Fluorides, aromatic

The controlled thermal decomposition of dry aromatic diazonium fluoborates to yield an aromatic fluoride, boron trifluoride and nitrogen is known as the Schiemann reaction. Most diazonium fluoborates have definite decomposition temperatures and the rates of decomposition, with few exceptions, are easily controlled. Another procedure for preparing the diazonium fluoborate is to diazotise in the presence of the fluoborate ion. Fluoboric acid may be the only acid present, thus acting as acid and source of fluoborate ion. The insoluble fluoborate separates as it is formed side reactions, such as phenol formation and coupling, are held at a minimum temperature control is not usually critical and the temperature may rise to about 20° without ill effect efficient stirring is, however, necessary since a continuously thickening precipitate is formed as the reaction proceeds. The modified procedure is illustrated by the preparation of -fluoroanisole ... 

Applications in agrochemicals [42, 43], pharmaceuticals [44,45], and positron emission tomography (PET) [46, 47, 48 49] have resulted in the resuscitation of the Wallach reaction The Wallach technique provides high-specific-activity F-radiolabeled aromatic fluoride for PET studies, in contrast to the low-specific-ac-tivity product by the Balz-Schiemann route... 

With the nitro group successfully introduced, the aromatic fluoride substituent in 11 was ready to undergo the nucleophilic aromatic substitution with the hydrox-ypyridine 9. The reaction proceeded smoothly in DMF at 55 °C using an equimolar amount of cesium carbonate as the base and provided a 90% isolated yield of 23 after crystallization. With compound 23 in hand, only the reduction of the nitro... 

The photolysis of crystalline diazonium tetrafluoroborates and hexa-fluorophosphates affords a convenient route to aromatic fluorides<53) ... 

SNAr substitutions of activated aromatic halides, especially aromatic fluorides, provide useful means for the construction of aromatic diethers or amines. Primary and secondary amines react with l, 2-dihalo-4,5-dinitrobenzene to give nitro group substitution at room temperature. The halogen substituents on the ring remain unsubstituted and can be used in further transformation (Eq. 9.5).8... 

Aromatic fluorides, synthesis of, 5, 4 Aromatic hydrocarbons, synthesis of, 1, 6 30, 1... 

Schnur and co-workers " summarized typical reactions that can be performed on functional groups of substituted 2,4-oxazolidinediones without ring opening. These reactions include reduction with iron-acetic acid, chlorosulfonation, nucleophilic displacements of aromatic fluorides, and acid hydrolysis with HCl/formic acid. Nonetheless, there are examples of useful ring cleavage reactions involving 2,4-oxazolidinediones. 

An appreciable increase in the yield of some aromatic fluorides with hexafluorophosphoric acid, compared to the fluoroboric acid method, has been observed. Outstanding in this respect is the increase in yields of 2-fluorobenzoic acid (+52%), 4-fluorobenzoic acid ( + 49%),... 

K18F has been used to prepare 18F-labeIled aromatic fluorides by nucleophilic substitution on activated aromatic halides.88,90... 

Aromatic fluorides, chlorides, nitriles and amines Saturated cyclic compounds... 

Because of the presence of nitrogen in the aromatic ring, electrons in pyridine are distributed in such a way that their density is higher in positions 3 and 5 (the P-positions). In these positions, electrophilic substitutions such as halogenation, nitration, and sulfonation take place. On the contrary, positions 2, 4, and 6 (a- and y-positions, respectively) have lower electron density and are therefore centers for nucleophilic displacements such as hydrolysis or Chichibabin reaction. In the case of 3,5-dichlorotrifluoropyridine, hydroxide anion of potassium hydroxide attacks the a- and y-positions because, in addition to the effect of the pyridine nitrogen, fluorine atoms in these position facilitate nucleophilic reaction by decreasing the electron density at the carbon atoms to which they are bonded. In a rate-determining step, hydroxyl becomes attached to the carbon atoms linked to fluorine and converts the aromatic compound into a nonaromatic Meisenheimer complex (see Surprise 67). To restore the aromaticity, fluoride ion is ejected in a fast step, and hydroxy pyridines I and J are obtained as the products [58],... 

