Efficient heterogeneous silver nanoparticles catalyzed one-pot synthesis of 5-substituted 1H-tetrazoles

Article abstract of DOI:10.1016/j.molcata.2014.05.008

Silver nanoparticles (AgNPs), characterized by TEM, EDX and UV studies were used as an efficient heterogeneous catalyst for the synthesis of 5-substituted 1H-tetrazoles from various nitriles possessing different functional groups in excellent yields. All

Full text of DOI:10.1016/j.molcata.2014.05.008

Journal of Molecular Catalysis A: Chemical 392 (2014) 150–156
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Efficient heterogeneous silver nanoparticles catalyzed one-pot
synthesis of 5-substituted 1H-tetrazoles
Pavnesh Mani, Chiranjeev Sharma, Satyanand Kumar, Satish Kumar Awasthi∗
Chemical Biology Laboratory, Department of Chemistry, University of Delhi, New Delhi 110007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Silver nanoparticles (AgNPs), characterized by TEM, EDX and UV studies were used as an efficient hetero-
geneous catalyst for the synthesis of 5-substituted 1H-tetrazoles from various nitriles possessing different
functional groups in excellent yields. All title compounds were characterized by spectroscopy (1H NMR,
13C NMR and IR) and crystallography.
Received 28 March 2014
Received in revised form 13 May 2014
Accepted 13 May 2014
Available online 24 May 2014
© 2014 Published by Elsevier B.V.
Keywords:
Silver nanoparticles
Tetrazoles
[3 + 2] Cycloaddition
Heterogeneous catalysis
1. Introduction
nitriles using 50 mol% Zn(II) salts [18] which provided simple use
of transition metal catalysts in the synthesis of various tetrazoles.
Tetrazoles are nitrogen containing heterocyclic compounds
which are studied extensively due to their wide range of biolog-
ical and commercial applications [1]. Tetrazoles have gained wide
attention due to its use in drug design as an isosteric replacement
for carboxylic acids [2]. Application of tetrazoles includes its use in
pharmaceuticals, explosives and as precursors of a variety of nitro-
gen containing heterocyclic compounds like imidoylazides [3,4]. In
addition, they have been successfully used in the field of material
sciences and synthetic organic chemistry as analytical reagents and
synthons [5,6]. Synthesis of tetrazole ring is a crucial step in organic,
medicinal and synthetic chemistry. The various methods for syn-
thesis of tetrazoles are well documented in literature. 5-Substituted
1H-tetrazoles are synthesized by reaction between hydrazoic acid
and isocyanides, isocyanides and trimethysilyl azide, cyclization
between primary amines/their salts with an orthocarboxylic acid
ester and sodium azide [7–10].
In the last one decade, the use of silver nanoparticles for catal-
ysis have also gained wide attention due to its enhanced physical,
chemical and biological properties as compared to their macro
scaled counterparts [19]. AgNPs are synthesized by several phys-
ical, chemical and biological methods [20–22]. To the best of our
knowledge, no report is available where the silver nanoparticles
have been utilized for the synthesis of tetrazole analogs. This led us
to investigate whether the silver nanoparticles could be useful for
tetrazole synthesis.
Herein we report the utility of silver nanoparticles for one-pot
synthesis of 5-substituted 1H-tetrazoles via (3 + 2) cycloaddition in
high yields in continuation of our work on catalysis for the synthesis
of various pharmacologically active compounds [11]. It is an exten-
sion of the ongoing research work in our laboratory on design and
synthesis of antimicrobial agents [23], and X-ray analysis of small
molecules [24].
Numerous catalysts used in the synthesis such as Lewis acids,
AgNO3 [11], Fe(OAc)2 [12], In(OTf)3 [13], PCl5 [14], Yb(OTf)3 [15],
Cu2O [16] and natrolite zeolite [17] are well documented. Sharp-
less and co-workers gave a simple and most efficient procedure
for the synthesis of tetrazoles by the addition of sodium azide to
2. Experimental
2.1. Materials
All nitriles were purchased from Alfa Aesar (A Johnson Matthey
Company, Great Britain). Silver nitrate (AgNO3 99.8%), sodium
borohydride (NaBH4 98%) and sodium azide were purchased from
Sigma–Aldrich Chemicals and used as it is. Double-distilled water
was used for the preparation of all aqueous solutions. All solvents
and reagents were obtained commercially and used as received.
∗
Corresponding author. Tel.: +91 11 27666646x121/134;
mobile: +91 9582087608.
E-mail addresses: skawasthi@chemistry.du.ac.in,
satishpna@gmail.com (S.K. Awasthi).
http://dx.doi.org/10.1016/j.molcata.2014.05.008
1381-1169/© 2014 Published by Elsevier B.V.

