Oxidative transformation of N-substituted 3-aminopyrazoles to azopyrazoles using electrogenerated bromine as a mediator

Article abstract of DOI:10.1007/s11172-018-2102-y

The one-pot process of anodic transformation of N-alkyl-3-aminopyrazoles into azopyrazoles under conditions of membraneless electrolysis in an aqueous solution of NaBr was studied for the first time. It was found that under these conditions the aminopyraz

Full text of DOI:10.1007/s11172-018-2102-y

Russian Chemical Bulletin, International Edition, Vol. 67, No. 3, pp. 510—516, March, 2018
510
Oxidative transformation of N-substituted 3-aminopyrazoles
to azopyrazoles using electrogenerated bromine as a mediator*
B. V. Lyalin,a V. L. Sigacheva,a V. A. Kokorekin,a,b,c T. Ya. Dutova,a G. M. Rodionova,b and V. A. Petrosyana
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. E-mail: petros@ioc.ac.ru
bI. M. Sechenov First Moscow State Medical University
of the Ministry of Health of the Russian Federation (Sechenov University),
8, str. 2 ul. Trubetskaya, 119991 Moscow, Russian Federation
cAll-Russian Research Institute of Phytopathology,
5 ul. Institut, 143050 Bol´shiye Vyazemy, Moscow Region, Russian Federation
The one-pot process of anodic transformation of N-alkyl-3-aminopyrazoles into azopyrazoles
under conditions of membraneless electrolysis in an aqueous solution of NaBr was studied for
the first time. It was found that under these conditions the aminopyrazoles, which do not have
a substituent at position 4, transform into the corresponding 4,4´-dibromoazopyrazoles. The
corresponding yield was in the interval of 28—80%, depending on the structure of the products.
The transformation of 4-substituted aminopyrazoles resulted in the formation of azopyrazoles
in the yields lying within 62—86% when this process was implemented under conditions with
the anodically generated Br2 acting as a mediator. A convenient method of anodic synthesis of
azopyrazoles in an aqueous medium without the use of additives of chemical oxidants was
proposed. The process is environmentally sound and is characterized by a high atom effic-
iency (>85%).
Key words: mediated electrochemical synthesis, bromine as a mediator, aminopyrazoles,
azopyrazoles, cyclic voltammetry.
An important branch of modern electroorganic chem-
the possibility of using electrogenerated Cl2 (NaOCl) as
a mediator in a one-step transformation of N-alkyl-3-
aminopyrazoles to azopyrazoles under conditions of
membraneless electrolysis of an aqueous solution of NaCl.
However, it turned out that the adsorption of the starting
aminopyrazole inhibits the anodic generation of Cl2 and,
correspondingly, the generation of NaOCl. As a result, the
yield of the target product did not exceed 3%, therefore,
this approach to the synthesis of azopyrazole proved to be
inefficient. Nevertheless, the synthesis of azopyrazoles was
achieved using a two-step process,4 namely, the electro-
generation of NaOCl in the first step and its reaction with
the aminopyrazole added to the reaction mixture in the
second step.
istry, which is related to the development of efficient
methods of synthesis, is the development of electrocatalytic
processes using certain mediators regenerated during
electrolysis.1 This makes it possible to achieve the trans-
formation of substrates under mild conditions, as well as
to increase the selectivity, environmental friendliness, and
efficiency of the synthesis. One of the most promising and
practically unexplored directions in this field is the elec-
trosynthesis of azohetarenes based on the electrocatalytic
(mediated) oxidation of the corresponding aminohetar-
enes. Recently, we were able to demonstrate2 for the first
time the possibility of electrosynthesis of azopyrazoles by
oxidative transformation of N-alkylaminopyrazoles on
a Ni anode in an aqueous alkali medium using electro-
generated NiO(OH).
