N-arylation of azoles with low basicity by 1,4-dimethoxybenzene during undivided electrolysis

Article abstract of DOI:10.1023/A:1020979426942

The reactions of 1,4-dimethoxybenzene with 4-nitropyrazole, 3,4-dinitro-5-methylpyrazole, 1,2,4-triazole, 3-nitro-1,2,4-triazole, and tetrazole were studied during undivided amperostatic electrolysis on a Pt electrode in MeCN, CH₂Cl₂, and MeOH. The main reaction products were 2-azolyl-1,4-dimethoxybenzenes and (or) 1,4-diazolyl-1,4-dimethoxycyclohexa-2,5-dienes. In all cases except 1,2,4-triazole, N-arylation occurs only in the presence of the Alk ₄N⁺ salts of azoles or 2,4,6-trimethylpyridine as a base. The mechanism of the reactions is discussed.

Full text of DOI:10.1023/A:1020979426942

Russian Chemical Bulletin, International Edition, Vol. 51, No. 8, pp. 1523—1532, August, 2002
1523
NꢀArylation of azoles with low basicity by 1,4ꢀdimethoxybenzene
during undivided electrolysis
ꢀ
V. A. Chauzov, V. Z. Parchinskii, E. V. Sinel´shchikova, A. V. Burasov, B. I. Ugrak,
N. N. Parfenov, and V. A. Petrosyan
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: petros@ioc.ac.ru
The reactions of 1,4ꢀdimethoxybenzene with 4ꢀnitropyrazole, 3,4ꢀdinitroꢀ5ꢀmethylꢀ
pyrazole, 1,2,4ꢀtriazole, 3ꢀnitroꢀ1,2,4ꢀtriazole, and tetrazole were studied during undivided
amperostatic electrolysis on a Pt electrode in MeCN, CH2Cl2, and MeOH. The main reacꢀ
tion products were 2ꢀazolylꢀ1,4ꢀdimethoxybenzenes and (or) 1,4ꢀdiazolylꢀ1,4ꢀdimethoxyꢀ
cyclohexaꢀ2,5ꢀdienes. In all cases except 1,2,4ꢀtriazole, Nꢀarylation occurs only in the presꢀ
ence of the Alk4N+ salts of azoles or 2,4,6ꢀtrimethylpyridine as a base. The mechanism of the
reactions is discussed.
Key words: paired electrosynthesis, Nꢀarylation, azoles, azole anions, 1,4ꢀdimethoxyꢀ
benzene.
The reactions of 1,4ꢀdimethoxybenzene (DMB) with
various azoles (pyrazoles, triazoles, and tetrazole) under
amperostatic undivided electrolysis on Pt electrodes in
MeCN and Alk4N+ salts of azoles or Bu4NClO4 as a
supporting electrolyte afford1—4 orthoꢀsubstitution prodꢀ
ucts 1, ipsoꢀbisaddition products 2, and, in some cases,
ipsoꢀsubstitution products 3. We have established1,2 for
the first time the formation of bisadducts 2 among
electrolysis products and the possibility of using
azoles or their combination with 2,4,6ꢀtrimethylpyridine
(symmꢀcollidine, CL) instead of the corresponding anꢀ
ions in the starting reaction mixture.
It has recently been found2 that the regularities which
determine the yield and ratio of products 1 and 2 for
3,5ꢀdimethylpyrazole (DMP), pyrazole (Pyr), and 3,5ꢀdiꢀ
methylꢀ4ꢀnitropyrazole (DMNP) depend on the nature
of the solvent (MeCN or CH2Cl2), basicity of the meꢀ
dium, and amount of the electricity passed and can be
described by the stages presented in Scheme 1.
According to this scheme, the reaction of the
Hꢀbonded AzH•B azole complex (B = AzH, CL) with
the DMB radical cation 4 affords intermediates 5 and 6,
which undergo further oxidation. The key stage deterꢀ
mining the ratio of products 1 and 2 in the case of DMP
and Pyr is the intramolecular rearrangement of the
1ꢀazolylꢀ1,4ꢀdimethoxyarenonium cation (7) to the
1ꢀazolylꢀ2,5ꢀdimethoxyarenonium cation (8). In this
case, the cathodic process is related to the deprotonation
of onium intermediates BH+ formed during electrolysis.
In development of these works, we studied the reguꢀ
larities of Nꢀarylation in systems containing DMB and
relatively less basic and more acidic (compared to DMP
and Pyr) azoles (Table 1), viz., 4ꢀnitropyrazole (NP),
3,4ꢀdinitroꢀ5ꢀmethylpyrazole (DNMP), 3ꢀnitroꢀ1,2,4ꢀ
triazole (NTA), tetrazole (T), and 1,2,4ꢀtriazole (TA).
The latter is similar in basicity to Pyr* but its acidity is
* The high basicity of TA is a result of the protonation of the
N(4) atom rather than N(2) as in pyrazoles.5 The accepted
classification of azoles to compounds with high and low basicꢀ
ity is conventional and reflects the specific features of their
electrochemical Nꢀarylation.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1402—1410, August, 2002.
1066ꢀ5285/02/5108ꢀ1523 $27.00 © 2002 Plenum Publishing Corporation

1524
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Chauzov et al.
Scheme 1
B is AzH, CL
much higher and close to that of NP. In order to examꢀ
ine the composition of the electrolysis products, as in
the previous studies,1,2 we widely used NMR spectroꢀ
scopic monitoring, which allowed us to detect hydrolytiꢀ
cally labile compounds 2 in the final reaction mixture.
basic azoles are compared with those for DMP, Pyr, and
DMNP obtained by us previously2 (Table 2).
