Fluoroaromatics

It should be noted (and can be seen from Table 3.2) that there can be significant solvent effects upon the chemical shifts of fluorobenzenes. 

Complete NMR Analysis of o-, m-, and p-Nitrofluoro-benzenes. The complete set of NMR data for one series of o-, m-, and p-disubstituted fluorobenzene compounds, that of the nitrofluorobenzenes, will serve to further exemplify the interplay of 19F, 13C, and 1H chemical shifts and coupling constants that provide unique 

Coupling Constants. The usual three-bond H-H coupling constant in fluorobenzenes is about 8 Hz, whereas the four-bond coupling constant is between 1 and 3 Hz. Five-bond coupling is usually not observed. Similarly, the three-bond F-H coupling constant is about 8 Hz, the four-bond value 5-6 Hz, and the five-bond coupling constant about 1 Hz. 

The F coupling to carbon can vary considerably for the carbon directly substituted (ipso), depending on its substitution environment, 

Ipso (one-bond) coupling of H to C is consistently between 165 and 172 Hz, whereas its two-bond coupling constants (0-5 Hz) are usually much smaller than three-bond H-C couplings (4-10 Hz). 

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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). 

The preparation of fluoroaromatics by the reaction of KF with perhaloaromatics, primarily hexachloroben2ene, has received considerable attention. Two methods were developed and include either the use of an aprotic, polar solvent, such as /V-methy1pyrro1idinone (8), or no solvent (9). These methods plus findings that various fluoroaryl derivatives are effective fungicides (10) prompted development of a commercial process for the production of polyfluoroben2enes (11). The process uses a mixture of sodium and potassium fluorides or potassium fluoride alone in aprotic, polar solvents such as dimethyl sulfoxide or sulfolane. 

Fluoronaphthalenes and other fused-ring fluoroaromatics, Side-chain fluotinated aromatics,... 

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

Fluoroaromatics are produced on an industrial scale by diazotization of substituted anilines with sodium nitrite or other nitrosating agents in anhydrous hydrogen fluoride, followed by in situ decomposition (fluorodediazoniation) of the aryldiazonium fluoride (21). The decomposition temperature depends on the stabiHty of the diazonium fluoride (22,23). A significant development was the addition of pyridine (24), tertiary amines (25), and ammonium fluoride (or bifluoride) (26,27) to permit higher decomposition temperatures (>50° C) under atmospheric pressure with minimum hydrogen fluoride loss. 

The Balz-Schiemaim reaction is a useful laboratory and industrial method for the preparation of fluoroaromatics. The water-insoluble diazonium fluoroborate is filtered, dried, and thermally decomposed to give the aryl fluoride, nitrogen, and boron trifluoride (28—30). 

Drugs. Ring-fluotinated aromatics have found broad pharmaceutical appHcations, eg, in tranquilizers, hypnotics, sedatives, antibacterial agents (qv), etc. Representative monofluorinated dmgs are Hsted in Table 4. Arprinocid [5579-18-15] is a fluoroaromatic-based veterinary dmg that has found wide acceptance as a coccidiostat for chicken feed. 

Liquid Crystals. Based on worldwide patent activity, numerous compounds containing fluoroaromatic moieties have been synthesized for incorporation into liquid crystals. For example, fluoroaromatics are incorporated in ZLI-4792 and ZLI-4801-000/-100 for active matrix displays (AMD) containing super fluorinated materials (SFM) (186,187). Representative stmctures are as follows. 

Dyes. In contrast to benzotrifluorides and fluoropyrknidines, limited commercialization has developed for dyes containing a fluoroaromatic group. FluorophenyUiydrazines have been converted to (fluorophenyl)pyrazolones, which are disperse dyes for cellulose acetate and nylon (192). 

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). 

D. G. Mooney, An Overview of the Shell Fluoroaromatics Explosion, Hazards XI—New Directions in Process Safety Symposium Series No. 124, Institution of Chemical Engineers, Rugby, UK. 1991. 

Elemental Huonne as a Legitimate Reagent for Selective Fluonnation of Orgamc Compounds Fluoroaromatic Compounds Synthesis, Reactions, and Commercial Applications New Aspects of Carbonylations Catalyzed by Transition Metal Complexes Polyfluoroaromatics An Excursion m Carbamon Chemistry ... 

The fluoroxy reagents react readily with activated aromatic systems (Table 1) to give moderate yields of fluoroaromatic compounds. The fluorine atom shows a preference for ortho orientation because of complexation between the fluoroxy reagent and the ring substituent [75, 22] Nucleophilic attack by the substrate on... 

The aryl tin compounds are better substrates for fluorination because they give high yields of fliiorinated aromatics and they may be fluorinated with acetyl hypofluorite, cesium fluoroxysulfate, or fluorine [52, 54 (equation 28). Aryl boronic esters react with cesium fluoroxysulfate to produce fluoroaromatics [55] (equation 29). 

Arenediazonium hexafluorophosphates represent a promising alternative to diazonium fluoroborates because of decreased water solubility and, in some instances, higher yields of fluoroaromatics [27, 28] (equation 6)... 

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

Fluoroaromatics are now produced m 75-90% yields on an industrial scale by this method The nonorganic layer containing water, hydrogen fluoride, and sodium bifluoride is treated with sulfur trioxide, and anhydrous hydrogen fluoride is recycled by distillation [54 (equation 13)... 

Chromium complexes of fluoroaromatics undergo fluorine replacement more readily and in high yield [24] (equation 14). 

Studies of the S Ar mechanism have involved theuse of 2,4-dmitrofluoroben-zene as a substrate The S, jAr reaction of fluoroaromatics is catalyzed by both aromatic and alphatic amines [42. 43 44, 45, 46 47, 48, 49] Diamines [50] and... 

Among other fluoroaromatic lithium compounds, 2,2 -dilithioperfluoro-biphenyl was investigated No secondary alcohols as mentioned previously m similar reactions are noted in any examples [55]... 

A new thermal preparation ot fluorinated species is copyrolysis Copyrolysis of fluorinated compounds like perfluorobenzene, fluorinated aromatic anhydndes, and fluorinated heteroaromatics with tetrafluoroethylene or other fluonnated olefins is a useful method of preparing fluorinated olefins [88 89], functionalized fluoroaromatics [90 91 92, 93, 94, 95], fluonnated benzocycloalkanes [80, 96, 97, 98, 99, 700], fluorinated heterocycles [80, 93, 101, 102, 103], and fluonnated polycyclic compounds [104] (equations 19 and 20)... 

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