An efficient and economical synthesis of 5-substituted 1 H -tetrazoles via Pb(II) salt catalyzed [3+2] cycloaddition of nitriles and sodium azide

Article abstract of DOI:10.1016/j.crci.2015.11.016

A simple, mild and efficient method is developed for the synthesis of 5-substituted 1H-tetrazoles. Out of three used Pb(II) catalysts, lead chloride (PbCl₂) has been found to be an efficient catalyst for [3+2] cycloaddition of NaN₃ with aromatic and aliphatic nitriles to afford 5-substituted 1H-tetrazoles. The catalyst is reusable up to four cycles with consistent activity. The cost effectiveness and easy availability of the catalyst, simple methodology, excellent yield and easy work-up are the additional advantages.

Full text of DOI:10.1016/j.crci.2015.11.016

C. R. Chimie xxx (2016) 1e8
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Full paper/Memoire
An efficient and economical synthesis of 5-substituted
1H-tetrazoles via Pb(II) salt catalyzed [3þ2] cycloaddition
of nitriles and sodium azide
Rama Kant, Vishal Singh, Alka Agarwal*
Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, UP, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple, mild and efficient method is developed for the synthesis of 5-substituted 1H-
tetrazoles. Out of three used Pb(II) catalysts, lead chloride (PbCl2) has been found to be an
efficient catalyst for [3þ2] cycloaddition of NaN3 with aromatic and aliphatic nitriles to
afford 5-substituted 1H-tetrazoles. The catalyst is reusable up to four cycles with consis-
tent activity. The cost effectiveness and easy availability of the catalyst, simple method-
ology, excellent yield and easy work-up are the additional advantages.
Received 12 September 2015
Accepted 24 November 2015
Available online xxxx
Keywords:
5-Substituted 1H-tetrazoles
[3þ2] cycloaddition
Lead chloride
ꢀ
© 2015 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Recyclability
X-ray analysis
1. Introduction
Such diversified applications of tetrazoles have promp-
ted us to make a significant effort towards their synthesis.
Tetrazoles are an important class of nitrogen containing
heterocycles with a wide range of medicinal and com-
mercial applications [1,2]. The moiety has given a platform
for the synthesis of many drugs such as sartan family drugs
(Candesartan and Losartan) and antihistaminic drugs
(Pemiroplast and Pranlukast) (Fig. 1) [3,4]. Tetrazoles are
widely used in information recording systems [5], high-
density energy materials [6], antifoggants in photography
[7], propellants and explosives [8]. These are also studied as
catalysts in asymmetric synthesis [9], ligands in coordina-
tion chemistry [10], cis-peptide bond mimics [11], lipo-
philic spacers [12], and ion and peptide chelating agents
[13]. In addition, they have been used as resistants to
metabolic degradation as well as chemical oxidants [14].
The synthesis of 5-substituted 1H-tetrazoles was first re-
ported by Hantzsch and Vagt in 1901, which is based on
[3þ2] cycloaddition of azide with organic nitriles [15]. Since
then, many reports have appeared in the literature for the
synthesis of 5-substituted 1H-tetrazoles under the influ-
ence of several catalysts and different solvent conditions.
The numerous catalysts and their methodology have also
been reported till date such as copper triflates [16a],
Fe(OAc)2 [16b], CdCl2 [16c], ZnBr2 [16d], triethyl amine hy-
drochloride [16e], (CH3)2SnO [16f], COY zeolites [17a],
mesoporous ZnS nanospheres [17b], Zn hydroxyapatite
[17c], Zn/Al hydrotalcite [17d], Cu2O [17e], Pd(PPh3)4 [17f],
and nanocrystalline ZnO [17g] and CuFe2O4 nanoparticles
[17h]. More recently, some newer catalysts such as
Yb(OTf)3$ꢀH2O [18a], B(C6F5)3 [18b], gold nanoparticles and
auric chloride [18c] have also been reported for tetrazole
synthesis. Although sodium azide has been used as the azide
source in most of the above mentioned protocols, silicon [6],
* Corresponding author. Tel.: þ91 5426702173.
