Features of the synthesis of 1,1′-Phenylenebis(1H-tetrazoles) and their transformations in basic environment

Article abstract of DOI:10.1134/S1070428010020247

Reactions of substituted 1,3- and 1,4-phenylenediamines with sodium azide and triethyl orthoformate in the presence of acetic acid led to the formation in high yields of the corresponding 1,12 -phenylenebis(1Htetrazoles). The presence of electron-acceptor

Full text of DOI:10.1134/S1070428010020247

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 2, pp. 291−297. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.N. Vorob’ev, A.V. Baranovskii, P.N. Gaponic, O.A. Ivashkevich, 2009, published in Zhurnal Organicheskoi Khimii,
2010, Vol. 46, No. 2, pp. 295−301.
Features of the Synthesis of 1,1'-Phenylenebis(1H-tetrazoles)
and Their Transformations in Basic Environment
A. N. Vorob’eva, A. V. Baranovskiib, P. N. Gaponicc, and O. A. Ivashkevichc
aRepublican Unitary Enterprise “Belmedpreparaty,” Minsk, 20007 Belarus
e-mail: orivtfs@belmedpreparaty.com
bInstitute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
cResearch Institute of Physicochemical Problems at Belorussian State University, Minsk, Belarus
Received March 5, 2009
Abstract—Reactions of substituted 1,3- and 1,4-phenylenediamines with sodium azide and triethyl orthoformate
in the presence of acetic acid led to the formation in high yields of the corresponding 1,12 -phenylenebis(1H-
tetrazoles). The presence of electron-acceptor groups in the molecules of the initial diamines reduces the yield of
the target heterocycles. With 2-nitro-1,4-phenylenediamine the prevailing product was 2-nitro-4-(1H-tetrazol-1-
yl)aniline. The obtained bistetrazoles in basic environment suffer an opening of one or both heterocycles forming
cyanamides.
DOI: 10.1134/S1070428010020247
The growing interest to the synthesis of new
with respect to the synthesis of phenylenebistetrazoles.
functionally substituted tetrazole derivatives is due to the
In the preceding research [9, 10] concerning a limited
inherent to this class compounds biological activity,
range of substrates with equivalent or similar in the
chemical and metabolic stability, high energy store and
capability of complex formation [1–3].
reactivity amino groups it was demonstrated that both
amino groups of phenylenediamine underwent the
Bi- and polynuclear tetrazoles attract attention as
chelating agents and initial compounds for building up
one-, two-, and three-dimensional metal-containing
supramolecular structures and developing materials with
unusual magnetic properties, photo- and thermochromism
([3–5] and references cited there). Besides bicyclic
tetrazoles are promising for the synthesis both of
tetrazole-containing and other bifunctional and
macroheterocyclic systems [6], and also of linear
oligoheterocycles [7]. The application of 1,12 -(1,3-
phenylene)bistetrazole was described as an effective
ligand in the catalyzed by palladium salts cross-coupling
of aryl halides and arylboric acids [8].
heterocyclization disregarding the reaction conditions and
the reagents ratio. The opening of the tetrazole ring under
the action of bases practically important for the synthesis
of N-arylcyanamides and 5-amino-1-aryltetrazoles [10–
13] was not virtually investigated on the mentioned
phenylenebistetrazoles: Only the behavior was described
of two simplest compounds of this series lacking other
substituents [10]. The published data are insufficient for
evaluating the applicability of these reactions to the
functionally-substituted phenylenediamines and
phenylenebistetrazoles. In the present study we attempted
to reveal the features of this processes depending on the
presence and the type of substituents in the initial
compounds.
Although a large amount of information exists on the
opportunities of 1,3- and 1,4-phenylenebistetrazoles
application, the development of approaches to their
synthesis is scanty.An efficient procedure for preparation
of 1-substituted tetrazoles by the heterocyclization of
appropriate amines under the treatment with sodium azide
and triethyl orthoformate in acetic acid was poorly studied
In the synthesis of phenylenebistetrazoles a series of
appropriate 1,3- and 1,4-phenylenediamines was used
containing substituents with donor and acceptor electronic
effects (CH3, OCH3, Cl, NO2) that were located
symmetrically and unsymmetrically with respect to amino
groups. With phenylene-diamines Ia, Ib, Id the
291

VOROB’EV et al.
292
heterocyclization readily proceeded resulting in the
corresponding bistetrazoles IIa, IIb, IId in high yields
(Scheme 1). 1,12 -(2-Chloro-1,4-phenylene)bis(1H-
tetrazole) (IIc) was obtained in a considerably lower yield
as was known to be characteristic of the heterocyclization
of the ortho-halosubstituted arylamines due to the steric
hindrances and the negative inductive effect of halogen
atoms reducing the basicity of the amino group [13].
