Catalytic Synthesis of 5-Substituted Tetrazoles: Unexpected Reactions and Products

Article abstract of DOI:10.1002/jhet.3542

Tetrazoles are incredibly useful organic molecules with a wide range of applications from medicinal chemistry as carboxylic acid isosteres to high energy density materials in space research. In an effort to develop an easy protocol for the synthesis of te

Full text of DOI:10.1002/jhet.3542

Month 2019
Catalytic Synthesis of 5-Substituted Tetrazoles: Unexpected Reactions
and Products
a
Mohmmad Y. Wani,
Manuela R. Silva,b Balu Krishnakumar,c Santosh Kumar,c Abdullah S. Al-Bogami,a
*
a
c
*
Faisal M. Aqlan, and Abilio J. F. N. Sobral
aChemistry Department, Faculty of Science, University of Jeddah, P.O. Box 80327, Jeddah 21589,
Kingdom of Saudi Arabia
bCFisUC, Department of Physics, University of Coimbra, Coimbra P-3004-516, Portugal
cDepartamento de Quίmica, Universidade de Coimbra, Rua Larga, Coimbra 3004-535, Portugal
*E-mail: mwani@uj.edu.sa; asobral@ci.uc.pt
Received September 4, 2018
DOI 10.1002/jhet.3542
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
Tetrazoles are incredibly useful organic molecules with a wide range of applications from medicinal
chemistry as carboxylic acid isosteres to high energy density materials in space research. In an effort to de-
velop an easy protocol for the synthesis of tetrazoles from nitriles, we used nano-Ag-TiO2 as an efficient het-
erogeneous catalyst for the reaction of various nitriles and sodium azide to afford 5-substituted tetrazoles in
excellent yields. By this method, a wide variety of aryl nitriles underwent [3 + 2] cycloaddition to afford
tetrazoles in excellent yields. Further reaction of tetrazoles with ethylchloroacetate resulted in the formation
of expected products, except for a bis-tetrazole, which underwent ring opening and subsequent reaction to
afford an unusual product. The bis-tetrazole also formed an unusual polymeric sodium complex in aq. NaOH
solution. X-ray crystallography revealed a distorted octahedral geometry for the complex, which forms a
three-dimensional network of chains interlinked by bis-tetrazole moieties through a network of H-bonds.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
demand for improved and less tedious protocol which
allows an effective transformation in the presence of a
wide range of functional groups [2,6–12]. In recent years,
there has been increasing emphasis on the use and design
of environment friendly solid catalysts to reduce the
amount of toxic waste. Heterogeneous catalysis is widely
used in industrial applications because of the facile
separation, which often results in lower operating costs.
On the other hand, homogeneous catalysis has limited
industrial applications due to the difficult and costly
catalyst separation and recovery [13]. Different
heterogenous catalytic systems have been employed for
the synthesis of tetrazoles [2,14]. Most of these methods
suffer from disadvantages such as the fact they require a
large excess of sodium azide, higher temperatures, and
longer reaction times. Nano-TiO2 and nano-Ag have been
used as catalysts separately [15,16], but with longer
reaction times and tedious separation process. Sulfated
titania has also been reported to be an efficient catalyst
[14], but the more acidic nature of this catalyst hampers
its use. Compared to Ag, nano Ag-TiO2 is cost efficient
and easily separable, and we used this catalyst for the
synthesis of tetrazoles.
Tetrazole, a five-membered nitrogen heterocycle, scarce
in nature has been of much scientific attention, owing to
its rich and diverse chemical properties [1,2]. Most of the
applications of this class of compounds are related to the
acid–base properties of the tetrazole ring. In fact,
the tetrazole acid fragment, –CN4H, has similar acidity to
the carboxylic acid group, –CO2H, and is almost isosteric
with it [1]. Due to the high enthalpy of formation,
tetrazole decomposition results in the liberation of two
nitrogen molecules and a significant amount of energy.