E-mail address: agarwal.dralka@gmail.com (A. Agarwal).
http://dx.doi.org/10.1016/j.crci.2015.11.016
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1631-0748/© 2015 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: R. Kant, et al., An efficient and economical synthesis of 5-substituted 1H-tetrazoles via Pb(II)
salt catalyzed [3þ2] cycloaddition of nitriles and sodium azide, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/
j.crci.2015.11.016

2
R. Kant et al. / C. R. Chimie xxx (2016) 1e8
Fig. 1. Chemical structure of pharmacologically important tetrazole drugs.
tin [19a] and organoaluminum azides [19b] have also been
reported. Some of the above mentioned catalysts suffer
from usual drawbacks such as long reaction time, expensive
reagents, stoichiometric amounts of catalysts, strong Lewis
acids, low yield and water sensitivity. Moreover, hydrazoic
acid formed in situ is toxic, volatile and explosive [16f]. For
example, Jamison et al. [20] and Kappe et al. [21] reported an
innovative method for the synthesis of 5-substituted 1H-
tetrazoles by using a continuous-flow microreactor, in this
method, hydrazoic acid is used safely that formed in situ but
it required higher temperature (190e260 ꢁC) for synthesis.
Moreover, Sharpless et al. [22] have also reported an effi-
cient method for tetrazole synthesis with the use of a stoi-
chiometric amount of Zn salt. However, this method also
requires high temperature for sterically hindered aromatic
and alkyl inactivated nitriles. Thus, there is still some scope
to improve and develop new, simple and efficient synthetic
methodologies to minimize these drawbacks.
2. Experimental
2.1. Materials and methods
All reagents and solvents were obtained commercially
and used without further purification. Nuclear magnetic
resonance (1H and 13C) spectra were recorded on a JEOL GS-
400 model FT-NMR (400 MHz for 1H and 100 MHz for 13C)
spectrometer and processed with Delta software. The
chemical shifts were measured in parts per million (ppm)
on the delta (d) scale relative to the resonance of tetra-
methylsilane (TMS) as the internal reference. FT-IR spectra
were recorded in KBr pellets in the range of
4000e400 cmꢂ1 at room temperature using a Perkin Elmer
400 FT-IR spectrometer. A single crystal of tetrazole (15b)
for X-ray diffraction was mounted on glass fibers. The X-ray
diffraction intensity data were measured at 293 K by using
the X-ray scan technique on a Bruker AXS SMART APEX
Single Crystal X-ray Diffractometer with a CCD-detector
Our research is mainly based on the design and syn-
thesis of biologically active compounds [23]. To diversify
our research, we focused our aim to find new catalysts for
tetrazole synthesis. A literature survey reveals that lead is
widely used in organic synthesis as organolead com-
pounds. They are prepared by using lead(II) chloride with
Grignard reagents in most of the cases [24]. Pb(II) reagents
have been used as catalysts in one pot synthesis of qui-
noxalines [25a], substituted pyrroles [25b], aldol reactions
[25c], oligo(C) formation from the 5-monophosphorimi
dazolide of cytidine [25d], oxidation of guanine [25e] and
direct growth of single-walled carbon nanotubes [25f]. To
the best of our knowledge, no report is available for the
synthesis of tetrazoles catalyzed by Pb(II) salts. This led us
to investigate whether Pb(II) salts could be useful for the
synthesis of 5-substituted 1H-tetrazoles. In this study, we
report an efficient method for the synthesis of 5-
substituted 1H-tetrazoles from nitriles and sodium azide
catalyzed by Pb(II) salts under mild conditions.
using graphite mono-chromatized Mo-K
a
radiation
(
l
¼ 0.71073 Å). The data were corrected for Lorentz-
polarization as well as for absorption effects. The struc-
ture of the compound was solved by the direct method
using the program SHELXS-97, and was refined by using the
full-matrix least-squares technique on F2 by SHELXL97.
Scattering factors incorporated in SHELXL97 were used. All
calculations were carried out using the WinGX package of
the crystallographic program and PLATON. ORTEP-3 and
Mercury were used to generate molecular graphics.