Cross-linked styrene/2-(4-chlorophenyl)prop-l-ene copolymer grafted to a tetraphenylphos-phonium salt is an effective reusable catalyst for the synthesis of aromatic fluorides from aromatic chlorides in the presence of potassium fluoride. ... 

Not only is thermal fluorodediazoniation possible, but the corresponding pliotochemically induced process is also possible (see Vol. E 10a, p 703). Several aromatic fluorides can be prepared viti diazotization and pliotochemically induced fluorodediazoniation of aromatic amines in anhydrous hydrogen fluoride-organic base solutions. In general, no fluoroaromatic compounds can be isolated if the fluorodediazoniation stage is carried out without photochemical irradiation under similar conditions (rt). 

The synthesis of 7-azaindoles is a challenging task and there are few efficient routes to substituted derivatives. In the laboratory of C. Thibault, the concise and efficient synthesis of 4-fluoro-1/-/-pyrrolo[2,3-jb]pyridine was achieved. The fluorination was carried out using the Balz-Schiemann reaction. The aromatic amine precursor was prepared via the Buchwald-Hartwig coupling of the aryl chloride with A/-allylamine followed by deallylation. The diazonium tetrafluoroborate intermediate was generated at 0 C and it decomposed spontaneously in 48% HBF4 solution to afford the desired aromatic fluoride. 

Sawaguchi, M., Fukuhara, T., Yoneda, N. Preparation of aromatic fluorides facile photo-induced fluorinative decomposition of arenediazonium salts and their related compounds using pyridine-nHF. J. Fluorine Chem. 1999, 97, 127-133. 

Fukuhara, T., Sekiguchi, M., Yoneda, N. Facile preparation of aromatic fluorides by thefluoro-dediazoniation of aromatic diazonium tetrafluoroborates using HF-pyridine solution. Chem. Lett. 1994,1011-1012. 

In this way it has been possible to prepare the aromatic fluorides-In accordance with the older views it was believed that the aromatic fluorides could not be obtained from the diazo-compounds in the same way in which the analogous chlorides, bromides, and iodides are prepared recently however they have been obtained by the direct decomposition of the diazo-fluorides. 

Aryl fluoroformates can be decarboxylated into aromatic fluorides by gas-phase decomposition at 600-800 C [380,382], or at around 300 C by passing the vaporized aromatic fluoroformate over an alumina catalyst [86]. 

The Balz-Schiemann reaction for the introduction of fluorine into an aromatic nucleus involves forming the amine, then the diazonium fluoborate, which in turn decomposes into an aromatic fluoride (104,106,107). One of the reviews (104) of this reaction gives tables of the compounds prepared by this method. 

It has been already reported that, with organosoluble ammonium chlorides, water favours the Retro-Halex reaction which competes with hydrolysis. Similar experiments showed that this process does not occur under heterogeneous conditions (aromatic fluoride and solid KC1 or CsCl in aprotic solvent), whatever are the substrates, the solvent and the source of inorganic chloride, provided that the water content of the latter remains around or below 1 % by weight. This point has been confirmed independently in a very recent paper (ref. 41). However, when 10 % wt of water is added to potassium chloride, the Retro-Halex has been observed, though hydrolysis was the major process (ref. 17) ... 

We have begun examining Route A using a niline (19) as a model for 7 (Scheme 6). Reaction of 19 with commercially available 4-fluorobenzene-sulfonylchloride (6) gave 20 in 90% yield. Compound 20 results from selective reaction at the sulfonyl chloride in the presence of the aromatic fluoride. The temperature of the reaction was cmcial for success at 40°C, a mixture of 20 and 21 was obtained, but at 0°C, only 20 was formed. Compound 21 arises from a double addition of an iline. This latter reaction gives us reason to believe that the nucleophilic aromatic substitution needed to prepare our key model compound 22, representing 17 in Route A (Scheme 5), will be possible. 

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