Therefore, several tetrazole derivatives have been
explored as explosives, propellant components for
missiles and as gas generators for airbags in the
automobile industry [3,4]. The four nitrogen atoms
connected in succession may be involved in protolytic
processes, and many physical, chemical, physicochemical,
and biological properties of tetrazoles are closely related
to their ability to behave as acids and bases [1,2,5].
Different synthetic methods and diverse studies are
dedicated to tetrazoles, and a number of synthetic
methods are already available, but there still exists a
© 2019 Wiley Periodicals, Inc.

M. Y. Wani, M. R. Silva, B. Krishnakumar, S. Kumar, A. S. Al-Bogami,
F. M. Aqlan, and A. J. F. N. Sobral
Vol 000
Moreover, derivatization of tetrazoles is being pursued
to prepare diverse functionalized compounds for use in
chemical industry. Alkylation is reported to be a simple
and important route to prepare diverse tetrazole
derivatives, and alkylation with alkyl halides, dialkyl
sulphates, diazomethane, o-chloro carbonyl compounds,
methyl chloromethyl ether, α-methylstyrene, etc. has been
reported [17–20]. Normally, all these reactions have
resulted in the synthesis of desired products. Our study
for the first time reports the ring opening of 5-(4-2H-
tetrazole-5-yl)-phenyl-1H-tetrazole on reaction with
ethylchloroacetate. The ring opening and subsequent
reaction with ethylchloroacetate resulted in the synthesis
of an unexpected acetohydrazide product. The ring
opening property of bis-tetrazole obtained in this study
could be explored as a new synthetic route, or this
compound can be used as a new starting scaffold for the
preparation of diverse range of organic compounds. We
also report a serendipitous synthesis of a rare polymeric
bis-tetrazole-sodium complex obtained from the same bis-
tetrazole.
Results revealed that the nature of solvents plays an
important role.
Reactions in polar protic solvents such as methanol
and ethanol (Table 2; entries 1 and 2) result in only
20% and 10% product formation while acetonitrile
(Table 2; entry 3) gives 30% product. Other solvents such
as tetrahydrofuran, chloroform, and 1,4-dioxane (Table 2;
entries 4–6) also gave unsatisfactory results with no
product formation after 24 h. Water was also not a
suitable solvent for this reaction (Table 2; entry 7).
Dimethylformamide (DMF) was found to be
comparatively the best solvent for this reaction (Table 2;
entry 8). Moderate to good yield is obtained on increasing
the quantity of sodium azide from 1 to 1.5 equivalents.
The optimum amount of Ag-TiO2 was found to be 20 mg
(Table 1) in the presence of nitrile (1 mmol) and sodium
azide (1.5 mmol) in DMF (1 mL).
We next examined different benzonitriles possessing a
wide range of functional groups to understand the
scope and generality of the Ag-TiO2 catalyzed reaction
(Table 3). The nature of the substituent on the
benzonitrile did not affect the reaction time. Due to the
insignificant effect of the substituents on the reaction, the
effect of electron withdrawing and releasing groups is not
clear. Interestingly, 1,4-dicyanobenzene afforded a double
addition product (Table 3; entry 10), contrary to the
reported mono addition product in literature [14]. The
double addition product offers a bis-tetrazole, in which
two tetrazole rings are separated by a phenyl ring.
RESULTS AND DISCUSSION
First, we optimized the amount of nano Ag-TiO2
catalyst required in the reaction between benzonitrile and
sodium azide (Table 1; Scheme 1). The reaction
conditions were standardized, and effects of solvents,
temperature, and catalyst loading were investigated.
Demko and Sharpless reported that coordination of
nitrile to the Lewis acidic Zn2+ is the source of the
catalytic effect in the formation of 1H-tetrazoles [12].
Subsequently, nucleophilic attack by azide followed by
hydrolysis affords tetrazole. A plausible mechanism for
Ag-TiO2 catalyzed synthesis of tetrazoles could be
thought to be driven by the coordination of the nitrile
with the Lewis acid sites of Ag-TiO2, which undergoes
[3 + 2] cycloaddition with the readily available azide. A
Table 1
Preparation of 5-phenyltetrazole using varying amounts of nano-Ag-TiO2
at 120°C in DMF.
