Activated Fuller's earth as an inexpensive, eco-friendly, efficient catalyst for the synthesis of 5-aryl 1-H-tetrazole via [3+2] cycloaddition of nitriles and sodium azide

Article abstract of DOI:10.1016/j.tetlet.2016.11.049

A simple and efficient method for the preparation of 5-aryl 1-H-tetrazoles was developed from various aryl nitriles and sodium azide (NaN₃) via [3+2] cycloaddition reaction using activated Fuller's earth as an efficient heterogeneous catalyst.

Full text of DOI:10.1016/j.tetlet.2016.11.049

Accepted Manuscript
Activated Fuller’s earth as an inexpensive, eco-friendly, efficient catalyst for
the synthesis of 5-Aryl 1-H- tetrazole via [3+2] cycloaddition of nitriles and
sodium azide
Deelip S. Rekunge, Krishna S. Indalkar, Ganesh U. Chaturbhuj
PII:
S0040-4039(16)31517-9
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.11.049
TETL 48335
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
18 October 2016
8 November 2016
11 November 2016
Please cite this article as: Rekunge, D.S., Indalkar, K.S., Chaturbhuj, G.U., Activated Fuller’s earth as an
inexpensive, eco-friendly, efficient catalyst for the synthesis of 5-Aryl 1-H- tetrazole via [3+2] cycloaddition of
nitriles and sodium azide, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.11.049
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Graphical Abstract
Activated Fuller’s earth as an inexpensive, eco-friendly,
efficient catalyst for the synthesis of 5-Aryl
1
-H-tetrazole via [3+2] cycloaddition of nitriles and
sodium azide
Deelip S. Rekunge, Krishna S. Indalkar, Ganesh U. Chaturbhuj*

1
Tetrahedron Letters
Activated Fuller’s earth as an inexpensive, eco-friendly, efficient catalyst for the
synthesis of 5-Aryl 1-H- tetrazole via [3+2] cycloaddition of nitriles and sodium
azide
Deelip S. Rekunge, Krishna S. Indalkar, and Ganesh U. Chaturbhuj
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai- 400019, India
ARTICLE INFO
ABSTRACT
Article history:
Received
A simple and efficient method for the preparation of 5-aryl 1-H-tetrazoles was developed from
various aryl nitriles and sodium azide (NaN ) via [3+2] cycloaddition reaction using activated
3
Received in revised form
Accepted
Available online
Fuller’s earth as an efficient heterogeneous catalyst. This catalyst has advantageous of cost,
stability, recovery, reusability, and ecological benefits along with high product yield, and mild
protocol.
Keywords:
Catalyst
2
016 Elsevier Ltd. All rights reserved.
Activated Fuller’s earth
Tetrazole
Nitrile
Nowadays chemistry of heterocycles has acquired enormous
importance. Tetrazoles which belongs to the heterocyclic class
boundaries with regard to scope and reaction conditions; e.g. cost
of synthesis, harsher reaction conditions, longer reaction time,
lower yields, and the use of expensive, explosive and toxic
1
has attracted considerable importance because of
wide
2,
3
22
usefulness
and applications as heterocyclic ligands in
reagents. In order to overcome these limitations, Sharpless and
coordination chemistry, material sciences, pharmaceuticals,
co-workers reported a relatively simple, convenient, and safe
4
-8
9
explosives, photography as well as plant growth regulators. A
well-known tetrazole, dimethyl thiazolyl diphenyl tetrazolium
bromide (MTT) is used in the MTT cell proliferation
procedure for the synthesis of tetrazole by the addition of sodium
23, 24
azide to nitriles catalyzed by (50 mol %) Zn (II) salts.
In spite
of the advantages of homogeneous catalysts, this procedure
hinders its use in the industry due to difficulty in recovery of Zn
(II) salts. Several catalyst have been reported for the addition of
1
0
assay. Biphenyl tetrazoles are intermediates to synthesize sartan
drugs (Figure 1). Tetrazoles have been extensively used as a
4
25
bioisostere of carboxylic acids in molecular design, and also
sodium azide to nitriles such as mesoporous ZnS, silica sulfuric
1
1
26
27
28
used in the preparation of imidoylazides . Tetrazoles containing
acid, FeCl
3
2-9SiO
2
,
NaHSO
3
4
-SiO
2
,
chitosan derived magnetic
1
2
30
31 32
molecules possess various biological activities viz. antiulcer,
ionic liquid, AgNO
hydrotalcite, Zn hydroxyapatite, AlCl
Pd(PPh
, CoY zeolite, CAN-HY-zeolite, Zn/Al
13
33
34
35
22
36
anticonvulsant,
antiviral, antibacterial, antifungal, anti-
3
,
Et
3
N·HCl, TBAF,
1
4
15
16
37
38
39
47
inflammatory, antihistaminics, and antitubercular.
3 4
) ,
3 2
ZnO, Zn-Cu alloy, Ln(OTf) –SiO .
The usual method for preparation of tetrazole is through the
The reported catalytic methods are time consuming, with the
stringent conditions, and utilizing costly, air sensitive, non-
17,18-21
addition of azide ion to organic nitrile.
Various methods
have been reported for the preparation of 5-aryl 1-H-tetrazoles;
3 4
recoverable, toxic metal catalysts (e.g., Pd(PPh ) ). Therefore, the
however, most of the methods have certain
development of a more efficient, convenient, scalable catalyst
that addresses these limitations.
Recent reports revealed that the clay or silica based solid
acid catalysts played a pivotal role under heterogeneous
40
conditions by catalyzing organic transformations. This is due to
tangible benefits like non-corrosiveness, ease of preparation,
handling, regeneration, low cost, and insolubility in most of the
organic solvents. The catalytic activity of clays is due to their
Bronsted as well as Lewis acidic characters in their natural
4
1-43
form.
Fuller’s earth is a commercially available, non-toxic,
eco-friendly, economic material. These qualities of Fuller’s earth
makes it safer and suitable for both laboratories as well as
industrial processes. Fuller’s earth has been used to analyze color
Figure 1. Drugs of sartan series.
—
——

