosphine-modified fluoroar-enechromium complexes proceed rapidly and with high efficiency, and are thus appropriate for the development of solid-phase versions for use in combinatorial synthesis (Scheme 18). 

A greater array of amine substrates has also been explored for this reaction utilizing the 4-fluorobromobenzene as the fluoroarene. The results (Table 1) show excellent yields (85 - 93 %) for the primary (7) and secondary (8, 9) amines. Although no reaction was observed with aniline, 93 % yield was obtained with N-methylaniline (8). Derivatives prepared from the cyclic amines, morpholine (10) and piperidine (11), were also obtained in excellent yields of 82 - 98 %. A preliminary attempt at a disubstitution reaction using two equiv of piperazine Avith one equiv of 4-bromofluorobenzene gave the disubstituted product (12) in only 35 % yield. However, it is likely that this yield could be improved using an excess of... 

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