Entry
Ag-TiO2 (g)
Time (h)
Yield (%)a
1
2
3
4
0.01
0.02
0.025
1
1
1
1
1
1
1.5
8
60
98
98
98
20
50
93
94
82
0.05
5
No catalyst
Bare TiO2
Nano TiO2/SO24ꢀ
30 mol% Ag
Nano TiO2
6
Table 2
7b
8b
9b
Effect of different solvents on the reaction.
Entrya
Solvent
Time (h)
Yield (%)b
14
aIsolated yield.
1
2
3
4
5
6
7
8
Methanol
Ethanol
Acetonitrile
THF
Chloroform
1,4-dioxane
H2O
24
24
24
24
24
24
24
1
20
10
30
bResults taken for comparison from the previous studies [14–16],
respectively.
No reaction
No reaction
No reaction
No reaction
98
Scheme 1. General synthesis of 5-substituted tetrazoles using AgTiO2 as
catalyst.
DMF
aReaction conditions: nitrile (1 mmol), sodium azide (1.5 mmol), catalyst
(20 mg), and reflux.
bIsolated yield.
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Synthesis and Unusual Reactions of 5-Substituted Tetrazoles
Table 3
Synthesis of different tetrazoles using Ag-TiO2 as catalyst.
Entry
1
Nitrile
Tetrazole
Yield (%)b
98
Ref.
Myznikov et al. [5]
2
3
98
98
Herr [1]
Najmeh et al. [7]
4
5
93
93
Najmeh et al. [7]
Myznikov et al. [5]
6
96
Myznikov et al. [5]
7
8
9
98
95
95
Myznikov et al. [5]
Herr [1]
Myznikov et al. [5]
10
11
98
96
Present study
Mona and Sepideh [14]
(Continues)
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M. Y. Wani, M. R. Silva, B. Krishnakumar, S. Kumar, A. S. Al-Bogami,
F. M. Aqlan, and A. J. F. N. Sobral
Vol 000
Table 3
(Continued)
Entry
12
Nitrile
Tetrazole
Yield (%)b
92
Ref.
Mona and Sepideh [14]
aReaction conditions: nitrile (1 mmol), sodium azide (1.5 mmol), and catalyst (20 mg), at 120°C in DMF;
bIsolated yield.
final acidification results in the precipitation of the product.
The Ag-TiO2 catalyst was recovered from the reaction
mixture by simple filtration and washing with water and
ethylacetate followed by drying in an oven at 100°C
for 1 h. From each experiment, more than 95% of the
Ag-TiO2 catalyst was recovered. The recovered catalyst
was reused three times without any loss of activity. The
columns with close proximity between neighboring
aromatic rings, thus suggesting the existence of π…π
interactions.
Alkylation of tetrazoles usually yields a mixture of N1
and N2 isomers, but the presence of substituents has a
marked effect on deciding the ratio of the N1 and N2
isomer. “Electronic effects are dominant, with electron-
donating substituents at C5 favouring alkylation at N1
while electron-withdrawing substituents favour N2.”
Besides, temperature and solvent can also lead to changes
in the N1:N2 alkylation ratios. However, we exclusively
got the N2 alkylated products for all mono-tetrazole
derivatives. But the reaction of bis-tetrazole did not give
the expected product, which underwent ring opening and
subsequent reaction with ethylchloroacetate to afford an
unusual bis-acetohydrazide product S2.6 (Scheme 3). The
same product was obtained regardless of the replacement
of acetone as solvent with DMF or decreasing the
1
products were characterized by IR, H-NMR, 13C-NMR,
ESI MS, and from melting points. The disappearance of
one strong and sharp absorption band (CN stretching
band), and the appearance of an NH stretching band
in the IR spectra, was evident for the formation of
1
5-substituted 1H-tetrazoles. H-NMR, 13C-NMR, and ESI
MS spectra also supported the formation of tetrazoles
from nitriles as evidenced from the reported
data [8,11,12,14]. The spectroscopic data of the bis-
tetrazole S1.1 (Table 3; entry 10) is given in Supporting
Information.