Corresponding author. Tel.: +91-22-33612212; fax: +91-22-24145614; e-mail: gu.chaturbhuj@gmail.com

2
Tetrahedron
additives in food products and as an adsorbent in
Table 1.
pharmaceutical & cosmetics. However, to the best of our
knowledge, the applications of Fuller’s earth for organic
transformation have seldomly reported. Fuller’s earth was
Solvent optimization studies for the synthesis of 5-aryl 1-H-tetrazole.
44
reported as a catalyst for synthesizing bis(indolyl)methanes.
This inspired us to develop a new, eco-friendly activated Fuller’s
earth as a catalyst. In continuation of our efforts towards the
development of eco-friendly green catalytic methodology, we
herein report an alternative, simple, and heterogeneous catalyst
for the synthesis of 5-aryl 1-H-tetrazole.
a
Entry
1.
Catalyst
by wt %
10
10
10
10
10
10
10
Solvent
Temperature
( C)
120
reflux
reflux
reflux
reflux
120
Time
(h)
12
6
6
6
6
1.5
1.5
Yield
(%)
0
0
0
18
30
78
91
⁰
No solvent
Acetonitrile
Tetrahydrofuran
Water
Ethanol
DMF
2
3
.
.
⁰
The Fuller’s earth clay was treated with 5% HCl, at 100
C
4.
5.
6.
7.
for 4 h to activate, cooled to room temperature. Insoluble solid
was filtered, wash with distilled water till free from acid, dried at
⁰
48
1
00 C till constant weight. This treatment increases its
DMSO
120
45, 46
adsorption capacity, specific surface area, and pore volume.
a
Isolated yield.
The catalyst was characterized by various analytical techniques
such as Fourier transform infrared spectroscopy (FTIR), X-ray
diffraction (XRD), scanning electron microscopy (SEM), and
energy dispersive X-ray spectroscopy (EDAX) (Figure 2). FTIR
spectrum of the catalyst was recorded to ascertain the functional
groups. The catalyst exhibited characteristic absorption bands at
The average elemental distribution mapping of the catalyst by
EDAX showed silicon: aluminum: oxygen: in the ratio of 34.94:
3.63: 46.11 wt % over different areas.
Initially, our study was aimed to determine the suitability of
the catalyst under different reaction conditions. For the
-1
3398 and 1656 cm that could be assigned to the OH stretching
preliminary experiment, mixture of benzonitrile, a
a
and bending of the free OH groups, which can be regarded as
representative substrate and sodium azide (1:1.5 equiv.) were
used to synthesize 5-phenyl 1-H-tetrazole. The results are
summarized in Table 1.
-1
‘
‘Bronsted active sites’’ of the catalyst. The bands at 1026 cm
-1
correspond to Si-O-Si stretching of silicates and at 1118 cm for
-1
Al-OH stretching. Stretching at 987 cm represents Al-OH-Al
deformation vibration. The surface morphology of catalyst in the
SEM image clearly indicated that the catalyst is amorphous
nature with aggregates of particles in µm range. Powder XRD
The effect of solvents on product yield was studied. Solvent
played a prominent role on the yield of the product (Table 1,
entries 2-7). In acetonitrile, THF, and under solvent-free
condition reactions were fruitless even in the presence of a
0
pattern of catalyst showed the significant peak around 25.02 , and
0
catalyst
(Table
1,
entries
1-3).
2
6.21 which indicated an amorphous nature.
Figure 2. (a) FTIR spectrum; (b) SEM image; (c) XRD pattern; (d) EDAX.