Scheme 1.
R
H2N
NH2
Iа_Id
R
NaN3, HC(OEt)3
N
The heterocyclization of 2-nitro-1,4-phenylenediamine
(Ie) proceeded differently. According to the data of 1H
and 13C NMR the reaction led to the formation of a mix-
ture of a bistetrazole and a tetrazolylaniline (the product
of tetrazole formation from one of the amino groups) in
a ratio 1:9. This is indicated by the presence in the
1H NMR spectrum of the mixture obtained of three
signals with the chemical shifts characteristic of hydrogen
atoms of 1-aryl-tetrazoles (δ 9.97, 10.09, and 10.31 ppm,
intensity ratio 9:1:1) and a broad proton signal of a primary
amino group (δ 7.79 ppm). The positions, type, and
intensity of the other signals confirm the assumed
composition of the mixture.
N
N
N
AcOH
N
N
N
IIа_IId
N
Me
R
Me
(a),
=
Me (b),
Cl
OMe
(c),
(d).
The structure of the obtained tetrazolylaniline was
established with the use of a number of one-and two-
dimensional NMR procedures. The assignment of the
signals of three hydrogen atoms of the aromatic ring was
done based on the character and the parameters of their
spin-spin couplings in the 1H NMR spectrum. The signals
of three corresponding unsubstituted carbon atoms in the
13C NMR spectrum were identified using the spectrum
with the polarization transfer (DEPT), and also the
spectrum of the hetronuclear correlation [1H, 13C] HSQC.
The analysis of the correlation spectrum [1H, 13C] HMBC
made it possible to assign the signals of the other carbon
atoms of the tetrazolylaniline molecule. It is important
isolated by column chromatography failed evidently
because of its low basicity.
This uncommon behavior of 2-nitro-1,4-phenylene-
diamine under the heterocyclization conditions apparently
originates from the significant difference in the reactivity
of the groups both in the initial compound and in the
monotetrazole derivatives IIIe and IVe. The essentially
higher basicity of the amino group located in the meta-
position with respect to the nitro group of the initial
phenylenediamine resulted in higher probability of the
reaction involving this group. Presuming that the
heterocyclization of the amino groups of phenylene-
diamines proceeds successively, it is possible to conclude
that the main product of the first stage is 2-nitro-4-
tetrazolylaniline (IIIe). π-Acceptor properties of the
tetrazolyl substituent in the molecule of tetrazolylaniline
IIIe result in the additional decrease in the basicity of
the second amino group, therefore the proceeding of the
second reaction state with the formation of bistetrazole
IIe becomes impossible, and tetrazolylaniline IIIe remains
intact to the end of the process. On the contrary, the
basicity of the amino group in the minor product IVe
containing electron-acceptor substituents in the meta- and
para-positions remains sufficient for the reaction, and this
isomer totally converts into bistetrazole IIe.
1
that in the homonuclear correlation spectrum [1H, H]
COSY the signal of the tetrazole hydrogen (δ 9.97 ppm)
has two cross-peaks of similar intensity with hydrogen
atoms belonging to the arene system (δ 7.86 and 8.44
ppm). This interaction shows the contiguity of the tetrazole
substituent to the two unsubstituted positions of the aryl
fragment. It is possible to conclude from the above
analysis that the compound obtained is 2-nitro-4-(tetrazol-
1-yl)aniline (IIIe). The corresponding 3-nitroisomer IVe
was not found in the reaction products even in traces
(Scheme 2).
The reaction of phenylenediamine Ie under more
stringent conditions and also in the presence of excess
reagents did not result in larger yield of bistetrazole IIe.
The attempts on heterocyclization of tetrazolylaniline IIIe
The described reaction is the first example of
tetrazolation proceeding selectively involving only one of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

293
FEATURES OF THE SYNTHESIS OF 1,1'-PHENYLENEBIS(1H-TETRAZOLES)
Scheme 2.
NO2
N
N
NH2
N
N
NO2
NH2
NO2
III
e
NaN3, HC(OEt)3
AcOH
NaN3, HC(OEt)3
AcOH
N
N
N
N
H2N
N
N
+
N
N
NO2
Ie
IIe
N
N
H2N
N
N
IVe
Scheme 3.
