Phosphomolybdic acid (H3Mo12O40P) as a reusable heterogeneous catalyst for the synthesis of 5-substituted 1 H-Tetrazoles via [2+3] cycloaddition of nitriles and sodium azide

Article abstract of DOI:10.1080/00397911.2011.557515

An efficient and practical protocol for the preparation of 5-substituted 1H-tetrazole derivatives is reported using phosphomolybdic acid as an effective heterogeneous catalyst. Good yields, simple methodology, and easy workup make this protocol more attractive for the diversity-oriented synthesis of these heterocycle libraries. The catalyst can be recycled three times with good yields.

Full text of DOI:10.1080/00397911.2011.557515

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Phosphomolybdic Acid (H3Mo12O40P) as a
Reusable Heterogeneous Catalyst for the
Synthesis of 5-Substituted 1H-Tetrazoles
via [2 + 3] Cycloaddition of Nitriles and
Sodium Azide
Santosh Takale a , Smita Manave a , Kiran Phatangare a , Vikas
Padalkar a , Nitin Darvatkar b & Atul Chaskar a c
a C. K. Thakur Research Centre, Navi Mumbai, India
b Institute of Science, Mumbai, India
c Dipartimento Di Chimica, Materiali Ed Ingegneria Chimica “Giulio
Natta” Politecnico Di Milano, Milan, Italy
Available online: 19 Dec 2011
To cite this article: Santosh Takale, Smita Manave, Kiran Phatangare, Vikas Padalkar, Nitin Darvatkar
& Atul Chaskar (2012): Phosphomolybdic Acid (H3Mo12O40P) as a Reusable Heterogeneous Catalyst for
the Synthesis of 5-Substituted 1H-Tetrazoles via [2 + 3] Cycloaddition of Nitriles and Sodium Azide,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 42:16, 2375-2381
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Synthetic Communications1, 42: 2375–2381, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.557515
PHOSPHOMOLYBDIC ACID (H3Mo12O40P) AS A
REUSABLE HETEROGENEOUS CATALYST FOR THE
SYNTHESIS OF 5-SUBSTITUTED 1H-TETRAZOLES VIA
[2 þ 3] CYCLOADDITION OF NITRILES AND SODIUM
AZIDE
Santosh Takale,1 Smita Manave,1 Kiran Phatangare,1
Vikas Padalkar,1 Nitin Darvatkar,2 and Atul Chaskar1,3
1C. K. Thakur Research Centre, Navi Mumbai, India
2Institute of Science, Mumbai, India
3Dipartimento Di Chimica, Materiali Ed Ingegneria Chimica ‘‘Giulio Natta’’
Politecnico Di Milano, Milan, Italy
GRAPHICAL ABSTRACT
Abstract An efficient and practical protocol for the preparation of 5-substituted 1H-tetra-
zole derivatives is reported using phosphomolybdic acid as an effective heterogeneous cata-
lyst. Good yields, simple methodology, and easy workup make this protocol more attractive
for the diversity-oriented synthesis of these heterocycle libraries. The catalyst can be
recycled three times with good yields.
Keywords [2 þ 3] Cycloaddition; heteropoly acid; nitriles; sodium azide; tetrazoles
INTRODUCTION
Tetrazoles, a group of heterocyclic compounds, have various advantages and
play profound roles in coordination chemistry, medicinal chemistry, material chem-
istry, explosives, rocket propellants, and agriculture.[1–8] Besides this tetrazoles are
also being used in syntheses of diverse drug intermediates.[6] In the literature a num-
ber of methods are cited to produce tetrazoles; the most convenient methods are
addition of azide ions to either organic nitrites or cyanamides,[9–12] and addition
of sodium azide to nitriles with stoichiometric amount of Zn(II) salts.[13–15] Though
these are the convenient methods,[16–23] they have their own limitations, including
Received October 7, 2010.
Address correspondence to Atul Chaskar, C. K. Thakur Research Center, Navi Mumbai 410 206,
India. E-mail: achaskar@rediffmail.com
2375

2376
S. TAKALE ET AL.
Scheme 1. Synthesis of 5-substituted 1H-tetrazole.
use of harsh reaction conditions and expensive reagents, generation of highly toxic
by-products, and poor yield of product[24–27]
.
Adhering to our objective of developing a protocol that could fulfill the necess-
ity for mild, environmentally compatible, less expensive, and safe synthetic meth-
ods[28–30], we have developed a new protocol for the preparation of 5-substituted
1H-tetrazoles from a wide variety of nitriles using phosphomolybdic acid as a hetero-
geneous solid acid catalyst (Scheme 1).
RESULTS AND DISCUSSION
Initially, the reaction of benzonitrile with sodium azide was carried out in
dimethylformamide (DMF) at 80 ꢀC as a model reaction to examine the effect of
various catalysts on the yield and rate of reaction for the preparation of 5-substituted
1H- tetrazoles, in comparison with phosphomolybdic acid. We found that the yield
and the rate of reaction were quite good when phosphomolybdic acid was used as
catalyst (Table 1).
To identify optimum reaction conditions for preparation of 5-substituted 1H-
tetrazoles, various solvents were studied (Table 2) at different temperatures by react-
ing benzonitrile with sodium azide in the presence of phosphomolybdic acid.
Encouragingly, we noticed that when DMF was used as a solvent, the product
was obtained with complete conversion, as indicated by thin-layer chromatography
(TLC). The conditions identified were used further to study the scope of the trans-
formation of other nitriles to 5-substituted 1H-tetrazole derivatives. Keeping all
Table 1. Influence of various catalysts on the preparation of 5-substituted 1H- tetrazolesa
Entry
Catalyst
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
BiCl3
CdCl2
InCl3
CeCl3
AlCl3
09
14
12
12
9.5
08
14
10
04
65
53
40
52
73
65
42
61
89
Bi(NO3)3
CuCl2
FeCl3
Phosphomolybdic acid
aReaction conditions: benzonitrile (1 mol), sodium azide (1.5 mol), catalyst (2 mol %).
bIsolated yield.