3
Table 2.
Table 3.
Catalyst loading and temperature optimization study for the synthesis of 5-
Comparison of the efficiency of activated Fuller’s earth with literature
phenyl 1-H-tetrazole.
reported catalysts for the synthesis of 5-phenyl 1-H-tetrazole.
a
a
Entry
Catalyst
by wt %
0
Solvent
Temperature
( C)
Time
(h)
12
Yield
(%)
0
Entry
Catalysts
Condition
Time
(h)
Yield
(%)
91
Ref.
⁰
1
2
3
4
5
6
7
8
9
.
.
.
.
.
.
.
.
.
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
120
120
120
120
120
rt
80
100
150
1.
Activated Fuller’s DMSO/120
1.5
This
work
33
⁰
5
1.5
1.5
1.5
1.5
6
1.5
1.5
1.5
80
91
92
93
20
56
84
87
earth
C
⁰
10
20
30
10
10
10
10
2.
CAN-HY-Zeolite
DMF/ 110
C
4
93
88
88
3
4
5
.
.
.
Silica sulfuric
acid
DMF/reflux
DMF/MeOH/
5
27
47
Ln(OTf)
3
–SiO
2
7.5
⁰
1
00 C
⁰
⁰
⁰
NaHSO
4
- SiO
2
DMF/ 120
DMF/ 120
DMF/ 120
C
C
C
10
12
12
91
79
84
29
28
34
a
6.
7.
FeCl -SiO2
Isolated yield.
3
The yields were lower in polar protic solvents (Table 1, entries 4
and 5), while polar aprotic solvents gave good yields, and DMSO
was best amongst two (Table 1, entries 6 and 7). The temperature
optimization showed that at room and lower temperature, the
reaction proceeded slowly with lower yields, while yield
gradually increased with temperature till a plateau of 120
Zn/Al
hydrocalcite
Zn
Hydroxyapatite
CoY Zeolite
⁰
⁰
8
9
.
.
DMF/ 120
DMF/ 120
C
C
12
14
78
90
35
32
⁰
a
C
Isolated yield
⁰
(Table 2, entries 3, 6- 8). In the absence of the catalyst at 120 C,
There are various catalysts reported for tetrazole synthesis.
no reaction occurred in 12h (Table 2, entry 1). The catalyst
loading of 10 wt % was found to be adequate for the maximum
yield (Table 2, entries 1-5).
Here the present study is compared with other reported catalysts
used for the synthesis of 5-phenyl 1-H-tetrazole which indicates
that activated Fuller’s earth has an advantage in many cases with
respect to reaction conditions, time and yields (Table 3, entries 1-
9
).
Table 4.
4
9
Activated Fuller’s earth catalyzed synthesis of 5-aryl 1-H –tetrazole.
X= CH, N
a
Entry
Substrate
Product
Time (h)
Yield (%)
1
.
1
.5
91
2
3
.
.
2
.5
81
2
85
4
5
.
.
1
2
.5
90
89

4
Tetrahedron
a
Entry
Substrate
Product
Time (h)
3
Yield (%)
6
.
87
7
8
.
.
3
7
88
77
9
.
6
6
8
80
82
78
1
1
0.
1.
1
2.
3
83
a
Isolated yield.
time with lower yields (Table 4, entries 8 -11). Heteroaromatic
nitrile gave moderate yield in comparable reaction time (Table 4,
entry 12). We also attempted the reaction of aliphatic nitriles
under optimized reaction condition without success.
To explore the scope and applicability of the catalyst, the
optimal reaction conditions were applied to functionalized
4
9
benzonitriles and the results are summarized in Table 4. The
reaction time and yields for aromatic nitriles bearing electron
withdrawing and electron donating groups have a significant
difference, apparently due to the electrophilic character of
nitriles. The unsubstituted aromatic nitriles and those bearing
electron withdrawing substituents at ortho and para position took
shorter reaction time, and gave corresponding tetrazoles in higher
yields (Table 4, entries 1–7), in contrast to this, those with
electron donating groups at ortho and para position took a long
Recyclability of the catalyst is an important attribute for the
industrial suitability. Therefore, the reusability of the catalyst was
investigated using benzonitrile as substrate (Table 3, entry 1)
over four cycles. After completion of each cycle, the catalyst was
separated by filtration and residue was washed with methanol to
0
remove the organic traces. The catalyst was dried at 60 C for 1h
and used for successive cycles with no remarkable loss of yield
No. of cycles
Figure 4. A possible mechanism of 5-Aryl 1-H-tetrazole synthesis by
Activated Fuller’s earth.
Figure 3. Recyclability of the catalyst.