In the present work, these studies were continued using
the electrogenerated Br2 as the mediator. We note that the
possibility of the transformation of 5-amino-4-cyano-1-
phenyl-1Н-pyrazole into the corresponding azo derivative
in the presence of Br2 was described earlier.3
At the same time, it is known3 that the reaction of
aminopyrazoles with reagents containing an electrophilic
halogen proceeds through the generation of N-halo-
aminopyrazoles and can lead to the formation of the
corresponding azopyrazoles. This prompted us to study4
Results and Discussion
In the previous work,4 the CV method was used to show
(Fig. 1, a) that the addition of even small amounts
* Dedicated to Academician of the Russian Academy of Sciences
I. P. Beletskaya.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 0510—0516, March, 2018.
1066-5285/18/6703-0510 © 2018 Springer Science+Business Media, Inc.

Transformation of N-substituted 3-aminopyrazoles
I/mA
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 3, March, 2018
511
oxidation of the Cl– ion), the addition of aminopyrazole
a
1 does not inhibit the anodic generation
A
of halogen. The decrease in the intensity
0.8
red
of the peak E (the reduction of Br2, Ep
=
0.6
0.4
= 0.69 V) with the addition of aminopyr-
a
azole 1 (by 12%) can be explained by the
consumption of the electrogenerated Br2
following the mechanism, which we con-
0.2
A´
sider below (Scheme 1).
C
0
Taking into account these results, in the present work we
studied the possibility of a one-pot synthesis of azopyrazole
under conditions of membraneless electrolysis of an aque-
ous solution of NaBr, so that the electrogeneration of Br2
as an oxidizer and its subsequent reaction with aminopyr-
azole proceeded in the cell simultaneously, considerably
simplifying the process in question. As in the previous
work,4 aminopyrazole 1 was used as the model substrate.
In addition, the influence of the structure of aminopyr-
azoles on their electrooxidative transformation was studied
using compounds 2—5 as examples.
–0.2
B
–0.4
–0.4
I/mA
3.0
0
0.4
0.8
E/V (rel. sat.c.e.)
b
D
D´
2.5
2.0
1.5
1.0
0.5
0
C
–0.5
–1.0
R1 = Et, R2 = R3 = H (2); R1 = R2 = Me, R3 = H (3);
R1 = R3 = Me, R3 = H (4); R1 = Et, R2 = H, R3 = Me (5)
E
Galvanostatic electrolysis with the transmission of the
theoretically required amount of electricity (Q = Qt =
= 2 F per 1 mole of aminopyrazole 1) resulted in the for-
mation of 3-amino-4-bromo-1-methyl-1Н-pyrazole (6)
in 37% yield, whereas the target 1,2-bis(1-methyl-1Н-
pyrazol-3-yl)diazene (7) was formed only in trace amounts
(1.5% yield based on aminopyrazole 1) (Table 1, entry 1).
From the obtained results it follows that under selected
conditions of the single-step electrooxidation, the main
reaction is the bromination of the aminopyrazole 1 at
position 4. In principle, there are three possible transfor-
mation pathways of Br2 generated on the anode (see
Scheme 1). The reaction of Br2 with alkali generated on
the cathode (pathway I) can lead to an equilibrium mixture
of NaOBr and HOBr. However, the contribution of this
process at Q = Qt = 2 F mol1 is negligible if the alkali
concentration is considerably lower than the concentration
of the initial aminopyrazole 1 (see Table 1, entries 1—7).
Another possibility of generating HOBr involves the revers-
ible reaction of Br2 with Н2О (pathway II), with the
equilibrium of this reaction being shifted5 towards Br2 by
a considerable extent. Therefore, it is expected that under
conditions of the one-pot process in question, the contri-
bution of these pathways, leading to the generation of
HOBr, to the main reaction will be small. It is more likely
that the major contribution to the process under consid-
–0.4
0
0.4
0.8
E/V (rel. sat.c.e.)
Fig. 1. Cyclic voltammograms of 1 M aqueous solution of NaNO3
in the presence of NaCl (с = 0.3 mol L–1) (a) and NaBr (с =
= 0.3 mol L–1) (b). Conditions: Pt electrode, ν = 0.1 V s–1. A,
A´, D, and D´ are the oxidation peaks of the Cl¯ (A, A´) and
Br– ions (D, D´) in the absence (A and D) and in the presence
(A´, D´) of aminopyrazole 1 (с = 2•10–3 mol L–1), B and E are
the reduction peaks of Cl2 and Br2, respectively, and C is the
oxidation peak of aminopyrazole. Potentials (E) are measured
relative to the saturated calomel electrode. Figure 1 is available
in full color on the web page of the Journal (http://www.link.
springer.com/journal/11172).
of 3-amino-1-methyl-1Н-pyrazole (1) to the solution under
study reduced the intensity of the chloride ion oxidation
ox
peak (Ep = 1.42 V) by a factor of ~10 (cf. peaks A and
A´). In combination with the results of electrolysis, this
indicates the inhibition of the Cl2 electrogeneration step.