2.2. General procedure for the synthesis of tetrazoles
Benzonitrile (103 mg, 1 mmol) and sodium azide
(97.5 mg, 1.5 mmol) were dissolved in 2 ml of dry DMF in a
25 ml round bottom flask. PbCl2 (27.8 mg, 0.1 mmol, 10 mol
%) was added to the reaction mixture and stirred at 120 ꢁC
for 8 h under nitrogen. After completion of the reaction (as
Please cite this article in press as: R. Kant, et al., An efficient and economical synthesis of 5-substituted 1H-tetrazoles via Pb(II)
salt catalyzed [3þ2] cycloaddition of nitriles and sodium azide, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/
j.crci.2015.11.016

R. Kant et al. / C. R. Chimie xxx (2016) 1e8
3
monitored by TLC), the reaction mixture was cooled to
room temperature and 10 ml of ice water was added fol-
lowed by addition of 3 N HCl until the reaction mixture
became strongly acidic (pH 2e3). The reaction mixture was
extracted three times with 20 ml ethyl acetate. The organic
layer was washed with brine solution and dried over
anhydrous sodium sulfate, and was evaporated under
reduced pressure to give a white solid product of 5-phenyl
1H-tetrazole with 81% yield. The obtained products were
sufficiently pure and characterized by IR, 1H NMR, and 13C
NMR and compared with reported spectral data. The
compound 15b was also characterized by X-ray crystallo-
graphic analysis.
Scheme 1. Reaction of nitriles with sodium azide catalyzed by PbCl2.
With the catalytic species chosen, studies were carried
out to find the mildest reaction conditions for the synthesis
of tetrazoles. Thus, the reaction conditions were stan-
dardized by monitoring the effect of catalyst loading, sol-
vents (Table 1) and temperature (Table 2). The effect of
catalyst loading was investigated in terms of product yield.
In the absence of catalysts at 120 ꢁC, no reaction occurred
even after 12 h stirring (Table 1, entry 1). When the reaction
was performed in the presence of 5 mol% PbCl2, the product
was isolated in a lower yield (40%) in a longer reaction time
(Table 1, entry 5). This yield was improved to 81% in a short
reaction time when the reaction was carried out in the
presence of 10 mol % of PbCl2 (Table 1, entry 4). Further, on
increasing the concentration of the catalyst up to
15e20 mol%, there was no significant increase in yield
(Table 1, entries 6 and 7). Hence 10 mol % of lead chloride
was considered as an optimum catalyst concentration. The
nature of solvents also played an essential role for the
investigation of reaction time and product yield in experi-
ments. It was observed that the reaction in polar protic
solvents such as ethanol (Table 1, entry 9) resulted in only
15% product formation while in non-protic solvents such as
toluene and THF (Table 1, entries 10 and 11) only 28% and
11% products were formed. Other solvents such as aceto-
nitrile, acetone and 1,4-dioxane (Table 1, entries 12e14)
also gave unsatisfactory results with no product formation
even at elevated temperatures and 24 h stirring. We also
tried a reaction in water towards the use of green solvents
in reaction media but the desired product did not form
(Table 1, entry 15). The best yields were obtained in DMF
(Table 1, entries 4e7) while moderate yield was obtained in
DMSO (Table 1, entry 8). On the basis of the above studies,
DMF was found to be a better solvent for tetrazole synthesis
than DMSO and other solvents.
3. Results and discussion
We aim to develop a better catalytic system by screening
three Pb(II) salt catalysts [PbCl2, Pb(NO3)2, and
Pb(CH3COO)2] for their ability to catalyze the [3þ2] cyclo-
addition between benzonitrile and sodium azide in dime-
thylformamide (Table 1). Out of these, Pb(CH3COO)2
afforded 5-phenyl 1H-tetrazole in poor yield (55%) while
Pb(NO3)2 afforded 5-phenyl 1H-tetrazole in moderate yield
(69%). Moreover, these catalysts took a longer time (18h and
12h respectively) for the completion of the reaction. PbCl2
gave better yield (81%) in a shorter reaction time (8h).
Therefore, Pb(NO3)2 and Pb(CH3COO)2 catalysts were
eliminated from the scope of the present study. Further,
PbCl2 is a stable salt, water tolerant and easy to handle.
Overall, PbCl2 is an excellent option and was thus selected
for further studies for the synthesis of tetrazoles (Scheme 1).
Table 1
Optimization of the reaction conditions for the synthesis of tetrazole (1b)a.
N N
N
C
N
N
H
C
Catalyst
+
NaN3
Solvent, Temp,
Time, Yield %
1a
1b
Entry Catalyst [mol %] Solvent
Temp (ꢁC) Time (h) Yieldb (%)
1.
2.
3.
4.
5.
6.
7.
8.
