From fluoroaromatics

Potassium organophosphide reagents also continue to find applications in synthesis. Direct displacement of fluoride from fluoroaromatic substrates by potassium diphenylphosphide is the key step in the synthesis of the phosphi-noarylsulfoxides (88), water-soluble phosphino-amino acid systems, e.g. (89), ° and the chiral benzoxazine system (90). Related displacement of fluoride by potassium monophenylphosphide has been used to prepare a series of hydrophilic triarylphosphines, e.g. (91). Among new phosphines prepared by conventional displacement reactions by potassium diphenylphosphide on... 

As previously mentionned, the possibility of a reverse reaction, that is the formation of chloroaromatics from fluoroaromatics, must be investigated, especially with onium halides since, in this case, no solubility problem can disturb the eventual equilibria. Table 6 indicates that tetrabutyl ammonium or phosphonium chlorides, when dried, react to a very limited extend with fluoroaromatics, even in concentrated medium with very activated substrates like 2,4-dinitrochlorobenzene (ref. 17). 

Unit sales prices of from 800 to 900 fine chemicals are fisted weekly in the Chemical Marketing Reporter. This number reflects those fine chemicals produced and sold in industrial quantities. Some market studies on fine chemicals, fisting important product families, such as side chains for P-lactam antibiotics (qv). A/- and A-heterocycfic compounds, fluoroaromatics, etc, do exist (14,15). 

Diazotization Routes. Conventional Sandmeyer reaction conditions are not suitable to make fluoroaromatics. Phenols primarily result from high solvation of fluoride ion in aqueous media. 

Eused-ring polycycHc fluoroaromatics can be made from the corresponding amino fused-ring polycycHc or from preformed fluoroaromatics, eg, 4-fluorophenyl-acetonitrile [459-22-3] (275). Direct fluorination techniques have been successfully appHed to polycycHc ring systems such as naphthalene, anthracene, benzanthracenes, phenanthrene, pyrene, fluorene, and quinoHnes with a variety of fluorinating agents xenon fluorides (10), acetyl hypofluorite (276), cesium fluoroxysulfate (277), and electrochemical fluorination (278,279). 

Other Uses. Other appHcations for sodium nitrite include the syntheses of saccharin [81-07-2] (see Sweeteners), synthetic caffeine [58-08-2] (22), fluoroaromatics (23), and other pharmaceuticals (qv), pesticides (qv), and organic substances as an inhibitor of polymerization (24) in the production of foam blowing agents (25) in removing H2S from natural gas (26) in textile dyeing (see Textiles) as an analytical reagent and as an antidote for cyanide poisoning (see Cyanides). 

Table 3. Synthesis of ort/io-Substituted Fluoroaromatics from Nitrite Esters, Boron Trifluoride, and Hydrogen Fluoride [26]...

In fluorine-18 chemistry some enzymatic transformations of compounds already labelled with fluorine-18 have been reported the synthesis of 6-[ F] fluoro-L-DOPA from 4-[ F]catechol by jS-tyrosinase [241], the separation of racemic mixtures of p F]fluoroaromatic amino acids by L-amino acylase [242] and the preparation of the coenzyme uridine diphospho-2-deoxy-2-p F]fluoro-a-o-glucose from [ F]FDG-1-phosphate by UDP-glucose pyrophosphorylase [243]. In living nature compounds exhibiting a carbon-fluorine bond are very rare. 

Direct fluorination, therefore, is not particularly effective for the preparation of mono-fluorinated aromatic compounds from monosubstituted precursors since, in these cases, electrophilic fluorination gives mixtures of isomeric products. However, when there are two or more groups in the aromatic substrate which activate the same carbon atom towards electrophilic attack, as in the case of 4-fluorobenzoic acid (Table 5), then direct fluorination is an efficient method for the preparation of fluoroaromatic compounds (Fig. 57) [148]. 

The largest tonnage product, fluorobcnzcnc (3), is manufactured by the diazotization of aniline (1) in strong aqueous hydrogen fluoride. The intermediate diazonium fluoride 2 is decomposed in situ without isolation from solution. Despite the considerable safety and corrosion problems presented by the reaction mixtures, the technology was developed in the 1980s to provide a worldwide capacity of several thousand tons. Other fluoroaromatics such as fluorotoluenes are also manufactured by this route. 

Diazotization in the presence of boron trifluoride enables diazonium tetrafluoroborates to be isolated from the reaction mixture and purified. Subsequent controlled decomposition produces the required fluoroaromatic. Although explosion hazards and the toxicity of the isolated salts are significant concerns with this process, known as the Balz-Schiemann process, 4,4 -di-fluorobenzophenone (BDF. 6) has been prepared by this route as a monomer for the production of the engineering plastic poly(ether ether ketone) , or PEEK , by condensation with 1,4-dihydroxybenzene in the presence of potassium carbonate. BDF 6 is superior to its chlorine analog because in aromatic systems the nucleophilic displacement of fluorine is more facile than that of chlorine, leading to a shorter polymerization time and a better quality product containing less degradation impurities. 

Arenediazonium hexafluoroantimonates were described as early as 1935,275 but their fluorodediazoniation was only studied much later.276 They deliver fluoroaromatics in better yields than other diazonium salts only when electron-withdrawing groups (N02, C02H) are present on the ring. Otherwise, antimony(V) fluoride formed in the reaction acts as a strong Lewis acid and catalyzes the formation of byproducts. The phenomenon is more pronounced with diazonium hexafluoroarsenates which deliver fluoro compounds in acceptable yields only from nitroanilines.276 With unsubstituted or electron-releasing substituted anilines, difluo-rinated arenearsonic acids are often the major product. 

As the formation of diazonium salts from the acid decomposition of aryltriazenes is obviously all the more rapid since the acid is stronger, the decomposition of triazenes with strong acids, in the presence of fluoride, has been studied in order to give the most rapid access to [I8F]fluoroaromatics. Reaction with methanesulfonic acid at 70-80°C is best for this purpose301-302 and gives products with a high specific activity, e.g. formation of 11.301 It should be noted that such a reaction unambiguously confirms the ionic character of the fluorodediazoniation process. 

Tetracarbonyl(trifluoromethyl)iron(II) iodide reacts with C-C bond formation to give per-fluoroethene. Tetracarbonyl(perfluorohexyl)iron(II) iodide gives several products, but no per-fluorohexene resulting from /1-elimination has been found.148 However, reductive defluorination of perfluoro(methylcyclohexane) has been reported with dicarbonyl(ty5-cyclopcn-tadienyl)iron(III).212 The defluorination is accompanied by substitution of fluorine with the cyclopentadienyl anion and proton abstraction from the solvent, the latter is well known in the chemistry of fluoroaromatics with the cyclopentadienyl anion. 

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