The general comparison of the results of electrolysis
for the highly basic azoles (DMP, Pyr, TA) and azoles
with low basicity (DMNP, NP, NTA, DNMP, and T)
indicates that in the absence of basic additives the
Nꢀarylation of azoles of the latter group occurs very
limply, and the formation of minor (in most cases, <2%)
amounts of substitution products 1 is probably deterꢀ
mined by the arylation of the azole anions formed by the
direct deprotonation6 of the azoles on the Pt cathode
(see Table 2, cf. entries 7, 9, 17, 33 and 1, 20, 22) rather
than to the direct arylation of the azoles (as in the case
of DMP, Pyr, and TA). In turn, the addition of CL to
the electrolyte slightly affects the change in the total
current efficiency (CE) of Nꢀarylation products 1 and 2
for the first group of azoles, while in the case of lowꢀ
basic azoles, when CL or the Alk4N+ salts of azoles are
added, the total CE of compounds 1 and 2 multiply
increases (see Table 2, cf. entries 2, 21, 23 and 8, 10,
15, 34, 35).
Results and Discussion
An undivided electrolysis. The results presented below
for the electrolysis of systems containing DMB and lowꢀ
Table 1. The pKa values of some azoles5 and collidine
Azolea
pKa
Azolea
pKa
Ib
IIc
Ib
IIc
DMP
Pyr
DMNP
NP
15
4.06
2.48
–0.45
–2.00
—
TA
NTA
T
Imidazole
CL
10.04
5.98
4.90
14.4
—
2.45
14.21
10.65
9.64
–3.65
–2.68
6.99
d
DNMP
—
7.43
A change in the electrolysis conditions has different
effects on the ratio of products 1 and 2 for azoles with
low and high basicity. This is illustrated by the results of
Nꢀarylation of DMP and NP. For example, in the elecꢀ
trolysis with DMP, an increase in the basicity of the
medium due to the addition of CL favors the formation
of 2a and hinders the formation of 1a, and an increase in
the acidity of the medium (the addition of AcOH) has an
a DMP is 3,5ꢀdimethylpyrazole, Pyr is pyrazole, DMNP is
3,5ꢀdimethylꢀ4ꢀnitropyrazole, NP is 4ꢀnitropyrazole, DNMP
is 3,4ꢀdinitroꢀ5ꢀmethylpyrazole, TA is 1,2,4ꢀtriazole, NTA is
3ꢀnitroꢀ1,2,4ꢀtriazole, Т is tetrazole, CL is collidine.
b Azole under study.
c Conjugate acid.
d The pKa value is unknown but evidently close to pKa of
3,4ꢀdinitropyrazole (5.48).

NꢀArylation of azoles during undivided electrolysis
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1525
opposite effect. By contrast, in the electrolysis with NP,
an increase in the basicity of the medium upon replaceꢀ
ment of CL by the NP salt (the basicity of CL is lower
than that of the NP anion, see Table 1) increases the CE
of product 1d, decreases the CE of 2d, and leads to the
ipsoꢀsubstitution product 3a (see Table 2, cf. entries 10,
15, and 16). The addition of AcOH to a mixture of NP
and CL results, evidently, in the protonation of the latꢀ
ter, decreases the nucleophilicity of the NP complex
with CL, and thus hinders Nꢀarylation (see Table 2,
cf. entries 10 and 12).
CH2Cl2 as a solvent instead of MeCN, 1a is formed
predominantly, while in the electrolysis with NP under
similar conditions only a decrease in the CE of product
2d was observed (see Table 2, cf. entries 1 and 4, 5 and 6,
10 and 12, and 13 and 14).
The results obtained in the electrolysis with NTA are
similar on the whole to those for NP, namely, comꢀ
pounds 1g and 2g are formed in low CE in the presence
of CL, and if CL is replaced by the NTA salt, their total
CE noticeably increases, primarily due to product 1g
(see Table 2, entries 31 and 32). It is of interest that in
the case of DNMP, the only Nꢀarylation product is 1e,
whose CE are the same for electrolysis in the presence
In turn, in the electrolysis with DMP by passing 2 F
electricity at the DMP : DMB = 0.5 molar ratio or with
Table 2. Yields of products of the electrochemical Nꢀarylation of azoles by 1,4ꢀdimethoxybenzene (DMB) as functions of the
electrolysis conditionsа (results of the known works2,3 necessary for comparison are included)
Entry
Azoleb
Azole : DMB (mol)
(amount of electricity
per mole of DMB/F)
Solꢀ
vent
Additiveс (moles
per mole of DMB)
Current efficiencies
of products (%)
1
2
1
2
3
4
5
6
7
8
DMP2
DMP2
DMP2
DMP2
DMP2
DMP2
DMNP2
DMNP2
NP
1.5 (2)
1.5 (1)
1.5 (2)
1.5 (2)
1.5 (2)
0.5 (1)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
MeCN
MeCN
MeCN
CH2Cl
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
CH2Cl2
MeCN
—
28
15
38
45
35
22
10
<2
<2
4
30
42
14
—
—
19
—
24
—
52
10
—
CL (0.5)
AcOH (1.5)
—
—
—
—
CL (0.5)
9
—
10
11
12
NP
NP
NP
CL (0.5)
CL (0.5)
CL (0.5)
—
<2
AcOH (0.5)
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
NP
NP
NP
NP
DNMP
DNMP
DNMP
Pyr2
Pyr2
TA
0.5 (2)
0.5 (1)
1.0 (2)
1.25 (2)
1.5 (2)
1.5 (2)
1.0 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
0.5 (2)
0.5 (2)
0.5 (2)
1.5 (2)
1.0 (2)
1.5 (2)
1.0 (2)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
CH2Cl2
MeCN
CH2Cl2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
CL (0.5)
CL (0.5)
—
—
10 d,e
8 f
<2
6
6 g
<2
<2
7
13
22
29
43
—
—
—
23
38
40
56
17
—
33
7
<2
—
19
10
18
—
—
—
—
—
CL (0.5)
—
—
CL (0.5)
—
TA
CL (0.5)
AcOH (1.5)
2
Pyr2
Pyr2
TA
13
40
8
—
AcOH (1.5)
TA
Pyr2
TA
—
—
—
—
—
h
—
TA
—
CL (0.5)
—
—
3
NTA
NTA
T
T3
28 i
4 j
—
—
88 j,k
(to be continued)

1526
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Chauzov et al.