N
N
R
R
H
R
R
_
N
N
B
N
N
-N
-N
VIа_VIe
N
N
_BH
N
N-
N
-N2
N
N
N
N
N
N
N
N
N
VIIIа_VIIIe
N
Vа_Ve
IIа_IIe
N
N
N
H+
H+
N
N
R
R
HN
HN
N
NH
N
N
N
N
VIIа_VIIe
IXа_IXe
the amino groups of a diamine. This result has both
a theoretical importance consisting in the outlining the
factors influencing the heterocyclization of primary
amines and in the extending the limits of the method
application, and practical prospects of the use in
multistage processes including stages of regioselective
functionalization.
followed by the elimination of a nitrogen molecule from
unstable heterocyclic carbanion V and the formation of
cyanamide anion VI or VIII. The rate of the process is
affected by the strength of the base, properties of the
solvent, and the lability of the hydrogen of the heterocycle
that is sufficient in most 1-aryltetrazoles for the ready
occurring of the reaction [13].
The obtained phenylenebistetrazoles IIa–IIe were
subjected to transformation under basic conditions yielding
cyanamides VII and IX aiming at extension of the
application field and at the study of the special features
of this reaction possessing a significant practical potential
(Scheme 3). The mechanism of the process involves the
abstraction of a hydrogen atom from the tetrazole ring
At room temperature in bistetrazoles containing
methyl (IIa, IIb) and methoxy (IId) groups the
transformation occurs with only one tetrazole ring
notwithstanding the amount of the base in the reaction
mixture. The second heterocycle reacts with a notable
rate only at the temperature exceeding 60–70°C. This
results are consistent with previously published findings
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

VOROB’EV et al.
294
The ratio of isomeric products of reaction between substituted
1,4-phenylenebistetrazoles and NaOH–DMSO
on the behavior of unsubstituted 1,3- and 1,4-phenyl-
enebistetrazoles in basic environment [10]. The observed
difference in the reactivity of two heterocycles in the
molecules of phenylenebistetrazoles evidently originate
from a strong electron-donor effect of the anion form of
the cyanamide group in the intermediate VI sharply
decreasing the mobility of the hydrogen atom in the second
tetrazole ring. The reaction of phenylenebistetrazoles IIc
and IIe results in the transformation of both heterocycles
already at room temperature as shows the lack in the IR
spectra of the reaction products of the characterictic
absorption band in the region 3120–3145 cm–1
corresponding to the stretching vibrations of C-–H bond.
This fact may be due to the partial compensation of the
donor effect of the cyanamide anion by the electron-
acceptor functional groups (Cl and NO2 respectively)
present in the molecules of these substrates The high
reactivity of dicyanamides IX led to the formation in situ
of intractable products of their hydrolysis and solvolysis
[13] impeding the separation of compounds IX in a pure
state.
The results of analyses showed that two tetrazole rings
in the initial compounds are not equivalent with respect
to the base attack. The substituent in the aryl fragment
builds up steric hindrances reducing the possibility of the
base attack on the tetrazole ring located in the ortho-
position. However this effect is not decisive due to
noncoplanar position of the tetrazole and aryl rings in the
molecules of 1-aryltetrazoles demonstrated by XRD
studies and quantum-chemical calculations [14–16].
A significant role belongs to the electronic effect of the
substituent: The effect of the electron-donor groups acts
in the same direction as their steric influence, whereas
the electron-acceptor groups increase the possibility of
the cleavage of the tetrazole ring in the ortho-position.
In the series of studied bistetrazole the ratio of isomeric
cleavage products varied from 30:70 to 95:5 (see the
table). The reason here consists also in the influence of
the electronic effect of the substituents on the mobility
of the hydrogen atoms of the tetrazole rings, first of all
the ring situated in the ortho-position to this substituent.
Our interest attracted the factors governing the
prevailing direction of attack of the basic agent in the
case of phenylenebistetrazoles with unsymmetrical
location of substituents. To this end bistetrazoles IIa, IIc–
IIe were brought into the reaction with an equimolar
amount of NaOH. The ratio of isomeric tetrazolylphenyl-
cyanamides VII and VII' was measured by the methods
of one-and two-dimensional NMR. 1H NMR spectra of
obtained isomeric mixtures contained two signals in the
region characteristic of CH protons of 1-aryltetrazoles
(δ 9.5–10.5 ppm). In the spectra [1H, 1H] NOESY these
signals have cross-peaks with the proton signals of the
aryl fragment presnt in the ortho-position with respect to
the tetrazole moiety. In the spectra of isomers VII one
cross-peak is observed with a doublet signal having a
coupling constant of 8.5 Hz. In contrast, isomers VII' in
each case gave two cross-peaks of the hydrogen atom
of the heterocycle with protons observed in the 1H NMR
spectrum as a narrow doublet (1.8 Hz) and a doublet of
doublets (8.5 and 1.8 Hz). From these data we assigned
the signals of heterocyclic protons to regioisomeric
structure VII and VII', and from the integral curve we
estimated their quantitative ratio (see the table). The
validity of signals assignment was confirmed by the
presence of cross peaks between the methyl and
heterocyclic protons in structures VIIa and VIIe, and
also the adequate correlation NMR spectra [1H, 13C]
HSQC and HMBC.
