Vinyltetrazoles: IV. Microwave activation of metal-catalyzed arylation of C- and N-vinyltetrazoles

Article abstract of DOI:10.1134/S1070428014060207

Microwave-assisted Heck arylation of C- and N-vinyltetrazoles has been accomplished for the first time. Microwave irradiation has been shown to considerably promote the arylation of tetrazoles.

Full text of DOI:10.1134/S1070428014060207

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 6, pp. 888–891. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © D.V. Aleshunina, P.A. Aleshunin, T.V. Artamonova, V.A. Ostrovskii, 2014, published in Zhurnal Organicheskoi Khimii, 2014,
Vol. 50, No. 6, pp. 903–906.
Dedicated to Full Member of the Russian Academy of Sciences
O.N. Chupakhin on his 80th anniversary
Vinyltetrazoles: IV.* Microwave Activation of Metal-Catalyzed
Arylation of C- and N-Vinyltetrazoles
D. V. Aleshunina, P. A. Aleshunin, T. V. Artamonova, and V. A. Ostrovskii
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: va_ostrovskii@mail.ru
Received April 14, 2014
Abstract—Microwave-assisted Heck arylation of C- and N-vinyltetrazoles has been accomplished for the first
time. Microwave irradiation has been shown to considerably promote the arylation of tetrazoles.
DOI: 10.1134/S1070428014060207
Tetrazole (a five-membered aromatic nitrogen-con-
taining heterocycle) and its derivatives are used in
various fields of human activities, including defense
and space engineering, fire-fighting systems, medicine,
electronics, etc. [2]. A specific place in this series of
heterocyclic compounds is occupied by vinyltetrazoles.
The presence in their molecules of a vinyl group ac-
tivated by the heterocycle underlies their use as mono-
mers for the preparation of high-molecular-weight
polynitrogen compounds, poly(vinyltetrazoles). Poly-
(vinyltetrazoles) are promising as components of
actuating media of highly efficient gas generators,
polymer base of binders for fuels, blasting powders,
and energy-rich composite materials, flocculants, ion-
exchange resins, catalysts, super moisture adsorbents,
and immobilizers for various media. Vinyltetrazoles
are also important as intermediate products in total
syntheses of biologically active compounds [2, 3].
zoles include the use of toxic and explosive reagents,
low yields of intermediate and target products, low
concentration of the main substance in the products,
side polymerization processes, and hence unsatisfac-
tory reproducibility of the results [1–3]. In view of the
above stated, development of efficient procedures for
the synthesis of styryltetrazoles is a topical problem.
We previously reported on the synthesis of C- and
N-styryltetrazoles via metal-catalyzed arylation of C-
and N-vinyltetrazoles according to Heck [1]. Despite
essential advantages of the proposed procedure, the
complete conversion of initial vinyltetrazoles required
a fairly long reaction time, up to 20 h. Obviously,
an important problem in the chemistry of styryltetra-
zoles is minimization of time consumption for the
Heck arylation of vinyltetrazoles. Successful solution
of this problem should reduce the probability of spon-
taneous uncontrolled polymerization of styryl-
tetrazoles.
In recent time, much attention has been given to
styryltetrazoles [1–3]. It is known that styryl deriva-
tives of tetrazole exhibit antibacterial and antiallergic
properties [4]. Styryltetrazoles constitute a series of
promising monomers whose polymerization could give
rise to unique high-molecular-weight products and
materials.
In recent time, microwave (MW) activation has
been widely used to accelerate various chemical pro-
cesses [5–7]. Examples of tetrazole synthesis under
microwave irradiation have also been reported [8–10].
There are published data on pronounced promoting
effect of MW radiation on reactions catalyzed by palla-
dium and other metal salts, including Heck arylation of
alkenes [11–13]. We anticipated that microwave ac-
tivation should considerably reduce the reaction time
in the synthesis of C- and N-styryltetrazoles.
However, particular practical applications of styryl-
tetrazoles are restrained due to their relatively low
accessibility. General disadvantages of the existing
methods for the synthesis of vinyl-substituted tetra-
For this purpose, we tried to obtain C- and
N-styryltetrazoles by Heck arylation under conditions
* For communication III, see [1].
888

