Perfluoroalkylation aromatic compounds

Table 6, Perfluoroalkyl Aromatic Compounds Prepared via the Reaction of Perfluoroalkylcopper Reagents with lodo-or Bromoaromatic Compounds...

After a brief survey of the history of valence-bond isomers of aromatic compounds, new syntheses and the reactions of these isomers reported in the last decade are reviewed. In the second chapter, the valence-bond isomers of homoaromatic compounds, especially benzene derivatives, are described and in the third chapter those of heterocyclic compounds. Photoreactions of perfluoroalkylated aromatic compounds afford valence-bond isomers in high yields. These isomers are very stable and useful for the synthesis of highly strained compounds. Therefore, the emphasis is put on the chemistry of trifluoromethylated benzvalenes, Dewar thiophenes, and Dewar pyrroles. 

As early as the 1940s Emeleus and Haszeldine [17] discovered that perfluoroalkyl iodides are not only cleaved into perfluoroalkyl radicals by light but also that they add readily to a variety of olefins to yield telomers and 1 1 adducts [18]. This kind of radical chain reaction can also be initiated by high temperatures (Scheme 2.100). The addition of perfluoroalkyl iodides to olefins is a very important method for synthesis of partially fluorinated alkanes, polymers, oligomers, and their derivatives [19]. The synthesis of some perfluoroalkyl aromatic compounds can also be achieved [20]. 

The reaction apparently involves fluoroalkylcopper species, which may be preformed before addition of an iodoaromatic compound, and these are thermally and hydrolytically fairly stable. Bromoaromatic compounds are less reactive but may be used. The reaction has been employed to prepare a variety of trifluoromethyl- and other perfluoroalkyl-aromatic compounds, and, from perfiuoro-aw-di-iodoalkanes, perfluoroalkylene-linked aromatic polymers. ... 

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)... 

Perfluoroalkylation of substituted benzenes and heterocyclic substrates has been accomplished through thermolysis of perfluoroalkyl iodides in the presence of the appropriate aromatic compound Isomeric mixtures are often obtained W-Methylpyrrole [143] and furan [148] yield only the a-substituted products (equation 128) Imidazoles are perfluoroalkylated under LTV irradiation [149] (equation 129). 4-Perfluoroalkylimidazoles are obtained regioselectively by SET reactions of an imidazole anion with fluoroalkyl iodides or bromides under mild conditions [150] (equation 130) (for the SET mechanism, see equation 57)... 

FITS reagents), has undergone considerable development recently [141,142,143, 144, 14S. These compounds, available fromperfluoroalkyhodides (equation 76), are very effective electrophilicperfluoroalkylating agents They react with carban-lons, aromatic compounds, alkenes, alkynes, silyl enol ethers, and other nucleophiles under mild conditions to introduce the perfluoroalkyl moiety mto organic substrates (equation 77) (see the section on alkylation, page 446). 

Much of the research on the SbCls-catalyzed halogenation of arenes has focused on the chlorination and bromination of perfluoroalkyl-substituted aromatics [14]. The reaction of organic disulfides with electron-rich aromatic compounds under catalysis with SbCls and AgSbFg affords unsymmetrical aryl sulfides in modest yields [15a]. Electrophilic sulfinylation and sulfonation can be similarly effected by SbCls [15a-c]. Alkyl- and halobenzenes give thiocyano derivatives when treated with a mixture of SbCls and Pb(SCN)2 in CCI4 [16],... 

A Dewar isomer of unsubstituted pyridine was identified by Wilzbach, but it was very unstable.63 Other Dewar isomers of six-membered heterocycles, isolated and fairly stable, are substituted with perfluoroalkyl groups. However, 1,2-dihydroheterocyclic compounds such as a-pyrone or a-pyridone derivatives are easily photoisomerized to bicyclic Dewar isomers, which are useful for the synthesis of cyclobutadienes. The photochemistry of 1,2-dihydroheterocyclic compounds will be discussed, followed by those of fully aromatic compounds. 

To make preparative use of perfluoroalkyl radicals they must first be generated by a method which does not interfere with other functional groups present in the reaction system. Because of their predominantly electrophilic nature, the most important reaction partners for these radicals are either highly polarizable ( soft ) u-elec-tron systems (for example thiolates, selenides or phosphites) or, preferably, electron-rich r-systems (for example olefins and some aromatic compounds). 

Scheme 2.100 Photo-initiated and thermally initiated radical additions of perfluoroalkyl iodides and bromides to olefins and aromatic compounds [11],...