Table 2 (continued)
Entry
Azoleb
Azole : DMB (mol)
(amount of electricity
per mole of DMB/F)
Solꢀ
vent
Additiveс (moles
per mole of DMB)
Current efficiencies
of products (%)
1
2
35
36
37
38
39
40
41
42
43
44
45
T
T
T
T
1.5 (2)
1.5 (2)
0.5 (2)
0.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
1.5 (2)
MeCN
CH2Cl2
MeCN
MeCN
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
CL (0.5)
CL (0.5)
CL (0.5)
CL (0.5)
—
CL (0.5)
CL (0.5)
CL (0.5)
CL (0.5)
CL (0.5)
CL (0.5)
50 j
52 j
29 j
21 k
—
—
—
—
—
—
—
15 j
7 l
9 m
DMP2
T
T
NTA
DNMP
NP
TA
20 j,n, 52 j,o
5 j,p, 30 j,o,p,q
5 r, 18 o
3 s, 16 o
—
t,u, 7 o
<2 v, 10 o
7
11
a Electrolysis was carried out vs. an 0.022 М solution of Bu4NClO4 (0.5 moles per mole of DMB).
b
DMP is 3,5ꢀdimethylpyrazole, DMNP is 3,5ꢀdimethylꢀ4ꢀnitropyrazole, NP is 4ꢀnitropyrazole, DNMP is 3,4ꢀdinitroꢀ5ꢀ
methylpyrazole, Pyr is pyrazole, TA is 1,2,4ꢀtriazole, and NTA is 3ꢀnitroꢀ1,2,4ꢀtriazole, and T is tetrazole.
c CL is collidine.
d Me4N+ salt of NP (0.5 moles per mole of DMB) was used instead of Bu4NClO4.
e The reaction mixture contains 1ꢀ(4ꢀmethoxyphenyl)ꢀ4ꢀnitropyrazole (3a), 8% yield.
f Me4N+ salt of NP (0.25 moles per mole of DMB) was used instead of Bu4NClO4, the yield of compound 3a being 4%.
g Bu4N+ salt of DNMP (0.5 moles per mole of DMB) was used instead of Bu4NClO4.
h The yield of 1ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,4ꢀtriazole (3b) was 12%.
i Me4N+ salt of NTA (0.5 moles per mole of DMB) was used instead of Bu4NClO4.
j A mixture of the Nꢀisomers.
k Bu4N+ salt of T (0.5 moles per mole of DMB) was used instead of Bu4NClO4.
l One Nꢀisomer.
m The yield of 1,1,4,4ꢀtetramethoxycyclohexaꢀ2,5ꢀdiene (12) was 52%.
n A mixture of the Nꢀisomers of 1,1,4ꢀtrimethoxyꢀ4ꢀtetrazolylcyclohexaꢀ2,5ꢀdiene (10h) is also formed (38% yield).
o After additional heating (5 h, 110 °C).
p Tetrazole was added to the reaction mixture after the end of electrolysis before MeOH was distilled off (70 °C, 20 Torr, 30 min).
q A mixture of the isomers of 10h is also formed (43% yield).
r After the solvent was distilled off (70 °C, 20 Torr, 30 min), the yield of 1,1,4ꢀtrimethoxyꢀ4ꢀ(3ꢀnitrotriazolꢀ1ꢀyl)cyclohexaꢀ2,5ꢀ
diene (10g) was 13%.
s After the solvent was distilled off (70 °C, 20 Torr, 30 min), the yield of 1,1,4ꢀtrimethoxyꢀ4ꢀ(5ꢀmethylꢀ3,4ꢀdinitropyrazolꢀ
1ꢀyl)cyclohexaꢀ2,5ꢀdiene (10e) was 13%.
t After the solvent was removed (20 °C), the yield of 12 was 12% and the yield of 1,1,4ꢀtrimethoxyꢀ4ꢀ(4ꢀnitropyrazolꢀ1ꢀyl)cyclohexaꢀ
2,5ꢀdiene (10d) was 3%.
u After the solvent was distilled off (70 °C, 20 Torr, 30 min), the yield of 12 6% and the yield of 10d was 11%.
v After the solvent was removed (20 °C) or distilled off (70 °C, 20 Torr, 30 min), the yield of 12 was 21% and the yield of
1,1,4ꢀtrimethoxyꢀ4ꢀ(1,2,4ꢀtriazolꢀ1ꢀyl)cyclohexaꢀ2,5ꢀdiene (10f) was 38%.
of both CL and DNMP salt (see Table 2, cf. enꢀ
tries 18 and 19).
the solvent). Perhaps, it is for this reason that the relaꢀ
tive concentration of 2h can differ substantially (not the
total CE of 1h and 2h) in parallel experiments. With
CH2Cl2 as the solvent, the total yield of 1h and 2h and
their ratio remain virtually unchanged, and electrolysis
with an excess of DMB affords a mixture of Nꢀisomers of
1h in low yields (see Table 2, entries 36 and 37). The
latter fact and the predominant consumption of one of
the isomers at the final stages of electrolysis (see Table 2,
entry 38), as in the case of Pyr and TA, indicate, most
likely, the easiness of electrooxidation of product 1h.
