Green synthesis of the 1-substituted 1H-1, 2, 3, 4-tetrazoles over bifunctional catalyst based on copper intercalated into Mg/Al hydrotalcite modified magnetite nanoparticles

Article abstract of DOI:10.1002/aoc.5682

An effective one-pot, convenient process for the synthesis of 1- substituted 1H-tetrazoles from triethyl orthoformate, amines, and sodium azide is described using copper (II) doped and immobilized on functionalized magnetic hydrotalcite (Fe₃O₄/HT-NH₂ Cu^II) as a novel recyclable catalyst. The application of this catalyst allows the synthesis of a variety of tetrazoles in good to excellent yields in water. The new catalyst was characterized using Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), vibration sample magnetometry (VSM) and inductively coupled plasma analysis (ICP-OES). This new procedure offers several advantages such as short operational simplicity, practicability, and applicability to various substrates and the absence of any tedious workup or purification. The loading amount of Cu^II (doped and immobilized) on functionalized magnetic hydrotalcite was indicated to be 4.66 mmol g^?1, obtained from the ICP-OES analysis. Also, the excellent catalytic performance, thermal stability, and separation of the catalyst make it an excellent heterogeneous system and a useful alternative to other heterogeneous catalysts. Also, the catalyst could be magnetically separated and reused six times without significant loss of catalytic activity.

Full text of DOI:10.1002/aoc.5682

Received: 5 January 2020
DOI: 10.1002/aoc.5682
Revised: 3 March 2020
Accepted: 5 March 2020
F U L L P A P E R
Green synthesis of the 1-substituted 1H-1, 2, 3, 4-tetrazoles
over bifunctional catalyst based on copper intercalated into
Mg/Al hydrotalcite modified magnetite nanoparticles
Mehri Salimi
| Azadeh Zamanpour
Department of Chemistry, College of
Sciences, University of Birjand, Birjand,
97175-615, Iran
An effective one-pot, convenient process for the synthesis of 1- substituted 1H-
tetrazoles from triethyl orthoformate, amines, and sodium azide is described
using copper (II) doped and immobilized on functionalized magnetic
hydrotalcite (Fe3O4/HT-NH2 CuII) as a novel recyclable catalyst. The applica-
tion of this catalyst allows the synthesis of a variety of tetrazoles in good to
excellent yields in water. The new catalyst was characterized using Fourier
transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning
electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), ther-
mogravimetric analysis (TGA), vibration sample magnetometry (VSM) and
inductively coupled plasma analysis (ICP-OES). This new procedure offers sev-
eral advantages such as short operational simplicity, practicability, and appli-
cability to various substrates and the absence of any tedious workup or
purification. The loading amount of CuII (doped and immobilized) on
Correspondence
Mehri Salimi, Department of Chemistry,
College of Sciences, University of Birjand,
Birjand 97175-615, Iran.
Email: msalimi@birjand.ac.ir;
m_salimi4816@yahoo.com
functionalized magnetic hydrotalcite was indicated to be 4.66 mmol g−1
,
obtained from the ICP-OES analysis. Also, the excellent catalytic performance,
thermal stability, and separation of the catalyst make it an excellent heteroge-
neous system and a useful alternative to other heterogeneous catalysts. Also,
the catalyst could be magnetically separated and reused six times without sig-
nificant loss of catalytic activity.
K E Y W O R D S
Fe3O4/HT-NH2-CuII nanoparticles, hydrotalcite, one-pot, sodium azide, Tetrazole, triethyl
orthoformate
1 | INTRODUCTION
nucleus is of much current importance. In recent years
several synthetic methods have been reported for the
Tetrazoles have received considerable interest in recent
times because of their comprehensive utility. Among
them, 1-substituted tetrazoles have attracted much atten-
tion and have been used in a variety of synthetic and
medicinal chemistry applications as well as in material
science, including propellants and explosives.[1–5] They
are also regarded as biologically equivalent to the carbox-
ylic acid groups.[6] Thus, the synthesis of this heterocyclic
preparation of 1-substituted 1H tetrazoles.[7–11] One of
the most efficient and conventional methods for the syn-
thesis of 1-substituted 1H-tetrazoles is through [3 + 2]
cycloaddition reaction between hydrazoic acid, primary
amines, and triethyl orthoformate moieties.[12,13]
Some drawbacks suffer from this protocol, such as
toxic procedure, acidic condition, and usage of a highly
polar solvent. Recently, researchers attempt to avoid
Appl Organometal Chem. 2020;e5682.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5682