P. Mani et al. / Journal of Molecular Catalysis A: Chemical 392 (2014) 150–156
151
Fig. 3. Energy dispersive X-ray spectroscopy (EDX) of AgNPs.
layer was extracted again with ethylacetate (3 × 20 mL). The com-
bined organic layer was concentrated in vacuo to yield the crude
white crystalline solid 5-phenyltetrazole in 82–93% yield. The crude
tetrazole was then recrystallized by mixture of solvents (50% ethyl
acetate in hexane) and subsequently characterized by 1HNMR,
13CNMR, IR and crystallography.
Fig. 1. UV–vis absorption spectrum of AgNPs.
2.2. Synthesis of catalyst
4. Results and discussion
The catalyst AgNps was prepared according to the literature
[23]. The aqueoussolutionof 10 ml of 0.001 Msilvernitrate(AgNO3)
and 30 ml of 0.001 M sodium borohydride (NaBH4) were prepared
separately and ice-cooled. The AgNO3 solution was added dropwise
in NaBH4 solution with vigorous stirring for 5 min. The mixture was
left still for 1 h and then stirring continued again for 10 min. The yel-
low coloration of the solution confirms the formation of AgNps in
the solution.
Silver nanoparticles were synthesized according to the reported
procedure [25] and characterized using the surface plasmon reso-
nance absorption in the UV–vis region. The UV–vis spectrum of
AgNps shows characteristic absorption band at 399 nm for the
yellow colored solution which is in agreement with the previous
reports (Fig. 1) [26].
The morphological analysis of AgNps have been carried out
using TEM, which suggests that the silver nanoparticles are not
aggregated and the average size of the particle is estimated
to be 40–42 nm (Fig. 2). High resolution transmission electron
microscopy (HRTEM) image of AgNps as marked with the red frame
(Fig. 2b) shows the interplanar spacing to be about 0.96 nm.
Moreover, Energy Dispersive X-Ray Spectroscopy (EDX) anal-
ysis (Fig. 3) shows a strong signal in the silver region which again
confirms the formation of silver nanoparticles. In the present study,
metallic AgNPs show typical optical absorption peak approximately
at 3 keV due to surface plasmon resonance consistent with the lit-
erature value [25]. This analysis reveals that the nano-structures
were formed solely of silver. The additional peaks in the EDX for
3. General procedure for preparation of 5-substituted
1H-tetrazole
Briefly, AgNPs (20 mol%) was added to the reaction mixture of
the solution of benzonitrile (0.206 g, 2 mmol) in DMF (3 ml) and
sodium azide (0.195 g, 3 mmol) with stirring for 8 h at 120 ◦C. The
reaction was monitored by TLC and solvent removed in vacuo
on completion of reaction. The crude product was then diluted
by ice cooled water and centrifuged. The pH of the solution was
adjusted to 2–3 by addition of 6 N HCl and extracted with ethyl-
acetate. The resultant organic layer was separated and aqueous
Fig. 2. Transmission electron microscopy (TEM) of AgNPs.

