Vinyltetrazoles: I. Synthesis of NH-unsubstituted 5-vinyltetrazole

Article abstract of DOI:10.1134/S1070428010110126

The NH-unsubstituted 5-vinyltetrazole was obtained in 55% yield by exhaustive methylation of 5-(β-dimethylaminoethyl)tetrazole with dimethyl sulfate at the terminal dimethylamino group with the subsequent elimination of a proton from the α-CH₂ group and Hofmann β-cleavage of the intermediate 5-(β-trimethylammoniumethyl)tetrazolide methyl sulfate. The microwave irradiation was shown to reduce 5-fold the time of the synthesis of the initial substrate, 5-(β-dimethylaminoethyl)tetrazole. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070428010110126

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 11, pp. 1678−1681. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.A. Ostrovskii, P.A. Aleshunin, V.Yu. Zubarev, E.A. Popova, Yu.N. Pavlyukova, E.A. Shumilova, R.E. Trifonov, T.V. Artamonova, 2010,
published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 11, pp. 1671−1674.
Dedicated to the memory of Professor G.I. Koldobskii
Vinyltetrazoles: I. Synthesis
of NH-Unsubstituted 5-Vinyltetrazole
V. A. Ostrovskii, P. A. Aleshunin, V. Yu. Zubarev, E. A. Popova, Yu. N. Pavlyukova,
E. A. Shumilova, R. E. Trifonov, and T. V. Artamonova
St. Petersburg State Technological Institute (Technical University), St. Petersburg, 190013 Russia
e-mail: VA_Ostrovskii@mail.ru
Received October 5, 2009
Abstract—The NH-unsubstituted 5-vinyltetrazole was obtained in 55% yield by exhaustive methylation
of 5-(β-dimethylaminoethyl)tetrazole with dimethyl sulfate at the terminal dimethylamino group with the
subsequent elimination of a proton from the α-CH2 group and Hofmann β-cleavage of the intermediate
5-(β-trimethylammoniumethyl)tetrazolide methyl sulfate. The microwave irradiation was shown to reduce 5-fold
the time of the synthesis of the initial substrate, 5-(β-dimethylaminoethyl)tetrazole.
DOI: 10.1134/S1070428010110126
NH-Unsubstituted 5-vinyltetrazole (I) and its alkyl
derivatives, e.g., II and III, have a considerable practical
interest as substrates for preparation of polymers with
a high nitrogen content, poly(vinyl-5-yltetrazoles) [1].
These polymers and materials based thereon are required
by to-day medicine and engineering [2]. The poly(vinyl-
5-yltetrazoles) can underlie the filter materials for the
purification of the biological fluids from heavy metal
ions and radionuclides [3], superabsorbents of moisture
[4], efficient energy-rich materials [5].
tion with methyl iodide in acetonitrile in the presence of
triethylamine, and the ratio was established of isomeric
reaction products, 1- (II) and 2-methyl-5-vinyltetrazoles
(III). The reactions involving the vinyl group of tetra-
zole I save the polymerization processes [1] are virtu-
ally unknown notwithstanding the obvious possibility
to obtain in this way new promising compounds. The
development of research in this field of the tetrazole
chemistry is hampered by the limited availability of the
initial compound, NH-unsubstituted 5-vinyltetrazole (I).
Evidently the development of an efficient procedure of
the synthesis of NH-unsubstituted 5-vinyltetrazole (I)
is an urgent task.
Up till now only few chemical reactions of NH-
unsubstituted 5-vinyltetrazole (I) are known at the en-
docyclic nitrogen atoms. Arnold and Thatcher showed
that the acylation of 5-vinyltetrazole (I) with acetic
anhydride followed by the thermolysis of the interme-
diate N-acyl derivative occurring with elimination of a
nitrogen molecule led to the formation of 2-methyl-5-
vinyl-1,3,4-oxadiazole [6]. The reaction of 5-vinyltet-
razoles I–III with PdCl2 resulted in the formation of
coordination compounds of the general formula PdL2Cl2
[7]. On replacing in these processes palladium chloride
with CuCl2 or NiCl2 the arising coordination compounds
do not contain chlorine in their composition. Therefore
Kizhnyaev and Kruglova [7] suggest that here the ligand
is the corresponding anionic form 5-vinyltetrazolide. In
[8] the rate constants were measured of tetrazole I alkyla-
N N
N N
N
N
N
N CH3
N
N
N
H
N
CH3
I
II
III
The most wide-spread preparation method for NH-
unsubstituted 5-R-tetrazoles is the 1,3-dipolar cycload-
dition of azides to nitriles. Recently versatile versions of
this process were developed permitting the preparation
of various 5-R-tetrazoles (R = Alk, Ar, Ht) in good yield
and under relatively mild conditions [3]. However the
only example of the synthesis of NH-unsubstituted 5-vi-
nyltetrazole (I) directly from acrylonitrile was reported
1678

VINYLTETRAZOLES: I. SYNTHESIS OF NH-UNSUBSTITUTED 5-VINYLTETRAZOLE
1679
in [6]. Arnold and Thatcher described the synthesis of
NH-unsubstituted 5-vinyltetrazole (I) in 55% yield by
the reaction of Al(N3)3 with acrylonitrile in dry THF un-
der a nitrogen atmosphere. This method did not become
extensively used for the sufficient conversion of reagents
required a long (24 h) heating of the reagents in THF [6].
