Fluonnation aromatics

Ring-fluonnated aromatics have found wide applications in pharmaceuticals, crop protection chemicals, polymer intermediates, liquid crystals, etc [10] Routes based on aromatic amines represent one of the major synthetic approaches to these compounds The scope and the techniques have been sufficiently described in reviews [//, I2 and monographs [13, 14, fi] Therefore, only reactions and techniques published after 1971 are discussed... 

In the Schmidt reaction of fluonnated dicarboxyhc acids, the appropnate amides can be obtained in fairly good yield [48] Complications arise from possible cychzation if the fluorine atom is in the 8 position relative to the newly formed amino group [/] Fluonnated aromatic ethers, upon heating in dimethylformamide, undergo Smiles rearrangement to give diarylamines [49, 50] (equation 11)... 

The primary function of this section is to organize data to faalitate NMR structure elucidation of organofluonne compounds Selectively fluonnated aliphatics are emphasized, whereas fluonnated aromatics are covered m less detail Inorganic nitrogen, phosphorus, silicon, and sulfur fluondes are not included, although compounds containing these and other heteroatoms attached to CF3 are the focus of multmuclear data presented later (see Table 16)... 

Almost all of the biomedical research done in the 25 years following the liquid-breathing work was conducted with commercially available fluorocarbons manufactured for various industnal uses by the electrochemical Simons process (fluonnation in a hydrofluoric acid solution) or the cobalt fluoride process (fluori-nation with this solid in a furnace at about 200 C) These processes tended to yield many by-products, partly because they were, to some extent, free radical reactions and partly because it was difficult to easily achieve complete fluonnation Aromatic hydrocarbons gave better products with the cobalt tnfluonde [73] method, whereas saturated hydrocarbons yielded better products with fluonnation using diluted or cooled gaseous fluorine (Lagow) Incompletely fluormated matenal was either... 

Antibactenal agents - [ANTIAGING AGENTS] (Vol 2) - [ANTIBIOTICS - SURVEY] (Vol 2) -for aquaculture [AQUACULTURECHEMICALS] (Vol 3) -organobromines as [BROMINE COMPOUNDS] (Vol 4) -nng-fluonnated aromatics as [FLUORINE COMPOUNDS, ORGANIC - FLUORINATED AROMATIC COMPOUNDS] (Vol 11)... 

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

Mmy fluonnated aromatic compounds are alkylated with alkyl halides under Fnedel-Crafts conditions For example, the intramolecular alkylation of 3-fluoro-A-(chloroace-tyl)amhne with aluminum chlonde gives 6-fluorooxmdole [5] (equation 5) Similarly, 3 -chloro-4-fluoropropiophenone affords 5-fluoroindanone [6] (equation 6)... 

Other well-known reactions are those offluorinated olefins with fluoride ion and negatively substituted aromatic compounds leading to the formation of per-fiuoroalkylated aromatic compounds The reaction may be considered an amonic version of a Fnedel Crafts process and can result in introduction of one or several perfluoroalkyl substituents [/ /] Aromatic substrates include substituted and unsuhstiluled perfiuorobenzenes [J3l, 212, 213, 214], fiuorinated heterocycles [131, 203, 215, 216, 217, 218, 219, 220, 221, 222, 223],perchlorinated heterocycles [224] (equation 44), and other activated aromatic compounds [225] (equation 45) The fluonnated olefins can be linear or cyclic [208] (equation 46)... 

Vanadium pentafluoride replaces benzylic hydrogen by fluonne but also adds fluonne to the aromatic system, giving fluonnated cyclohexadienes and cyclohexenes [5] (equation 5)... 

Systems usually fluonnated by electropositive fluorine reagents include acti-vated alkenes (enol ethers, enol acetates, silyl enol ethers, and enamines), activated aromatic systems, certain slightly activated carbon-hydrogen bonds, and selected organometallics. 

Polynuclear aromatics react with fluoroxy reagents to give high yields of ortho substitution products accompanied by varying yields of geminal difluoro products Thegeminal difluonnation occurs presumably by an addition-elimination mechanism [27 28, 29, 30, 31, 32] Unactivated aromatic systems are fluorinated in lower yield to give monofluonnated products (Table 1, entries 6 and 7) Examples of fluonnation of polynuclear systems [/5, 21, 25, 30, 32, 7 ] are shown m equations 7-10... 

The preparation of aromatic fluorine compounds may be accomplished by direct fluorination or by fluonnation of organometallic intermediates. Tlte ipso fluorination of an aryl organometallic derivative with a positive fluorine reagent allows control over the regioselectivity of the fluorination and offers advantages in the preparation of F-labeled materials [II, 50],... 

The fluorination of organometallics with Al-fluoroamide reagents has received Only limited attention. Grignard reagents, both aliphatic and aromatic, are converted to organofluonne compounds. Both the electron transfer and the Sf,j2 ntechamsms have been considered in these processes [SO, 81, 82], The reactions 0 exemplified in equation 46 [48, 69, 70, 71, 75] Organosilanes are also fluonnated [71] (equation 47)... 

Xenon difluoride may be used as the pure reagent or as a graphi te intercalate for the effective fluonnation of polynuclear aromatics [86 87] (equations 49 and 50)... 

Carboxylic acids react with xenon difluoride to produce unstable xenon esters The esters decarboxylate to produce free radical intermediates, which undergo fluonnation or reaction with the solvent system Thus aliphatic acids decarboxylate to produce mainly fluoroalkanes or products from abstraction of hydrogen from the solvent Perfluoro acids decarboxylate in the presence of aromatic substrates to give perfluoroalkyl aromatics Aromatic and vinylic acids do not decarboxylate [91] (equation 51)... 

Most aliphatic [95, 184, 185, 186, 187], aromatic [95 186,188], md heterocyclic [189,190] ketones react with DAST in the usual way to give geminal difluoro derivatives Fluonnation of cycloaliphatic ketones, in particular, is often accompanied by a spontaneous dehydrofluorination to form considerable amounts of... 

Heavily fluonnated aminobenzenes, pyridines, and pyrimidines are diazotized in strong-acid media Solid sodium nitrite added directly to the fluonnated amine dissolved in 80% hydrofluonc acid, anhydrous hydrogen fluoride, or (1 1 wt/wt) 98% sulfuric acid in (86 14 wt/wt) acetic and propionic acids affords the electrophilic fluoroarenediazonium ion Addition of an electron rich aromatic to the resultant diazonium solution gives the fluoroareneazo compound [10 II] (equa tions 9 and 10)... 

The presence of a tnalkylsUyl group in a fluonnated organic compound may be useful to direct further transformations of that matenal Yet m some instances it IS the fluonnated substituent that controls the reactions of the tnalkylsdyl group Contrary to predictions, treatment of tert-hnlyX 3-tnfluoromethyl-6-tnmethylsilyl-phenyl carbamate with rert-butyllithium results m metallation of one of the methyl groups attached to silicon rather than that of the aromatic nng [90] (equation 75)... 

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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