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1.1. Anodic monofluorination of aromatic compounds

        Knuniants and Rozhkov [6, 22, 24] have discovered the possibility of a partial fluorination of aromatic compounds on a platinum anode at potentials below the standard potential of fluorine emission, the reaction being carried out in an electrolytic medium comprising acetonitrile and bifluorides of quaternary ammonium bases via generation of the carbocation of an aromatic substrate upon its oxidation on the anode followed by reaction with fluoride ion. This approach provides a basis for many processes yielding monofluorinated derivatives of the aromatic and heterocyclic series.

The process of selective anodic fluorination runs according to the ECEC mechanism (electrochemical reaction -> chemical reaction-> electrochemical reaction-> chemical reaction). The first stage is generation of the cation-radical of a substrate by its electrochemical oxidation, the cation-radical reacting with fluoride-ion yielding a benzenium radical. The subsequent electrochemical oxidation yields a bensenium cation, its stabilization by proton detachment resulting in the final product of the reaction [5].

Upon electrochemical fluorination on a platinum anode at 2.5 V (relative to Ag/Ag⁺ at 0.01 M] in acetonitrile containing R₄NF * mHF (where R = Me, Et, I-Pt, n-Bu; n = 2,3,4) and Et₃N* 3HF, benzene forms fluorobenzene at a 20-45% yield [29-32]. A substantial yield of fluorobensene (55%) has been obtained by anodic fluorination of benzene in Et₄NF*3HF as electrolyte [33, 34]. Monaco et al [16] have shown that, in the Et₄NF*3HF system, only fluorobenzene is formed as the principal product contaminated by minor amounts of 1,4-difluorobenzene and products of further fluorination. In the presence of other solvents, tetrafluorobenzene derivatives are obtained [35]. A number of reports describe electrochemical fluorination of benzene in R₄NF* mHF yielding fluorobenzene in combination with not only isomeric difluorobenzenes (mainly 1,4-difluorobenzene [29, 36, 37] but, also, fluorinated cyclohexadienes [29]. The final products of fluorination of benzene and fluorobenzene are electrochemically stable 3,3,6-trifluoro-1,4-cyclohexadiene (yield 66-70%) and 3,3,6,6-tetrafluoro-1,4-cyclohezadiene (yield 71-76%).

 The anode material is usually platinum, however, ruthenium and its alloys with more than 80% Rh may be employed as well, the electrolyte used in such cases being RR¹R²R³NF*(HF)_n [38].

The accumulation of halogen atoms in benzene ring results in high yields of fluorinated cyclohexadienes. Thus, electrolytic fluorination (platinum anode, Et₄NF*mHF) of 1,2,4-trifluorobenzene produces a mixture of 1,3,3,6,6-pentafluorocyclohexadiene-1,4 and 2,5,5,6,6- pentafluorocyclohexadiene-1,3, the total yield being 90% [39]. Fluorinated cyclohexadienes-1,4 will also be formed from 1,4-difluorobenzene and 1,4-difluoro-2-bromobenzene [27].

Difluorobenzene and 1,2,3-trifluorobenzene on a Pt anode (2.5 V) in Et₄NF *mHF (m = 4, 4.36) and at a 98-99% conversion, as a rule, also yield mixtures of fluorinated cyclohexadienes, i.e., tetra- and pentafluorocyclohexadienes [40], which is not accompanied by the formation of polymeric films on the electrode and by discoloration of the electrolyte solution.

A similar picture is observed upon electrochemical fluorination of bromobenzene [41], chlorobenzene [42, 43], 1-bromo-4-fluorobenzene, and 1,4-difluorobenzene [41].

Anodic fluorination of chlorobenzene in Et₄NF* mHF (m = 4, 4.45, 4.7) on a Pt anode at 2.3V or 2.5V results in primary fluorination products 1-chloro-2-fluorobenzene and 1-chloro-4-fluorobenzene at a 1:3 molar ratio [42]. At the final stage of electrolysis, these compounds are fluorinated resulting in a high yield of 1-chloro-3,6,6-trifluoro-1,4-cyclohexadiene or a mixture of 3-chloro-3,6,6-trifluoro1,4-cyclohexadiene, 2-chloro-5,6,6-trifluoro-1,3-cyclohexadiene, and 3,3,6,6-tetrafluoro-1,4-cyclohexadiene, respectively.

It should be noted that in the fluorination process it is possible to replace bromine with fluorine. In the first case, 1-bromo-3,6,6-trifluoro-1,4-cyclohexadiene and 3-bromo-3,6,6-trifluoro-1,4-cyclohexadiene have been obtained. Electrochemical fluorination of 1-bromo-4-fluorobenzene in Et₄NF*mHF (m = 4,0, 4.45, 4.7) produces 1-bromo-3,3,6,6-tetrafluoro-1,4-hexadiene, whereas the same with 1,4-difluorobenzene results in 3,3,6,6-tetrafluoro-1,4-cyclohexadiene [41]. Besides, replacement of bromine by fluorine is possible under this conditions [41]. The further stages run according to fluorination of 1,4-difluorobenzene.