The use of the inert gas did not prevent the polymerization
processes under the fairly severe conditions of the synthe-
sis [9]. The potential hazards in the handling of aluminum
azide, fairly sensitive to the mechanical action initiating
explosive, should also be taken into consideration [10].
Our attempts at the preparation of NH-unsubstituted
5-vinyltetrazole (I) directly from acrylonitrile apply-
ing virtually all known now versions of the 1,3-dipolar
cycloaddition of azides to nitriles, including the popular
now method developed by Sharpless et al. [11] also were
unsuccessful. The use of efficient polymerization inhibi-
tors, like ionol, and the performance of the process in the
atmosphere of an inert gas failed to prevent the forma-
tion of polymeric products. Therefore we focused on the
alternative methode of introducing the vinyl substituent
into the position 5 of the tetrazole ring.
was formed which further suffered the β-elimination
of trimethylamine (Hofmann deamination) to transform
into NH-unsubstituted 5-vinyltetrazole (I). Note that in
this reaction it is fundamentally important to carry out
the alkylation of the initial tetrazole IV in such way as
to exclude the formation of the side products of alkyla-
tion at the endocyclic nitrogen atoms (see the scheme).
5-(β-Dimethylaminoethyl)tetrazole (IV) was pre-
pared as previously published in [14], by the 1,3-di-
polar cycloaddition of dimethylammonium azide to
β-dimethylaminopropionitrile. This method is simple in
performing, relatively safe, and the necessary reagents
are fairly available. However the overall time for the
completion of the synthesis of 5-(β-dimethylaminoethyl)-
tetrazole (IV) is long, 18 h. To reduce the reaction time
we intensified the process by microwave irradiation. Note
that the microwave activation is more and more used in
the processes of 1,3-dipolar cycloaddition, in particular,
in those resulting in the formation of NH-unsubstituted
5-R-tetrazoles [3, 15–17]. In this study we observed
a significant promotion effect: The application of the
microwave irradiation additionally to the common con-
vection heating 5-fold reduced the reaction time (to 3 h).
In the paper [6] of Arnold and Thatcher the “alter-
native “ version of the preparation of 5-vinyltetrazole
(I) was described involving the synthesis of an inter-
mediate 5-(2-chloroethyl)tetrazole by the reaction of
3-chloropropionitrile with Al(N3)3 followed by the
dehydrochlorination of the exocyclic substituent in the
position 5 of the tetrazole ring. However the stage of
the dehydrochlorination also proceeded with difficul-
ties and resulted in a low yield of the target product.
The later attempts at “simplifying” the dehydrochlo-
rination of the 5-(2-chloroethyl)tetrazole by varying
the temperature, solvent, adding the polymerization
inhibitor [12] did not fundamentally improved the ver-
sion reported in [6]. Another approach to the sysnthesis
of derivatives of 5-vinyltetrazole (I) was developed in
[13]. Here the results were presented on the study of
the kinetics and mechanism of Hofmann deamination
of isomeric N-methyl-5-(β-trimethylammoniumethyl)
tetrazoles methylsulfates leading to the formation of
the corresponding N-methyl-5-vinyltetrazoles II and
III. Partially applying the method described in [13]
we developed a new procedure of the synthesis of NH-
unsubstituted 5-vinyltetrazole (I). This method is based
on the synthesis of 5-(β-dimethyl-aminoethyl)tetrazole
(IV) and its subsequent methylation at the terminal
dimethylamino group.As a result of the selective alkyla-
tion 5-(β-trimethylammoniumethyl)-tetrazolide (VI)
According to the deamination mechanism [13] the
conversion of 5-(β-trimethylammonium)tetrazolide
(VI) into NH-unsubstituted 5-vinyltetrazole (I) requires
a proton elimination from the methylene group in the
α-position to the tetrazole ring of the bipolar ion VI (see
the scheme). The formed anion VII suffers Hofmann
β-elimination of trimethylamine and transforms into
5-vinyltetrazolide (VIII). The proton addition to the
endocyclic nitrogen atom of tetrazolide VIII results in
the formation of NH-unsubstituted 5-vinyltetrazole (I).