The effect of the reaction conditions and of the type
of applied base on the direction of the process and the
isomers ratio was studied by an example of 2-methyl-
1,4-phenylenebistetrazole (IIa). It was established that
the temperature maintained in the course of the reaction
between the base and the tetrazole affects the rate of
the process and the extent of the side reactions (hydrolysis
or solvolysis of cyanamides [13]), but not the ratio of the
regioisomers VIIa:VII' a.
For instance, at 0°C the reaction completion by the
data of TLC monitoring required about 20 h. The HPLC
of the products revealed the presence of isomeric
cyanamides VIIa and VII'a at the content of their
hydrolysis products less than 1%. At 20°C the reaction
completed in 1 h; therewith the extent of cyanamide
hydrolysis reached ~15%. The maintaining the reaction
mixture at 80°C for 20 min besides the completion of
ring opening led to virtually total hydrolysis of cyanamides
whose content was <3%. The ratio of isomeric
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

295
FEATURES OF THE SYNTHESIS OF 1,1'-PHENYLENEBIS(1H-TETRAZOLES)
a spectrophotometer detector Waters 996 (λ 254 nm),
a column Purospher RP-18 (250×4.6 mm), packed with
silica gel C18 with an average particle diameter 5 μm and
porosity 90 .As mobile phases acetonitrle mixtures with
water were used supplied to the column on conditions of
linear gradient.
tetrazolyl-arylcyanamides and also of their hydrolysis
products in all cases remained approximately constant.
The use for bases of sodium methylate and butyllithium
also did not affect this ratio. The reaction with sodium
methylate completed at 20°C within 1 h and afforded
a mixture of isomeric cyanamides VIIa and VII'a free
of impurities of their hydrolysis or solvolysis products.
Heterocyclization of phenylenediamines Ia–Ie.
To a dispersion of 0.01 mol of phenylenediamine Ia–Ie
and 1.43 g (0.022 mol) of sodium azide in 10 ml (0.06 mol)
of triethyl orthoformate was added dropwise at vigorous
stirring 9.2 ml (0.16 mol) of glacial acetic acid, the mixture
was stirred for 4 h at 70–80°C. On cooling to the reaction
mixture was added 200 ml of 3% HCl. The separated
precipitate was filtered off, washed with water, and dried
in a vacuum.
Thus the procedure of the synthesis of 1-substituted
tetrazoles by the heterocyclization of primary amines,
triethyl orthoformate, and sodium azide in acetic acid in
the majority of cases is suitable for preparation of
binuclear tetrazoles from the corresponding m- and p-
phenylenediamines. In the presence in the molecule of
the initial phenylenediamine of an electron-acceptor
substituent the yield of the phenylenebistetrazole
decreases and appears a possibility of the formation of
a monotetrazole product. The obtained phenylenebis-
tetrazoles in the system NaOH–DMSO undergo the
heterocycle opening forming the corresponding
cyanamides. The direction of the base attack is affected
by the position and electronic effects of the substituents
in the aryl ring of the substrate, whereas the reaction
conditions and the type of the applied base influence only
the rate of the process and also the probability and
character of the side processes to which are prone the
obtained cyanamides.
In event of the heterocyclization of 2-nitro-1,4-
phenylenediamine (Ie) the precipitate was dissolved in a
minimum volume of methanol, the solution was applied
to a column packed with silica gel L 40/100, and subjected
to chromatography, eluent ethyl acetate–methanol, 5:1.
We obtained 105 mg (8%) of bis-tetrazole IIe and 745 mg
(72%) of 2-nitro-4-(tetrazol-1-yl)aniline (IIIe).