Nil
DMF
DMF
120
120
120
120
120
120
120
120
78
12
12
18
8
14
8
NRc
69
55
81
40
83
82
56
15
28
11
0
The reaction was also carried out using 10 mol % of PbCl2
at different temperatures (Table 2). Among the various
temperature ranges tested, it was found that there was an
increase in the yield with increase in temperature up to
Pb(NO3)2 [10]
Pb(CH3COO)2 [10] DMF
PbCl2 [10]
PbCl2 [5]
DMF
DMF
DMF
DMF
DMSO
EtOH
Toluene
THF
CH3CN
Acetone
PbCl2 [15]
PbCl2 [20]
PbCl2 [10]
PbCl2 [10]
PbCl2 [10]
PbCl2 [10]
PbCl2 [10]
PbCl2 [10]
PbCl2 [10]
PbCl2 [10]
8
16
24
24
24
24
24
24
24
Table 2
9.
Effect of temperature on the synthesis of 5-phenyl 1H-tetrazole(1b) in
DMF.
10.
11.
12.
13.
14.
15.
110
65
80
Entry
Catalyst
Temp (ꢁC)
Time (h)
Yield (%)
60
0
0
0
1.
2.
3.
4.
5.
6.
PbCl2(10 mol %)
PbCl2(10 mol %)
PbCl2(10 mol %)
PbCl2(10 mol %)
PbCl2(10 mol %)
PbCl2(10 mol %)
35(RT)
60
80
100
120
140
17
14
14
14
8
0
22
45
68
81
75
1,4-Dioxane 100
H2O 100
a
Reaction conditions: Benzonitrile (1 mmol), NaN3 (1.5 mmol) are used
at given temp.
b
c
Experimental yield.
In the absence of catalysts, no reaction occurred after 12 h.
8
Please cite this article in press as: R. Kant, et al., An efficient and economical synthesis of 5-substituted 1H-tetrazoles via Pb(II)
salt catalyzed [3þ2] cycloaddition of nitriles and sodium azide, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/
j.crci.2015.11.016

4
R. Kant et al. / C. R. Chimie xxx (2016) 1e8
Table 3 (continued)
Table 3
PbCl2 catalyzed synthesis of 5-substituted 1H-tetrazolesa.
Entry Substrate [a]
Product [b]
Time (h) Yieldb (%)
N N
N
10 mol % PbCl2
N
N
H
N
N
C
+
NaN3
C
R
CN
DMF, 120 oC,
Time, Yield %
N
HN
R
8bd
Br
8
10
80
8a
1b-17b
1a-17a
Br
O(CH2)5CH3
O(CH2)5CH3
Entry Substrate [a]
Product [b]
Time (h) Yieldb (%)
N
N
N
N
HN
N
CN
HN
CN
N
1
8
81, 74c
9bd
9
12
78
9a
Br
1b
1a
Br
O(CH2)14CH3
O(CH2)14CH3
N
N
N
HN
N
N
CN
HN
N
CN
2
8
79
2b
2a
10b
10a
NH
10
10
74
Br
Br
N N
HN
NH
O
CH3
O
CN
N
CH3
3
8
77
N
HN
N
N
3b
3a
Cl
CN
Cl
11b
11a
O2N
11
10
78
N
HN
N
CN
O2N
NH
N
NH
O
4
8
80
75
CH3
4b
O
4a
Cl
N
CH3
N
Cl
N
HN
N
N
N
N
CN
CN
N
HN
5
10
12b
O
5b
12a
O
5a
12
10
83
HN
CH3
CN
HN
CH3
N
N
N
HN
6
10
78
6b
Br
N
HN
N
N
Br
OH
6a
7a
CN
OH
13bd
N
N
13a
CN
N
HN
HN
HN
13
10
73
7
10
80
7b
Br
OCH3
N
Br
N
N
N
OCH3
N
N
O2N
O2N
Please cite this article in press as: R. Kant, et al., An efficient and economical synthesis of 5-substituted 1H-tetrazoles via Pb(II)
salt catalyzed [3þ2] cycloaddition of nitriles and sodium azide, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/
j.crci.2015.11.016

R. Kant et al. / C. R. Chimie xxx (2016) 1e8
5
Table 3 (continued )
Entry Substrate [a]
protected amine, N-(4-cyanophenyl)benzamide, at the
para-position gave the corresponding 1H-tetrazole in
excellent yield (83%, Table 3, entry 12) while N-(4-
cyanophenyl)acetamide gave lower yield (74%, Table 3,
entry 10). Introduction of the nitro group at the meta
position in N-(4-cyanophenyl)acetamide resulted in an
improved yield (78%, Table 3, entry 11). When, the nitrile
containing N-alkylated amine with nitrogen containing
functionality, 4-({[1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl]
methyl}amino)benzonitrile gave lower yield (73%, Table 3,
entry 13) as compared to the protected amino nitriles. In
addition to this, heterocyclic nitriles can also be used to
prepare tetrazoles efficiently using PbCl2 as the catalyst
(Table 3, entry 4). This methodology was also applied for the
synthesis of benzyl tetrazoles in excellent yields, however, it