Evidently the fundamentally important condition for
the successful proceeding of their reaction sequence is
the correct choice of the pH of the reaction solution.
We based on several considerations in selecting the pH.
Firstly, during the methylation with dimethyl sulfate the
terminal dimethylamino group should exist in a “free”
state. Only under this condition the selective exhaustive
alkylation should occur giving tetrazolide VI. In keeping
with the known [14] indices of the acidity constants in
water of the tetrazole ring of compound IV (pKa 3.39)
and the basicity constant of the terminal dimethylamino
+
group (pKBH 9.39) it is presumable that in the course of
alkylation the pH >10.5 should be maintained. Secondly,
the important condition of the selective exhaustive alkyla-
tion is the reagents ratio. We showed that for the selective
alkylation the equimolar ratio of the reagents, tetrazole IV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 11 2010

OSTROVSKII et al.
1680
Scheme.
N
N
N
N
_
N
N
Me2NH2N3
DMF
NaOH H2O
CN
Me2N
N
N
Me2N
N
Me2N
H
IV
V
N
N
N
N
_
_
N
+
+
(MeO)2SO2
NaOH
_
Me3N
N
V
Me3N
N
NaOH H2O
VII
VI
H
N
N
H+
_
N
N
N N
VII
_Me3N
N N
VIII
I
DMSO-d6 using as internal references the signals of
the residual protons (δ 2.5 ppm) and carbon atoms
(δ39.5ppm)ofthesolvent.Thereactionswerecarriedout
with the microwave heating in a laboratory installation
MLS ETHOS P/N 44072 at constant irradiation (60 W)
and constant control of the internal temperature. The
chromatographic analyses were carried out using a liquid
chromatograph Shimadzu LC-10Avp equipped with
a UV detector, column 250 × 4.6 mm with an inverse
phase Supelko C18, particles size 5 μm, temperature
control of the column at 30°C, eluent acetonitrile–0.1%
H3PO4, 1:9, analytical wavelengths 200 and 218 nm
by the procedure described in [8]. The control of pH
of water solutions was performed on a device Cyber-
Scan pH-510/Ion-510. Mass spectra were measured
on a liquid chromatograph-mass spectrometer Waters
LCT Premier (ESI, TOF). IR spectra were recorded
on a spectrophotometer Shimadzu FTIR 8400 from
pellets with KBr. Elemental analysis was carried out
on an analyzer LECO CHNS(O) 932. The homogeneity
of compounds obtained was proved by TLC on Merck
Kieselgel 60F245 plates, spots visualization under UV
irradiation (λ 254 nm) or in iodine vapor.
and dimethyl sulfate, should be used. The exess alkylating
agent (compared to the equimolar amount) resulted (ac-
cording to HPLC) to the undesired formation of alkylation
products at the endocyclic nireogen atoms, N-methyl-5-
vinyltetrazoles II and III. Interestingly in this case, as
show the HPLC data, first appears the chromatographic
peak corresponding to 1-methyl-5-vinyltetrazole (II), and
only after some time of the reaction, the peak correspond-
ing to 2-methyl-5-vinyltetrazole (III). This fact does not
contradict the mechanism discussed in [13]: According
to the latter, the rate of the formation of tetrazole II from
the 1-methyl-5-(β-trimethylammoniumethyl)tetrazole
is significantly (21-fold) faster than the formation of
tetrazole III. Finally, in keeping the suggestions of [13],
for the elimination of the proton from the α-methylene
group of the bipolar ion VI (see the scheme) in the reac-
tion solution the pH ≥ 13 should be maintained.
Taking into account all the mentioned conditions we
conserved the pH 13–14 throughout the total process of
the synthesis up to the formation of tetrazolide VII (see
the scheme). According to HPLC data, the conversion of
tetrazole IV of 86% was reached already in 3 h after the
start of the reaction.
5-(β-Dimethylaminoethyl)tetrazole (IV). To a solu-
tionof12.6g(154mmol)ofdimethylaminehydrochloride
in 40 ml of DMF was added at stirring 10.0 g (154 mmol)
of sodium azide. The dispersion obtained was heated at
40–50°C over 2 h. On cooling the precipitate of sodium
chloridewasfilteredoff.Tothefiltratewasaddedatstirring
15.1 ml (134 mmol) of β-dimethylaminopropionitrile.