1,12-(2-Methyl-1,4-phenylene)bis(1H-tetrazole)
(IIa). Yield 82%, mp 183–184°C (decomp.). IR spectrum,
ν, cm–1: 3113 (C–H), 1470 (C5=N4), 1389 (C5–N1), 1096,
1042, 1015, 995 (tetrazole). 1H NMR spectrum, δ, ppm:
2.28 s (3H, CH3), 7.87 d (1Harom, J 8.5 Hz), 8.03 d.d
(1Harom, J 2.2, J 8.5 Hz), 8.16 d (1Harom, J 1.8 Hz),
9.93 s (1HHt), 10.20 s (1HHt). 13C NMR spectrum, δ,
ppm: 17.4 (CH3), 119.7 (CHarom), 123.8 (CHarom), 128.1
(CHarom), 133.4 (Carom), 134.9 (Carom), 135.9 (Carom), 142.5
(CHHt), 144.7 (CHHt). Found, %: C 47.49; H 3.36;
N 49.33. C9H9N8. Calculated, %: C 47.37; H 3.53;
N 49.10.
EXPERIMENTAL
In syntheses were used reagents and solvents of no
less than ”pure” grade or additionally purified. The
solutions of sodium methylate and butyllithium were
prepared by procedures from [17]. The melting points of
compounds synthesized were measured on a device
Electrothermal IA9200 in open capillaries. IR spectra wre
recorded on an IR Fourier spectrophotometer Nicolet
Protege 460 from pellets with KBr. One-dimensional (1H
1,12-(2,4-Dimethyl-1,4-phenylene)bis(1H-
tetrazole) (IIb). Yield 60%, mp 206–207°C (decomp.).
IR spectrum, ν, cm–1: 3137 (C–H), 1478 (C5=N4), 1401
(C5–N1), 1095, 1046, 1016, 1000 (tetrazole). 1H NMR
spectrum, δ, ppm: 2.23 s (6H, CH3), 7.21 s (1Harom),
7.91 s (1Harom), 9.87 s (2HHt). 13C NMR spectrum, δ,
ppm: 17.1 (CH3), 124.0 (CHarom), 131.2 (Carom), 134.4
(CHarom), 136.1 (Carom), 144.7 (CHHt). Found, %: C 49.37;
H 4.21; N 46.14. C10H10N8. Calculated, %: C 49.58;
H 4.16; N 46.26.
1
and 13C) and two-dimensional NMR spectra ([1H, H]
COSY, [1H, 1H] NOESY, [1H, 13C] HSQC, and [1H, 13C]
HMBC) were registered on a spectrometer Bruker
Avance 500 [operating frequencies 500 (1H) and
125 MHz (13C)] using the standard programs. (CD3)2SO
was used as solvent, concentration of measured solutions
20 mg/ml. Chemical shifts are reported with respect to
the residual signals of solvent. The individuality of
compounds synthesized was proved by TLC on Merck
60 F254 plates. The quantitative estimation of the
composition of isomeric mixtures was carried out by
HPLC. The system included a Waters 600E pump,
1,12-(2-Chloro-1,4-phenylene)bis(1H-tetrazole)
(IIc). Yield 38%, mp 161–162°C (decomp.). IR spectrum,
ν, cm–1: 3145, 3124 (C–H), 1462 (C5=N4), 1396 (C5–
N1), 1092, 1057, 1011, 995 (tetrazole). 1H NMR spectrum,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

VOROB’EV et al.
296
δ, ppm: 8.13 d (1Harom, J 8.6 Hz), 8.23 d.d (1Harom, J 1.9,
J 8.6 Hz), 8.51 d (1Harom, J 1.9 Hz), 10.02 s (1HHt),
10.26 s (1HHt). 13C NMR spectrum, δ, ppm: 121.0
(CHarom), 123.0 (CHarom), 130.1 (CHarom), 130.3 (Carom),
131.7 (Carom), 136.0 (Carom), 142.8 (CHHt), 145.1 (CHHt).
Found, %: C 39.01; H 2.11; N 45.29. C8H5ClN8.
Calculated, %: C 38.65; H 2.03; N 45.07.
observed, and the reaction mixture self-heated. The
stirring was continued for 15–20 min after the visual end
of nitrogen liberation. The completion of the reaction was
monitored by TLC. The reaction mixture was 5-fold
diluted with water, filtered, and acidified with HCl to pH
3–4. The precipitate was filtered off, washed with water,
and dried in a vacuum.
1,12-(2-Methoxy-1,4-phenylene)bis(1H-
tetrazole) (IId). Yield 63%, mp 182–183°C (decomp.).
IR spectrum, ν, cm–1: 3177, 3155 (C–H), 1483 (C5=N4),
1370 (C5–N1), 1093, 1024, 1002, 989 (tetrazole).1H NMR
The cleavage of bistetrazole IIe under the above
conditions proceeded very vigorously with the formation
of a mixture of tetrazolylphenylcyanamides, phenylene-
dicyanamide, unreacted initial compound, and hydrolysis
products. The attempts to isolate the target cyanamides
from the mixture resulted in their further degradation.