The distinction in behavior of DMP and T during elecꢀ
trolysis in MeOH is of interest. In the case of DMP,
The results of Nꢀarylation of T is noteworthy in that
the CE of 1h (forms as a mixture of two Nꢀisomers in a
ratio of ∼3 : 2) is very high and the overall CE of the
Nꢀarylation product reaches 90% in most cases. This
noticeably exceeds the CE of the Nꢀarylation products
not only for the lowꢀbasic azoles but even for the most
reactive highly basic DMP (see Table 2, cf. entries 1, 2
and 34, 35). What is also unusual in this case is that the
obtained mixture of Nꢀisomers of 1h and 2h is transꢀ
formed into an almost pure mixture of Nꢀisomers of 1h
after brief heating (in particular, during distillation of

NꢀArylation of azoles during undivided electrolysis
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1527
compound 1а is formed in a low CE (9%), and the main
reaction product is the oxidative ipsoꢀbismethoxylation
product of DMB, viz., 1,1,4,4ꢀtetramethoxycyclohexaꢀ
2,5ꢀdiene, in 52% CE (see Table 2, entry 39),2 whereas
in the case of T we obtained a mixture of Nꢀisomers
(∼2 : 1) of 1h (20% CE) and 1,1,4ꢀtrimethoxyꢀ4ꢀtetrazoꢀ
lylcyclohexaꢀ2,5ꢀdiene (38% CE) (see Table 2, entry 40).
The formation of products of this type, viz., ketal derivaꢀ
tives of paraꢀquinone, upon Nꢀarylation in MeOH was
observed for other azoles with low basicity as well (see
Table 2, entries 42—45). Since these results are imporꢀ
tant for understanding the mechanisms of formation of
products 1 and 2, the corresponding experimental data
will be considered below together with the discussion of
these problems.
The electrochemical behavior of TA resembles in part
that of Pyr with similar basicity. During electrolysis with
Bu4NClO4 as the supporting electrolyte, TA efficiently
reacts with DMB in the absence of basic additives to
form product 2f predominantly, and the CE of the latter,
as in the case of Pyr, increases when CL is added (see
Table 2, entries 20—23). However, the conditions favorꢀ
ing the formation of product 1 in the case of DMP and
Pyr (the addition of AcOH or electrolysis in CH2Cl2) do
not afford the desired result in the electrolysis with TA
(see Table 2, entries 24—27). In turn, electrolysis with
an excess of DMB (TA : DMB = 0.5), which also affords
predominantly 1 in the case of DMP, is accompanied
here by the formation of ipsoꢀsubstitution product 3b*
(see Table 2, cf. entries 5, 28, and 29) rather than 1f.
However, it is of note that it is the ipsoꢀbisaddition prodꢀ
uct 2f that is presumably the precursor of 3b, because
only 2f was found in the reaction mixture when a halved
amount of electricity (1 F) was passed (see Table 2,
entry 30). As for the absence or a low content of
1f among the reaction products in all experiments
with TA, this is reasoned, most probably, by its easy
electrooxidation, as in the case of 1b during Nꢀarylation
of Pyr.2
attack by 4, can also be useful for azoles with low basicꢀ
ity (NP, NTA), whose electrolysis in the presence of CL
differs from that in the presence of the salt of the correꢀ
sponding azole. By the way, this fact indicated that NP
and NTA form complexes with CL but remain in the
nonionized form. The corresponding experiment was perꢀ
formed for NP, and the conditions of entry 10 were
chosen as model with the only distinction that the double
amount of CL was used to prevent the deactivation of
the pyrazole component of the reaction mixture (anodic
electrolysis is accompanied by proton generation). In
the qualitative respect, the results obtained are compaꢀ
rable with those of the experiment in the undivided cell,
although the composition of the reaction products someꢀ
what differed. This can be explained by the objective
difference in experimental conditions. For example, elecꢀ
trolysis of the NP—DMB—CL system gave a mixture of
1d и 2d in 9 and 37% CE respectively (cf. entry 10 in
Table 2). Note that only resinꢀlike products are formed
upon electrolysis of the NP—DMB system in the abꢀ
sence of CL in the anodic compartment of the divided
cell. On the whole, our experiments additionally subꢀ
stantiate the hypothesis1,2 about the involvement of the
nonionized AzH•B complexes as nucleophilic coreactants
in the electrochemical Nꢀarylation of azoles.
Regularities of Nꢀarylation of azoles with low basicity.
The above presented, often contradictory experimental
results can be explained if we introduce several concepts
concerning the stage of interaction of the azole nucleoꢀ
phile (see Scheme 1) with intermediates bearing a posiꢀ
tive charge, such as radical cation 4 and arenonium
cation 7.
Based on the concept about the substantial differꢀ
ence in electrophilicity of the orthoꢀ and ipsoꢀpositions
of these intermediates, we believe that the involvement
of the azole anion is preferential for orthoꢀsubstitution,
whereas ipsoꢀsubstitution can involve both the azole anꢀ
ion and a complex of nonionized azole. This point needs
to be discussed in more detail. The presence of methoxy
groups in intermediates 4 and 7 undoubtedly favor
the localization of the positive charge mainly on the
ipsoꢀcarbon atoms of the ring. For these reasons, the
ipsoꢀattack on ions 4 or 7 by the azole nucleophile reꢀ
quires relatively small energy expenses. This process ocꢀ
curs, evidently, even when these ions come close to the
nonionized azole complex (dipole), as is shown in
Scheme 2, and the more so when they approach to the
azole anion.
Thus, a whole series of distinctions, which follows
from a comparison of the data of Nꢀarylation of azoles
with high and low basicity, needs Scheme 1 presented
above to be refined. This will allow the correct descripꢀ
tion of the regularities of Nꢀarylation of the lastꢀmenꢀ
tioned azoles.
Electrolysis in a divided cell. The previously estabꢀ
lished2 Nꢀarylation of such a highly basic azole as DMP
during electrolysis in the anodic compartment of a diꢀ
vided cell confirmed unambiguously the possibility of
direct reaction of the nonionized form of DMP with
radical cation 4 (see Scheme 1). This procedure, which
allows the elucidation of the object of the electrophilic
By contrast, the orthoꢀattack in the interaction of
intermediates 4 or 7 with a nucleophile needs the localꢀ
ization of the positive charge on one of the orthoꢀposiꢀ
tions. This is associated with substantial polarization of
these intermediates leading to the formation of an enerꢀ
getically less favorable structure. This structure is eviꢀ
dently formed with the lowest expenses when intermediꢀ
* The formation of ipsoꢀsubstitution products 3a,b will be disꢀ
cussed elsewhere.