At the same time, the addition of aminopyrazole 1 to
the aqueous solution of NaBr does not considerably affect
the morphology of the curve, merely shifting the peak D
(Epox = 1.12 V) corresponding to the oxidation of the Br–
ox
ion by 0.12 V towards the anode region (peak D´, Ep
=
= 1.24 V) (see Fig. 1, b). In this case, the intensities of the
peaks D and D' remain practically equal. Thus, during the
process of oxidation of the Br– ion (in contrast to the

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Russ. Chem. Bull., Int. Ed., Vol. 67, No. 3, March, 2018
Lyalin et al.
Table 1. The effect of electrolysis conditions on the yield and the composition of the products of electro-
oxidative transformation of 3-amino-1-methyl-1Н-pyrazole (1) in an aqueous solution of NaBra
Entry
Concentration
NaBr/mol L–1
ja
Q/Qt
Conversion of
pyrazole 1 (%)
Product yieldb (%)
/mA cm–2
6
7
8
1
1
1
2
3
2
2
2
2
2
160
160
160
160
130
100
120
100
100
1
1
1
1
1
1
1
4
4
141
140
162
156
161
163
165
190
100
37
29
49
45
43
54
54
77
59
1.5
4.0
2.1
2.0
1.9
2.0
2.1
—
—
—
—
—
—
—
—
15
28
2 c
3
4
5
6
7
8
9d
—
a Conditions: RTOA, Ti cathode, с1 = 0.03 mol L–1, Т = 25 C, Qt = 2 F per 1 mole of aminopyrazole 1.
b Based on the starting 3-aminopyrazole 1.
c Electrolysis was carried out in the presence of a base, 0.006 mole of NaHCO3.
d To maintain pH 7 of the solution, 48% HBr was gradually added during electrolysis.
Scheme 1
eration will be made by the reaction proceeding along the
pathway III.
resulted in a decrease in the yield of aminopyrazole 6 (from
37 to 29%) and a slight increase in the yield of azopyrazole
7 (from 1.5 to 4%), which is probably due to the partial
binding of HBr formed by pathway II (see Scheme 1), as
well as to some shift in the reaction equilibrium towards
the formation of HOBr, which is a stronger electrophilic
agent than Br2.6
The effect of the anodic current density (ja), concentra-
tion of NaBr, and the amount of transmitted electricity
(Q, F per 1 mole of the starting aminopyrazole 1) on the
yield and composition of the products of electrooxidative
transformation of aminopyrazole 1 under conditions of
the single-step galvanostatic process was studied (see Table 1).
We note that the assumption that the process proceeds
along pathway III (see Scheme 1) has received additional
experimental confirmation. Thus, electrolysis in the pres-
ence of a base (NaHCO3) (see Table 1, entries 1 and 2)
Varying ja (from 30 to 120 mA cm–2; see Table 1,
entries 3 and 5—7) and the concentration of NaBr (from
1 to 3 mol L–1; entries 1, 3, and 4) did not considerably
affect the yield (1.5—2.1%) of azopyrazole 7. However,
an increase in the yield of aminopyrazole 6 by 17%

Transformation of N-substituted 3-aminopyrazoles
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 3, March, 2018
513
(cf. entries 1 and 6) at a conversion of the starting amino-
pyrazole 1 equal to 63% was observed at ja = 100 mA cm–2
and сNaBr = 2 mol L–1. This indicates the advisability of
increasing the amount of transmitted electricity Q because
the solution after electrolysis contained a considerable
amount (up to 40%) of unreacted aminopyrazole 1. Indeed,
an increase in Q/Qt to 4 (cf. entries 6 and 8) led to an
increase in the conversion of aminopyrazole 1 to 90% and
the yield of aminopyrazole 6 to 77%, as well as to the
formation of a small amount of azopyrazole 8 (5% yield). This
is due to an increase in the amount of electrogenerated
Br2 with an increase in Q and, as a consequence, to a deeper
conversion of aminopyrazole 1 as a result of the following
transformations: aminopyrazole 1 2-amino-4-bromo-
pyrazole 6  dibromo-
pyrazole 8 with the yield of product 6 decreasing (from
77 to 58%) (cf. entries 8 and 9), which is apparently due
to a partial transformation of aminopyrazole 6 to azo-
pyrazole 8.