The heating of the reaction mixture was performed in two
ways:
Thus the method we developed makes it possible to
obtain NH-unsubstituted 5-vinyltetrazole (I) in a plausible
yield and a high content of the target substance from
relatively available and safe in handling reagents.
EXPERIMENTAL
1H and 13C NMR spectra were registered on
a spectrometer Bruker DPX-300 at operating frequencies
300.1 and 75.5 MHz respectively from solutions in
(a) Convection heating. The reaction mixture was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 11 2010

VINYLTETRAZOLES: I. SYNTHESIS OF NH-UNSUBSTITUTED 5-VINYLTETRAZOLE
1681
heated at 110°C while stirring and kept for 18 h.
Research (grant 08-03-00247) and of the Council
of Grants of the President of the Russian Federation
(Program for the State support of young Russian
scientists MК-1354.2009.3).
(b) Microwave heating. The reaction mixture was
placed into the reactor of the microwave installation and
was heated at 110°C (60 W) while stirring over 3 h.
The reaction mixture was first cooled to the room
temperature, then to 0oC. The precipitate was filtered
off and washed with acetone (3×20 ml). Yield 12.7 g
(67%), colorless crystals, mp 196°C (a), 197°C (b). IR
spectrum, ν, cm–1: 2900, 3030 (C–H, stretch.), 1340 m
(C–H, bend.), 1510, 1380, 1250, 1110, 1080, 1060
(tetrazole ring). 1H NMR spectrum (D2O), δ, ppm:
2.86 s (6H, NMe2), 3.23 t (2H, CβH2, J 7.3 Hz), 3.47 t
(2H, CαH2). 13C NMR spectrum, δ, ppm: 20.33 (CαH2),
42.78 (NMe2), 55.96 (CβH2), 158.48 (CN4). Mass
spectrum: m/z 142.110 [M + H]+. Found, %: C 42.4;
H 7.67; N 49.93. C5H11N5. Calculated, %: C 42.54;
H 7.85; N 49.61. M 141.1743.
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14. Ostrovskii, V.A., Poplavskii, V.S., and Shcherbinin, M.B.,
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Chem., 2009, p. 5287.
1H-5-Vinyltetrazole (I). To a solution of 10 g
(70 mmol) of 5-(β-dimethylaminoethyl)tetrazole (IV) in
70 ml of water was added at stirring and cooling 5.7 g
(141 mmol) of NaOH. The solution obtained (pH ≈ 14)
was stirred for 15 min at 20°C, then was added dropwise
9.9 g (78 mmol) of freshly distilled dimethyl sulfate.
The solution obtained was heated at 50–60°C and stirred
for 3.5 h. On completion of the reaction the solution
was cooled to 5°C and 0.1 g of ionol (polymerization
inhibitor) was added, then dropwise was added 10%
hydrochloric acid till pH ≈ 2. The solution obtained was
extracted with ethyl acetate (7×30 ml), the combined
extract was dried with anhydrous Na2SO4, the solvent
was removed in a vacuum. The residue was crystallized
from chloroform. Yield 3.7 g (55%) colorless crystals,
mp 125°C. IR spectrum, ν, cm–1: 2318–3116 (N–H),
1647 (C=C), 1558, 1458, 1372, 1296, 1122, 1053
(tetrazole ring). 1H NMR spectrum (DMSO-d6), δ,
ppm: 5.93 d (1H, CH2=CH, J 10.8 Hz), 6.54 d (1H,
CH2=CH, J 17.7 Hz), 6.86 d.d (1H, CH2=CH, J 10.8,
J 17.7 Hz), 16.3 br.s (1H, NH). 13C NMR spectrum, δ,
ppm: 119.55 (CH2), 125.7 (CH), 154.43 (CN4),. Mass
spectrum: m/z 97.0500 [M + H]+. Found, %: C 37.59;
H 4.21; N 58.20. C3H4N4. Calculated, %: C 37.50;
H 4.20; N 58.31. M 96.0907.
ACKNOWLEDGMENTS
16. Alterman, M. and Hallberg, A., J. Org. Chem., 2000,
vol. 65, p. 7984.
The study was carried out under the financial
support of the Russian Foundation for Basic
17. Roh, J., Artamonova, T.V., Vávrová, K., Koldobskii, G.I.,
and Hrabálek, A., Synthesis, 2009, p. 2175.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 11 2010