5
and produced a pure product comparable to fresh catalyst
Figure, 3).
33. Kantam, M. L.; Kumar, K. S.; Raja, K. P. J. Mol. Catal. A: Chemical
006, 247, 186.
3
2
(
4. Lakshmi Kantam, M.; Balasubrahmanyam, V.; Kumar, K. S. Synth.
Commun. 2006, 36, 1809.
5. Matthews, D. P.; Green, J. E.; Shuker, A. J. J. Comb. Chem. 2000, 2, 19.
6. Amantini, D.; Beleggia, R.; Fringuelli, F.; Pizzo, F.; Vaccaro, L. J. Org.
Chem. 2004, 69, 2896.
7. Gyoung, Y. S.; Shim, J.; Yamamoto, Y. Tetrahedron Lett. 2000, 41, 4193.
38. Lakshmi Kantam, M.; Kumar, K.; Sridhar, C. Adv. Synth. Catal. 2005,
347, 1212.
The possible mechanism of synthesis of 5-aryl 1-H-tetrazole
3
3
is depicted in Figure 4. We strongly believe that the Lewis acid
character of Al present on the surface of the catalyst activates
nitrile towards the [3+2] cycloaddition via coordination bond
with the lone pair of electrons of the nitrogen of nitriles. Hence,
the Lewis acidity is responsible for the catalysis.
3
3
9. Aridoss, G.; Laali, K. K. E. J. Org. Chem. 2011, 76, 6343.
40. Bandgar, B.; Kasture S.; Tidke K.; Makone S.S. Green Chem. 2000, 2,
52.
Conclusion
1
4
4
4
1. Ponde, D.; Borate, H.; Sudalai, A.; Ravindranathan, T.; Deshpande, V.
Tetrahedron Lett. 1996, 37, 4605.
2. Upadhya, T.; Daniel, T.; Sudalai, A.; Ravindranathan, T.; Sabu, K. Synth.
Commun. 1996, 26, 4539.
3. Shaikh, N. S.; Gajare, A. S.; Deshpande, V. H.; Bedekar, A. V.
Tetrahedron Lett. 2000, 41, 385.
In conclusion, the activated Fuller’s earth is an inexpensive,
eco-friendly, efficient heterogeneous catalyst for the [3+2]
cycloaddition of sodium azide and a wide variety of nitriles to
form 5-aryl 1-H-tetrazoles with excellent to good yields. The
catalyst can be easily prepared, used, recovered and recycled with
no loss of catalytic activity.
44. Kapuriya, N.; Kakadiya, R.; Savant, M. M.; Pansuriya, A. M.; Bhuva, C.
V.; Patel, A. S.; Pipaliya, P. V.; Audichya, V. B.; Gangadharaiah, S.;
Anandalwar, S. M. Indian J. Chem. Part B 2012, 51, 1032.
4
4
4
Acknowledgements
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6. Valenzuela Díaz, F. R.; Santos, P. D. Quím. Nova 2001, 24, 345.
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Tetrahedron Lett. 2014, 55, 3557.
The authors are grateful to University Grant Commission for
their financial support.
4
8. Preparation of activated Fuller’s earth catalyst: Fuller’s earth
Appendix A. Supplementary data
(commercial) 10 g was stirred with 100 ml of distilled water to separate
water soluble material if any. The suspended solid was filtered, washed
with distilled water, and dried in an oven at 100 C for 1h. In a 250 ml
⁰
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/00.0000/
round bottom flask containing 50 ml of 5% HCl solution, added 5 g of
⁰
solid obtained from above treatment. The mixture was heated at 100
C
References and notes
for 4 h, cool to room temperature, and filtered; the residue was washed
with distilled water till neutrality. Resultant activated fuller's earth was
1
2
3
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Organomet. Chem. 2013, 738, 41.
⁰
dried at 100 C till constant weight.
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Katritzky, A. R.; Rees, C. W. Compr. Heterocycl. Chem.; Pergamon
Press, 1984.
4
9. General procedure for the synthesis of 5-aryl 1-H -tetrazoles: To a DMSO
3 ml) solution of nitrile (1 mmol), and sodium azide (1.5 mmol), was
(
.
Dehghani, F.; Sardarian, A. R.; Esmaeilpour, M. J. Organomet. Chem.
0
added catalyst (10 wt %). The reaction mixture was stirred to 120 C in
an oil bath. The reaction was monitored by TLC. After completion of the
reaction, the mixture was filtered to separate the catalyst. The filtrate was
quenched with water (30 ml), acidified with 5N HCl (20 ml) to
precipitate the product, extracted with ethyl acetate (2 X 20 ml). The
combined organic layers were washed with water, dried over sodium
sulphate and evaporated under reduced pressure to give the product.
2
013, 743, 87.
4
5
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6
Tetrahedron
Highlights:




Simple, efficient and green method for preparation of 5-aryl 1-H-tetrazoles.
Preparation, characterization and application of activated Fuller’s earth.
Recyclable catalyst with no significant loss in activity.
Method tolerates a variety of functional groups.