Earlier,8 using the protonation of 3-aminopyrazole (1)
upon treatment of Н3О+ as an example, it was shown that
the electrophilic transformation in question involves pri-
marily the N(2) atom of the pyrazole ring. From this, it
follows that the N(2) atom of the pyrazole ring in 3-amino-
pyrazoles has a greater reactivity with respect to electro-
philes than the nitrogen atom of the NH2 group. Therefore,
it is not surprising that the primary product of the reaction
of the electrogenerated Br2 with aminopyrazole 1 is
3-amino-4-bromopyrazole 6 (with its subsequent conver-
sion to azopyrazole 8 with a large amount of anodically
generated Br2), whereas azopyrazole 7 is formed only in
insignificant amounts.
azopyrazole 8. In amino-
pyrazole 6, the position 4 of
the pyrazole ring is occup-
Based on the results obtained in this work and in the
work,4 the mechanism of the process in question can be
described by Scheme 2.
ied and, as a result, it does
not undergo bromination,
but can be involved into
The reaction of Br2 with aminopyrazole 1 presented in
Scheme 2 should be considered as an electrophilic substitu-
tion involving two reaction centers of molecule 1, i.e., the
N(2) atom of the pyrazole ring and the nitrogen atom of the
amino group. The attack an the N(2) atom of the pyrazole
ring by Br2 after the elimination of the HBr molecule
results in the formation of 3-amino-4-bromopyrazole 6,
whereas the reaction of Br2 with aminopyrazole 1 at the
NH2 group gives azopyrazole 7. The formation of com-
pound 7 proceeds through the generation of intermediate
N-bromoaminopyrazole 1´ with the subsequent realization of
the steps 1´7´7. Similarly, azopyrazole 8 is formed by
the sequence of steps 66´8´8 from aminopyrazole 6.
an oxidative N—N-homocoupling to form azopyrazole 8.
The low yield of product 8 is apparently explained by
the alkalization of the electrolyte due to the formation of
an excess amount of alkali under conditions of prolonged
membraneless electrolysis of the aqueous solution of NaBr
in the presence of aminopyrazole 1. In order to bind the
formed alkali (the ОН¯ anion oxidizes7 more easily than
the Br– ion and can prevent the anodic generation of Br2),
a 48% aqueous solution of HBr was added in portions to
the electrolyte (see entry 9) during electrolysis to maintain
pH 7 of the medium. This procedure contributed to
a considerable increase (from 5 to 28%) in the yield of azo-
Scheme 2

514
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Lyalin et al.
Further, we studied the dependence of the yield and
presence of a Me group at position 5 of 3-aminopyrazole
3 leads to an increase in its reactivity in comparison with
aminopyrazole 2.
the composition of the products of electrooxidative trans-
formation of aminopyrazoles on their structure and, first
of all, on the presence of a substituent at position 4 in the
ring (Table 2). The structures of products 9—14 obtained
as a result of oxidative transformation of 3-aminopyrazoles
2—5 are shown below.
Thus, the efficiency of electrochemical transformation
of N-alkyl-3-aminopyrazoles, which do not have sub-
stituents at position 4, depends on the amount of transmitted
electricity. In particular, 4-bromoaminopyrazole is formed
at Q = 2 F mol–1, while at Q = 8 F mol–1 it undergoes
transformation to the corresponding 4,4´-dibromoazo-
pyrazole. It should be emphasized that in the first step (see
Scheme 2, step 16), the electrogenerated Br2 acts as
a brominating agent, while in the second step (Scheme 2,
step 68) it is a mediator of the conversion of 4-bromo-
aminopyrazole to the corresponding azo derivative.