We further set out to synthesize some tetrazole
derivatives by alkylation reaction using ethylchloroacetate.
This route offers many structurally diverse polyfunctional
tetrazole derivatives. Normally, the alkylation reaction
is straight forward and results in the formation of desired
products. Reaction of tetrazoles with ethylchloroacetate
under standard conditions gave expected products
(Scheme 2), which were confirmed by different
spectroscopic techniques and X-ray crystallography as
shown in Figure 1. The X-ray crystallography analysis
shows that S2.3 and S2.5 crystallize in the common
monoclinic space group P21/c with one molecule per
asymmetric unit. In both structures, the molecules pack in
temperature to 0°C. S2.6 as shown in Figure 2
crystallizes in the triclinic P-1 space group, with half of a
molecule in the asymmetric unit cell. The center of
inversion lies in the center of the molecule. The central
atoms are located in a common plane with the substituted
carboxylic group lying almost perpendicular to the central
plane. The short bond distance N1-C4 [1.262 Å] accounts
for a double bond.
Due to the high enthalpy of formation, tetrazole
decomposition results in the liberation of two nitrogen
molecules and a significant amount of energy. As a
general rule, the tetrazole ring can undergo cleavage in
three different ways: (a) through the (N-1) (N-2) and
(N-3) (N-4) bonds, releasing molecular nitrogen and
forming a diazirine derivative; (b) through the (N-1)
(C-5) and (N-3) (N-4) bonds; and (c) through (N-1) (N-2)
and (N-4) (C-5) bonds. In the two latter cases, the precise
nature of the products varies depending on the
substituents present in the tetrazole ring, but one of the
products is always an azide, which then can undergo
subsequent reactions, most of times eliminating N2 to
form the nitrene that then can further react to form the
final product. Literature data suggest that 2-substituted
Scheme 2. Alkylation of tetrazoles and formation of expected products
S2.1–S2.5.
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Synthesis and Unusual Reactions of 5-Substituted Tetrazoles
Figure 1. Oak Ridge thermal ellipsoid plot diagram of alkylated tetrazoles S2.3 and S2.5 drawn at the 50% probability level. [Color figure can be viewed
at wileyonlinelibrary.com]
Scheme 3. Unexpected reaction of bis-tetrazole.
tetrazoles feature facile elimination of N2 under a variety of
experimental conditions to yield highly reactive nitrilimine
intermediates (Scheme 4). These species undergo 1,3-
dipolar cycloaddition reaction with dipolarophiles to yield
diverse heterocyclic scaffolds [21,22].
The ring opening of tetrazoles has also been found to be
substituent dependent where electron-deficient substituents
at position 2 accelerate the rates and electron-donating
moieties slow down the ring opening [26,27]. The
presence of these groups at position 5 shows a reciprocal
effect. But the overall effect of a substituent at position 2
on the rate of formation of nitrilimines is more profound
than that of a group at position 5 of the tetrazoles ring
[23,24].
The coordination compounds of alkali metals on the
other hand are rare owing to their large size and small
Journal of Heterocyclic Chemistry
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M. Y. Wani, M. R. Silva, B. Krishnakumar, S. Kumar, A. S. Al-Bogami,
F. M. Aqlan, and A. J. F. N. Sobral
Vol 000
Figure 2. X-ray crystallographic structure of acetohydrazide product obtained after ring opening of bis-tetrazole S2.6. [Color figure can be viewed at
wileyonlinelibrary.com]
Scheme 4. Ring opening of tetrazoles.
Figure 3. Oak Ridge thermal ellipsoid plot diagram of S2.7 drawn at the 50% probability level. [Color figure can be viewed at wileyonlinelibrary.com]
Figure 4. Packing diagram of S2.7 showing the chain formation. [Color figure can be viewed at wileyonlinelibrary.com]
charge. Complexation of sodium and its higher congeners
is an uncommon phenomenon, although not completely
absent and in some crystalline solids, the coordination
number ranges from 4 to 12 [25]. We obtained a bis-
tetrazole (Table 3; entry 10) from the above synthetic
procedure, which was found to be insoluble in common
organic solvents except dimethyl sulfoxide (DMSO).