took a longer time for the completion of reactions (Table 3,
entries 14e17). From the above results, it is concluded that
PbCl2 is an excellent catalyst for the synthesis of
5-substituted 1H-tetrzoles which tolerate a wide range of
substituents irrespective of the electronic nature and posi-
tion of the substituents on an aromatic ring involved in
conversion. Moreover, the authenticity of this approach was
also confirmed by X-ray crystallographic analysis of tetra-
zole compound 15b. For the X-ray study, good quality
crystals of compound 15b were grown in a mixture of
solvents (hexane:ethyl acetate, 2:8) by allowing slow
evaporation at room temperature. The X-ray structure of the
compound contains one molecule in the asymmetric unit
(Fig. 2) and crystallized in the monoclinic crystal system
with the P21/c space group, having the unit cell parameters:
Product [b]
Time (h) Yieldb (%)
N
HN
CN
N
N
14
12
14
14
80
74
76
14b
14a
N
HN
CN
N
N
H3C
15
H3C
e
15b
15a
N
HN
CN
N
N
16
16b
16a
CH3
CH3
HN
N
CN
N
N
17
12
81
17b
17a
Cl
Cl
aThe reaction of nitriles with NaN3 (1.5 equiv) was conducted in DMF in
the presence of 10 mol % of PbCl2 at 120 ꢁC.
bExperimental yield.
cYield after the fourth cycle.
dNovel compounds.
eCrystal structure and network of hydrogen bonding.
120 ꢁC (Table 2, entries 1e5). Further, there was no increase
in the yield with increase in temperature (Table 2, entry 6).
Hence,10 mol % of catalyst at 120 ꢁC in DMF was considered
as an optimal condition for the synthesis of 5-substituted
1H-tetrazoles in the present study.
We next examined the scope of the PbCl2 promoted
[3þ2] cycloaddition of structurally diverse organic nitriles
and sodium azide to form 5-substituted 1H-tetrazoles and
the results are summarized in Table 3. In the case of
aromatic nitriles, electron withdrawing and donating
groups have a significant influence on the yield of products
and reaction time. The aromatic nitriles containing an
electron withdrawing group at the para-position gave
better yields (Table 3, entries 2 and 3), while an electron
donating group at the para-position gave lower yield
comparatively in a longer reaction time (Table 3, entry 5).
The nitriles containing both electronwithdrawing as well as
electron donating groups gave better yield (Table 3, entries
6e9), when compared to the nitrile containing an electron
donating group (Table 3, entry 5). The nitriles containing
Fig. 2. Ortep diagram of tetrazole 15b.
Please cite this article in press as: R. Kant, et al., An efficient and economical synthesis of 5-substituted 1H-tetrazoles via Pb(II)
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j.crci.2015.11.016

6
R. Kant et al. / C. R. Chimie xxx (2016) 1e8
Fig. 3. 2D network of hydrogen bonding in tetrazole 15b.
a ¼ 7.8256(6) Å, b ¼ 11.919(10) Å, c ¼ 9.8796(8) Å,
96.769(4)ꢁ, 915.08(13) Å3,
and
The role of catalysts in the synthesis of tetrazoles is
shown in Scheme 2. Presumably, the mechanism of the
reaction proceeds through formation of Pb(N3)2 in situ by
the action of NaN3 on Pb(II) salts [26], which facilitates the
[3þ2] cycloaddition reaction with nitriles to form 5-
substituted 1H-tetrazole products.
b
¼
V
¼
Z
¼
4
Dx ¼ 1.265 g cmꢂ1. The crystal structure of tetrazole is
stabilized by NeH/N (a) and CeH/N (b) intermolecular
hydrogen bonding that exhibit a two-dimensional (2D)
network. This network is decoded systematically and
consistently into recognized terminological notations
(Fig. 3).
The recovery or recyclability of catalysts is an important
issue for chemical industries. Therefore, the recovery and
Scheme 2. Plausible mechanism for the synthesis of tetrazoles catalyzed by Pb(II) salts.
Please cite this article in press as: R. Kant, et al., An efficient and economical synthesis of 5-substituted 1H-tetrazoles via Pb(II)
salt catalyzed [3þ2] cycloaddition of nitriles and sodium azide, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/
j.crci.2015.11.016

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References
[1] (a) T.J.A. Graham, A.G. Doyle, Org. Lett. 14 (2012) 1616e1619;
(b) M.I. Fernandez-Bachiller, C. Perez, L. Monjas, J. Rademann,
M.I. Rodríguez-Franco, J. Med. Chem. 55 (2012) 1303e1317;
(c) S.G. Das, B. Srinivasan, D.L. Hermanson, N.P. Bleeker, J.M. Doshi,
R. Tang, W.T. Beck, C. Xing, J. Med. Chem. 54 (2011) 5937e5948;
(d) H. Xue, Y. Gau, B. Twamley, J.M. Shreeve, Chem. Mater. 17
(2005) 191e198;
(e) Q. Ye, Y.M. Song, G.X. Wang, K. Chen, D.W. Fu, P.W. Chan,
J.S. Zhu, S.D. Huang, R.G. Xiong, J. Am. Chem. Soc. 128 (2006)
6554e6555.
[2] (a) J. Roh, K. Vavrova, A. Hrabalek, Eur. J. Org. Chem. (2012)
6101e6118;
Fig. 4. Recyclability of the PbCl2 catalyst.
(b) L.V. Myznikov, A. Hrabalek, G.I. Koldobskii, Chem. Heterocycl.
Compd. 43 (2007) 1e9;
(c) S. Wu, A. Fluxe, J. Sheffer, J.M. Janusz, B.E. Blass, R. White,
C. Jackson, R. Hedges, M. Muawsky, B. Fang, G.M. Fadayel, M. Hare,
L. Djandjighian, Bioorg. Med. Chem. Lett. 16 (2006) 6213e6218;
(d) G.I. Koldobskii, Russ. J. Org. Chem. 42 (2006) 469e486.
[3] W. Guo-xi, S. Bao-ping, R. Zong-ling, Synth. Commun. 20 (2008)
3577e3581.
reusability of lead chloride were investigated (Fig. 4). The
catalyst was recovered easily at the end of the reaction by
simple filtration due to its negligible solubility in water [27].
The recovered catalyst was washed with ethyl acetate &
ethyl alcohol and dried under vacuum for further use. Our
experiments showed that the recycled catalyst was reused
over four catalytic cycles with only negligible loss of activity
(Table 3, entry 1). The 1H NMR spectra of 5-phenyl 1H-tet-
razole synthesized by using the recovered catalyst after the
fourth cycle confirmed the purity of the products (Fig. S1).
[4] V.A. Ostrovskii, R.E. Trifonov, E.A. Popova, Russ. Chem. Bull. Int. Ed.
61 (2012) 768e780.
[5] G.I. Koldobskii, V.A. Ostrovskii, Usp. Khim. 63 (1994) 847e865.
[6] S.J. Wittenberger, B.G. Donner, J. Org. Chem. 58 (1993) 4139e4141.
[7] R.C. Tuites, T.E. Whiteley, L.M. Minsk, US Patent 1,245,614 1917.
[8] (a) V.A. Ostrovskii, M.S. Pevzner, T.P. Kofmna, M.B. Shcherbinin,
I.V. Tselinskii, Targets Heterocycl. Syst. 3 (1999) 467e526;
(b) M. Hiskey, D.E. Chavez, D.L. Naud, S.F. Son, H.L. Berghout,
C.A. Bome, Proc. Int. Pyrotech. Semin. 27 (2000) 3e14.
[9] K.R. Knudsen, C.E.T. Mitchell, S.V. Ley, Chem. Commun. (2006)
66e68.
4. Conclusions
[10] X.S. Wang, Y.Z. Tang, X.F. Huang, Z.R. Qu, C.M. Che, P.W.H. Chan,
R.G. Xiong, Inorg. Chem. 44 (2005) 5278e5285.
[11] D.D. Beusen, J. Zabrocki, U. Slomczynska, R.D. Head, J.L.F. Kao,
G.R. Marshall, Biopolymers 36 (1995) 181e200.
[12] F. Himo, Z.P. Demko, L. Noodleman, K.B. Sharpless, J. Am. Chem. Soc.
125 (2003) 9983e9987.
[13] E. Lodyga-Chruscinska, D. Sanna, G. Micera, L. Chruscinski, J. Olejnik,
R.J. Nachman, J. Zabrocki, Acta Biochim. Pol. 53 (2006) 65e72.
[14] T. Eicher, S. Hauptmann, The Chemistry of Heterocycles, Thieme,
NewYork, NY, 1995, p. 212.
In the present study, three Pb(II) salts have been used to
catalyze the [3þ2] cycloaddition between benzonitrile and
sodium azide in dimethylformamide at 120 ꢁC. PbCl2 was
found to be the best catalyst with respect to yields and
reaction times for the synthesis of tetrazoles. Substrates
with electron withdrawing groups are found to be more
reactive than those with electron donating groups whereas
aromatic nitriles are more reactive than benzyl nitriles.
Additionally, heterocyclic nitriles can also be used to pre-
pare tetrazoles using this catalyst. Thus, this methodology
should provide a facile route for the synthesis of other 5-
substituted 1H-tetrazoles too.
[15] A. Hantzsch, A. Vagt, Justus Liebigs Ann. Chem. 314 (1901) 339e369.
[16] (a) L. Bosch, J. Vilarrasa, Angew. Chem., Int. Ed. 46 (2007)
3926e3930;
(b) J. Bonnamour, C. Bolm, Chem.dEur. J. 15 (2009) 4543e4545;
(c) G. Venkateshwarlu, A. Premalatha, K.C. Rajanna, P.K. Saiprakash,
Synth. Commun. 39 (2009) 4479e4485;
(d) M.Y. Wani, A.R. Bhat, A. Azam, I. Choi, F. Athar, Eur. J. Med.
Chem. 48 (2012) 313e320;
(e) J. Roh, T.V. Atramonova, K. Vavrova, G.I. Koldobskii, A. Hrabalek,
Synthesis 13 (2009) 2175e2178;
Acknowledgments
RK is thankful to CSIR HRDG New Delhi, India (Grant no.
09/013(0541)/2014-EMR-I) for a Junior Research Fellowship
and AA is thankful to Banaras Hindu University, Varanasi,
India for financial assistance. We are also grateful to Dr. M.
Nethaji, Department of Inorganic & Physical Chemistry,
Indian Institute of Science, Bangalore for X-ray analysis.
(f) S.J. Wittenberger, B.G. Donner, J. Org. Chem. 58 (1993)
4139e4141.
[17] (a) J. Braun, W. Keller, Ber. Dtsch. Chem. Ges. 65 (1932)
1677e1680;
(b) L. Lang, B. Li, W. Liu, Li. Jiang, Z. Xu, G. Yin, Chem. Commun. 46
(2010) 448e450;
(c) M.L. Kantam, V. Balasubrahmanyam, K.B. Shiva Kumar, Synth.
Commun. 36 (2006) 1809e1814;
(d) M.L. Kantam, K.B. Shiva Kumar, K.P. Raja, J. Mol. Catal. A: Chem.
247 (2006) 186e188;
(e) T. Jin, F. Kitahara, S. Kamijo, Y. Yamamoto, Tetrahedron Lett. 49
(2008) 2824e2827;
Appendix A. Supplementary data
Supplementary data (The spectral data of the synthe-
sized tetrazoles are given in supplementary information for
this article. CCDC-1011441 for compound 15b contains the
supplementary crystallographic data that can be obtained
free of charge at http://www.ccdccam.ac.uk/const/
(f) Y.S. Gyoung, J.G. Shim, Y. Yamamoto, Tetrahedron Lett. 41
(2000) 4193e4196;
(g) M.L. Kantam, K.B. Shiva Kumar, C. Sridhar, Adv. Synth. Catal. 347
(2005) 1212e1214;
(h) B. Sreedhar, A.S. Kumar, D. Yadav, Tetrahedron Lett. 52 (2011)
3565e3569.