Reactions with reductively and oxidatively generated [26] perfluoroalkyl radicals have also been successfully used for perfluoroalkylation of aromatic compounds (Scheme 2.103). For the reductive initiation, the single electron transfer (SET) necessary for formation of the radical anion priming the reaction sequence can be provided either by a reductive reagent (for example HOCH2SO2Na) [27] or by an electron-rich aromatic substrate itself [28]. The oxidatively induced variant enables the perfluoroalkylation of more electron-deficient aromatic substrates, for example quinoline. 

A similar method of activation of the perfluoroalkyl silane is used for nucleophilic addition or substitution of trifluoromethyl moieties to obtain electron-deficient fluorinated aromatic compounds [91] (Scheme 2.137). 

The rate constants for the single steps of the chain reaction, namely the coupling of radical with nucleophile, the electron transfer to the aromatic compound and the dissociation of the radical anion have been determined by electroanalytical techniques, and its scope by way of cathodic induction has been demonstrated [159]. The reaction has been extended to substrates other than aromatics. For example, perfluoroalkylation of purine and pyrimidine bases can be achieved by cathodic initiation [160[. 

Similar results are reported for the perfluorodimethyl compound. The introduction of fluoro-substituents and particularly perfluoroalkyl groups thus imparts a notable increase in the ease of formation and stability of valence bond isomers of aromatic compounds, and the physical properties of those involved in the light-induced interconversion of perfluoro-1,3,5- and -1,2,4-trimethylbenzenes have also been discussed by the Manchester group.14 15 The energetics of the back reaction (i.e. valence-bond isomer to benzenoid compound) have been studied, and it is interesting to note that in the conversion of Dewar acetophenone into acetophenone, the location of the excitation starts off mr -like but ends as... 

Majority of known perfluoroalkylated aromatic heterocyclic compounds contain one or several nitrogen atom(s) in the aromatic ring. Examples of fluoroalkylated aromatic six-membered heterocycles containing atoms, such as phosphorous or antimony are extremely rare and this is the reason why this chapter is mostly limited to preparation and chemical transformations of nitrogen-cotitammg aromatic heterocycles, providing limited number of references to only few known examples of trifluoromethyl s-1,3,5,2,4,6-triazatriphosphinines. 

Full details (see Vol. 1, p. 185) of the Japanese work on the preparation of trifluoromethylarenes from trifluoroiodomethane and iodoarenes in the presence of copper powder and a dipolar aprotic solvent have become available, and it appears that the best solvent in some cases is pyridine. This method (but with DMF as solvent) has also been used to prepare the compounds PhR [R = Me03C (CF3)3, CF3 0 (CF2)2, or perfluoro-2-tetra-hydrofurfuryl] in good yields from iodobenzene and the corresponding polyfluoroiodo-compounds. Perfluoroalkyl-copper compounds are very probably involved in such reactions, and the reactions of preformed n-perfluoroheptylcopper in dimethyl sulphoxide with the aromatic carbon-hydrogen bonds of benzene, toluene, p-xylene, nitrobenzene, and chlorobenzene also lead to (perfluoroalkyl)arenes (some replacement of chlorine occurs in the case of chlorobenzene). Homolytic substitution by perfluoro-heptyl radicals, perhaps within the co-ordination sphere of the copper atom,... 

MCM-41-supported metal (Yb, Zn) bis[(perfluoroalkyl)sulfonyl]imides were reported as effective catalysts for nitration of aromatic compounds with 1 eq. of 65 wt% nitric acid in the liquid phase Equation (8.68). The enhanced electron-drawing and steric effects from longer perfluori-nated alkyl chains were found to promote this action. Water exhibits also a positive effect. The catalysts were recycled without substantial loss of catalytic activity [103]. 

Copper, Sflver and Gold.—Perfluoroalkyl iodides and iodoaromatic compounds react with copper in aptotic solvents to give good yields of perfluoro-alkylated aromatic compounds ... 

Chen and Li have studied the photoinduced electron transfer reactions of perfluoroalkyl iodides both with a variety of nucleophiles and with electron-rich aromatic compounds. - A photoinduced electron... 

Fig. 15. Tilt angles of the different molecular fragments as a function of temperature for polyphilic compound FsHnOCB aromatic core (circles), alkyl chain (crosses) and perfluoroalkyl chain (diamonds) (Ostrovskii et al. [45])...

The steric bulk of the perfluoroalkyl group can be demonstrated by examining crystal structures of suitable compounds. For example, the crystal structure of the para-substituted phenol clearly shows the size of the C6F13 group with respect to the aromatic ring (Figure 3.5). 

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