Nucleophilic Aromatic Substitution for Heteroatoms
J . Org. Chem., Vol. 67, No. 8, 2002 2551
peak potential and intensity of the remaining nitroarene
reduction wave) (columns 6, 10, and 4, Tables 1 and 2).
In all cases, the yield of formation of σ-complexes is
superior to 40% and its formation is fast.
After exhaustive controlled potential electrolysis, at
oxidation peak potential (column 8, Tables 1 and 2) plus
c.a. 100 mV, the rearomatized substituted compound
(NASX product: ArNu, column 9, Tables 1 and 2) is
obtained. Electrochemical efficiency goes from 0.50 to
2.00 (column 11, Tables 1 and 2). The values higher than
1.0 can be explained considering that the electrochemical
oxidation of σX-complexes produces the displacement of
the fast equilibrium (Scheme 4) to the right; that is to
say, more reactant σ -complexes23 are produced during
the electrochemical reaction. The reaction is clean,
recovering only starting material (column 2, Tables 1 and
2) apart from the substitution product. When CN- (Table
1, entries 3, 4, 7, and 8; Table 2, entries 1, 2, 5, 6, and 7)
(Scheme 5)11a and n-BuNH2 (Table 1, entries 6 and 9;
Table 2, entry 3) are used, a NASH product was obtained
in a yield lower than 15%.
In the reaction between CH3O- and 1,3-dinitrobenzene
(1:1) (Table 2, entry 4), 100% σ-complex is produced and
only 5% of the substituted product, 3-nitroanisole, is
obtained (NASX process). The formation of 1-hydride-1-
methoxy-2,4-dinitrocyclohexadienyl anion (95%) leads,
after one-electron oxidation, to starting material (95%).
It is important to underline that the oxidation peak
potential of σX-complexes is very dependent on the nature
of leaving group, X-. For Cl- or F-, the potential is
∼1.35-1.40 V, for CH3O-, it is ∼ 0.90-1.00 V, and for
NO2-, it is ∼0.60-0.80 V vs SCE. For the σH-complexes
the oxidation peak potential is mainly dependent on the
number of nitro groups present in the aromatic ring:11
oxidation peak potential for two nitro groups complexes
< oxidation peak potential for three nitro groups com-
plexes.
F igu r e 2. (a) Cyclic voltammetry of 2a - (mixture 2a (1,1)-
and 2a (1,3)-) (6.0 mM) in DMF + 0.1 M n-Bu4NBF4 at 10 °C.
Scan rate 1.0 V/s, glassy carbon disk electrode (0.05 mm
diameter). The scan is in the potential range 0.00/1.50/-1.00/
0.00 V. (b) Cyclic voltammetry of 2a - (2a (1,3)-) (6.0 mM) in
DMF + 0.1 M n-Bu4NBF4 at 10 °C. Scan rate 1.0 V/s, glassy
carbon disk electrode (0.05 mm diameter). The scan is in the
potential range: 0.00/1.00/-1.00/0.00 V.
Since the electrochemical oxidation mechanism of σH-
complexes involves two electrons (NASH process)11 and
we have just shown that the corresponding oxidation of
σX-complex involves one-electron (NASX process), it is
possible to determine by direct measure of the relative
intensity of the peak potentials, their relative concentra-
tions. From the voltammogram (Figure 2), the ratio of
σH-complex/σX-complex ) 30:70 is in good accordance to
what is reported in the literature.16
In summary, the cyclic voltammmetry allows us to (a)
determine the type and number of the evident extension
of this work, (b) determine the σ-complexes present in
the solution (number of waves, peak potential wave) and
their relative amounts (intensity of peak wave), and (c)
establish the clean evolution of the σ-complexes to the
rearomatized nitroaromatic compounds when oxidized by
observing the reduction of the rearomatized products. (d)
It should be possible, in principle, to achieve the final
substitution products by performing exhaustive electroly-
sis of solutions of σ -complexes at precise applied poten-
tials. Therefore, the evident extension of this work is to
obtain substituted products, by means of electrochemical
oxidation methods, in the SNAr reactions with different
nucleophiles.
The results described in Tables 1 and 2 demonstrate
that the electrochemical methodology is a powerful tool
for the synthesis of fluorine, thiolate, and alkoxy com-
pounds and for the amination and the cyanation of
aromatic compounds.
Ha logen a s Lea vin g Gr ou p . Syn th esis of F lu or o
Com p ou n d s 6 (Ta ble 1, En tr y 1). Using, for instance,
chloronitro,compounds, we obtain fluoronitro compounds
by replacement of a Cl for a F. By mixing 1-chloro-2,4-
dinitrobenzene 7 with tetramethylammonium fluoride
under nitrogen atmosphere in DMF and followed by
electrochemical oxidation at 1.4 V passing 1 F, we obtain
Sanger’s reactant in good yield (60%). The products can
be easily separated by column chromatography. Further-
more, the reactant is fully recovered (40%), and the
electrochemical reaction is therefore totally selective.
Electrochemical oxidation of intermediate σ-complexes
allows the substitution of other halogens (chloride) by
fluoride in very mild conditions and it is therefore
complementary to the well-known fluorodenitration24 as
an election method to introduce fluorine in aromatic
compounds. Our results open a new way for obtaining
fluoro compounds, which are especially important due to
their chemical and biological applications.
Syn th etic Scop e. The σ-complexes were prepared by
careful stoichiometric addition of different Nu- (CN-, F-,
CH3O-, C2H5S-, and n-BuNH2) to solutions 25 mM of the
nitroarenes, 2-9, in dry DMF + 0.1 M n-BuNBF4 under
inert atmosphere at 10 °C. Their characterization was
carried out by means of cyclic voltammetry (oxidation
(23) For the NASH, the H + loss after the first one-electron oxidation
inactivates the nucleophile and the reaction stops.
(24) (a) Clark, J . H.; Smith, D. K. Tetrahedron Lett. 1985, 26, 2233.
(b) Clark, J . H.; Boechat, J . J . Chem. Soc., Chem. Commun. 1993, 921.