Defluorination-aromatization

Scheme 2.27 Industrial-scale methods for reductive defluorination—aromatization of perfluorocycloaliphatic precursors, which again are accessible by the cobalt trifluoride process [74].

Scheme 2.28 Reductive defluorination-aromatization under milder reaction conditions suitable for laboratory-scale synthesis of perfluoro-olefins and related products (Hg = photochemically excited mercury) Cp = pentamethylcyclopentadienyl [75. 76].

Although Fe deposition has been less studied than other metals, some reports are available. Deposition on fluorinated organic films, such as partially fluorinated decanethiolate/Au SAMs, shows extensive defluorination of the molecular group to form Fe(II) fluorides, with no evidence for reactions with the C atoms of the chains [75]. Further, for an aromatic thiolate/Au SAM, no degrading side reactions were observed [33]. 

Aromatic molecules with fluorine or fluorine-containing substituents frequently have high bioactivity [39] and are therefore used for medical and agrochemical applications, in which they are deliberately introduced to organisms and/or the environment (Fig. 2). They are typically less bioaccumulative and less environmentally persistent than saturated fluorocarbons, and may be degraded oxidatively under aerobic conditions, where defluorination may or may not occur.5 The world market for fluoroaromatics was estimated at 10,000 tonne per annum in... 

The derivative 109, bearing fluorine-18 on an aromatic ring in a site stable to metabolic defluorination, has been prepared14015 as in equation 63, involving reaction of fluoride ion... 

The halogens on aromatic rings may be activated by an electron-withdrawing group located at the ortho and para positions. />Fluorobenzoic acid, as its sodium salt in an aqueous solution, was hydrogenolyzed to give benzoic acid and then more slowly converted to cyclohexanecarboxylic acid over platinum catalyst.235 With Raney Ni or Raney Co alloy and alkali, it was also defluorinated.231... 

Either fusion with alkali metals or reaction with aUcali-metal complexes with aromatic hydrocarbons will break down most fluorocarbon systems, due to the high electron affinities of these systems. Such reactions form the basis of some methods of elemental analysis [13], the fluorine being estimated as hydrogen fluoride after ion exchange. Surface defluorination of PTFE occurs with alkali metals and using other techniques [14]. Per-fluorocycloalkanes give aromatic compounds by passage over hot iron and this provides a potential route to a variety of perfluoroaromatic systems (Chapter 9, Section IB). 

Perfluoroaromatic compounds can be obtained by reductive aromatization of readily accessible perfluorocycloaliphatic precursors [73]. Defluorination can be accomplished by contact with hot (500 °C) iron or iron oxide. After reducing the per-fluoroaliphatic compound the metal surface can be regenerated by passage of hydrogen gas. This method has been scaled up to a continuous flow process for industrial synthesis of a variety of perfluorinated aromatic compounds (Scheme 2.27). 

Reductive agents other than iron can also lead to aromatization or partial desaturation of perfluorocycloaliphatic derivatives. Photochemically activated ammonia (NHj/Hg ) as the reducing agent leads to subsequent aminolysis products [75]. Others are complex catalytic systems which achieve the defluorination even at room temperature [8, 76] (Scheme 2.28). 

In contrast to carbon-fluorine activation reactions of alkenes or aromatics, the conversion of fluorinated alkanes and cycloalkanes to alkenes and aromatics is well documented. For instance, Grabtree and Burdeniuc discovered metal-based photochemical systems which are useful for the defluorination of perfluorocarbons. " Irradiation of per-fluoromethylcyclohexane or perfluoroisopentane in the presence of decamethylferrocene and LiOTf provides a route to prepare perfluoroalkenes (Scheme 14). These reactions conform to the general equation (vi)a (Scheme 4) with... 

Another example of an F-label that has been incorporated in alkyne-containing peptides through the Huisgen click reaction involves l-(azidomethyl)-4-[ F]-fluorobenzene (21, Figure 5.11), which was published by Thonon et al. [26]. One advantage of such an aromatic fluoride over the previously shown aliphatic ones is the improved the resistance toward in vivo defluorination [27]. 

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