1528
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Chauzov et al.
Scheme 2
the AzH•CL complex results in the appearance (or an
increase in the relative content) of 1 in the electrolysis
products (see Table 2, cf. entries 10 and 15, 31 and 32).
At the same time, unlike the data of electrolysis inꢀ
volving the NP or NTA complexes with CL, in elecꢀ
trolysis with complexes of DNMP or T with CL the
corresponding compounds 1e,h are the main or even
single products. The use of a DNMP—DNMP salt mixꢀ
ture gives the same result (see Table 2, cf. entries 18, 19
and 34, 35). We believe that complexes of less acidic
azoles (TA, NP, NTA) (see Table 1) with CL, like comꢀ
plexes of highly basic azoles,2 are nonionized. In the
case of more acidic azoles (DNMP, T), the Az—H bond
in the Az—H•B complex is likely much more polar, up
to the formation of the tight Az–H•B+ ion pair. This
conclusion can be favored to some extent by the fact that
solutions of mixtures of DNMP or T with CL in MeCN
exhibit higher electric conductivity than solutions of TA,
NP, or NTA mixtures with CL in MeCN.* Of course,
this cannot serve as the direct proof for the ionic strucꢀ
ture of the DNMP and T complexes with CL but can
indicate its rather easy ionization upon approaching to
cationic intermediate 4 or 7. In turn, the latter explains
the differences in the experimental results mentioned
above.
ates 4 or 7 approach to the anion, as is shown in Scheme 3,
and its formation is much more difficult when they apꢀ
proach to a dipole (nonionized azole complex).
Scheme 3
An increase in the acidity of the azoles upon introꢀ
duction of nitro groups into the ring is accompanied by a
decrease in their nucleophilicity due to a considerable
shift of the electron density from the N atoms of the
rings to the nitro groups. This manifests in a decrease in
the total CE of products 1 and 2 on going, e.g., from
DMP to DMNP, from NP to DNMP, and from TA to
NTA (see Table 2, cf. entries 1 and 7, 10 and 18, 23
and 31). In turn, the high total current efficiencies of 1h
and 2h (see Table 2, entries 34—36) for the most acidic
azole studied, T, evidently point to the unexpectedly
high nucleophilicity of the corresponding anion. This is
associated, most likely, with the specificity of delocalꢀ
ization of the negative charge in the latter, viz., mainly
on the contiguous N atoms, which are, on the whole, the
object of the electrophilic attack (αꢀeffect). Note that an
increase in nucleophilicity caused by this type of effect
predetermines, most likely, the possibility of involveꢀ
ment of triazoles and pyrazoles in the process considꢀ
ered. This conclusion can be confirmed by the experiꢀ
mental fact that imidazole, which is more basic than
isomeric Pyr but does not contain contiguous N atoms
(see Table 1), does not virtually react with DMB under
Note, however, that this assumption explains only
the specific feature of the orthoꢀattack of ions 4 and 7
because the "pantophagy" of their ipsoꢀposition should
result in all cases in the formation of compounds 6, 7,
and further 2 (see Scheme 1). This forced us to introꢀ
duce the second concept about the irreversibility of the
orthoꢀattack on 4 and 7 and reversibility (equilibrium
character) of the ipsoꢀattack. The lower the nucleophiꢀ
licity and basicity of Az– and the higher acidity of AzH,
the higher the reversibility. In fact, this differentiates the
nucleophilic attacks of the ipsoꢀ and orthoꢀpositions, deꢀ
termining the former as the kinetically controlled and
the latter as the thermodynamically controlled process.
The data presented in the Section on undivided elecꢀ
trolysis and in Table 2 agree with both concepts. For
example, in the case of NP and NTA, the use of the
Alk4N+ salt of azole as the azole component instead of
* This is indicated, for example, by the fact that during
amperostatic electrolysis of a mixture of DNMP or T with CL
the resistance of the cell is almost independent of the presence
or the absence of a supporting electrolyte; however, it increases
∼10ꢀfold during electrolysis of mixtures of TA, NP, or NTA
with CL in the absence of the supporting electrolyte.

NꢀArylation of azoles during undivided electrolysis
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1529
conditions similar to those used in entries 20, 21, and 24
(see Table 2).
rearrangement 7h → 8h in the electrolysis with T occurs,
most likely, in a different manner, for example, as an
intermolecular cineꢀsubstitution (Scheme 5).
According to our data,2 in the electrochemical
Nꢀarylation of DMP and Pyr, the rearrangement of the
arenonium cations 7 → 8 makes a considerable contriꢀ
bution to the formation of 1 (see Scheme 1). However,
such a rearrangement seems highly improbable for the
lowꢀbasic azoles studied in this work. This follows, for
example, from the fact that changes in the solvent and in
the acidicꢀbasic properties of the medium (see above) do
not affect the yield and the ratio of the electrolysis prodꢀ
ucts.2 Nevertheless, the exceptional easiness of the transꢀ
formation of a mixture of compounds 1h и 2h, which is
formed upon electrolysis with T, into product 1h after
brief heating or even upon storage at ∼20 °C can be exꢀ
plained only by the rearrangement 7h → 8h (Scheme 4).
The fact that one of the Nꢀarylation products of T in
MeOH (Scheme 6), viz., 1,1,4ꢀtrimethoxyꢀ4ꢀtetrazolylꢀ
cyclohexaꢀ2,5ꢀdiene (10h) (see above), can also be transꢀ
formed into 1h but upon prolong heating (5 h, 110 °C) is
an argument in favor of Scheme 5. The much more
drastic conditions of this rearrangement as compared
with the transformation 2h → 1h can be explained by the
necessity to eliminate such a poorly leaving group as
methoxyl in the stage of cineꢀsubstitution.
Scheme 6
Scheme 4
`
The results of undivided electrolysis in MeOH proꢀ
vide a very helpful information for the understanding of
the regularities of Nꢀarylation of azoles. First, note that
under these conditions the higher CE of product 1h comꢀ
pared to that of product 1a is evidently due to the higher
nucleophilicity of the T•CL complex compared to that
of the DMP•CL complex (see Table 2, cf. entries 39
and 40). As for product 10, its formation according to
Scheme 1 could formally be explained by different selecꢀ
tivities of two consecutive ipsoꢀreactions of intermediꢀ
ates 4 and 7 with the nucleophiles present in the solution
(MeOH and T•CL complex). However, we managed to
show that in this case yet another route of formation of
compound 10h is possible, and this route is not directly
related to the electrochemically generated electrophilic
intermediates. It is shown experimentally (see Table 2,
entry 41) that under mild conditions (30 min, 70 °C) the
virtually quantitative and irreversible exchange interacꢀ
tion occurs between T and the product of electrochemiꢀ
cal methoxylation of DMB, viz., 1,1,4,4ꢀtetramethoxyꢀ
cyclohexaꢀ2,5ꢀdiene (12), to form compound 10h. A
possible route of this transformation includes the formaꢀ
tion of cation 11 due to acid catalysis performed by T
(Scheme 7). In this case, further heating of the reaction
mixture also produces product 1h according to Scheme 6.
Note. Here and in Schemes 5—7 Az is the tetrazole residue
(a mixture of Nꢀisomers).
Earlier2 we concluded that during electrolysis with
highly basic azoles such a rearrangement occurs as the
intramolecular orthoꢀarylation of the adjacent N atom in
azole. However, in the case of T with very low basicity
(see Table 1), the existence of the fourꢀmembered tranꢀ
sition state 9 (see Scheme 4) casts some doubt. In fact, a
similar rearrangement is not observed (see Table 2, enꢀ
tries 22, 26, and 27) for electrolysis with TA, which is
much more basic than T (see Table 1). For this reason,
Scheme 5

1530
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Chauzov et al.
Note that according to the published data7 the transforꢀ
mation of cyclohexadiene 12 into orthoꢀsubstituted DMB
derivatives under the action of nucleophilic reagents
(alcohols, thiols, etc.) is catalyzed by Hꢀacids or Lewis
acids and often requires prolong heating.
in the case of NP, the major part of diene 12 is primarily
transformed by the azole into 10d (see Scheme 7) and
then into a mixture of 1d и 2d, while in the case of TA
only product 10f can likely undergo such a transforꢀ
mation. These results can be explained in terms of
Scheme 8, which differs from Scheme 6 in the alternaꢀ
tive formation of products 2d,f due to both the insuffiꢀ
cient nucleophilicity of the azole component for the exꢀ
clusive orthoꢀ(but not ipsoꢀ) attack and the relatively low
acidity of NP and TA stabilizing compounds 10d,f
and 2d,f.
Scheme 7
Scheme 8
The specific feature of this reaction is the use of the
azole—CL (3 : 1) system, which provides both acid caꢀ
talysis (AzH) and the presence of an efficient nucleoꢀ
phile (AzH•CL) even under mild conditions. In addiꢀ
tion, the intermediate formation of the ipsoꢀsubstitution
product 10 has been established for the first time for
similar processes. Thus, when the T—CL—DMB system
is used in МеОН, not only compound 10h, but also
cyclohexadiene 12 can be the real primary product of the
electrochemical reaction.
Electrolysis of the AzH—DMB—CL systems with
DNMP and NTA in MeOH (see Table 2, entries 43
and 42) is characterized by the same regularities. The
main electrolysis products are compounds 10e,g (CE 13%
for each) and 1e,g (CE 5 and 3%, respectively). As in the
case of T, heating of the obtained reaction mixtures (5 h,
110 °C) results in the transformation of 10e,g into 1e,g
in ∼100% yield (see Table 2, entries 43 and 42), which is
in accord with Scheme 6. No diene 12 was formed in the
cases considered (as in the electrolysis of T). Less acidic
NP and TA behave in a different manner (see Table 1):
the main electrolysis products are compounds 10d,f (CE 3
and 38%) and 12 (CE 12 and 28%, respectively); the
formation of product 1 was observed only in the case of
TA (CE ∼1% (1d)) (see Table 2, entries 44 and 45).
Changes in the composition of the reaction mixtures
during distillation of the solvent (70 °C, 20 Torr, 30 min)
are observed only for NP, namely, cyclohexadiene 12 is
partially transformed by the azole into 10d (CE 11%).
Under more drastic conditions (5 h, 110 °C), similar
transformations are observed in both cases, viz., the forꢀ
mation of products 1d,f (CE 7 and 10%, respectively)
and 2d,f (7 and 11%, respectively). According to the CE
The results presented demonstrate first of all the speꢀ
cific features of electrochemical Nꢀarylation of azoles
with low basicity in МеОН, which affords solvolysis prodꢀ
ucts 10 and 12. Nevertheless, some of these results are
very useful for the understanding of the general regulariꢀ
ties of the process considered. For example, the transꢀ
formations of 12 into 10 and then into 1 (see Schemes 6
and 7), which were experimentally confirmed for the
most acidic azoles, are a serious argument in favor of the
above assumptions about the reversibility of the ipsoꢀ
attack of electrophilic intermediates 4 and 7 by the azole
nucleophiles and the irreversibility of their orthoꢀattack.
The fact that heating of compounds 10d,f for the least
polar NP and TA complexes with CL produces mixtures
of 1d,f and 2d,f confirms, most likely, the second asꢀ
sumption about the preferential occurrence of the orthoꢀ
attack of cation 7 (and, probably, radical cation 4) only
in the presence of the azole anion or a sufficiently polar
AzH•CL complex.
Thus, as applied to azoles with low basicity (acidic),
Scheme 1 proposed by us previously for the electroꢀ
chemical Nꢀarylation of highly basic azoles by DMB
should be refined taking into account the above assumpꢀ
tions (see Schemes 4—7) about the reversibility of some
stages* and the possibility of the intermolecular mechaꢀ
nism of rearrangement of the arenonium ions 7 → 8
(Scheme 9).
To finish the discussion of the possible mechanisms
of Nꢀarylation of the azoles (see Schemes 1 and 9), we
* Note that the reversibility of these stages is also real for highly
basic azoles when electrolysis is carried out in the presence of
acids, e.g., AcOH.2

NꢀArylation of azoles during undivided electrolysis
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1531
Scheme 9
(Lancaster), and NP and DNMP were prepared according to a
previously described procedure.8 Acetonitrile was purified and
dried by boiling with and distillation from KMnO4 and double
distillation from P2O5 followed by distillation from calꢀ
cined K2CO3.
note that the assumption on the possibility of formation
of orthoꢀarylation products 1 due to the intraꢀ or interꢀ
molecular transformations 7 → 8 agrees completely with
the experimental results. This transformation in the final
stage of electrolysis allows us to believe (at least forꢀ
mally) that the stage commonly accepted for similar proꢀ
cesses (methoxylation, cyanation, etc.), viz., orthoꢀatꢀ
tack of radical cation 4 by a nucleophile, can be excluded.
Moreover, the relatively high rate of the ipsoꢀattack of
arenionim cations 7 by the nucleophile compared to the
orthoꢀattack observed in several cases assumes that the
ipsoꢀattack in the case of radical cation 4 followed by the
fast oxidation of intermediate 6 (on the electrode or by
ion 4 acting as a mediator) is also preferential. For these
reasons, the stages of the orthoꢀattack of radical cation 4
with the formation of radical 5 followed by its subseꢀ
quent oxidation are designated in Scheme 9 by dotted
arrows as theoretically possible but presently having no
necessary experimental substantiation.
Amperostatic electrolysis of DMB (2 mmol) in 45 mL of
reaction mixtures with different compositions was carried out
under argon at the controlled current (I = 50 mA), passing 1 or
2 F electricity per mole of DMB (see Table 2). After terminaꢀ
tion of the electrolysis, the solvent was distilled off on a rotary
evaporator at the temperature ≤70 °C (25—30 Torr), and the
residue was analyzed by 1H NMR. Electrolysis was performed
under conditions similar to those described previously.1 For
spectroscopic characteristics used for identification of the seꢀ
ries of compounds 1 and 2 and the procedure for the determiꢀ
nation of the current efficiencies of 1 and 2 (calculated per
twoꢀelectron transformation of DMB) without their isolation
from a solution, see Ref. 1.
A porous glass diaphragm was used for electrolysis with
divided cathodic and anodic compartments. The cell volume
and surface areas of the Pt electrodes were approximately the
same as those for undivided electrolysis.
The examples of experiments given below describe isolaꢀ
tion of the target products, which corroborate the conclusions
about their nature drawn from the spectroscopic data.
In entry 10 (see Table 2), the residue after distillation of the
solvent (20—35 °С, 25 Torr) was triturated with ether and the
ethereal extract was concentrated in vacuo. After chromatoꢀ
graphic purification of the residue on silica gel using benzene
as the eluent, 1,4ꢀdimethoxyꢀ1,4ꢀdi(4ꢀnitropyrazolꢀ1ꢀyl)cycloꢀ
hexaꢀ2,5ꢀdiene (2d) was obtained in 42% yield (220 mg)
with m.p. 110 °С. Found (%): C, 46.40; H, 3.95; N, 23.12.
C14H14N6O6. Calculated (%): C, 46.41; H, 3.89; N, 23.2. The
Experimental
1
H
NMR spectra of solutions of samples in a
DMSOꢀd6—CCl4 (1 : 1, v/v) mixture were recorded on a Bruker
ACꢀ300 instrument.
Tetrabutylammonium perchlorate was prepared by the exꢀ
change reaction of the corresponding bromide with NaClO4
followed by recrystallization from EtOH. Tetraalkylammonium
salts of azoles were synthesized by a general procedure3 using
commercial DMB, TA, NTA, and T with 98—99% purity

1532
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Chauzov et al.
1H NMR spectrum of cyclohexadiene 2d was identical with
that described previously.1
Compounds 1e,g were obtained analogously (see Table 2,
entries 18 and 32).
1,4ꢀDimethoxyꢀ2ꢀ(5ꢀmethylꢀ3,4ꢀdinitropyrazolꢀ1ꢀyl)benzene
(1e). The yield was 20 mg (4%). Found (%): C, 46.60; H, 3.90;
N, 18.10. C12H12N4O6. Calculated (%): C, 46.76; H, 3.92;
N, 18.18. 1H NMR, δ: 2.60 (s, 3 H, Me); 3.80, 3.83 (both s,
3 H, 2 MeO); 7.04—7.17 (m, 3 H, C6H3).
1,1,4ꢀTrimethoxyꢀ4ꢀ(3ꢀnitrotriazolꢀ1ꢀyl)cyclohexaꢀ2,5ꢀdiene
(10g). 1H NMR, δ: 3.20, 3.25, 3.60 (all s, 9 H, 3 MeO);
5.07—6.16 (m, 4 H, C6H4); 8.60 (s, 1 H, C2HN4O2).
1,1,4ꢀTrimethoxyꢀ4ꢀ(tetrazolꢀ1ꢀ and ꢀ2ꢀyl)cyclohexaꢀ2,5ꢀ
diene (10h) (mixture of Nꢀisomers, 2 : 1). 1H NMR, δ:
3.20—3.30, 3.60 (all br.s, 9 H, 3 MeO); 4.97—6.15 (m, 4 H,
C6H4); 8.50, 8.84 (both s, 1 H, CHN(4)).
1,1,4,4ꢀTetramethoxycyclohexaꢀ2,5ꢀdiene (12). 1H NMR,
δ: 3.20 (s, 12 H, 4 MeO); 6.00 (s, 4 H, C6H4).
1,4ꢀDimethoxyꢀ2ꢀ(3ꢀnitroꢀ1,2,4ꢀtriazolꢀ1ꢀyl)benzene (1g).
The yield was 95 mg (19%), m.p. 118 °С. Found (%): C, 48.10;
H, 3.99; N, 22.50. C10H10N4O4. Calculated (%): C, 48.00;
H, 4.03; N, 22.39. 1H NMR, δ: 3.82, 3.92 (both s, 3 H, 2 MeO);
7.05—7.30 (m, 3 H, C6H3); 9.13 (s, 1 H, C2HN4O2).
The spectroscopic (1H NMR) characteristics of compounds
used for the identification and determination of their content
in reaction mixtures are presented below.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 00ꢀ03ꢀ
32870а) and the "Leading Scientific Schools" program
(Grant 00ꢀ15ꢀ97328).
References
1,4ꢀDimethoxyꢀ2ꢀ(1,2,4ꢀtriazolꢀ1ꢀyl)benzene (1f). 1H NMR,
δ: 3.80, 3.90 (both s, 3 H, 2 MeO); 6.94—7.35 (m, 3 H, C6H3);
8.04, 8.85 (both s, 1 H, C2H2N3).
1. V. A. Chauzov, V. Z. Parchinskii, E. V. Sinel´shchikova, and
V. A. Petrosyan, Izv. Akad. Nauk, Ser. Khim., 2001, 1215
[Russ. Chem. Bull., Int. Ed., 2001, 50, 1274].
2. V. A. Chauzov, V. Z. Parchinskii, E. V. Sinel´shchikova,
N. N. Parfenov, and V. A. Petrosyan, Izv. Akad. Nauk, Ser.
Khim., 2002, 917 [Russ. Chem. Bull., Int. Ed., 2002, 51, 998].
3. Kai Hu, M. E. Niyazymbetov, and D. H. Evans, Tetraꢀ
hedron Lett., 1995, 36, 7027.
4. M. E. Niyazymbetov, L. V. Mikhal´chenko, and V. A.
Petrosyan, Tez. dokl. Vsesoyuz. konf. "Aromaticheskoe
nukleofil´noe zameshchenie" [Abstrs. AllꢀUnion Conf. "Aromatic
Nucleophilic Substitution"], Novosibirsk, 1989, 91 (in Russian).
5. J. Catalan, J. L. M. Abbaud, and J. Elguero, Adv. Heterocycl.
Chem., 1987, 41, 250.
1,4ꢀDimethoxyꢀ2ꢀ(tetrazolꢀ1 and ꢀ2ꢀyl)benzenes (1h) (mixꢀ
1
ture of Nꢀisomers, 3 : 2). H NMR, δ: 3.76—3.89 (four s, 6 H,
2 MeO); 7.05—7.32 (m, 3 H, C6H3); 8.96, 9.59 (both s, 1 H,
CHN(4)) (cf. Ref. 3).
1,4ꢀDimethoxyꢀ1,4ꢀdi(tetrazolꢀ1ꢀ and ꢀ2ꢀyl)cyclohexaꢀ2,5ꢀ
1
dienes (2h) (mixture of mainly two isomers, 3 : 2). H NMR, δ:
3.28, 3.40 (both s, 6 H, 2 MeO); 6.79, 6.81 (both s, 4 H,
C6H4); 9.56, 9.70 (both s, 2 H, CHN(4)).
1
1ꢀ(4ꢀMethoxyphenyl)ꢀ1,2,4ꢀtriazole (3f). H NMR, δ: 3.82
(s, 3 H, MeO); 7.05, 7.72 (both d, 4 H, C6H4); 8.04, 9.01
(both s, 2 H, C2H2N3) (cf. Ref. 3).
1,1,4ꢀTrimethoxyꢀ4ꢀ(4ꢀnitropyrazolꢀ1ꢀyl)cyclohexaꢀ2,5ꢀ
diene (10d). 1H NMR, δ: 3.20, 3.23, 3.30 (all s, 9 H, 3 MeO);
6.31 (br.s, 4 H, C6H4); 8.10, 8.92 (both s, 2 H, C3H2N3O).
1,1,4ꢀTrimethoxyꢀ4ꢀ(5ꢀmethylꢀ3,4ꢀdinitropyrazolꢀ1ꢀ
yl)cyclohexaꢀ2,5ꢀdiene (10e). 1H NMR, δ: 2.70 (s, 3 H, Me);
3.30, 3.32, 3.62 (all s, 9 H, 3 MeO); 4.93—6.20 (m, 4 H, C6H4).
1,1,4ꢀTrimethoxyꢀ4ꢀ(1,2,4ꢀtriazolꢀ1ꢀyl)cyclohexaꢀ2,5ꢀdiene
(10f). 1H NMR, δ: 3.20, 3.25, 3.30 (all s, 9 H, 3 MeO); 6.25,
6.35 (both d, 4 H, C6H4); 7.80, 8.52 (both s, 2 H, C2H2N3).
6. V. A. Petrosyan, Izv. Akad. Nauk, Ser. Khim., 1995, 1411
[Russ. Chem. Bull., 1995, 44, 1353 (Engl. Transl.)].
7. B.ꢀT. Groebel, E. Konz, H. Millaner, and R. Pistorius, Synꢀ
thesis, 1979, 608.
8. R. Hüttel, F. Büchele, and P. Jochum, Chem. Ber., 1955,
88, 1377.
Received March 26, 2002;
in revised form July 1, 2002