VINYLTETRAZOLES: IV.
889
Scheme 1.
Pd(OAc)2, K2CO3
solvent, 120°C
PhHlg
N
N
N
Me
Me
N
N
Ph
+
H2C
N
N
N
N
I
III
Pd(OAc)2, PPh3, CuI, Cs2CO3
solvent, 120°C
N
N
Ph
Ph
N
N
Ph
+
PhHlg
CH2
N
N
N
II
IV
of microwave irradiation. As substrates we selected
2-methyl-5-vinyltetrazole (I) and 5-phenyl-2-vinyl-
tetrazole (II). As arylating agents we used aryl halides:
iodobenzene, bromobenzene, and chlorobenzene
(Scheme 1). In order to estimate the effect of MW
radiation on the Heck arylation of vinyltetrazoles I and
II, we used the same reagents as those indicated in [1].
In particular, the arylation of 2-methyl-5-vinyltetrazole
(I) was carried out in the presence of Pd(OAc)2 as
catalyst and K2CO3 as base. In the arylation of 5-phe-
nyl-2-vinyltetrazole (II), the combination of the cata-
lyst, ligand, and base was more complex: Pd(OAc)2,
CuI, PPh3, and Cs2SO3. In both cases, the choice of
catalyst and reactants was substantiated in [1].
rationalized by possible coordination of the tetrazole
ring to the catalyst [1].
We can conclude that the use of MW activation in
the synthesis of styryltetrazoles III and IV may be
regarded as advisable due to considerable shortening
of the reaction time as compared to traditional condi-
tions and high yields and acceptable purity of the
target products. The MW-assisted arylation of vinyl-
tetrazoles with iodobenzene in DMSO at 120°C
ensures preparation of styryltetrazoles III and IV with
the best yields in a few minutes.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
An important factor in experiments with MW radia-
tion is proper choice of the solvent [13]. For the MW-
assisted Heck arylation of vinyltetrazoles I and II we
selected DMSO, DMF, and 1,4-dioxane. These sol-
vents are frequently used in cross coupling reactions
[12, 14] and are characterized by different abilities to
absorb MW radiation [15]. The results are presented in
Tables 1 and 2. The obtained data show that the
strongest promoting effect of MW radiation is ob-
served in the metal-catalyzed arylation of C-vinyltetra-
zole I. Analogous effect in the reaction with N-vinyl-
tetrazole II is appreciably weaker, which may be
a Bruker DPX-300 spectrometer at 300.1 and
75.5 MHz, respectively, using CDCl3 as solvent and
reference (CHCl3, δ 7.26 ppm; CDCl3, δC 77.16 ppm).
The mass spectra were obtained on a Waters LCT
Premier LC/MS system (ESI, TOF) with positive ion
detection. The melting points were measured on a PTP
melting point apparatus at a heating rate of 1 deg/min
near the melting point. The properties of tetrazoles I–
IV were in agreement with published data [1, 16].
All reactions were carried out under argon. The
conversion of vinyltetrazoles and accumulation of the
Table 1. Heck arylation of 2-methyl-5-vinyltetrazole (I) under convection heating and microwave irradiation
Convection heating
time, h yield, %
Microwave irradiation
power, W
Solvent
DMF
PhHlg
time, min
yield, %
PhI
40 min
0.01.5
10
80
80
–
05
10
60
02
02
60
60
60
60
60
75
72
55
55
60
62
63
62
77
82
–
PhBr
PhCl
PhI
DMSO
30 min
01
85
81
–
81
82
–
PhBr
PhCl
PhI
10
1,4-Dioxane
15
–
–
PhBr
PhCl
15
–
–
15
–
–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 6 2014