As it was already noted above, the starting aminopyr-
azole 1 in the process in question has a dual reactivity,
which, apparently, is explained by the absence of a sub-
stituent at position 4 of the heterocycle. From this it follows
that by varying the structure of the initial pyrazole, it is
possible to influence to a certain degree the selectivity of
this process. In order to confirm this assumption, we
studied the transformations of N-alkyl-3-aminopyrazoles
with a substituent at position 4 in the pyrazole ring
(3-amino-1,4-dimethyl-1Н-pyrazole (4) and 3-amino-1-
ethyl-4-methyl-1Н-pyrazole (5)) and, therefore, unable
to undergo bromination under conditions of the one-pot
process. Electrolysis of compounds 4 and 5 (see Table 2,
entries 5 and 6) resulted in the formation of the corre-
sponding azopyrazoles, 1,2-bis(1,4-dimethyl-1Н-pyrazol-
3-yl)diazene (13) (62% yield) and 1,2-bis(1-ethyl-4-
methyl-1Н-pyrazol-3-yl)diazene (14) (51% yield). A pos-
sibility for the optimization of the process was shown
using aminopyrazole 5 as an example. It was found that
a twofold increase in the amount of electricity transmitted
during electrolysis contributed to a considerable (up to
86%) increase in the yield of the target product 14
(cf. entries 6 and 7). The conversion of the initial subst-
9, 10: R1 = Et, R2 = H (9); R1 = R2 = Me (10)
11—14: R1 = Et, R2 = H, R3 = Br (11 );
R1 = R2 = Me, R3 = Br (12); R1 = R3 = Me, R2 = H (13);
R1 = Et, R2 = H, R3 = Me (14)
As in the case of aminopyrazole 1, the membraneless
electrolysis (Q = 2 F mol–1) of an aqueous solution of
NaBr containing 3-amino-1-ethyl-1Н-pyrazole (2) or
3-amino-1,5-dimethyl-1Н-pyrazole (3) under optimal
conditions (see Table 1, entry 6) gave high yields of
3-amino-4-bromo-1-ethyl-1Н-pyrazole (9) (see Table 2,
entry 1) and 3-amino-4-bromo-1,5-dimethyl-1Н-pyrazole
(10) (see Table 2, entry 3), respectively.
Carrying out the same transformations of aminopyr-
azoles 2 and 3 with an increased amount of transmitted
electricity (Q = 8 F mol–1) while maintaining solution рН 7
during electrolysis resulted in 1,2-bis(4-bromo-1-ethyl-
1Н-pyrazol-3-yl)diazene (11) (58% yield) and 1,2-bis(4-
bromo-1,5-dimethyl-1Н-pyrazol-3-yl)diazene (12) (80%
yield) with a simultaneous decrease in the yields of bro-
moaminopyrazoles 9 and 10 to 31 and 3%, respectively
(Table 2, cf. entries 1 and 2, 3 and 4). On going from
aminopyrazole 2 to aminopyrazole 3, the yield of 4,4´-di-
bromoazo derivative increases. It can be assumed that the
Table 2. The influence of the structure of aminopyrazoles and the amount of transmitted elec-
tricity (Q) on the yield and the composition of the products of electrooxidative transformation
in an aqueous solution of NaBra
Entry
Aminopyrazole
Q/Qt
Product
Atom efficiency of
(yieldsb (%))
the synthesis of azopyrazolesc (%)
1
2
2
2
3
4
5
5
1
4
1
4
1
1
2
9 (46)
9 (31), 11 (58)
10 (54)
10 (3), 12 (80)
13 (62)
—
91
—
91
86
87
87
2d
3
4d
5
6
14 (51)
14 (86)
7
a
Conditions: RTOA, Ti cathode, concentration of aminopyrazoles 0.03 mol L–1; сNaBr
= 2 mol L –1, ja = 100 mA cm–2, Т = 25 C, Qt = 2 F per 1 mole of aminopyrazole.
b Based on the starting 3-aminopyrazole.
=
c The atom efficiency of the transformation 1  6 + 7 (see Table 1, entry 9) is 91%.
d To maintain pH 7 of the solution, 48% HBr was periodically added during electrolysis.