However, the compound was found to be soluble in aq.
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Synthesis and Unusual Reactions of 5-Substituted Tetrazoles
NaOH, and in keeping the solution for a few days, we
obtained single crystals, which were resolved by X-ray
single crystal structural analyses. Bis-tetrazole sodium
complex (S2.7) crystallizes as an octohydrate in the
triclinic space group P-1 with two sodium ions, two
5,50-(1,4-phenylene)ditetrazolate ions, and eight water
molecules in the asymmetric unit cell. The sodium ions
have similar surroundings (Fig. 3). They all have a
distorted octahedral coordination geometry defined by
five oxygen atoms and one nitrogen atom from the
organic moiety. The water molecules bridge the alkaline
ions in ladder chains that run along the [011] direction.
The bis-tetrazolate ions link the chains together, and the
crystal cohesion is reinforced through a three-dimensional
network of H-bonds (Fig. 4) (also see Tables S2 and S3).
Further studies are in progress at present.
NMR spectrometer using DMSO-d6/CDCl3 as solvent
with tetramethylsilane as internal standard. Splitting
patterns are designated as follows: s, singlet; d, doublet;
dd, doublet of doublets; t, triplet; and m, multiplet. The
ESI MS of all the compounds were recorded on a Bruker
amazon SL (ion trap instrument).
Synthesis of catalyst. Bare TiO2 and Ag-TiO2 catalysts
(1 wt % of Ag-TiO2) were prepared by reported procedures
(also see Fig. S3) [26,27].
General procedure for the synthesis of 5-substituted (1H,
2H)-tetrazoles.
In a round-bottom flask, benzonitrile
(1 mmol), sodium azide (1.5 mmol), and nano Ag-TiO2
(20 mg) were charged. Then, the reaction mixture was
stirred in distilled DMF (1 mL) at 120°C. The progress of
the reaction was monitored by thin-layer chromatography
(9:1 n-hexane: ethyl acetate). After completion of the
reaction, the catalyst was separated by centrifugation and
washed with doubly distilled water and acetone, and the
solid was treated with 3N HCl (20 mL) under vigorous
stirring. The aqueous solution finally obtained was
extracted twice with ethyl acetate. The combined organic
phase was washed with water and concentrated to
precipitate the crude crystalline solid. All products were
characterized by 1H-NMR, 13C-NMR, FTIR, and mass
spectra, and the data for the known compounds were
found to be identical with the literature [8,11,12,14]. Data
for the newly synthesized tetrazoles are given in
CONCLUSIONS
In conclusion, we have developed an efficient method
for the synthesis of 5-substituted (1H, 2H-tetrazoles) by
treatment of nitriles with sodium azide in the presence of
nano Ag-TiO2 as catalyst. The significant advantages
of this methodology are high yields, elimination of
dangerous and harmful hydrazoic acid, a simple work-up
procedure, and easy preparation and handling of the
catalyst. The catalyst can be recovered by filtration and
reused. Alkylation resulted in the ring opening
Supporting Information.
5-[4-(2H-Tetrazol-5-yl)phenyl]-1H-tetrazole (S1.1). White
1
and subsequent reaction of
a
bis-tetrazole with
solid; mp >250°C; H-NMR (DMSO-d6) δ (ppm):: 8.04–
8.24 (4H, m), 2.55 (1H, NH, br s), 13C-NMR (DMSO-d6)
δ (ppm): 162.5 (C=N), 136.6, 130.1; FTIR (ATR) νmax
(cmꢀ1): 3361 (N-H br stretch), 3000–2700 (C-H, Ar),
1587 (C=N), 1506 (C=C, Ar); ESI MS: m/z: 238.18
[M + Na+]+; 215.10 [M + H]+ (Table 3; entry 11).
ethylchloroacetate to afford an acetohydrazide product,
which crystallizes in the triclinic P-1 space group, with
half of a molecule in the asymmetric unit cell as revealed
by X-ray crystallography. This ring opening was not
observed in mono-tetrazole derivatives. Importantly, a
rare and new stable bis-tetrazole sodium complex was
Synthesis of substituted tetrazolyl-acetate derivatives.