PHOSPHOMOLYBDIC ACID
2377
Table 2. Optimization of reaction conditions for the preparation of 5-substituted 1H-tetrazolesa
Entry
Solvent
Time (h)
Temp. (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
CH3CN
THF
5
8
75
70
59
70
34
54
63
89
60
CH2Cl2
CCl4
7.5
7
38
55
MeOH
DMF
DMSO
7
55
80
4
8
100
aReaction conditions: benzonitrile (1 mol), sodium azide (1.5 mol), catalyst (2 mol %).
bIsolated yield.
these results in view, we decided to generalize the protocol by carrying out the reac-
tion of various aryl nitriles with sodium azide in the presence of phosphomolybdic
acid in DMF. All the products were obtained with 63 to 96% yields (Table 3). Physi-
cal and spectral data of known compounds are in agreement with the literature.
Products were characterized by physical constant, IR and NMR. Because we
used phosphomolybdic acid as a recyclable catalyst, after completion of reaction,
the catalyst was recovered. The reaction mixture was poured into ice-cold water
extracted with ethyl acetate, washed with water, and evaporated under reduced
pressure to get the product. The aqueous layer was evaporated under reduced press-
ure to get phosphomolybdic acid and reused two more times (Table 4).
EXPERIMENTAL
All commercial reagents were used as received without purification, and sol-
vents were of reagent grade. The reaction was monitored by TLC using 0.25-mm
E-Merck silica-gel 60 F254 precoated plates and visualized under ultraviolet light.
Melting points were taken in open capillaries and are uncorrected. The infrared
(IR) spectra were recorded on a Perkin-Elmer 257 spectrometer using KBr discs.
1H NMR and 13C NMR spectra were recorded on a VXR300-MHz instrument using
tetramethylsilane (TMS) as an internal standard.
A mixture of nitrile (1 mol), sodium azide (1.5 mol), and phosphomolybdic acid
(2 mol %) was stirred at 80 ꢀC in DMF for the appropriate time period, as indicated
in Table 3. After completion of reaction, the reaction mixture was poured on to
crushed ice, extracted with ethyl acetate, and washed with water. Ethyl acetate
extract was dried over anhydrous sodium sulfate and concentrated under reduced
pressure. The product obtained was purified by column chromatography.
Representative spectral data for 5(4-methoxyphenyl)-1H-tetrazole are as fol-
lows: IR (KBr) cmꢁ1: 3250, 1296, 1186, 1035, 750.1H NMR (DMSO-d6): d ¼ 3.79
(s, 3H), 7.11 (d, J ¼ 7.5 Hz, 2H), 7.91 (d, J ¼ 7.5 Hz, 2H), 11.0 (bs, 1H) ppm. 13C
NMR (DMSO-d6): d ¼ 56.10, 114.50, 116, 128, 155, 161 ppm. Elemental compo-
sition: Calc. C, 54.53%, H, 4.58%, N, 31.81%. Found: C, 54.61%, H, 4.82%, N,
32.07%.

2378
Entry
1
S. TAKALE ET AL.
Table 3. Preparation of 5-substituted 1H-tetrazoles in the presence of phosphomolybdic acida
Time
(h)
Mp
Yieldb (ꢀC)
Substrate
Product
Ref.
4
89
215 10, 16
2
3
4
4.3
4.5
4.5
85
81
83
247 11, 22
233
234
22
22
5
6
7
3.4
4.0
5.0
96
79
81
219
150
182
22
15
15
(Continued )

PHOSPHOMOLYBDIC ACID
2379
Table 3. Continued
Time
(h)
Mp
Yieldb (ꢀC)
Entry
Substrate
Product
Ref.
8
6.0
83
143
15
9
4.0
4.5
91
71
205
124
22
22
10
11
12
7.0
7.0
63
67
42
41
15
22
13
4.7
79
134
22
aReaction conditions: nitriles (1 mol), sodium azide (1.5 mol), catalyst (2 mol %). Solvent: DMF.
Temperature: 80 ꢀC.
bIsolated yield.
Table 4. Recyclability of the phosphomolybdic acid for preparation of 5-sub-
stituted 1H-tetrazoles
Run
Yielda (%)
1
2
3
89
84
80
aIsolated yield.

2380
S. TAKALE ET AL.
CONCLUSION
In conclusion, we have developed a green and highly efficient method for the
synthesis of 5-substituted 1H-tetrazoles by reacting nitriles with sodium azide in
the presence of phosphomolybdic acid as a catalyst. Good yields of product, short
reaction time, elimination of dangerous and harmful hydrazoic acid, a simple
workup procedure, easy preparation, and easy handling of the catalyst are some
of the advantages of this methodology.
ACKNOWLEDGMENTS
We appreciate the supportive environment at C. K. Thakur College. We
are thankful to Dr. S. T. Gadade, principal, C. K. Thakur College, for his generous
support. The authors are grateful to the University Grant Commission, New Delhi,
and to the University of Mumbai for financial support. We are extremely grateful to
Dr. Lucio Melone of Politecnico di Milano for helpful discussions.
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