Please cite this article in press as: R. Kant, et al., An efficient and economical synthesis of 5-substituted 1H-tetrazoles via Pb(II)
salt catalyzed [3þ2] cycloaddition of nitriles and sodium azide, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/
j.crci.2015.11.016

8
R. Kant et al. / C. R. Chimie xxx (2016) 1e8
[18] (a) A. Coca, E. Turek, Tetrahedron Lett. 55 (2014) 2718e2721;
(b) S.K. Prajapti, A. Nagarsenkar, B.N. Babu, Tetrahedron Lett. 55
(2014) 3507e3510;
[24] (a) R.W. Leeper, L. Summers, H. Gilman, Chem. Rev. 54 (1954)
101e167;
(b) G.J.M.V.D. Kerk, Ind. Eng. Chem. 58 (1966) 29e35.
[25] (a) S.A. Kotharkar, D.B. Shinde, J. Iran, Chem. Soc. 3 (2006) 267e271;
(c) S. Kumar, A. Kumar, A. Agarwal, S.K. Awasthi, RSC Adv. 5 (2015)
21651e21658.
(b) Sk.K.
Pasha,
V.S.V.
Satyanarayana,
A.
Sivakumar,
[19] (a) J.V. Dunica, M.E. Pierce, J.B. Santella, J. Org. Chem. 56 (1991)
2395e2400;
(b) V. Aureggi, G. Sedelmeier, Angew. Chem., Int. Ed. 46 (2007)
8440e8444.
[20] P.B. Palde, T.F. Jamison, Angew. Chem., Int. Ed. 50 (2011)
3525e3528.
K. Chidambaram, L.J. Kennedy, Chin. Chem. Lett. 22 (2011) 891e894;
(c) S. Nagayama, S. Kobayashi, J. Am. Chem. Soc. 122 (2000)
11531e11532;
(d) K. Kawamura, J. Maeda, Orig. Life Evol. Biosph. 37 (2007)
153e165;
(e) L. Banu, V. Blagojevic, D.K. Bohme, J. Phys. Chem. B 116 (2012)
11791e11797;
(f) Y. Zhang, W. Zhou, Z. Jin, L. Ding, Z. Zhang, X. Liang, Y. Li, Chem.
Mater. 20 (2008) 7521e7525.
[21] (a) B. Gutmann, J.P. Roduit, D. Roberge, C.O. Kappe, Angew. Chem.,
Int. Ed. 49 (2010) 7101e7105;
(b) B. Gutmann, T.N. Glasnov, T. Razzaq, W. Goessler, D.M. Roberge,
C.O. Kappe, Beilstein J. Org. Chem. 7 (2011) 503e517.
[22] (a) Z.P. Demko, K.B. Sharpless, Org. Lett. 3 (2001) 4091e4094;
(b) Z.P. Demko, K.B. Sharpless, J. Org. Chem. 66 (2001) 7945e7950.
[23] (a) M.K. Singh, M. Gangwar, D. Kumar, R. Tilak, G. Nath, A. Agarwal,
Med. Chem. Res. 23 (2014) 4962e4976;
[26] (a) F.D. Miles, J. Chem. Soc. (1931) 2532e2542;
(b)http://www.nature.com/nature/journal/v176/n4483/abs/
176653a0.html.
[27] (a) D.R. Lide, CRC Handbook of Chemistry and Physics, 79th ed.,
1998, pp. 8e108;
(b) M.K. Singh, R. Tilak, G. Nath, S.K. Awasthi, A. Agarwal, Eur. J.
Med. Chem. 63 (2013) 635e644;
(c) S.K. Dixit, N. Mishra, M. Sharma, S. Singh, A. Agarwal,
S.K. Awasthi, V.K. Bhasin, Eur. J. Med. Chem. 51 (2012) 52e59.
(b) T.L. Brown, H.E. LeMay, B.E. Bursten, Laboratory Experiments for
Chemistry, The Central Science, “Solubility-Product Constants for
Compounds at 25ꢁC”, 6th ed., 1994, p. 1017.
Please cite this article in press as: R. Kant, et al., An efficient and economical synthesis of 5-substituted 1H-tetrazoles via Pb(II)
salt catalyzed [3þ2] cycloaddition of nitriles and sodium azide, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/
j.crci.2015.11.016