Tetrazole (5-phenyl-2H-tetrazole) 1 mmol in dry acetone
and K2CO3 (1.5 mmol) was added ethylchloroacetate
(1 mmol) and refluxed for 12–24 h. In case of bis-
tetrazole, 2 mmol of ethylchloroacetate was used. The
reaction mixture was filtered hot, and the solvent was
distilled off from the filtrate. The crude ester thus
obtained was purified by recrystallization from ethanol.
isolated for the first time, which forms
dimensional network of chains interlinked by bis-
tetrazole moieties through network of H-bonds;
a three
a
properties desirable for high-energy density materials.
EXPERIMENTAL
Ethyl 2-(5-phenyl-2H-tetrazol-2-yl)acetate (S2.1).
Yield
62.5%; mp 145–147°C; IR νmax (cmꢀ1): 3020 (C–H, Ar),
1722 (C=O), 1635 (C=N), 1584 (C=C, Ar); 1H-NMR
(DMSO) δ (ppm): 7.98–7.45 (5H, m), 4.82 (2H, CH2, s),
4.11 (2H, CH2, m); 1.38 (3H, CH3, t); 13C-NMR
(DMSO) δ (ppm): 165.0 (C=O) 160.5 (C=N), 137.7,
129.0, 126.8, 124.0, 64.5, 48.2, 16.2; ESI-MS m/z:
[M + H] + 267.06.
General considerations. All chemicals were purchased
from Aldrich (Germany) and used as supplied unless other-
wise indicated. Melting points (m.p.) were performed
using a Mel-temp instrument, and the results are uncor-
rected. Reactions were monitored using thin-layer chroma-
tography using commercially available precoated plates
(Merck Kieselgel 60 F254 silica). Visualization was
achieved with UV light at 254 nm or I2 vapor staining.
Ethyl
2-(5-(4-chlorophenyl)-2H-tetrazol-2-yl)acetate
(S2.2). Yield 62.5%; mp 128–130°C; IR νmax (cmꢀ1):
3028 (C–H, Ar), 1722 (C=O), 1635 (C=N), 1584
Measurements.
1H and 13C-NMR spectra were
recorded at room temperature on a Bruker AVANCE 500
Journal of Heterocyclic Chemistry
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M. Y. Wani, M. R. Silva, B. Krishnakumar, S. Kumar, A. S. Al-Bogami,
F. M. Aqlan, and A. J. F. N. Sobral
Vol 000
(C=C, Ar), 758 (C–Cl); 1H-NMR (DMSO) δ (ppm):
7.98–7.45 (4H, m), 4.82 (2H, CH2, s), 4.11 (2H,
CH2, m); 1.38 (3H, CH3, t); 13C-NMR (DMSO) δ
(ppm): 162.2 (C=O) 154.5 (C=N), 137.7, 126.0, 124.8,
122.0, 118.2, 64.5, 48.2, 16.2; ESI-MS m/z:
[M + H] + 233.05.
Centre (CCDC). Any request to the CCDC for this
material should quote the full literature citation and the
reference numbers CCDC 1568228 (S2.3); 1568229
(S2.5); CCDC 1568226 (S2.6), and CCDC 1416396
(S2.7). Crystallographic details can be found in
Tables S1, S2, S3, and S4.
Ethyl
2-(5-(4-bromophenyl)-2H-tetrazol-2-yl)acetate
(S2.3). Yield 62.5%; mp 130–132°C; IR νmax (cmꢀ1):
3028 (C–H, Ar), 1722 (C=O), 1635 (C=N), 1584
(C=C, Ar), 758 (C–Br); 1H-NMR (DMSO) δ (ppm):
7.98–7.45 (4H, m), 4.82 (2H, CH2, s), 4.11 (2H,
CH2, m); 1.38 (3H, CH3, t); 13C-NMR (DMSO) δ
(ppm): 162.2 (C=O) 154.5 (C=N), 137.7, 126.0, 124.8,
122.0, 118.2, 64.5, 48.2, 16.2; ESI-MS m/z:
Acknowledgments. This work was supported by Fundação para
a Ciência e a Tecnologia (FCT) for M. Y. Wani (SFRH/BPD/
86581/2012), B. Krishnakumar, and S. Kumar (SFRH/BPD/
86507/2012). We also thank Centro de Química de Coimbra
(CQC), FCTUC, for their support. CQC is funded through
Project Pest – PEst-OE/QUI/UI0313/2014.