Thus, the use of tetraalkylammonium fluoropoly(hydrogen fluoride), R₄NF*mHF (R = Me, Et, Pr, m> 3.5), as an electrolyte for electrochemical fluorination of aromatic compounds containing several fluorine atoms usually yields fluorinated derivatives of cyclohexadienes and cyclohexene [43, 44].

Anodic oxidation of phenol in Et₃N* nHF results in 4,4-difluorocyclohexa-2,5-diene-1-on, and subsequent reduction with zinc in an acid aqueous medium provides for the possibility to obtain para-fluorophenol at a 60% yield [36, 37]. This approach may become an alternative to oxidative methods for the synthesis of para-fluorophenol.

It should be noted that anodic oxidation of anisole and phenetole, which have fluorine atom in the para-position, results in the formation of fluorinated dienons, which is possibly caused by dealkylating of an intermediate radical [45].

Electrochemical fluorination of (trifluoromethyl)benzene on a platinum anode at 2.5-2.7 V (relative to Ag/Ag⁺, 0.01 M) in Me₄NF*mHF or Et₄NF*mHF (m > 3.5) produces 2-fluoro-1-trifluoromethylbenzene and 3-fluoro-1-trifluoromethylbenzene at similar yields [45]. However, these products undergo further fluorination producing fluorinated cyclohexadienes. Thus, a further electrolysis converts the first compound into 3,6,6-trifluoro-1-trifluoromethyl-1,4-cyclohezadiene, and the second one into a mixture of 5,6,6-trifluoro-1-trifluoromethyl-1,3-cyclohexadiene, 3,6,6-trifluoro-1-trifluoromethyl-1,4-cyclohexadiene, and 5,5,6-trifluoro-1-trifluoromethyl-1,3-cyclohexadiene [46].

During electrolysis of isomeric fluorotoluenes in Et₄NF *4HF, fluorination of the benzol ring and methyl group occurs [47]. Two pathways realized as the generic case are shown on the scheme below:

In the general case if benzene ring contains CH₂E group process proceeds on the following way. At first the cation-radical is generated and then either it reacts with fluoride ion or proton elimination occurs. In the second case, benzyl-radical by its electrochemical oxidation yields benzyl-cation. The later reacts with fluoride-ion forming side chain fluorination product.

The anodic oxidation of polymethyl- and polyethyl derivatives of benzene in chloromethylene containing Et₄NF or Et₃N*3HF (44) was reported. The anodic fluorination of polymethyl benzenes in acetonitrile solution results in fluoromethylderivatives (Table 3) (49). The electrode material is platinum. The yield of monofluoromethylderivatives depends on stabilization of the intermediate cation by substitutes or on electrolyte concentration. Thus in case of hexamethylbenzene monofluoroderivatives amount to 88% at the electrolyte concentration is 0,1 mol, and 92% at 0,3 mol. At the same time acetonitrile addition leads to the formation of ArCH₂F 8 and ArCH₂NHCOCH₃ 9 mixture. Propotion of products in the mixture depends on the number of methyl group in benzene ring (26).

It is supposed that the process runs according to the scheme, which proposes the generation of intermediate benzyl-cation from in aromatic substrate (50).

Table 3. Elecrtrolytic fluorination of polymethylbenzene (platinum electrodes, 0,1 M Et₄NF•3HF electrolyte, fluorinate reagent: substrate ratio 4:1), MeCN (49).

Mono- and difluoroderivatives of polycyclic aromatic compounds (perylene, pyrene, triphenylene (Bu₄NF*3HF electrolyte) (51, 52), anthracene, 9-methylanthracene, 9-phenylanthracene (Et₃N*3HF electrolyte) (52, 53) are produced by electrolysis of its solutions in anhydrous acetonitrile at the platinum or graphite electrodes. The authors concluded that the formation of anodic fluorination products is controlled more likely with Coulomb's factor (charge of organic electrophile) than thermodynamic factor (proximity of energy MO H_xF_x+1^- and ArH) (52).
Anodic fluorination of 3-alkylidene in the medium Et₃N3HF/MeCN at the platinum electrodes brings to the fluoroacetamide formation (54).

In the case of stilbene and the compounds with multiple bond, an electrolysis in Et₄NF nHF and Et₃N•3HF electrolytes mainly gives the products of fluorine cis-addition to multiple bond (44). That was shown for cyclohexene and indene in much the same way (55).

To be continued 

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