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P. Mani et al. / Journal of Molecular Catalysis A: Chemical 392 (2014) 150–156
Table 1
carbon and copper can be attributed due to the carbon coating on
the copper grid.
Effect of catalyst and solvent on the formation of tetrazole 2a from 1a.
Sl no.
Catalyst
Solvent
Temp (◦C)
Time (h)
% Yield
The average size of AgNps is about 42 nm as calculated from DLS
measurements using Zetasizer Nano-ZS90, Malvern Instruments at
a scattering angle of 90◦ and constant temperature of 25 ◦C having
a polydispersity index of ∼0.2. Further, the zeta potential measure-
ments reveal that the complex is negatively charged with a zeta
potential of about −29.5 mV at the pH value of 4.0, indicating the
stability of this composite at this pH (Fig. 4).
Subsequently, AgNPs were used for the synthesis of 5-
substituted 1H-tetrazoles from various nitriles possessing a wide
range of functional groups.
The reaction conditions were standardized and effect of sol-
vents, temperature and catalyst loading were investigated to
achieve best result for the formation of 5-substituted 1H-tetrazoles.
Experiments revealed that the nature of solvents play an impor-
tant role. Reaction in polar protic solvents such as methanol and
ethanol (Table 1, entries 9 and 10) results in only 27% and 22% prod-
uct formation while acetonitrile (Table 1, entry 8) gave 36% product.
1.
2.
3.
4.
5.
6.
7.
8.
AgNPs (10 mol%)
AgNPs (10 mol%)
AgNPs (20 mol%)
AgNPs (20 mol%)
AgNPs (30 mol%)
AgNPs (30 mol%)
AgNPs (20 mol%)
AgNPs (20 mol%)
AgNPs (20 mol%)
AgNPs (20 mol%)
AgNPs (20 mol%)
AgNPs (20 mol%)
AgNPs (20 mol%)
AgNPs (20 mol%)
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
CH3CN
MeOH
EtOH
THF
CHCl3
1,4-Dioxane
H2O
120
60
120
60
120
60
120
80
63
75
65
60
14
16
8
10
8
48
25
92
55
94
53
57
36
27
22
-
8
8
24
24
24
24
24
24
24
9.
10.
11.
12.
13.
14.
-
-
-
100
100
Fig. 4. (a) Size distributions of AgNPs with maximum intensity at 42 nm. (b) Stable AgNPs at −29.7 mV in Zeta potential analysis.

P. Mani et al. / Journal of Molecular Catalysis A: Chemical 392 (2014) 150–156
153
Other solvents such as THF, chloroform and 1,4-dioxane (Table 1,
entries 11–13) also gave unsatisfactory results with no product for-
mation even at elevated temperature after 24 h. The quest for green
solvent motivated us to choose water as a reaction media but results
were not encouraging (Table 1, entry 14). Interestingly, good yields
were obtained with DMF (Table 1, entries 1–6) and DMSO (Table 1
entry 7). The higher yields of the products and comparative easier
work up procedure led us to choose DMF over DMSO.
Further, the experiments on the effect of catalyst loading sug-
gested 20 mol% catalyst is sufficient to perform (3 + 2) cycloaddition
Table 2
The synthesis of 5-substituted 1H-tetrazole with AgNPs under various substrates.a
S no.
Substrate
1
Time (h)
Product
2
Yieldb (%)
1
1a
8
2a
92
HN
N
CN
N N
OMe
OMe
Br
Br
Br
2
3
4
1b
1c
1d
8
8
8
2b
2cc
2d
93
86
87
HN
N
CN
OH
N N
OH
Br
HN
N
CN
N N
NH2
NH2
NO2
NO2
HN
N
CN
N N
O
O
HN
CH3
HN
CH3
O2N
O2N
5
1e
8
2e
82
HN
N
CN
N N
OEt
O
HN
O
N
NH
6
1f
8
2f
85
CN
NH
N
N
N

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P. Mani et al. / Journal of Molecular Catalysis A: Chemical 392 (2014) 150–156
Table 2 (Continued)
S no.
Substrate
1
Time (h)
Product
2
Yieldb (%)
O
O2N
HN
N
NH
7
1g
8
2g
89
CN
NH
N
N
N
O
HN
Cl
N
O2N
8
1h
8
2h
84
N
N
HN
CN
O
HN
O
N
Cl
9
1i
8
2i
92
CN
OMe
HN
N N
N
O
HN
10
1j
8
2j
93
N
NH
HN
N
N N
CN
OEt
O
HN
O2N
11
1k
8
2k
86
N
NH
CN
HN
N
N N