ALESHUNINA et al.
890
Table 2. Heck arylation of 5-phenyl-2-vinyltetrazole II under convection heating and microwave irradiation
Convection heating
time, h yield, %
Microwave irradiation
power, W
Solvent
DMF
PhHlg
time, min
yield, %
PhI
0.02.5
09
80
82
–
07
20
60
05
10
60
60
60
60
70
74
72
60
61
60
62
59
62
79
80
–
PhBr
PhCl
PhI
10
DMSO
02
78
80
–
75
78
–
PhBr
PhCl
PhI
0.04.5
10
1,4-Dioxane
15
–
–
PhBr
PhCl
15
–
–
15
–
–
arylation products were monitored by TLC on Kiesel-
gel 60F245 plates (Merck); spots were visualized under
UV light (λ 254 nm). Microwave-assisted reactions
were performed in an MLS ETHOS Milestone labora-
tory oven under continuous irradiation at a frequency
of 2450 MHz (maximum power 1000 W) and continu-
ous monitoring of the reaction temperature. The prod-
ucts were isolated by column chromatography on
Silica Gel 60 (0.063–0.200 μm, Merck).
ethanol. Colorless crystals, mp 87–88°C, Rf 0.4 (hex-
ane–CH2Cl2–EtOAc, 7:2.5:0.5). 1H NMR spectrum, δ,
ppm: 4.36 s (3H, CH3), 7.14 d (1H, CH=CHPh, J =
16.5 Hz), 7.34–7.42 m (3H, Ph), 7.54–7.58 m (2H,
Ph), 7.73 d (1H, CH=CHPh, J = 16.5 Hz). 13C NMR
spectrum, δC, ppm: 39.48 (CH3), 113.46 (CH=CHPh);
127.23, 128.93, 129.14, 135.75 (Ph); 136.37
(CH=CHPh), 164.46 (C5). Found: m/z 187.0921 [M +
H]+. C10H10N4. Calculated: M 186.2132.
2-[2-(E)-Phenylethenyl]-5-phenyltetrazole (IV).
Copper(I) iodide, 1.8 mmol, and vinyltetrazole II,
1.8 mmol, were dispersed in 2 mL of appropriate
solvent, 0.072 mmol of Pd(OAc)2, 0.21 mmol of PPh3,
9.0 mmol of PhHlg, and 2.7 mmol of Cs2CO3 were
added, and the subsequent procedure was the same as
above. Colorless crystals, mp 113–114°C, Rf 0.2 (hex-
2-Methyl-5-[2-(E)-phenylethenyl]tetrazole (III).
Phenyl halide, 9.0 mmol, was dissolved in 2 mL of
appropriate solvent, 0.072 mmol of Pd(OAc)2 was
added, and the mixture was heated under stirring to
50°C and kept for 20 min at that temperature. Vinyl-
tetrazole I, 1.8 mmol, and potassium carbonate,
3.6 mmol, were added to the solution, and the mixture
was heated in two ways.
1
ane–EtOAc, 8:2). H NMR spectrum, δ, ppm: 7.26–
7.56 m (8H, C6H5), 7.69 d (1H, CH=CHN, J =
14.5 Hz), 7.99 d (1H, CH=CHN, J = 14.5 Hz), 8.21–
8.23 m (2H, C6H5). 13C NMR spectrum, δC, ppm:
122.53 (CH=CHN), 124.95 (CH=CHN); 127.13,
127.23, 127.33, 129.10, 129.24, 129.31, 130.77, 133.20
(C6H5); 164.96 (C5). Found: m/z 249.2121 [M + H]+.
C15H12N4. Calculated: M 248.2825.
a. Convection heating. The mixture was heated
under stirring to 120°C.
b. Microwave heating. The mixture was placed into
the microwave furnace and was heated under stirring
to 120°C.
The mixture was heated for a time necessary to
complete the reaction.
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combined extracts were dried over anhydrous sodium
sulfate and evaporated to dryness under reduced pres-
sure. The residue was purified by column chromatog-
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