[M + H] + 212.01.
Ethyl 2-(5-(p-tolyl)-2H-tetrazol-2-yl)acetate (S2.4). Yield
62.5%; mp 145–147°C; IR νmax (cmꢀ1): 3028 (C–H, Ar),
1722 (C=O), 1635 (C=N), 1584 (C=C, Ar), 758 (C–C);
1H-NMR (DMSO) δ (ppm): 7.98–7.45 (4H, m), 4.82
(2H, CH2, s), 4.11 (2H, CH2, m); 1.38 (3H, CH3, t); 13C-
NMR (DMSO) δ (ppm): 165.0 (C=O) 158.5 (C=N),
133.1, 129.8, 125.0, 64.5, 55.2, 24.6, 14.5; ESI-MS m/z:
[M + H] + 247.14.
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Ethyl
2-(5-(4-methoxyphenyl)-2H-tetrazol-2-yl)acetate
(S2.5). Yield 62.5%; mp 132–134°C; IR νmax (cmꢀ1):
3028 (C–H, Ar), 1722 (C=O), 1635 (C=N), 1584 (C=C,
1
Ar); H-NMR (DMSO) δ (ppm): 7.98–7.45 (4H, m), 4.82
(2H, CH2, s), 4.11 (2H, CH2, m); 1.38 (3H, CH3, t);
13C-NMR (DMSO) δ (ppm): 166.0 (C=O) 162.5 (C=N),
159.1 (C-O), 137.7, 124.8, 122.0, 64.5, 55.0, 50.2, 14.5;
ESI-MS m/z: [M + H] + 263.10.
Diethyl-1,4-phenylenebis (methanylylidene)-bis(hydrazine-
2,1-diylidene)-diacetate (S2.6).
Yield 62.5%; mp 158–
160°C; IR νmax (cmꢀ1): 3028 (C–H, Ar), 1722 (C=O),
1635 (C=N), 1584 (C=C, Ar); 1H-NMR (DMSO) δ
(ppm): 8.45 (s, 1H, CH), 8.38 (s, 1H, CH), 8.25 (s, 2H,
CH) 8.00 (s, 4H, Ar), 4.82 (2H, CH2, s), 4.11 (2H, CH2,
m); 1.38 (3H, CH3, t); 13C-NMR (DMSO) δ (ppm):
165.0 (C=O) 154.5, 149.5 (C=N), 138.7, 129.8, 62.5,
13.2; ESI-MS m/z: [M + H] + 331.15.
X-ray crystallography. For the determination of the
crystal structure by X-ray diffraction, a crystal of the
aforementioned compounds were glued separately to a
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glass fiber and mounted on
a Bruker APEX II
diffractometer. Diffraction data were collected at room
temperature 293(2) K using graphite monochromated
MoKα (λ = 0.71073 Å). Absorption corrections were
made using SADABS [28]. The structures were solved
by direct methods using SHELXS-9725 and refined
anisotropically (non-H atoms) by full-matrix least
squares on F2 using the SHELXL-97 program [29].
PLATON [30] was used to analyze the structures and
for figure plotting. Atomic coordinates, thermal
parameters, and bond lengths and angles have been
deposited at the Cambridge Crystallographic Data
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Synthesis and Unusual Reactions of 5-Substituted Tetrazoles
[28] Sheldrick, G. M. SADABS; University of Göttingen:
Göttingen, Germany, 1996.
SUPPORTING INFORMATION
[29] Sheldrick, G. M. Acta Crystallogr Sect A: Foundations
Crystallogr 2007, 64, 112.
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
[30] Spek, A. L. J Appl Cryst 2003, 36, 7.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet