Expanded perlite: An inexpensive natural efficient heterogeneous catalyst for the green and highly accelerated solvent-free synthesis of 5-substituted-1H-tetrazoles using [bmim]N3 and nitriles

Article abstract of DOI:10.1039/c5ra21481e

A versatile, green and highly accelerated protocol for preparing 5-substituted-1H-tetrazoles is reported. In this method, 5-substituted-1H-tetrazoles are synthesized from nitriles and [bmim]N₃, in the presence of the expanded perlite as an inexpensive natural efficient heterogeneous catalyst, under solvent-free condition. A wide variety of aryl nitriles underwent [3 + 2] cycloaddition to afford the desired tetrazoles in good to excellent yields, rapidly. This method has the advantages of high yields, short reaction times, simple methodology, and easy work-up. The catalyst can be recovered by simple filtration and reused delivering good yields.

Full text of DOI:10.1039/c5ra21481e

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Expanded perlite: an inexpensive natural efficient heterogeneous
catalyst for the green and highly accelerated solvent-free
synthesis of 5-substituted 1H-tetrazoles using [bmim]N and
3
nitriles
Roya Jahanshahi, Batool Akhlaghinia*
Abstract: A versatile, green and highly accelerated protocol for preparing 5ꢀsubstituted
1
Hꢀtetrazoles is reported. In this method, 5ꢀsubstituted 1Hꢀtetrazoles are synthesized from
nitriles and [bmim]N , in the presence of the expanded perlite as an inexpensive natural
3
efficient heterogeneous catalyst, under solventꢀfree condition. A wide variety of aryl nitriles
underwent [3 + 2] cycloaddition to afford the desired tetrazoles in good to excellent yields,
rapidly. This method has the advantages of high yields, short reaction times, simple
methodology, and easy workꢀup. The catalyst can be recovered by simple filtration and
reused delivering good yields.
Keywords: Expanded perlite, 5ꢀSubstituted 1Hꢀtetrazoles, [3 + 2] Cycloaddition reaction,
Heterogeneous catalyst, Solventꢀfree

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Introduction
Recently, considerable attention has been paid to the use of green methods in the synthesis of
organic compounds. Catalysis organizes the foundation of chemical industry nowadays.
Therefore, replacement of environmentally hazardous catalysts with nonꢀtoxic, effectual and
reusable catalysts that have been associated with great reactivity, operational simplicity and
1
ꢀ11
nonꢀcorrosive nature is highly desired.
On the other hand removing solvent from the
reaction medium is a safety subject, while solvents are potentially toxic. Hence, utilizing the
solventꢀfree procedures is one of the proper options, particularly with respect to the Eꢀ
12
factor.
5ꢀSubstituted 1Hꢀtetrazoles are an imperative class of heterocycles with an extensive range of
13,14
15
16
applications in medicinal chemistry,
coordination chemistry,
agriculture,
17
18
photography, speciality explosives in materials science and information recording
19
systems. Furthermore, due to their similarity in acidity and planarity, they can function as
20
lipophilic spacers and carboxylic acid substitutes in pharmaceuticals. Synthesis of tetrazoles
2
1
was first reported in 1901, via the reaction of hydrazoic acid with nitriles. This approach
had some drawbacks, such as high toxicity, explosive nature, and low boiling point (37 ˚C) of
2
1
hydrazoic acid. The most widely used method for the preparation of 5ꢀsubstituted 1Hꢀ
tetrazoles involves [3 + 2] cycloaddition of an azide anion with organic nitriles in the
22,23
presence of different homogeneous and heterogeneous catalysts.
However, some of these
methods suffer from disadvantages such as harsh reaction conditions, inferior yields of the
desired product, long reaction times, formation of side products, stoichiometric amounts of
the catalyst, water sensitivity, use of toxic solvents, use of organic azide complexes such as
2
4
tin or silicon organic azides, and in situ generated hydrazoic acid.
In continuation of our recent studies on the development of new methods for tetrazoles
25ꢀ27
synthesis,
and according to the green chemistry legislations, herein, we are willing to

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report the superior activity of highly porous expanded perlite as a new green and efficient
heterogeneous catalyst, to catalyze [3 + 2] cycloaddition reaction between organic nitriles and
azide ion to corresponding 5ꢀsubstituted 1Hꢀtetrazoles, in high yields and purity (Scheme 1).
The advantage of this method compared with previously published procedures, is in using 1ꢀ
28
butylꢀ3ꢀmethylimidazolium azide [bmim]N ionic liquid as azide source (Scheme 1), in
3
29ꢀ44
place of the highly toxic reagents such as NaN
3
or TMSN
3
,
as well as using natural
catalyst, in solventꢀfree conditions instead of the most commonly used toxic solvents in this
3
1ꢀ37,39,41,45
context, such as DMF and DMSO.
Results and Discussion
46
Perlite is a naturally glassy volcanic rock which contains usually 2ꢀ6 % water. Unexpanded
(raw) perlite, can expands up to 10ꢀ20 times of its initial volume, upon heating to elevated
47
temperatures (700–1200 ˚C), which is then called "expanded perlite". This phenomenon is
due to the vaporization of the trapped water in the perlite structure. The resulting expanded
material is a bright white, due to the reflectivity of trapped water bubbles. The bulk density of
3
3
unexpanded perlite is around 1100 kg/m (1.1 g/cm ), while typical expanded perlite has a
3
3 48
bulk density of about 30–150 kg/m (0.03ꢀ0.150 g/cm ). Expanded perlite has several
advantages such as light weight, high porosity along with strong adsorbability, natural
abundance, admirable thermal and chemical stability, mechanical resistance, low cost, low
49ꢀ54
toxicity, nonꢀcorrosiveness and ease of handling.
Production and consumption of perlite
55
are very extensive. United States, China, Greece, Japan, Hungary, Armenia, Italy, Mexico,
55
Philippines and Turkey, are the leading countries in perlite production. Furthermore, Iran is
one of the best perlite suppliers in the Middle East that has several perlite resources specially
in Mianeh, Semnan, Birjand, Ferdows, etc. Expanded perlite is widely used in many
industries such as dyeing, food, drug, fuel oil, filter aid, filler in paint, enamels, glazes,

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5
6,57
plastics, and resins, etc.
The unique highꢀporous structure of expanded perlite makes it an
58
excellent support for the preparation of heterogeneous catalysts. Furthermore, expanded
5
9
perlite has multiꢀcatalytic active sites which confirms that it is a potential candidate for
59, 60
heterogeneous catalyst in organic chemistry.
Characterization of expanded perlite
Expanded perlite was identified by Xꢀray fluorescence analysis (XRF), FTꢀIR spectroscopy,
scanning electron microscopy and energy dispersive spectrometry (SEMꢀEDS).
XRF analysis of the catalyst
The chemical composition of the expanded perlite was determined by XRF (Table 1). As can
be seen in Table 1, the principal compositions of the expanded perlite are SiO and Al O .
2
2
3
Accordingly, expanded perlite is considered to be a natural aluminoꢀsilicate.
Table 1: Chemical composition of expanded perlite
Constituent
SiO
2
Al
2
O
3
K
2
O
Fe
2
O
3
Na
2
O
CaO MgO
Percentage 75.220 12.770 5.187 0.741 2.520 0.608 0.226
Constituent
Percentage
BaO
SO
3
ZrO
2
TiO
2
Rb
2
O
SrO MnO
0.087
0.060 0.014 0.110 0.012 0.008 0.066
FT-IR spectrum of the catalyst

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The FTꢀIR spectrum of expanded perlite was shown in Fig. 1a. There are five main
4
6
absorption bands in the infrared spectrum of expanded perlite, which were observed around
−1
−1
−1
−1
−1
−1
3
439 cm , 1625 cm , 1044 cm , 791 cm and 463 cm . The peaks at 3439 cm and
−1
1
625 cm are respectively assigned to the stretching and bending modes of the hydroxyl
groups which are attached to the surface of expanded perlite (mainly SiꢀOH groups) and the
5
8b
−1
−1
adsorbed water molecules. The peaks positioned at 1044 cm and 791 cm are ascribed to
61
Si–O stretching vibrations of SiꢀOꢀSi and SiꢀOꢀAl, respectively. O–Si–O bending vibration
−1 46
was observed at about 463 cm .
th
Fig. 1 FTꢀIR of (a) Fresh expanded perlite, (b) 6 Recovered expanded perlite, (c) Alumina,
(d) Silica.

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SEM analysis of the catalyst
Fig. 2 illustrates the scanning electronic microscopy (SEM) of nonꢀpowdered expanded
perlite (aꢀc) and finely powdered expanded perlite (dꢀf). It is clear that the morphology of the
nonꢀpowdered expanded perlite is a layer structure with high porosity. The layer thickness
size for nonꢀpowdered expanded perlite is around 844 nm – 1.794 ꢁm. It is important to say
that the layer structure of finely powdered expanded perlite was preserved whereas its porous
nature was taken down upon powdering process.

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Fig. 2 SEM images of nonꢀpowdered expanded perlite (aꢀc) and finely powdered expanded
perlite (dꢀf).
EDS analysis of the catalyst
The energy dispersive spectrum (EDS) of expanded perlite indicates the presence of Si, Al,
O, Fe, K, Na as the main components of the expanded perlite (see supporting information
)
which is in a good agreement with the XRF results.
To benefit the unique properties of highly porous expanded perlite as an efficient natural
green heterogeneous catalyst and to follow our interest in the synthesis of 5ꢀsubstitutedꢀ1
tetrazoles, we investigated the capability of expanded perlite to catalyze [3 + 2] cycloaddition
reaction of nitriles with azide ion to achieve the desired 5ꢀsubstitutedꢀ1 ꢀtetrazoles (Scheme
).
Hꢀ
H
1
Expanded perlite
N
R
(
0.05 g)
Solvent-free
10 °C
N
R
C
N + [bmim]N3
HN N
1
N
N
[
bmim]N3
n-Bu
=
Me
N3
Scheme 1 Synthesis of different structurally 5ꢀsubstitutedꢀ1
Hꢀtetrazoles in
the presence of the expanded perlite under solventꢀfree conditions.
3
The reaction of benzonitrile and [bmim]N was chosen as a model reaction for optimizing the
reaction conditions (Table 2). When the model reaction was examined under solventꢀfree
condition at 120 ºC in the absence of expanded perlite, very low yield of product was
acquired, even after a prolonged reaction time (Table 2, entry 1). In contrast, by using the

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same reaction conditions, in the presence of the expanded perlite, the desired product was
obtained in excellent yield after 10 min (Table 2, entry 2). This result implies to prominent
role of highly porous expanded perlite in the synthesis of 5ꢀphenylꢀ1Hꢀtetrazole. As
demonstrated in Table 2, at lower reaction temperature (110 ºC) the reaction progress was the
same as at 120 ºC (Table 2, entry 3), whilst further decreasing the reaction temperature (100
ºC), leads to lower yield of product (Table 2, entry 4). So, temperature plays an important
role in [3 + 2] cycloaddition reaction of nitriles with azide ion. Furthermore, the reaction was
carried out in several solvents such as DMSO, DMF, CH
dioxane, PEG and H O (Table 2, entries 5–13). On the basis of the data obtained from Table
, the best result was obtained in solventꢀfree condition (Table 2, entry 3). To improve the
yield of the reaction product, the effect of different molar ratios of reactants was examined
Table 2, entries 14, 15). According to this study, by decreasing the amount of azide ion to 1
3 3 3 2
CN, CHCl , toluene, CH NO , 1,4ꢀ
2
1
(
mmol, lower yield of the product was obtained in longer reaction time (Table 2, entry 14),
while additional amount of azide ion (2 mmol) was found to have no more effect on the
product yield (Table 2, entry 15). To study the efficacy of catalyst amount, preparation of 5ꢀ
phenylꢀ1
Hꢀtetrazole was performed under solventꢀfree condition at 110 ºC in the presence of
0.06 g and 0.04 g of catalyst. It is obvious from the results that the lower amount of catalyst
resulted only 70% yield of the product even after long period of time (Table 2, entry 16)
while further improvement of yield was not observed upon increasing the amount of catalyst
(
Table 2, entry 17). Hence 0.05 g of catalyst was considered as an optimum catalyst amount.
To study the effect of the expanded perlite porosity (as corroborated by SEM images (Fig.
)), on the [3 + 2] cycloaddition reaction of organic nitriles with azide ion, the model reaction
2
was performed in the presence of nonꢀpowdered expanded perlite. Very low yield of the
product was obtained in the presence of nonꢀpowdered expanded perlite (Table 2, entry 18).
In continuing of our study, by considering the main components of the expanded perlite (see

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XRF results in Table 1), we decided to probe the reactivity of each segment. For this purpose,
silica, alumina (neutral, acidic and basic) and mixture of 5.6:1 (w/w %) of silica : alumina
were used as catalyst in [3 + 2] cycloaddition reaction of benzonitrile and azide ion,
separately. As it is depicted in Table 2, neither these segments (silica and alumina), nor
mixture of silica : alumina (5.6:1 w/w %) have the efficiency of expanded perlite for
catalyzing this transformation (entries 19ꢀ23).
Table 2 Synthesis of 5ꢀphenylꢀ1Hꢀtetrazole under different reaction conditions.
Entry
Molar ratio
Nitrile : Azide
Catalyst
(g)
Temp
(˚C)
120
Solvent
Time
(h)
15
Isolated
Yield (%)
30
1
2
3
4
5
6
7
8
9
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1
ꢀ
ꢀ
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
ꢀ
120
ꢀ
10 min
95
95
90
75
68
trace
ꢀ
110
ꢀ
ꢀ
10 min
100
1
110
DMSO
DMF
1
110
1
Reflux
Reflux
Reflux
Reflux
Reflux
110
CH
3
CN
1
CHCl3
1
Toluene
1
trace
ꢀ
10
11
12
13
14
15
16
17
CH
3
NO
2
1
1,4ꢀDioxane
PEG
1
ꢀ
35 min
69
10
80
95
70
95
15
25
60
10
15
Reflux
110
H O
2
24
0.05
0.05
0.04
0.06
0.06
0.06
0.06
0.06
0.06
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
30 min
1:2
110
10 min
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
110
1
110
10 min
a
1
8
110
1
1
1
1
1
b
1
2
2
2
9
110
c
0
110
d
1
2
110
e
110

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f
2
3
1:1.5
0.06
110
ꢀ
1
43
a
b
c
d
e
f
Nonꢀpowdered expanded perlite was used as catalyst .
Silica was used as catalyst.
Neutral alumina was used as catalyst.
Basic alumina was used as catalyst.
Acidic alumina was used as catalyst.
A mixture of 5.6:1 (w/w %) of silica : alumina was used as catalyst.
With the optimum reaction conditions in hand and aiming to extend the scope of our
methodology, various structurally divergent nitriles possessing a wide range of functional
groups (Scheme 1) were employed as substrates for this reaction. The results are summarized
in Table 3. As the entries in Table 3 reveal, in spite of clear different effect of electrophilic
nature of nitrile on the reaction times and product yields, the catalysis proceeded well for a
wide variety of aryl nitriles, and provided the corresponding tetrazoles in high yields.
Reactions of electron poor nitrile compounds were completed within a short reaction time,
whereas electron rich nitriles required more reaction time to proceed properly, therefore it
seems that the more electronꢀpoor a nitrile, the faster it reacts. As it is depicted in Table 3, the
reaction completion for aromatic nitriles with electron withdrawing substituents at para
position took less time (10ꢀ25 min) for complete conversion of starting materials (Table 3,
entries 2ꢀ5). Interestingly 1,4ꢀdicyanobenzene (Table 3, entry 5) afforded the monoꢀaddition
product selectively, while in the reaction between sodium azide and 1,4ꢀdicyanobenzene in
6
2,22
the presence of Zn(II) salts the double addition product was reported.
nitrobenzonitrile results the desired product in longer reaction time due to steric effect and
electron donation of –NH substitution at ortho position (Table 3, entry 6). Moreover,
2ꢀAminoꢀ5ꢀ
2
aromatic rings with electron donating groups gave the corresponding tetrazoles in high yields,
although longer reaction times (20ꢀ60 min) were required (Table 3, entries 7ꢀ12). It is worth
to note that, aryl nitrile containing a free hydroxyl group at para and ortho positions gave
desired product in high yield after 30 and 20 min respectively (Table 3, entries 11 and 12).

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Hydroxyl group at ortho position render inductive effect which accelerates the cycloaddition
reaction of 2ꢀhydroxybenzonitrile. Phenanthreneꢀ9ꢀcarbonitrile with steric hindrance at 9
position produced the corresponding tetrazole after 45 min (Table 3, entry 13). Similarly,
heteroaryl nitriles were found to be extremely reactive substrate affording the relative
tetrazole rapidly in the presence of expanded perlite (Table 3, entries 14ꢀ16). We next
examined the cycloaddition of alkyl nitriles such as 2ꢀphenylacetonitrile, 3ꢀ
methylbutanenitrile and 4ꢀmethylpentanenitrile in the presence of the expanded perlite. It was
found that alkyl nitriles in the presence of expanded perlite reacted smoothly to give the
corresponding 5ꢀsubstitutedꢀ1Hꢀtetrazoles in excellent yields after 45ꢀ80 min (Table 3,
entries 17ꢀ19). The results obtained from Table 3 indicate that [3 + 2] cycloaddition reaction
of nitriles with azide ion in the presence of highly porous expanded perlite proceeds rapidly
irrespective of the electronic nature of nitrile compounds.
Table 3. Synthesis of different structurally 5ꢀsubstitutedꢀ1Hꢀtetrazoles in the presence of the
expanded perlite under solventꢀfree conditions.
Entry
R
Product
Time
Isolated Yield (%)
(min)
1
2
3
4
5
6
7
C
6
H
5
3a
3b
3c
3d
3e
3f
10
95
94
90
91
96
93
90
4ꢀClC
4ꢀBrC
4ꢀNO
6
H
4
15
6
H
4
25
2
C
6
H
4
10
4ꢀCNC H4
10
6
2ꢀNH 5ꢀNO C H
30
2
2
6
3
4ꢀEtOC
6
H
4
3g
35

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8
9
3,5ꢀdiꢀMeOC H4
3h
3i
60
57
50
30
20
45
20
35
20
45
80
65
92
94
94
85
93
84
95
91
89
95
90
91
6
4ꢀMeC H4
6
1
0
1
2
3
4
5
6
7
8
9
3ꢀMeC H4
3j
6
1
1
1
1
1
1
1
1
1
4ꢀOHC H4
3k
3l
6
2ꢀOHC H4
6
9ꢀphenanthrene
3m
3n
3o
3p
3q
3r
3s
4ꢀpyridine
2ꢀpyridine
2ꢀthiophene
C H CH
6
5
2
(CH ) CHCH
3
2
2
(CH
3
)
2
2 2
CH(CH )
All synthesized tetrazoles were known compounds and characterized by FTꢀIR spectroscopy,
mass spectrometry and comparison of their melting points with known compounds. In
1
13
addition, the structure of all products was certified by H NMR and C NMR spectroscopy.
In all cases, formation of 5ꢀsubstituted 1 ꢀtetrazoles was confirmed by disappearance of the
strong and sharp absorption band at about 2200 cm (related to the CN stretching vibration),
H
ꢀ1
ꢀ1
and the appearance of an absorption band at 3485ꢀ3329 cm (related to the NꢀH stretching
ꢀ1
vibration). Moreover, the FTꢀIR spectra of all products reveal peaks at 1469ꢀ1430 cm (due
ꢀ1
to scissoring bending CꢀH), 1293–1233 cm (due to N–N=N–), 1189–1110 and 1106ꢀ1041
ꢀ1
1
13
cm (due to tetrazole ring). In H NMR and C NMR spectra, a signal at 10.98ꢀ7.80 and
25ꢀ27
164–151 ppm are correspond to the NH and quaternary carbon NH–C=N respectively.
The plausible mechanism for the reaction pathway under current development is shown in
Scheme 2. As mentioned before, only poor yield of product was obtained in the absence of
expanded perlite even after a long reaction time (Table 2, entry 1). This fact, elucidated the
superior catalytic activity of expanded perlite in [3 + 2] cycloaddition reactions of various

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organic nitriles with azide ion. Since the role of catalyst in [3 + 2] cycloaddition reaction is
not apparent certainly, the next study was to understand which segment or feature of the
expanded perlite has the essential effect on catalyzing process. Assuming that the reaction
proceeds through hydrogen bonding of catalyst hydroxyls with nitrogen atom of nitrile, the
model reaction was also carried out in the presence of silica, alumina and a mixture of silica :
alumina (5.6:1 w/w %) (Table 2, entries 20ꢀ24). Although, the FTꢀIR spectra (Fig. 2) verified
the existence of more OH groups in silica and alumina than expanded perlite, the reaction
progress in the presence of each fundamental segments of perlite (silica, alumina and a
mixture of silica : alumina (5.6:1 w/w %)) was not satisfying. These results led us to conclude
that the hydroxyl groups of catalyst might affect the reaction progress but they had not the
dominate role.
Then, to study the effect of the expanded perlite porosity (which corroborated by SEM
images (Fig. 1)) on the [3 + 2] cycloaddition reaction of organic nitriles with azide ion, the
model reaction was performed in the presence of finely powdered and nonꢀpowdered
expanded perlite. Excellent yield of product was obtained in the presence of finely powdered
expanded perlite, while 5ꢀphenylꢀ1Htetrazole was obtained in 15 % yield in the presence of
nonꢀpowdered perlite (Table 2, entry 19). Consequently, [3 + 2] cycloaddition reaction of
organic nitriles with azide ion in the presence of expanded perlite was dependent on the
physical form of the catalyst, strongly. Thus, the porosity of expanded perlite has not vital
effect on the reaction rate.
5
9
The above findings instructed us to the presence of definite multiꢀcatalytic active sites on
the surface of expanded perlite which presumably has the principal catalytic role in this
transformation. By analogy with previous reports in the literature, as well as our recent
25ꢀ27
studies,
it is assumed that a ternary complex I between nitrile compound, azide ion and
expanded perlite would be formed in the transition state immediately as shown in Scheme 2.

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Subsequently, the nitrile functionality is activated through acidic sites of perlite surface
which accelerates the cyclization step by increasing the electrophilicity of nitrile group. Then,
the reaction proceeds via [3 + 2] cycloaddition between the C≡N bond of nitrile and azide ion
to form the intermediate II which is followed by formation of complex III upon protonolysis
by HCl (4 N). Complex III converted to more stable complex IV which is the desired 5ꢀ
substituted 1
Hꢀtetrazole. Finally expanded perlite reꢀinters the catalytic cycle. It is worth to
note that the expanded perlite was not destroyed in workꢀup procedure, since the expanded
46
perlite offers very good chemical stability in acidic condition. More investigation for the
clarification of the mechanism and scope of this reaction are presently in progress in our
laboratory.
Scheme 2 Proposed mechanism for the synthesis of 5ꢀsubstitutedꢀ1Hꢀtetrazoles in the
presence of the expanded perlite.

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Heterogeneous catalysis is quite desirable due to ease of separation and probable reusability
in further runs. Thus, the recyclability of expanded perlite was examined in the oneꢀpot
synthesis of 5ꢀphenylꢀ1Hꢀtetrazole 3a under optimized conditions. After completion of [3 +
2] cycloaddition reaction of benzonitrile with azide anion, the reaction mixture was acidified
and then the catalyst was separated by simple filtration from the reaction mixture. To remove
all organic components, the catalyst was washed with distilled water, methanol and ethanol
three times. The catalyst was dried at 100°C for 3 h. As it is illustrated in Fig. 3 no significant
loss in catalytic activity and product yield was observed even after six runs.
1
00
100
9
8
98
9
6
9
2
9
5
95
9
2
92
9
0
86
1
00
8
6
4
2
0
0
0
0
0
First
Second
Third
Fourth
Fifth
Sixth
Isolated Yield
Conversion
Fig. 3 [3 + 2] Cycloaddition reaction of benzonitrile with azide ion in the
presence of reused expanded perlite.

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th
The FTꢀIR spectrum of the 6 recovered expanded perlite was shown in Fig. 1b. It is worth
mentioning that the position, shape and relative intensity of all characteristic peaks are well
maintained. The results suggest no significant changes were observed in the chemical
structure of expanded perlite network even after six runs.
Experimental
General
The purity determinations of the products were accomplished by TLC on silica gel polygram
STL G/UV 254 plates. The melting points of products were determined with an
Electrothermal Type 9100 melting point apparatus. The FTꢀIR spectra were recorded on an
Avatar 370 FTꢀIR Therma Nicolet spectrometer. The NMR spectra were provided on Brucker
3 6 3
Avance 100, 300 and 400 MHz instruments in CDCl , DMSOꢀd and CD CN. Mass spectra
were recorded with Agilent Technologies (HP) 5973 Network Mass Selective Detector,
Shimadzu GCꢀMSꢀQP5050 instruments and a CH7A Varianmat Bremem instrument
(Germany) at 70 eV. Elemental compositions were determined with a Leo 1450 VP scanning
electron microscope equipped with an SC7620 energy dispersive spectrometer (SEMꢀEDS)
presenting a 133 eV resolution at 20 kV. The chemical compositions of the expanded perlite
were specified with Xꢀray fluorescence spectroscopy (XRF), using BRUKER axsꢀS4
EXPLORER spectrometer. All of the products were known compounds and they were
characterized by the FTꢀIR spectroscopy and comparison of their melting points with known
1
13
compounds. The structure of all products was further confirmed by H NMR, C NMR
spectroscopy, and mass spectrometry. Expanded perlite was obtained from Iran; Birjand
resources.
Providing of neat expanded perlite powder

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Finely powdered expanded perlite (10 g) was added to 400 mL methanol and ethanol (1/1
v/v) and stirred at room temperature for 24 h. to remove organic components. The resulting
suspension was filtered and washed by distilled water, methanol and ethanol three times
respectively. The grey resulting expanded perlite powder was dried at 100 ºC for 3 h.
63
Preparation of 1-butyl-3-methylimidazolium chloride
1ꢀChlorobutane (10.8 g, 0.8 mol) was added to 1ꢀmethyimidizole (8.2 g, 0.1 mol), in a round
bottomed flask equipped with a reflux condenser. The mixture was stirred at 70 ºC for 48 h.
After formation of two phases, the top layer which contains unreacted starting material was
decanted. Then ethyl acetate (30 mL) was added with entire mixing followed by its
decantation and this step was repeated three times. After the third decanting of ethyl acetate,
remaining solvent was removed by heating at 70 ºC. The obtained pale yellow liquid was
vacuum distilled and the resulting 1ꢀbutylꢀ3ꢀmethylimidazolium chloride was placed for
vacuum drying at 80 ºC in a vacuum drying oven.
2
8
Preparation of 1-butyl-3-methylimidazolium azide
Freshly prepared 1ꢀbutylꢀ3ꢀmethylimidazolium chloride (3.49 g, 20 mmol) and NaN
0 mmol) were added into 25 mL deionized water, and the mixture was stirred for 24 h at
3
(1.30 g,
2
room temperature. The solvent was removed under reduced pressure at 50 ºC. To separate 1ꢀ
butylꢀ3ꢀmethylimidazolium azide from the crude product (which contains azide ionic liquid
and NaCl), the resulting was washed with acetonitrile (3×10 mL). The remaining acetonitrile
was removed under high vacuum to yield yellow transparent liquid that became more viscous
upon extensive drying. Isolated yield was 92 % (3.33 g).
Typical procedure for preparation of 5-phenyl-1
perlite
H-tetrazole in the presence of expanded

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Finely powdered expanded perlite (0.05 g) was added to a mixture of benzonitrile (0.103 g, 1
mmol) and [bmim]N (0.271 g, 1.5 mmol).The resulting mixture was stirred at 110 C. The
3
˚
progress of the reaction was monitored by TLC. After completion of the reaction, the reaction
mixture was cooled and treated with HCl (4 N, 10 mL) and ethyl acetate (2×10 mL). The
catalyst was filtered and the resulting organic layer was washed with distilled water, dried
over anhydrous sodium sulfate and concentrated to give the crude solid crystalline 5ꢀphenylꢀ
1
0
Hꢀtetrazole (3a). The crude product was recrystallized from nꢀhexane/ethylacetate (1:1) and
.138 g of colourless crystals (95% Isolated Yield) was obtained.
Afterwards, to reuse the catalyst in the next runs, the separated catalyst from the reaction
mixture was washed with distilled water, methanol and ethanol three times to remove all
organic components and it was dried at 100°C for 3 h.
Conclusion
In conclusion, we have introduced highly porous expanded perlite as a green and high
efficient heterogeneous catalyst which exhibited superior catalytic activity for the oneꢀpot
synthesis of 5ꢀSubstituted 1Hꢀtetrazoles under solventꢀfree conditions. The essential catalytic
role of expanded perlite in this transformation is activation of nitrile through its surface multiꢀ
59
catalytic active sites. Stability, lowꢀtoxicity, low cost and recyclability are the significant
properties of this catalyst. In comparison with previously published procedures, 1ꢀbutylꢀ3ꢀ
methylimidazolium azide ([bmim]N
3
) ionic liquid was used as an azide source, in place of
the highly toxic reagents such as NaN or TMSN . Various nitriles reacted with azide ion at
3
3
110 ºC to yield the corresponding 5ꢀsubstitutedꢀ1Htetrazoles. The noteworthy advantages of
this approach are excellent yields of products, short reaction times (in comparison with the
previous existing methodologies), solventꢀfree conditions, simple workꢀup procedure, easy
handling of the catalyst, elimination of hazardous and harmful hydrazoic acid as well as toxic

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solvents such as DMF and DMSO. These are also the predominant features supporting this
method in a movement toward the green chemistry.
Acknowledgements
The authors gratefully acknowledge the partial support of this study by Ferdowsi University
of Mashhad Research Council.
Notes and references
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad
9177948974, Iran.
*
Corresponding author: Phone: +98-51-3880-5527, Fax: +98-51-3879-5457,
E-mail: akhlaghinia@um.ac.ir
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here].
1
2
Z. Miao, H. Zhao, H. Song and L. Chou, RSC Adv., 2014, 4, 22509.
N. Koukabi, E. Kolvari, M. A. Zolfigol, A. Khazaei, B. S. Shaghasemi and B. Fasahati,
Adv. Synth. Catal., 2012, 354, 2001.
3
4
5
6
S. Rahmani, A. Amoozadeh and E. Kolvari, Catal. Commun., 2014, 56, 184.
M. A. Zolfigol, Tetrahedron, 2001, 57, 9509.
D. Zareyee and M. Serehneh, J. Mol. Catal. A: Chem., 2014, 391, 88.
D. Elhamifar, M. NasrꢀEsfahani, B. Karimi, R. Moshkelgosha and A. Sh´abani,
ChemCatChem, 2014, 6, 2593.
7
8
H. Naeimi and Z. S. Nazifi, Appl. Catal., A, 2014, 477, 132.
Z. Hasan and S. H. Jhung, Eur. J. Inorg. Chem., 2014, 2014, 3420.

RSC Advances
Page 20 of 24
View Article Online
DOI: 10.1039/C5RA21481E
9
1
1
1
1
F. Nemati, M. M. Heravi and R. Saeedi Rad, Chin. J. Catal., 2012, 33, 1825.
0 B. Bandgar, A. V. Patil and O. Chavan, J. Mol. Catal. A: Chem., 2006, 256, 99.
1 Y.ꢀH. Liu, X.ꢀY. Tao, L.ꢀQ. Lei and Z.ꢀH. Zhang, Synth. Commun., 2009, 39, 580.
2 I. M. Pastor and M. Yus, Curr. Org. Chem., 2005, 9, 1.
3. (a) R. N. Butler, in Comprehensive Heterocyclic Chemistry II; A. R. Katritzky, C. W.
Rees, E. F. V. Eds. Scriven; Pergamon Press: Oxford, 1996; 4, 674; (b) R. N. Butler, in
Comprehensive Heterocyclic Chemistry II; A. R. Katritzky, C. W. Rees, Eds.; Pergamon
Press: Oxford, 1984, 5, 791.
14 J. Roh, K. Vávrová and A. Hrabálek, Eur. J. Org. Chem., 2012, 6101.
15 (a) Y. Tang, G. Wang, Q. Ye, R. Xiong and R. Yuan, Crystal Growth Des., 2007, 7, 2382;
(b) B. Li, S. Chen, Z. Chen, J. Chen, J. Guo and L. Liu, Cryst. Eng. Commun., 2011, 13,
6
1
4
1
1
1
2
2
2
2
1
2
2
2
610.
6 K. Kubendiran, J. Raguraman, S. R. M. Kamil and S. S. Shafi, Asian J. Res. Chem., 2011,
, 1915.
7 L. M. T. Frija, A. Ismael and M. L. S. Cristiano, Molecules, 2010, 15, 3757.
8 K. Koguro, T. Oga, S. Mitsui and R. Orita, Synthesis, 1998, 910.
9 A. Coca and E. Turek, Tetrahedron lett., 2014, 55, 2718.
0 R. J. Herr, Bioorg. Med. Chem., 2002, 10, 3379.
1 A. Hantzsch, A. Vagt, Justus Liebigs Ann. Chem., 1901, 314, 339.
2 Z. P. Demko and K. B. Sharpless, J. Org. Chem., 2001, 66, 7945.
3 For some selected examples, see: (a) D. P. Curran, S. Hadida and S.ꢀY. Kim, Tetrahedron,
999, 55, 8997; (b) J. V. Duncia, M. E. Pierce and J. B. Santella, J. Org. Chem., 1991, 56,
395; (c) A. Valentina and S. Gottfried, Angew. Chem., Int. Ed., 2007, 46, 8440.
4 S. J. Wittenberger and B. G. Donner, J. Org. Chem., 1993, 58, 4139.
5 B. Akhlaghinia and S. Rezazadeh. J. Braz. Chem. Soc., 2012, 23, 2197.

Page 21 of 24
RSC Advances
View Article Online
DOI: 10.1039/C5RA21481E
2
2
2
2
3
2
3
3
3
3
3
3
3
3
6 N. Razavi and B. Akhlaghinia, RSC Adv., 2015, 5, 12372.
7 S. S. E. Ghodsinia and B. Akhlaghinia, RSC Adv., 2015, 5, 49849.
8 H. Valizadeh, M. Amiri and E. Khalili, Mol. Divers., 2012, 16, 319.
9 B. Schmidt, D. Meid and D. Kieser, Tetrahedron, 2007, 63, 492.
0 D. Amantini, R. Beleggia, F. Fringuelli, F. Pizzo and L. Vaccaro, J. Org. Chem., 2004, 69,
896.
1 J. Bonnamour and C. Bolm, Chem. Eur. J., 2009, 15, 4543.
2 G. Aridoss and K. K. Laali, Eur. J. Org. Chem., 2011, 2011, 6343.
3 V. S. Patil, K. P. Nandre, A. U. Borse and S. V. Bhosale, E-J Chem., 2012, 9, 1145.
4 V. Rama, K. Kanagaraj and K. Pitchumani, J. Org. Chem., 2011, 76, 9090.
5 T. Jin, F. Kitahara, S. Kamijo and Y. Yamamoto, Tetrahedron Lett., 2008, 49, 2824.
6 B. Sreedhar, A. S. Kumar and D. Yada, Tetrahedron Lett., 2011, 52, 3565.
7 A. Teimouri and A. N. Chermahini, 2011, Polyhedron, 30, 2606.
8 M. A. Epishina, A. S. Kulikov, N. V. Ignat’ev, M. Schulte and N. N. Makhova,
Mendeleev. Commun., 2011, 21, 334.
9 L. V. Myznikov, Y. A. Efimova, T. V. Artamonova and G. I. Koldobskii, Russ. J. Org.
Chem., 2011, 47, 728.
3
4
7
4
4
4
2
4
4
0 B. Gutmann, J. P. Roduit, D. Roberge and C. O. Kappe, Angew. Chem. Int. Ed., 2010, 49,
101.
1 A. N. Chermahini, A. Teimouri and A. Moaddeli, Heteroat. Chem., 2011, 22, 168.
2 O. Marvi, A. Alizadeh and S. Zarrahi, Bull Korean Chem. Soc., 2011, 32, 4001.
3 J. Roh, T. V. Artamonova, K. Vavrova, G. I. Koldobskii and A. Hrabalek, Synthesis, 2009,
175.
4 D. Cantillo, B. Gutmann and C. O. Kappe, J. Am. Chem. Soc., 2011, 133, 4465.
5 V. Aureggi and G. Sedelmeier, Angew. Chem. Int. Ed., 2007, 46, 8440.

RSC Advances
Page 22 of 24
View Article Online
DOI: 10.1039/C5RA21481E
46 A. Majouli, S. Alami Younssi, S. Tahiri, A. Albizane, H. Loukili and M. Belhaj,
Desalination, 2011, 277, 61.
47 M. Alkan and M. Dogan, J. Colloid Interface Sci., 2001, 243, 280.
48 V. Blaskov, I. Stambolova, V. Georgiev, T. Batakliev, A. Eliyas, M. Shipochka, S.
Vassilev and D. Mehandjiev, Ozone Sci. Eng., 2015, 37, 252.
4
1
5
2
5
5
5
2
5
9 T. K. Erdem, C. Meral, M. Tokyay and T. Y. Erdogan, Cem. Concr. Compos., 2007, 29,
3.
0 S. N. Hosseini, S. M. Borghei, M. Vossoughi and N. Taghavinia, Appl. Catal. B: Environ.,
007, 74, 53.
1 O. Sengul, S. Azizi, F. Karaosmanoglu and M. A. Tasdemir, Energy Build., 2011, 43, 671.
2 S. Yilmazer and M. B. Ozdeniz, Build Environ., 2005, 40, 311.
3 M. Roulia, K. Chassapis, J. A. Kapoutsis, E. I. Kamitsos and T. Savvidis, J. Mater. Sci.,
006, 41, 5870.
4 D. Acosta, J. Martinez, C. Carera, E. Erdmann, E. Gonzo and H. Destéfanis, Lat. Am.
Appl. Res., 2006, 36, 317.
5
5
5
5 Z. Talip, M. Eral, and Ü. Hiçsönmez, J. Environ. Radioact., 2009, 100, 139.
6 Y. Kar, Waste Manage., 2011, 31, 1772.
7 N. Tekin, E. Kadın, O¨. Demirbas, M. Alkan, A. Kara and M. Dog ˘an, Micropor.
Mesopor. Mat., 2006, 93, 125.
8 (a) M. Nasrollahzadeh, S. M. Sajadi, A. RostamiꢀVartooni, M. Bagherzadeh and R. Safari,
5
J. Mol. Catal. A: Chem., 2015, 400, 22; (b) E. Kolvari, N. Koukabi and M. M. Hosseini, J.
Mol. Catal. A: Chem., 2015, 397, 68; (c) E. Kolvari, N. Koukabi, M. M. Hosseini and Z.
Khandani, RSC Adv., 2015, 5, 36828; (d) R. Sahraeian, S. A. hashemi, M. esfandeh and I.
Ghasemi, Polym. Polym. Compos., 2012, 20, 639; (e) D. N. Thanh, M. Singh, P. Ulbrich, N.
Strnadova and F. Štěpánek, Sep. Purif. Technol., 2011, 82, 93; (f) J. SkubiszewskaꢀZięba, B.

Page 23 of 24
RSC Advances
View Article Online
DOI: 10.1039/C5RA21481E
charmas, R. leboda and V. M. Gun’ko, Micropor. Mesopor. Mat., 2012, 156, 209; (g) S.
hasan, T. K. Ghosh, D. S. viswanath and V. M. Boddu, J. Hazard. Mater., 2008, 152, 826.
59 Y. Abrouki, A. Anouzla, H. Loukili, A. Chakir, M. A. Bahlaoui, A. Rayadh, M. Abrouki,
M. E. Idrissi, M. Zahouily, K. E. Kacemi, J. Bessiere, B. Marouf and S. Sebti, I. J. C., 2013,
1
, 1.
60 Y. Abrouki, A. Anouzla, H. Loukili, A. Chakir, M. Idrissi, A. Abrouki, A. Rayadh, M.
Zahouily, K. E. Kacemi, J. Bessiere, B. Marouf and S. Sebti, Am. J. Biol. Chem. Pharm. Sci.,
2
6
6
1
013, 1, 28.
1 K. Sodeyama, Y. Sakka and Y. Kamino, J. Mater. Sci., 1999, 34, 2461.
2 (a) F. Himo, P. Z. Demko, L. Noodleman and K. B. Sharpless, J. Am. Chem. Soc., 2002,
24, 12210; (b) F. Himo, P. Z. Demko, L. Noodleman and K. B. Sharpless, J. Am. Chem.
Soc., 2003, 125, 9983.
63 P. N. Tshibangu, S. N. Ndwandwe and E. D. Dikio, Int. J. Electrochem. Sci., 2011, 6
2201.

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Graphical Abstract
Expanded perlite: an inexpensive natural efficient heterogeneous catalyst for the green and highly
accelerated solvent-free synthesis of 5-
substituted 1H-tetrazoles using [bmim]N and
3
nitriles
Roya Jahanshahi, Batool Akhlaghinia*
A versatile, green and highly accelerated protocol
for preparing 5-substituted 1H-tetrazoles is reported
using expanded perlite as a heterogeneous catalyst.