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SALIMI AND ZAMANPOUR
using hydrazoic acid as poisonous gas during the synthe-
sis of tetrazoles. However, applying sodium azide in
acidic media, leading to the elimination of hydrazoic
acid, and by avoiding acidic conditions, the reaction
required a substantial excess of sodium azide.
methods (centrifugation and filtration) with magnetic
separation approaches is a fascinating technique. Thus,
the incorporation of magnetic nanoparticles (MNPs) into
the hydrotalcite structure[35,36] provides easy separation
of catalysts from the reaction mixture using an external
magnetic and also prevents MNP agglomeration.
Several catalysts have been also reported for the prep-
aration of tetrazoles using sodium azide, such as FeCl3-
SiO2,
In this research, we synthesized Fe3O4/HT-NH2-CuII
and developed a more efficient and convenient method
for the one-pot condensation of primary amines, triethyl
orthoformate, and sodium azide toward 1-substituted 1H-
tetrazoles in the presence of this nanocatalyst as a new
heterogeneous catalyst condition (Scheme 1).
ZnS nanoparticles,[14] montmorillonite K-10
[11]
clay,[15] nano-TiO2,[16] natrolite zeolite,[17] the Salen com-
plex of Cu (II) supported on superparamagnetic
Fe3O4@SiO2 nanoparticles[18] Fe3O4@tryptophan@Ni[19]
CoFe2O4@L-aspargine-Cu[20] CoFe2O4@Pr,[21] Fe3O4@R.
tinctorum/Ag NP[22] Pd NPs/rGO-T. Spicata[23] and mag-
netic nanocatalysts of copper and manganese.[24–26]
While many of the reported methods are worthwhile,
some of them have lots of limitations and suffer from
drawbacks such as low efficiency and high reaction tem-
peratures, prolonged reaction time, the cost of the cata-
lysts, and side reactions. Because of the limitations as
mentioned above, introducing a green and highly effi-
cient method using a new heterogeneous, magnetic reus-
able and nonhazardous nanocatalyst for the synthesis of
tetrazoles is of importance. Today organic synthesis con-
cerning the principle of green chemistry continues to be
explored.
2 | EXPERIMENTAL
2.1 | General
All chemical reagents and solvents were purchased from
Merck and Sigma-Aldrich chemical companies and were
used as received without further purification. The purity
determinations of the products were accomplished by
TLC on silica gel polygram STL G/UV 254 plates or GC
on a Shimadzu model GC-17A instrument. The FT-IR
spectra were recorded on pressed KBr pellets using a
Nicoet 800 FT-IR spectrometer at room temperature in
the range between 4000 and 400 cm−1. The NMR spectra
were obtained on Brucker Avance 300 MHz instruments
in DMSO-d6. All the yields refer to isolated products
after purification by thin-layer chromatography or
recrystallization.
Among the attempts made in connection with this
issue, also performing one-pot reactions (the combination
of more than two or three different reactants in a single
step through covalent bonds) using green and environ-
mentally friendly catalysts and mild reaction conditions
has been taken into consideration. For this purpose, to
improve the long-term durability and activity of catalysts,
hydrotalcite (HT) and magnetic hydrotalcite (MHT) have
been widely studied as promising supporting materials
for catalysts in organic reactions. Layered double hydrox-
ides (LDHs) are a class of anionic clays with the structure
based on brucite (Mg (OH)2)-like layers in which some of
the divalent cations have been replaced by trivalent cat-
2.2 | Preparation of HT (I)
To a solution containing Mg (NO3)2.6H2O (10.25 g,
40 mmol) and Al (NO3)3.9H2O (7.50 g, 20 mmol) in 60 ml
distilled water, a mixed solution (60 ml) containing
NaOH (4 g, 100 mmol) and NaHCO3 (2.1 g, 25 mmol)
ions yielding positively charged sheets. LDHs can be rep-
M3x + (OH)2]x+
was added drop by drop under vigorous stirring at 60 C.
2 +
ꢀ
resented by a general formula, [M
1−x
(An)x/n.mH2O (where M2+ and M3+ are di, and trivalent
metal ions and An indicates the interlayer anions such as
After 24 hr. The obtained white solid was filtered and
washed with deionized water until the pH reached 7 to
remove the alkali metal ions. The obtained Mg-Al
hydrotalcite (I) (molar ratio Mg/Al = 2) was then dried at
80 ꢀC for 12 hr.
−
CO23− , Cl−, SO24− ) with abundant surface hydroxyl
groups. The first known compound in this class of mate-
rials is the double hydroxide of Mg with Al, known as
hydrotalcite, which was found by Hochstetter in Sweden,
with a chemical formula of Mg6Al2(OH)16CO3.4H2O. The
Mg-Al mixed oxides which are chemically active sites for
use in catalytic reactions and also act as the anchoring
sites for metal nanoparticles.[27–34]
On the other hand, the separation of hydrotalcite
based catalysts from the reaction mixture is difficult to
some extent,[27] replacement of conventional separation
SCHEME 1 Synthesis of tetrazoles derivatives catalyzed by
Fe3O4/HT-NH2-CuII

SALIMI AND ZAMANPOUR
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2.3 | Preparation of Fe3O4/HT (II)
2.7 | A typical procedure for the
preparation of 1-substituted 1H-
1,2,3,4-tetrazoles
In a three-necked 500 Ml, round-bottom flask equipped
with an argon gas inlet tube and a dropping funnel, a
mixture of FeCl3.6H2O (2.1 g, 8 mmol) and FeCl2.4H2O
(1.05 g, 5.2 mmol) were dissolved in 100 ml deionized
water. Then, the resultꢀing mixture was mechanically
stirred for 10 min at 80 C under Ar atmosphere. After-
ward, hydrotalcite (I) (4 g) and NaOH solution (100 ml,
5%) were simultaneously added into the solution under
vigorous stirꢀring. The resulting brown mixture was
stirred at 80 C for 24 hr. Finally, the mixture was per-
mitted to cool to room temperature, and then Fe3O4/
HT (II) was collected by an external magnet and
washed with distilled water several times until the pH
reached 7. Subsequently, Fe3O4/HT (II) was dried at
A mixture of amine 5(a-l) (1 mmol), triethyl orthoformate
6 (1.4 mmol) and sodium azide (1.1 mmol) in the pres-
ence of 0.005 g Fe3O4/HT-NH2-CuII was added to water
(10ꢀml) as solvent and the reaction mixture was stirred at
90 C until monitoring with TLC showed no further pro-
gress in the conversion. When the reaction mixture came
to ambient temperature, nanocatalyst separated using an
external magnet, washed with EtOH and acetone, and
dried at room temperature for 24 hr for the next run use.
The reaction mixture was then extracted with ethyl ace-
tate (4 × 5 ml) the resulting solution dried over MgSO4
and evaporated to get a solid product. The residue was
concentrated and recrystallized from EtOAc–hexane mix-
ture (1:9). The structural assignment of their products is
based on 1H-NMR, and IR spectra.
ꢀ
50 C for 12 hr.
2.4 | Preparation of epichlorohydrin
functionalized fe3O4/HT (Fe3O4/HT-E) (III)
2.7.1 | Selected spectral data
Fe3O4/HT (II) (1.0 g) was incorporated with pure epichlo-
rohydrin (6 ml) and dispersed by sonication for 30 min.
After that, the mixture was refluxed for 72 hr. Succes-
sively, Fe3O4/HT-E (III) was magnetically collected,
washed with ethanol (5 × 10 ml) until removing the addi-
tional amount of epichlorohydrin, and then dried at
60 ꢀC under vacuum for 12 hr.
1-phenyl-1H-tetrazꢀole (Compound 1, Table 1): yellow
solid; m.p = 65–67 C, IR (KBr)/ V (cm−1): 3060 (C-H,
sp2 stretch Ar), 1680 (C=N), 1590, 1465 (C=C); (3120,
3060, 2918, 1748, 1680, 1590, 1501, 1465, 1391, 1207,
1091, 1052, 995, 960, 911, 880, 760, 686, 507); H NMR
(CDCl3, 300 MHz) δ (ppm): 7.53–7.75 (m, 5H, Ar), 9.11
(s, 1H tetrazole).
1
1-benzyl-1H-tetrazole (Compound 2, Table 1):
White solid; m.p = 132–133 ꢀC; IR (KBr)/ V (cm−1): 3060
(C-H, sp2 stretch Ar), 1643 (C=N), 1534, 1453 (C=C).
(3271, 2928, 2859, 1590, 1457, 1408, 1360, 1299, 1245,
1200, 1132, 1003, 956, 881, 750, 633); H NMR (CDCl3,
300 MHz) δ (ppm) 4.47–4.49 (s, 2H), 7.28–7.39 (m, 5H),
8.24 (s, 1H).
2.5 | Preparation of diethylenetriamine
functionalized Fe3O4/HT-NH2 (IV)
1
To a suspension of the obtained Fe3O4/HT-E (III)
(1 g) in ethanol (10 ml) (by sonication for 30 min),
diethylenetriamine (0.32 ml, 3 mmol) was added.
The resultant mixture was refluxed for 48 hr. Then,
Fe3O4/HT-NH2 (IV) was separated magnetically,
washed with ethanol (5 ×10 ml), and then dried at
1,2-di (1-H-tetrazole-1-yl) benzene (Compound
ꢀ
3, Table 1): White solid; m.p = 169–173 C, IR (KBr)/ V
(cm−1): 3060 (C-H, sp2 stretch, Ar), 1618 (C=N) 1457,
1588 (C=C); (3316, 3060, 3004, 2935, 2859, 1618, 1588,
1457, 1408, 1360, 1299, 1245, 1200, 1132, 1003, 956, 881,
750, 633); 1H NMR (CDCl3, 300 MHz) δ (ppm): 7.12–7.63
(m, 4H), 8.24 (s, 1HTetrazole).
ꢀ
60 C for 12 hr.
2.6 | Preparation of Fe3O4/HT-NH2-CuII
nanoparticles (V)
To a solution of Cu (OAc)2 (0.4 g, 2 mmol) in EtOH
(15 ml), the obtained Fe3O4/HT-NH2 (IV) (1 g)
(by sonication for 30 min) was added and stirred at for
12 hr. Afterwards, the resulting suspension was col-
lected using an external magnet and repeatedly
3 | RESULTS AND DISCUSSION
HT (I) was prepared through the co-precipitation method
and synthesis of Fe3O4/HT (II), HT (I) was performed
using an alkaline mixed salt-solution of ferrous and ferric
ions. Thereafter, the surface of Fe3O4/HT (II) was modi-
fied by epichlorohydrin and then by diethylenetriamine
ꢀ
washed with EtOH (4 ×10 ml) and dried at 80 C for
8 hr.

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SALIMI AND ZAMANPOUR
TABLE 1
Preparation of tetrazole derivatives using Fe3O4/HT-NH2-CuII catalystEntry
Substrate Product
Time(h)
1
Yield (%)
94
1
2
1
85
80
3
1.5
4
5
2.5
85
75
2
6
7
3
75
50
2.5
8
9
3
2
70
65

SALIMI AND ZAMANPOUR
5 of 14
TABLE 1 (Continued)
Substrate
Product
Time(h)
Yield (%)
55
10
1
11
1.5
90
12
13
2
45
85
1.5
14
15
3
3
65
50
16
2
85
(Continues)

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SALIMI AND ZAMANPOUR
TABLE 1 (Continued)
Substrate
Product
Time(h)
Yield (%)
17
3
trace
Reaction Conditions: amine (1 mmole), sodium azide (1.1 mmol), triethyl orthoformate (1.4 mmol), Fe3O4-HT-NH2-CuII, H2O (2 cc), 90 ꢀC
to produce Fe3O4/HT-E (III), and Fe3O4/HT-E-NH2
(IV) respectively. Then Cu (II) immobilized on Fe3O4/
HT-NH2(IV) in EtOH to obtain Fe3O4/HT-NH2-Cu
(II) (V) nanoparticles (Scheme 2).
analysis (TGA), vibrating sample magnetometer (VSM)
and inductively coupled plasma optical emission spec-
troscopy (ICP-OES).
The catalytic system was well characterized by
using various techniques such as Fourier transform
infrared spectroscopy (FT-IR), X-ray powder diffraction
(XRD), transmission electron microscopy (TEM), field
emission scanning electron microscopy (FE-SEM),
energy-dispersive X-ray (EDX), thermogravimetric
3.1 | FT-IR spectroscopy
Fourier transform infrared (FT-IR) spectroscopy evi-
dences the modification of Fe3O4/HT NPs surface.
Figure 1 illustrates the FT-IR spectra of HT (a), Fe3O4/
SCHEME 2 Preparation of catalyst (Fe3O4/HT-NH2-CuII)