P. Mani et al. / Journal of Molecular Catalysis A: Chemical 392 (2014) 150–156
155
Table 2 (Continued)
S no.
Substrate
1
Time (h)
Product
2
Yieldb (%)
N
Cl
O2N
N
NH
CN
12
1l
8
2l
89
HN
N
N N
OMe
N
NH
13
1m
8
2m
83
Cl
CN
NH
N
N
N
Reaction conditions: benzonitrile (2 mmol), NaN3 (3 mmol), AgNPs (20 mol%), DMF (2–3 ml), reaction time 8 h, 120 ◦C.
Experimental yield.
Crystal structure.
a
b
c
in significantly higher yields (Table 1, entry 3). However, 10 mol%
catalyst results in longer reaction time and lower yield (Table 1,
entries 1 and 2). Finally, using 30 mol% catalyst we observed only a
slight increase in the yield of product (Table 1, entries 5 and 6) at
same temperature. The low temperature at the same catalyst load-
ing also did not give better yield (Table 1, entries 2, 4 and 6). The
optimized procedure followed for the synthesis of 5-substituted
1H-tetrazoles in the present study is: DMF as solvent and 20 mol%
AgNPs as catalyst at 120 ◦C (Table 1, entry 3).
Substitution on aromatic ring produces difference in product
formation, however the variation of yield in various substitutions
is only 5%. The effect of electron donating and withdrawing group
is not clear in some cases, but in general, electron donating groups
were found to give somewhat less yield in comparison to elec-
tron withdrawing group as is the case of (Table 2, entries 2–5, 10
and 11) methoxy, hydroxyl, amine, acetylated amine, methoxy and
ethoxy group at para positions respectively. The methodology was
also found applicable with benzimidazoles transformation bearing
additional tetrazole moiety. Introduction of nitro group at meta
position shows improved yield (Table 2, entry 8). Additionally, het-
erocyclic tetrazoles can also be prepared efficiently using AgNPs
as catalyst (Table 2, entry 9). The protocol was also applied for
the synthesis of aliphatic tetrazoles to get excellent yield (Table 2,
entry 13). Hence, the above results show that the tetrazole for-
mation via [3 + 2] cycloaddition reaction tolerates a wide range of
substituents irrespective of their electronic behavior, positions and
independent of the type of aromatic ring involved in conversion.
Moreover, the authenticity of this approach was confirmed by X-
rays analysis of compound 2c. For the present study, X-ray quality
single crystals of compound 2c were grown in 50% ethyl acetate
in hexane by slow evaporation solution growth method at room
temperature. X-Rays structure revealed hydrated water molecule
in 1:1 stoichiometric ratio in the crystal lattice of tetrazole (Fig. 5).
Fig. 5. ORTEP diagram of compound 2c.
The tetrazole 2c was crystallized in an orthorhombic cell and Pbca
˚
space group with the following lattice parameter: a = 7.1637(8) A,
◦
◦
◦
˚
˚
b = 14.058(2) A, c = 18.350(2) A, ˛ = 90 , ˇ = 90 , ꢀ = 90 , V = 3283.02
(13) A and ꢁ = 1.862 g cm−3
.
3
˚
The role of AgNPs as a catalyst in the synthesis of tetrazoles is
shown in Fig. 6. Silver nanoparticles act as a Lewis acid activating
the nitrile groups via complexation. Hence, it enhances the elec-
trophilic character of cyanide group, which then reacts with sodium
azide to form tetrazoles.
The recyclability of the catalyst was determined using the reac-
tion and the conditions given in Scheme 1 (Fig. 7). The catalyst
could be recovered easily by simple centrifugation and reused after
washing with ethyl acetate and drying under vacuum. The recycled
catalyst showed moderate to good catalytic activity for subsequent
four catalytic cycles.

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P. Mani et al. / Journal of Molecular Catalysis A: Chemical 392 (2014) 150–156
this area are in progress in our laboratory to broaden the scope of
this and as well as other catalysts.
Acknowledgements
SKA is thankful to UGC, New Delhi, India (scheme no FN
37.410/2009) and in part the University of Delhi, Delhi, India for
financial assistance and USIC, University of Delhi, for NMR studies.
PM, CS and SK acknowledge the award of Research Fellowship from
UGC, New Delhi, India. We also acknowledge C M Pandey and Mohit
Tyagi for their kind suggestions.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/
j.molcata.2014.05.008.
Fig. 6. Plausible mechanism for AgNPs catalyzed tetrazole synthesis.
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