1582
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005
Petrosyan et al.
Table 1. Anodic acetoxylation of 1,4ꢀdimethoxybenzene (1).
Effect of the nature and the composition of the medium on the
yield of 2,5ꢀdimethoxyphenyl acetate (6d)а
Compound 6d could, in principle, be formed accordꢀ
ing to Scheme 1 via the sequence 1 → 2 → 3 → 4 → 5 → 6.
However, the fact that 6d is formed as the only product
implies that of the two competing routes of reaction beꢀ
tween the nucleophile and the intermediate arenonium
cation, 4 → 7 and 4 → 5, only the 4 → 5 route is impleꢀ
mented in the acetoxylation of 1 for some reason. One
more "oddity" distinguishing the anodic acetoxylation of 1
from related functionalizations of this compound attracts
attention. During the electrolysis of 1 in МеCN in the
presence of Et4NOАc as a nucleophile, no acetoxylation
takes place, unlike, for example, cyanation of 1 under
similar conditions.4,10 On the one hand, this obviously
indicates that the acetate ion is a weaker nucleophile. On
the other hand, it was found that the formation of 6d
requires that АcOH be present in the reaction mixture in
addition to Et4NOАc (cf. runs 2 and 3). The same is true
for acetoxylation of 1 in МеOH (cf. runs 4 and 5).
In our opinion, all these effects can be related to the
stability of the intermediate arenonium cation 4d preꢀ
sented in Scheme 2. If we assume, relying on the results of
calculations (see above) and contrary to the conclusions
made previously,6 that the ipsoꢀattack of the acetate ion
gives adsorbed radical 3d (see Scheme 2), as in the
cyanation of 1,10 this radical is expected to be oxidized
under the given conditions to arenonium cation 4d. Asꢀ
suming (cf. Ref. 6) that among the Az, NC, MeO, and
АcO substituents, AcO is the best leaving group, one may
infer that the arenonium cation 4d is least stable in the
series studied and the fragmentation rate of this cation
would be higher than the rate of reaction of 4d with a
nucleophile. In our opinion, this may account for the fact
that its acetoxylation in a medium containing only one
nucleophile (АcO–) does not take place (runs 3 and 4).
The situation changes when the electrolyzed system
contains АcOH together with АcO−. Previously3 (see
Scheme 1), we found that components of the medium
acting as acids have a pronounced influence on the comꢀ
peting ipsoꢀ or orthoꢀinteraction of the intermediate
arenonium cation 4 with the azole nucleophile. In prinꢀ
ciple, the same can be true for the anodic acetoxylation
of 1 (Scheme 3).
Run
Solvent
Salt
АсOH Yield of 6d
(3 mmol) (3 mmol) (%)
1
2
3
4
5
6
7
8
MeCN
MeCN
MeCN
МеОН
МеОН
Bu4NClO4
Et4NOАс
Et4NOАс
Et4NOАс
Et4NOАс
+
+
—
—
+
+
—
+
—
18
—
—
14.5 b
19
20
40
5 b
b
MeCN/CH2Cl2 (1 : 1) Et4NOАс
MeCN/CH2Cl2 (1 : 2) Et4NOАс
MeCN/CH2Cl2 (1 : 2) Et4NOАс
MeОН/CH2Cl2 (1 : 2) Et4NOАс
MeОН/CH2Cl2 (1 : 2) Et4NOАс
9
10
11
—
+
+
b
15
56
CH2Cl2
Et4NOАс
а Pt electrodes, Q = 2 F per mole of 1; I = 0.2 А; the amount of 1
is 2 mmol.
b
1,1,4,4ꢀTetramethoxycyclohexaꢀ2,5ꢀdiene is the major prodꢀ
uct of electrolysis.
synthesis of Nꢀdimethoxyphenylazoles.1—3 However, as
opposed to previous works,1—3 our numerous attempts to
perform this workup under the mildest possible condiꢀ
tions, including removal of the solvent at a temperature
of <20 °C, did not result in detection of even traces of
ipsoꢀbisꢀacetoxylation product 6d.
Note that the lack of direct experimental evidence
supporting the attack of the acetate ion on the ipsoꢀposiꢀ
tion of radical cation 2 prompted the authors6 to describe
the acetoxylation mechanism only in terms of the nucleoꢀ
phile attack on the orthoꢀposition (see Scheme 2). This
feature of oxidative acetoxylation of compound 1 distinꢀ
guishes it from a series of related processes such as
azolation,1—3 cyanation,4 and methoxylation5 for which
the ipsoꢀattack of the nucleophile in the functionalization
of 1 has been proven experimentally.
It is expedient to discuss the acetoxylation pattern in
more detail. First of all, note that 1 is more readily oxiꢀ
dized than АcO–; therefore, the transfer of the first elecꢀ
tron is followed by the chemical reaction of АcO– as a
nucleophile with radical cation 2. The spin density distriꢀ
bution in this radical cation calculated from ESR data
indicates that the ipsoꢀ rather than the orthoꢀposition is
most favorable for the nucleophilic attack.6 This concluꢀ
sion was also confirmed by quantumꢀchemical data9 on
the general positive charge distribution and the LUMO
electron density for radical cation 2. Thus, the structure
of the only isolated product of electrolysis, 2,5ꢀdimethoxyꢀ
phenyl acetate 6d is the only argument in favor of the
acetoxylation mechanism involving the orthoꢀattack of
the nucleophile (see Scheme 2). However, the pathway to
6d shown in Scheme 2 is by no means the only posꢀ
sible one.
In our opinion, during the rearrangement of
the arenonium cation 4d → 5d, which occurs by the
cineꢀsubstitution mechanism, the АcOH molecule does
not only assist the elimination of the acetoxy group but
simultaneously facilitates the orthoꢀattack of the acetate
ion due to the induced bond polarization. As regards the
ipsoꢀinteraction of cation 4d with the acetate ion, resultꢀ
ing in 7d, this should be completely shifted to the left in
the presence of АcOH, as is usually the case in the elecꢀ
trochemical Nꢀdimethoxyphenylation of azoles.3
Subsequently, our effort was aimed at the variation of
the experimental conditions in order to increase the yield