SALIMI AND ZAMANPOUR
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FIGURE 1 FT-IR spectra of HT (a), Fe3O4/
HT(b) and Fe3O4/HT-E (c) Fe3O4/HT-NH2 (d),
Fe3O4/HT-NH2-Cu(II) (e)
HT (b), Fe3O4/HT-E (c), Fe3O4/HT-NH2 (d) and Fe3O4/
HT-NH2- CuII (e). As shown in Figure 1a, the broadband
at 3479 cm−1 was indicative of the OH symmetric
stretching vibration of Mg–OH and Al–OH on the surface
of the hydrotalcite structure. The vibration mode at
1634 cm−1 could be attributed to the bending vibrations
of water molecules in a hydrotalcite structure. Also, the
absorption bands appearing at 1373 and 665 cm−1 cor-
responded to the asymmetric stretching vibration of C–O
(indicating the presence of CO23− ) and the angular bend-
ing mode of carbonate species, respectively. This shows
that the carbonate anions are present between the layers
of hydrotalcite. In Figure 1b, the FT-IR spectrum of
Fe3O4/HT (II), the intensity of the adsorption band at
1366 cm−1, became weaker because of the incorporation
of Fe3O4 into the HT structure.
Four new absorption bands confirmed the existence
of the grafted epoxy groups to the Fe3O4/HT framework
at 2926, 2856 (related to the C–H stretching vibrations),
1465 cm−1 (related to the C–H bending vibration) and
1157 (related to the C–O-C stretching vibration). Further-
more in the FT-IR spectrum of Fe3O4/HT-NH2
(Figure 1c), the appearance of a new band at 1526 cm−1
is assigned to the NH bending vibrations, could be
authenticated the existence of the anchored die-
thylenetriamine groups to the hydrotalcite. Finally, the
coordination of Cu (OAc)2 can be verified by the
stretching vibrations that appear at 1570 and 1409 cm−1
(corresponding to stretching modes of carboxylate
groups) and 609 cm−1 (corresponding to stretching vibra-
tions of Cu-N bond). Besides, this coordination can be
authenticated by decreasing the intensity and frequency
of the hydroxyl groups (Figure 1e).
3.2 | X-ray diffraction (XRD) analysis
The XRD patterns of HT (I) and Fe3O4/HT (II) have been
presented in Figure 2. As seen in Figure 2a, the as-syn-
thesized hydrotalcite nanoparticles exhibited characteris-
tic diffraction peaks at around 2θ = 11.9, 22.61, 34.7, 38.8,
45.9, 60.31, and 61.51 which fitted well to the crystal
planes of (003), (006), (012), (015), (018), (110), and (113)
of the hydrotalcite.38furthermore, in Figure 2b, in com-
parison with the pattern of the as-synthesized
hydrotalcite, additional peaks at 2θ = 29.9, 35.5, 43.4,
57.3, and 62.91 were found which can be assigned to the
(220), (311), (400), (511), and (440) planes, proving the
presence of the magnetic (Fe3O4) phase as a cubic lattice
in the hydrotalcite structure. On the other hand, the
intensity of diffraction peaks for the LDH@Fe3O4 is
lower than that of pure LDH, guessed due to the smaller
size of the particles.
3.3 | SEM-EDS images and SEM image
with combined EDS-elemental mapping
The surface morphology of Fe3O4/HT-NH2- CuII was
shown in Figure 3. As given in Figure 3, the as-synthe-
sized HT (I) shows irregular plate-like morphology, rep-
resenting the character of layered materials. It is

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SALIMI AND ZAMANPOUR
FIGURE 2 The XRD patterns of (a) HT (I),
(b) Fe3O4/HT (II)
FIGURE 3 SEM image of Fe3O4/
HT-NH2-Cu(II)
FIGURE 4 EDAX spectra of Fe3O4/
HT-NH2 -CuII

SALIMI AND ZAMANPOUR
9 of 14
mentioned, that Fe3O4 NPs were dispersed on the surface
of plate-like sheets of HT.
Moreover, the EDS analysis confirmed the presence of
Al, Mg, O, C, N, Fe, and Cu elements in the nanocatalyst
structure, as shown in Figure 4. And also, the substantial
intensity of CuII indicated the successful coordination of
CuII on the surface of Fe3O4/HT-NH2 (Figure 5).
3.4 | Thermal gravimetric analysis
(TGA)
To investigate the thermal stability of Fe3O4/HT-NH2 -
CuII, TGA analysis was carried under an air atmosphere
at a heating rate of 10 ꢀC min−1 from 25 to 900 ꢀC
(Figure 6).
FIGURE 6 The TGA thermograms of Fe3O4/HT-NH2-CuII
TGA thermogram of Fe3O4/HT-NH2-CuII (IV) is
shown in Figure 6. The results showed weight loss steps.
Evaporation of the absorbed physical and chemical water
on the catalyst surface or between the layers happened at
35–260 C (6. 5%). The Second step (260–400 C, 11.34%)
is due to the loss of the interlayer carbonate and hydroxyl
groups.62 weight loss (9.66%) at 400–800 ꢀC could be
assigned to the removal of organic functional groups
grafted on the surface of the catalyst.
3.5 | Vibrating sample magnetometer
(VSM) analysis
ꢀ
ꢀ
Magnetic characterization of Fe3O4/HT and Fe3O4/HT-
NH2-CuII was investigated using vibrating sample mag-
netometry at room temperature (Figure 7). As illustrated
in Figure 7 the magnetization value of Fe3O4/HT-NH2-
CuII (9.961 emu g−1) is lower than the magnetization
FIGURE 5 Elemental mapping
of Mg, Al, Fe, C, N, O, and Cu

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SALIMI AND ZAMANPOUR
FIGURE 7 Magnetization curves of Fe3O4/
HT and Fe3O4/HT-NH2-CuII
value of Fe3O4/HT (18.837 emu g−1) due to the immobili-
zation of the Cu complex of diethylenetriamine on the
surface of Fe3O4/HT. It is worth noting that both Fe3O4/
HT and Fe3O4/HT-NH2-CuII are superparamagnetic,
which can be attributed to the presence of Fe3O4 NPs. On
the other hand, the magnetic property of Fe3O4/HT-NH2-
CuII was enough for separated easy and rapid of
nanocatalyst from the reaction mixture with a permanent
magnet.
Also, the ICP analysis showed that 296.081 mg equal
4.66 mmol of copper was anchored on 1.000 g of the
catalyst.
3.6 | Optimization of the catalyst
The subsequent purpose of the synthesis of tetrazole was
to optimize the reaction conditions. Therefore, the cata-
lytic efficiency was studied in the one-pot three-compo-
nent synthesis of 1-substituted 1H-1, 2, 3, 4-tetrazoles as
a model substrate in different reaction conditions
(amount of the catalyst, temperature, and solvent nature
and amount of the solvent).
FIGURE 8 The effect of time in the synthesis of 1H-
1,2,3,4-tetrazole by Fe3O4/HT-NH2-CuII
Reaction conditions: sodium azide (1.1 mmol), aniline (1 mmol),
triethyl orthoformate (1.4 mmol), 2 ml of H2O, 0.005 g of Fe3O4/
HT-NH2-CuII
ꢀ
solvent. The yield is approximately 10% at 25 C, even
3.7 | The effect of temperature
though the mixture was stirred for the lengthy reaction
time. While the reaction temperature has been increased
to 70 ꢀC, the yield also enhanced, and when the tempera-
ture grew up to 90 ꢀC, the excellent yield has been
obtained.
Typically the result of the effect temperature is shown in
Figure 8 [sodium azide (1.1 mmol), aniline (1 mmol);
triethyl orthoformate (1.4 mmol)], which is H2O as a