Transformation of N-substituted 3-aminopyrazoles
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 3, March, 2018
515
Scheme 3
R = Me (4, 13), Et (5, 14)
rate was 88%. We assume that in the case of 4-substi-
tuted 3-aminopyrazoles these results confirm transforma-
tions of the type 11´7´7 (see Scheme 2) in which,
as shown in Scheme 3, electrogenerated Br2 acts as
a mediator.
Experimental
Electrooxidation was carried out with stirring in a ther-
mostated (25 C) membraneless cell equipped with a ruthenium-
titanium oxide anode (RTOA) (S = 7.1 cm2) and a Ti cathode
(S = 10 cm2), using a DC source B5-8 (galvanostatic mode) and
a coulometer designed by the Special Design Bureau of the
N. D. Zelinsky Institute of Organic Chemistry of the Russian
Academy of Sciences.
Cyclic voltammograms (CV curves) were recorded in
a thermostated (25 C) cell using an Elins P-30JM potentiostat
(Russia) at a potential sweep rate v = 0.1 V s–1. The working
electrode was a Pt disk with a diameter of 1 mm embedded into
Teflon (before each measurement, the electrode was cleaned by
mechanical polishing). The auxiliary electrode was a Pt plate
(S = 3 cm2). The potentials were measured with respect to the
aqueous saturated calomel electrode (SCE) connected with the
test solution by a bridge with a supporting electrolyte (1 M aque-
ous solution of NaNO3).
In conclusion, we note that for the first time we inves-
tigated the possibility of the oxidative one-pot transforma-
tion of N-alkylated 3-aminopyrazoles to azopyrazoles
under conditions of membraneless electrolysis of an aque-
ous solution of NaBr. It was demonstrated that these
transformations take place with the involvement of electro-
generated Br2, which acts as a mediator. It was found that
under these conditions, 3-aminopyrazoles that do not have
a substituent at position 4 in the pyrazole ring are converted to
the corresponding 4,4´-dibromoazopyrazoles in 28—80%
yield (depending on the structure) with complete con-
version of the initial aminopyrazole. At the same time, the
transformation of 4-substituted 3-aminopyrazoles proceeds
with the participation of anodically generated Br2 as
a mediator and leads to the formation of the corresponding
azopyrazoles in 62—86% yield. Thus, we proposed a con-
venient method for the electrosynthesis of azopyrazoles
in an aqueous medium without the use of chemical oxi-
dants. The process is environmentally friendly and is
characterized by a high (>85%, Table 2) atom efficiency.*
1H and 13С NMR spectra of products were obtained on
a Bruker Avance 300 spectrometer (300.13 МHz for 1H and
75.47 МHz for 13C) in CDCl3, using Me4Si as a reference. High
resolution electrospray ionization (ESI) mass spectra were ob-
tained on a Bruker micrOTOF II instrument. Thin-layer chrom-
atography was carried out on Merck plates. Light petroleum ether,
EtOAc, CHCl3, silica gel (0.035—0.070 mm, 60 Å) used for
column chromatography, and 3-amino-1-methyl-1Н-pyrazole (1)
are commercially available products (Acros Organics). The start-
ing compounds 3-amino-1-ethyl-1Н-pyrazole (2), 3-amino-1,5-
dimethyl-1Н-pyrazole (3), 3-amino-1,4-dimethyl-1Н-pyrazole
(4), and 3-amino-4-ethyl-1-methyl-1Н-pyrazole (5) were pro-
vided by the UAB Crea-Chim (Lithuania).
* Atom efficiency9 is a quantitative indicator introduced by
R. Sheldon for assessing processes from the viewpoint of "green
chemistry". It is calculated as the ratio of the molar weight of the
target product to the sum of the molar weights of all products in
the stoichiometric reaction equation.
Electrooxidation of aminopyrazole 1 (see Table 1). Amino-
pyrazole 1 (0.291 g, 0.003 mol) and an aqueous solution of NaBr

516
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 3, March, 2018
Lyalin et al.
(100 mL) (concentrations were as follows: 1 М in entries 1 and
2, 2 M in entries 3 and 5—9, and 3 М in entry 4) were placed in
a cell. In experiment 2, NaHCO3 (0.504 g, 0.006 mol) was
added to the solution. The electrolysis was carried out at the
following currents: 426 mA for entries 1—4, 213 mA for entry 5,
710 mA for entries 6, 8, and 9, and 852 mA for entry 7. In ex-
periment 9, 48% aqueous solution of HBr was periodically
added to the reaction mixture to maintain рН 7. After passing
2 F of electricity per 1 mole of the starting aminopyrazole 1
(Q = 579 C) for entries 1—7 or 8 F (Q = 2316 C) for entries 8
and 9, the electrolysis was stopped, the reaction mixture was
stirred for 1 h and analyzed by TLC (eluent light petroleum
ether—ethyl acetate (1 : 1)). Then, the mixture obtained was
diluted with concentrated HCl (to рН  3) and the products were
extracted with CHCl3 (3×30 mL). The extracts were combined,
dried with anhydrous MgSO4, and concentrated in vacuo. The
products were isolated using column chromatography on SiO2
(eluent light petroleum ether—ethyl acetate). The following
compounds were isolated: 1,2-bis(1-methyl-1Н-pyrazol-3-yl)-
diazene (7) (entries 1—7; the product was identified by m.p.
201—202 C (cf. Refs 2 and 4: m.p. 201 C) and the reported2,4
1Н NMR spectra) and 1,2-bis(4-bromo-1-methyl-1Н-pyrazol-
3-yl)diazene (8) (entries 8 and 9, the product was identified by
NMR spectroscopy and high resolution mass spectrometry).
The aqueous layer obtained after extraction was concen-
trated in vacuo, diluted with NaOH with stirring (to рН  10),
and treated as described above. This resulted in the isolation of
3-amino-4-bromo-1-methyl-1Н-pyrazole (6) (entries 1—9; the
product was identified by m.p. 97 C (cf. Ref. 10: m.p. 97—98 C)
and the reported5 1Н NMR spectra) and unreacted aminopyr-
azole 1 (entries 1—8; the starting compound was identified by
TLC and NMR spectroscopy).
1,2-Bis(4-bromo-1-ethyl-1Н-pyrazol-3-yl)diazene (11). Yellow
crystals. M.p. 154—156 C. Rf 0.34 (eluent light petroleum
ether—ethyl acetate (1 : 2)). 1H NMR, : 1.46 (t, 6 Н, Me,
J = 7.1 Hz); 4.27 (q, 4 Н, СН2, J = 7.1 Hz); 7.53 (s, 2 Н, СН).
13C NMR, : 15.2 (2 Me), 48.5 (2 CH2), 89.1 (2 CBr), 130.8 (2 CH),
157.1 (2 CN). Found: m/z 376.9542 [M + H]+. C10H1379Br2N6.
Calculated: [M + H]+ = 376.9543.
1,2-Bis(4-bromo-1,5-dimethyl-1Н-pyrazol-3-yl)diazene (12).
Yellow crystals. M.p. 247—249 C. Rf 0.47 (eluent chloroform—
methanol (5 : 1)). 1H NMR, : 2.36 (s, 6 H, CH3); 3.92 (s, 6 H,
CH). 13C NMR, : 10.3 (2 СМе), 38.0 (2 NMe), 89.5 (2 CBr),
139.8 (2 CMe), 147.9 (2 CN). Found: m/z 376.9544 [M + H]+.
C10H1379Br2N6. Calculated: [M + H]+ = 376.9543.
1,2-Bis(1,4-dimethyl-1Н-pyrazol-3-yl)diazene (13) was iden-
tified by m.p. 189—191 C (cf. Ref. 4: m.p. 190 C) and the re-
ported4 1Н and 13С NMR spectra.
1,2-Bis(1-ethyl-4-methyl-1Н-pyrazol-3-yl)diazene (14). Yellow
crystals. M.p. 127—129 C. Rf 0.23 (eluent light petroleum
ether—ethyl acetate (1 : 5)). 1H NMR, : 1.45 (t, 6 H, CH3,
J = 7.2 Hz); 2.34 (s, 6 H, CH3); 4.26 (q, 4 H, CH2, J = 7.2 Hz);
7.21 (s, 2 H, CH). 13C NMR, : 10.5 (2 CMe), 15.6 (2 NCH2Me),
47.6 (2 CH2), 110.0 (2 CH), 129.4 (2 CMe), 160.0 (2 CN). Found:
m/z 247.1668 [M + H]+. C12H19N6. Calculated: [M + H]+
= 247.1668.
=
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 16-03-00173 a).
References
1. R. Francke, R. D. Little, Chem. Soc. Rev., 2014, 43, 2492.
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syan, Arkivoc, 2017, Rart iii, 55.
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Textbook], 4th ed., revised, Khimiya, Moscow, 1981, 566 pp.
(in Russian).
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of Organic Compounds. Vol. 1. Stereochemistry. Hydrocarbons. Halo
Compounds, Ed. J. F. Stoddart, Pergamon Press, Oxford—New
York—Toronto—Sydney—Paris—Frankfurt, 1980.
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book of Analytical Chemistry], Khimiya, Moscow, 1965,
390 pp. (in Russian).
8. J. Catalán, M. Menéndez, J. Laynez, R. M. Claramunt,
M. Bruix, J. De. Mendoza, J. Elguero, J. Heterocycl. Chem.,
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9. R. A. Sheldon, I. Arends, U. Hanefeld, in Green Chemistry
and Catalysis, Wiley-VCH, Weinheim, 2007, p. 2.
10. M. J. Costales, J. C. Van-Hertum, W. A. Kloschick, Pat. US
5201938; Chem. Abstr., 1993, 119, 180806z.
1,2-Bis(4-bromo-1-methyl-1Н-pyrazol-3-yl)diazene (8). Yellow
crystals. M.p. 211—213 C. Rf 0.13 (eluent light petroleum ether—
ethyl acetate (1 : 5)). 1H NMR, : 4.02 (s, 6 H, Me); 7.50 (s, 2 H,
CH). 13C NMR, : 40.4 (2 Me), 90.1 (2 CBr), 132.9 (2 CH),
157.5 (2 CN). Found: m/z 348.9217 [M + H]+. C8H979Br2N6.
Calculated: [M + H]+ = 348.9230.
Electrooxidation of aminopyrazoles 2—5 (see Table 2). Amino-
pyrazole 2—5 (0.003 mol) and 2 М aqueous solution of NaBr
(100 mL) were placed in the cell and electrolysis was carried out
at a current of 710 mA. In experiments 2 and 4, 48% aqueous
solution of HBr was periodically added to the reaction mixture
to maintain рН 7. After passing 2 F of electricity per 1 mole of
the starting aminopyrazole (Q = 579 C, entries 1, 3, 5, and 6),
4 F (Q = 1158 C, entry 7), or 8 F (Q = 2316 C, entries 2 and 4),
the reaction mixture was stirred, worked-up, and analyzed as
described above.
3-Amino-4-bromo-1-ethyl-1Н-pyrazole (9). An oil. Rf 0.53
1
(eluent light petroleum ether—ethyl acetate (2 : 1)). H NMR,
: 1.45 (t, 3 Н, Me, J = 7.1 Hz); 3.43 (br.s, 2 Н, NH2); 3.96
(q, 2 Н, СН2, J = 7.1 Hz); 7.19 (s, 1 Н, СН). 13C NMR, : 15.3
(Me), 47.2 (CH2), 79.9 (CBr), 128.9 (CH), 151.8 (CNH2).
Found: m/z 191.9958 [M + 2 H]+. C5H1079BrN3. Calculated:
[M + 2 H]+ = 191.9954.
3-Amino-4-bromo-1,5-dimethyl-1Н-pyrazole (10). White
crystals. M.p. 111—113 C. Rf 0.14 (eluent light petroleum ether—
ethyl acetate (1 : 10)). 1H NMR, : 2.14 (s, 3 H, Me); 3.57—3.62
(m, 5 H, Me + NH2). 13C NMR, : 11.8 (2 СМе), 37.8 (2 NMe),
108.7 (СBr), 138.9 (CMe), 152.0 (CNH2). Found: m/z 189.9972
[M]+. C5H879BrN3. Calculated: M = 189.9974.
Received December 11, 2017;
in revised form January 19, 2018;
accepted January 30, 2018