Therefore the cleavage of this bistetrazole was carried
out in DMSO-d6. The composition of the product obtained
was immediately evaluated by NMR.
spectrum, δ, ppm: 4.00 s (3H, CH3), 7.75 d.d (1Harom
J 2.0, J 8.5 Hz), 7.92 d (1Harom, J 1.9 Hz), 8.00 d (1Harom
,
,
J 8.5 Hz), 9.89 s (1HHt), 10.24 s (1HHt). 13C NMR
spectrum, δ, ppm: 57.2 (CH3), 106.4 (CHarom), 113.4
(CHarom), 123.0 (Carom), 127.4 (CHarom), 135.7 (Carom),
142.6 (CHHt), 144.8 (CHHt), 152.8 (Carom). Found, %:
C 44.49; H 3.12; N 45.67. C9H8N8O. Calculated, %:
C 44.26; H 3.30; N 45.88.
[3- and 2-Methyl-4-(1H-tetrazol-1-yl)phenyl]-
cyanamides VIIa, VII'a. Yield 88%. IR spectrum, ν,
cm–1: 3137 (C–H), 2222 (C≡N). Found, %: C 53.71;
H 3.89; N 41.77. C9H8N6. Calculated, %: C 53.99; H 4.03;
N 41.98.
1,12 -(2-Nitro-1,4-phenylene)bis(1H-tetrazole)
(IIe). Yield 8%, mp 182–183°C (decomp.). IR spectrum,
ν, cm–1: 3150 (C–H), 1458 (C5=N4), 1412 (C5–N1), 1087,
[3-Methyl-4-(1H-tetrazol-1-yl)phenyl]cyanamide
1
1058, 1046, 1028, 995 (tetrazole). H NMR spectrum, δ,
1
(VIIa). H NMR spectrum, δ, ppm: 2.10 s (3H, CH3),
ppm: 8.27 d (1Harom, J 8.7 Hz), 8.57 d.d (1Harom, J 2.0,
J 8.6 Hz), 8.93 d (1Harom, J 2.2 Hz), 10.03 C (1HHt),
10.32 C (1HHt). 13C NMR spectrum, δ, ppm: 118.7
(CHarom), 126.3 (Carom), 126.7 (CHarom), 130.5 (CHarom),
135.7 (Carom), 143.0 (CHHt), 143.9 (Carom), 144.8 (CHHt).
Found, %: C 36.89; H 1.90; N 48.88. C8H5N9O2.
Calculated, %: C 37.07; H 1.94; N 48.64.
6.99 d.d (1H, CH6, J 1.8, J 8.2 Hz), 7.06 d (1H, CH2,
J 1.8 Hz), 7.50 d (1H, CH5, J 8.4 Hz), 9.77 s (1HHt).
13C NMR spectrum, δ, ppm: 17.6 (CH3), 111.7 (CN),
113.7 (C6H), 117.4 (C2H), 128.3 (C4), 128.9 (C5H), 135.8
(C1), 141.0 (C3), 145.0 (CHHt).
[2-Methyl-4-(1H-tetrazol-1-yl)phenyl]cyanamide
1
(VII'a). H NMR spectrum, δ, ppm: 2.29 s (3H, CH3),
7.26 d (1H, CH6, J 8.1 Hz), 7.74–7.77 m (2H, CH3, CH5),
9.99 s (1H, CHHt). 13C NMR spectrum, δ, ppm: 17.5
(CH3), 112.4 (CN), 116.4 (C6H), 120.6 (C5H), 124.1
(C3H), 127.0 (C2), 128.9 (C4), 138.4 (C1), 142.4 (CHHt).
2-Nitro-4-(1H-tetrazol-1-yl)aniline (IIIe). Yield
72%, mp 210–211°C (decomp.). IR spectrum, ν, cm–1:
3138 (C–H), 1462 (C5=N4), 1393 (C5–N1), 1088, 1053,
1
1008 (tetrazole). H NMR spectrum, δ, ppm: 7.19 d (1H,
CH6, J 9.1 Hz), 7.79 br.s (2H, NH2), 7.86 d.d (1H, CH5,
J 1.9, J 9.0 Hz), 8.44 d (1H, CH3, J 1.9 Hz), 9.97 s (1HHt).
13C NMR spectrum, δ, ppm: 118.5 (C3H), 120.7 (C6H),
121.7 (C4), 129.0 (C5H), 129.2 (C2), 142.2 (CHHt), 146.5
(C1). Found, %: C 40.67; H 2.77; N 40.93. C7H6N6O2.
Calculated, %: C 40.78; H 2.93; N 40.76.
