Fluorinated aromatics, synthesis

NMR data on the most common fluorinated aromatics are presented in three categories. Monofluorophenyls and pentafluorophenyls have found the greatest application in synthesis and spectroscopy. Data for polyfluorinated benzenes are also presented. 

PENTAFLUOROPHENYLCOPPER TETRAMER, A REAGENT FOR SYNTHESIS OF FLUORINATED AROMATIC COMPOUNDS... 

Fluorinated dihalocarbenes have been used as central synthons in the synthesis of fluorinated aromatics from cyclopentadienes.62 The reaction proceeds via a fluorinated fused bicyclic cyclopropane, which upon heating undergoes a ring opening to achieve the ring expansion of the second cycle. 

Halogen exchange (halex). This procedure involves the displacement of an activated aromatic halogen with a fluorine anion [140,141]. It has been extensively used for the synthesis of fluorinated aromatic intermediates, such as 2,6-difluorobenzonitrile (Fig. 33) [142],... 

Fig. 32. Balz-Schiemann synthesis of fluorinated aromatic rings.

Fluorinated aromatic substrates have been used in the synthesis of fluorinated biaryl derivatives via S l reactions650. Substrates YC6H4Br (Y = F, CF3 or OCF3) were treated with the anions from 2,4-di-ter/-butylphenol, 2,6-di-tert-butylphenol, / ara-methoxyphenol, / 0ra-(trifluoromethoxy)phenol and 2-naphthol leading to the biaryls YC6H4—ArOH by C-arylation at the carbon atom ortho to the deprotonated hydroxyl group (C-l in 2-naphthol), but at the para carbon atom in 2,6-di-terr-butylphenol. 

Synthesis of Fluorinated Aromatic Compounds through Halogen Exchange... 

Table 12. Synthesis of Fluorinated Aromatics through Halogen Exchange Using Potassium Fluoride Catalyzed by Polymer-Supported Aminopyridinium Salts ...

Nevertheless, nucleophilic displacement of an activated aromatic nitro group by fluoride is much more common and constitutes an efficient method of linking fluorine to an aromatic ring. The availability and low cost of nitroaromatics make fluorodenitration an attractive alternative to halogen exchange for the synthesis of selectively fluorinated aromatic compounds via nucleophilic fluorination. Various salts, such as rubidium [ F]fluoride, - tctrabutylam-monium fluoride, or potassium fluoride. can be used as fluoride sources. 

Aromatic compounds Nucleophilic displacement of halide ion from haloaromatic compounds containing other electronegative substituents is well known this process has been widely exploited for the synthesis of fluorinated aromatic compounds (Table 2.1) and is discussed later (see Chapter 9, Section 11). 

Chlorine and iodine can be introduced into aromatic rings by electrophilic substitution reactions, but fluorine is too reactive, and only poor yields of monofluoroaromatic products are obtained by direct fluorination. Aromatic rings react with CI2 in the presence of FeCh catalyst to yield chlorobenzenes. This kind of reaction is used in the synthesis of numerous pharmaceutical agents, including the tranquilizer diazepam (Valium). 

---