[2,4-Dimethyl-5-(1H-tetrazol-1-yl)phenyl]-
cyanamide (VIIb). Yield 89%, ppm 180°C. IR spectrum,
1
ν, cm–1: 3133 (C–H), 2235 (C≡N). H NMR spectrum,
δ, ppm: 2.04 s (3H, CH3), 2.25 s (3H, CH3), 7.15 s
(1Harom), 7.34 s (1Harom), 9.83 s (1HHt). 13C NMR
spectrum, δ, ppm: 16.7 (CH3), 17.3 (CH3), 112.5 (CN),
113.2 (CHarom), 127.6 (Carom), 128.2 (Carom), 131.6 (Carom),
134.3 (CHarom), 136.1 (Carom), 144.9 (CHHt). Found, %:
C 56.07; H 4.71; N 39.23. C10H10N6. Calculated, %:
C 56.19; H 4.40; N 38.97.
Cleavage of phenylenebistetrazoles with bases.
a. With 0.01 mol of phenylenebistetrazole was mixed 10%
solution of NaOH (4.5 or 9.0 ml depending on the plan to
involve into the reaction one or both tetrazole rings). The
dispersion obtained was brought to the minimum controlled
temperature providing a sufficient reaction rate (20–60°C),
and at constant stirring was added dropwise 10–15 ml of
DMSO. Therewith a vigorous gas evolution was
[4-(1H-Tetrazol-1-yl)-3- and -2-chlorophenyl]-
cyanamides VIIc and VII'c. Yield 77%. IR spectrum,
ν, cm–1: 3134 (C–H), 2241 (C≡N). Found, %: C 43.64;
H 2.21; N 15.83. C8H5ClN6. Calculated, %: C 43.55;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

297
FEATURES OF THE SYNTHESIS OF 1,1'-PHENYLENEBIS(1H-TETRAZOLES)
liberation. To the mixture was added a 5-fold volume of
water, the organic solvents were distilled off in a vacuum
at the temperature not exceeding 40°C, the solution was
filtered and acidified with HCl to pH 3–4. The precipitate
was filtered off, washed with water, and dried in
a vacuum. The reaction product was identical to that
obtained by method a (TLC, HPLC).Yield 171 mg (86%).
H 2.28; N 16.07.
[4-(1H-Tetrazol-1-yl)-3-chlorophenyl]cyanamide
1
(VIIc). H NMR spectrum, δ, ppm: 7.17 d.d (1H, CH6,
J 1.7, J 8.7 Hz), 7.27 d (1H, CH2, J 1.6 Hz), 7.76 d (1H,
CH5, J 8.6 Hz), 9.87 c (1HHt). 13C NMR spectrum, δ,
ppm: 110.9 (CN), 114.9 (C6H), 116.3 (C2H), 125.6 (C4),
130.2 (C5H), 130.4 (C1), 142.6 (C3), 145.3 (CHHt).
[4-(1H-Tetrazol-1-yl)-2-chlorophenyl]cyanamide
REFERENCES
1
(VII'c). H NMR spectrum, δ, ppm: 7.43 d (1H, C6H,
J 8.8 Hz), 7.93 d.d (1H, C5H, J 1.4, J 8.6 Hz), 8.13 d
(1H, C3H, J 1.4 Hz), 10.05 s (1HHt). 13C NMR spectrum,
δ, ppm: 111.5 (CN), 117.8 (C6H), 120.8 (C2), 121.9 (C5H),
123.2 (C3H), 129.2 (C4), 137.0 (C1), 142.5 (CHHt).
1. Ostrovskii, V.A., Koldobskii, G.I., andTrifonov, R.E., Comp.
Heterocyclc. Chem. III, 2008, vol. 6, p. 257.
2. Koldobskii, G.I. and Ostrovskii, V.A., Usp. Khim., 1994,
vol. 63, p. 847.
3. Gaponik, P.N., Voitekhovich, S.V., and Ivashkevich, O.A.,
Usp. Khim., 2006, vol. 75, p. 569.
[3-Methoxy-4-(1H-tetrazol-1-yl)phenyl]-
cyanamide (VIId). Yield 79%. IR spectrum, ν, cm–1:
4. Yu, J.-H., Mereiter, K., Hassan, N., Feldgitscher, C., and
Linert, W., Cryst. Growth Des., 2008, vol. 8, p. 1535-.
5. Li, R.-Y., Wang, X.-Y., Liu, T., Xu, H.-B., Zhao, F.,
Wang, Z.-M., and Gao, S., Inorg. Chem., 2008, vol. 47,
p. 8134.
6. Zubarev, V.Yu., Filichev, V.V., Trifonov, R.E., and Ostrov-
skii, V.A., Mendeleev Commun., 1999, 9, p. 116.
7. Sauer, J., Pabst, G.R., Holland, U., Kim, H.-S., and
Loebbecke, S., Eur. J. Org. Chem., 2001, p. 697.
8. Gupta,A.K., Rim, C.Y., and Oh, C.H. Synlett., 2004, p. 2227.
9. Schweifer, J., Weinberger, P., Mereiter, K., Boca, M.,
Reichl, C., Wiesinger, G., Hilscher, G., van, Koningsbrug-
gen, P.J., Grunert, M., Linert, W. Inorg. Chim. Acta., 2002,
vol. 339, p. 297.
1
3141 (C–H), 2246 (C≡N). H NMR spectrum, δ, ppm:
3.85 s (3H, CH3), 6.74 d.d (1H, C6H, J 2.1, J 8.5 Hz),
6.79 d (1H, C2H, J 2.0 Hz), 7.64 d (1H, C5H, J 8.5 Hz),
9.72 s (1HHt), 10.77 br.s (1H, NH). 13C NMR spectrum,
δ, ppm: 56.3 (CH3), 99.4 (C2H), 107.0 (C6H), 111.3 (CN),
117.0 (C4), 127.5 (C5H), 141.9 (C1), 144.7 (CHHt), 153.1
(C3). Found, %: C 49.09; H 3.57; N 39.20. C9H8N6O.
Calculated, %: C 50.00; H 3.73; N 38.87.
[3-Nitro-4-(1H-tetrazol-1-yl)phenyl]cyanamide
1
(VIIe). H NMR spectrum, δ, ppm: 7.64 d (1Harom
,
J 9.0 Hz), 8.33 d.d (1HapOm, J 2.4, J 9.0 Hz), 8.71 d
(1Harom, J 2.4 Hz), 10.14 s (1HHt).
10. Gaponik, P.N., Karavai, V.P., Davshko, I.E., Degtya-
rik, M.M., and Bogatikov,A.N., Khim. Geterotsikl. Soedin.,
1985, p. 1528.
11. Karavai, V.P. and Gaponik, P.N., Inventor’s Certificate
1294804, 1987; SSSR Byull. Izobr., 1987, no. 9.
12. Vorobiov, A.N., Gaponik, P.N., Petrov, P.T., and Ivashke-
vich, O.A., Synthesis., 2006, 1307.
13. Vorob’ev, A.N., Gaponik, P.N., Matulis, V.E., and
Ivashkevich, O.A., Vestn. BGU, Ser. 2, 2006, no. 2, p. 13.
14. Matsunaga, T., Ohno, Y.,Akutsu, Y.,Arai, M., Tamura, M.,
and Iida, M., Acta Cryst., 1999, vol. C55, p. 129.
15. Lyakhov,A.S., Ivashkevich, D.O., Gaponik, P.N., Grigori-
ev, Yu.V., and Ivashkevich, L.S., Acta Cryst., 2000, vol. C56,
p. 256.
16. Lyakhov, A.S., Gaponik, P.N., Voitekhovich, S.V.,
Ivashkevich, L.S., and Kulak, A.A., Acta Cryst., 2001,
vol. C57, p. 1204.
[2-Nitro-4-(1H-tetrazol-1-yl)phenyl]cyanamide
1
(VII'e). H NMR spectrum, δ, ppm: 7.86 d (1Harom
,
J 2.6 Hz), 8.16 d.d (1Harom, J 2.5, J 9.2 Hz), 8.39 d
(1Harom, J 9.3 Hz), 10.20 s (1HHt).
b. To a dispersion of 228 mg (1 mmol) of phenylene-
bistetrazole IIa in 2 ml of 0.5 M solution of sodium
methylate in methanol was added dropwise at 20°C under
constant stirring 2 ml of DMSO. The mixture was stirred
for 15–20 min after the visual end of nitrogen liberation.
The completion of the reaction was monitored by TLC.
The reaction mixture was worked up as described in
procedure a. The reaction product was identical to that
obtained by method a (TLC, HPLC).Yield 154 mg (77%).
c. To a solution of 228 mg (1 mmol) of
phenylenebistetrazole IIa in tetrahydrofuran at 0°C while
constant stirring was added dropwise an equimolar
amount of butyllithium in ether solution. The stirring was
continued for 15–20 min after the visual end of nitrogen
17. Weygand-Hilgetag Organisch-chemische Experi-
mentierkunst, Hilgetag, G. and Martini, A., Eds., Leipzig:
JohannAmbrosius Barth, 1964.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010