SALIMI AND ZAMANPOUR
11 of 14
3.8 | The effect of the amount of catalyst
To check into the effect of the catalyst, systematic studies
were carried out within the existence of various numbers
of Fe3O4/HT-NH2-CuII (Figure 9). First of all, a control
experiment has been done in the lack of the Fe3O4/HT-
NH2-CuII catalyst to show the significant role of the cata-
lyst. Therefore, the catalyst was eliminated from the solu-
tion, and the more substrate added to typically the filtrate
where no extra tetrazole was produced below the similar
conditions. Second, various amounts of the Fe3O4/HT-
NH2-CuII was used, and the best yield seemed to be
obtained with 5 mg of catalyst.
3.9 | The effect of solvent
We checked out this reaction in various solvent
(Figure 10). The results showed that different solvents
affect the efficiency of the reaction. Acetonitrile is given
low yield (10%), while the use of solvents such as ethanol,
DMF can improve yields compared to acetonitrile.
Finally, when water is used, the results increased to 94%
better than other solvents examined here. In the absence
of a solvent, the results of the model reaction decreased
to 35%.
FIGURE 10 The effect of different solvents in the synthesis of
1H-1,2,3,4-tetrazole by Fe3O4/HT-NH2-CuII
Reaction conditions: sodium azide (1.1 mmol), aniline (1 mmol),
triethyl orthoformate (1.4 mmol), 0.005 g of Fe3O4/HT-NH2-CuII,
90 ꢀC
Different amounts of solvent were investigated in this
reaction. In the presence of diverse amounts of the sol-
vent, the reaction models do. Also, the optimum amount
of solvent is studied, and the results showed that 2 ml
required for optimized reaction conditions (Figure 11).
FIGURE 11 The effect of the amount of solvent in the
synthesis of 1H-1,2,3,4-tetrazole by Fe3O4/HT-NH2-CuIIReaction
conditions: sodium azide (1.1 mmol), aniline (1 mmol), triethyl
orthoformate (1.4 mmol), 0.005 g of Fe3O4/HT-NH2-CuII, 90 ꢀC
Some tetrazole derivative synthesized by the reaction
of different aromatic amine, triethyl orthoformate, and
sodium azide using Fe3O4/HT-NH2-CuII nano-catalyst
[aniline: 1 mmol; sodium azide: 1.1 mmol; triethyl
FIGURE 9 The effect of the amount of Fe3O4/HT-NH2-CuII in
the synthesis of 1H-1,2,3,4-tetrazole
ꢀ
orthoformate: 1.4 mmol; T = 90 C; H2O as a solvent].
To extend the range of diverse substrates, arylamines
with electron-releasing or electron-withdrawing group
Reaction conditions: sodium azide (1.1 mmol), aniline (1 mmol),
triethyl orthoformate (1.4 mmol), 2 ml of H2O

12 of 14
SALIMI AND ZAMANPOUR
also examined to undergo a one-pot reaction of the three
components of success for the synthesis of 1-substituted
1H-tetrazoles under H2O as a solvent (Table 1).
As can be observed in Table 2, this catalyst indicated
good catalytic efficiency in short times in comparison to
most of typically the reported works (Table 2).
A plausible mechanism for the synthesis of diverse
1-substituted 1H-tetrazoles of aromatic amine reaction,
triethyl orthoformate, and sodium azide in the presence
of Fe3O4/HT-NH2-CuII catalyst under H2O as a solvent
shown in Scheme 3. The suggested mechanism may be
due to Lewis acidity Cu catalysts, which can catalyze the
transformation of the dissociation of the triethyl
orthoformate and facile establishment of the intermedi-
ate to perform the cyclization reaction to produce the
corresponding product.
3.10 | The catalyst reusability and
stability
Reusability and recovery of catalyst are significant mainly
because of the environmental and even economic aspects,
so typically the reusability of the Fe3O4/HT-NH2-CuII cat-
alyst was also studied [reaction circumstances: aniline:
SCHEME 3 Proposed mechanism for preparation of
tetrazoles by Fe3O4/HT-NH2-CuII
TABLE 2
Comparison of results by Fe3O4/HT-NH2-CuII with various catalysts
Entry
Catalyst
Reaction conditions
Solvent free - 120 ꢀC
Solvent free - 120 ꢀC
Glycerol – r.t.
Time (h)
Yield (%)
80–94
83–95
84–95
56–78
70–92
85–93
78–97
50–90
Ref.
17
1
2
3
4
5
6
7
8
Natrolite zeolite
Cu NPs/bentonite
NHTf2
4
37
38
14
39
40
41
3
3
ZnS nanoparticle
ZnS nanoparticle
Ag2O
Solvent free - 130 ꢀC
3–7
0.5
0.5
0.5–3
1–3
US, DMF, r.t.
AcOH - 100 ꢀC
Fe3O4@silica sulfonic acid
Fe3O4/HT-NH2-CuII
Solvent free - 100 ꢀC
H2O – 90 ꢀC
This work
Reaction conditions: NaN3, RNH2, CH (OEt)3
FIGURE 12 Recyclability of Fe3O4/HT-
NH2-CuII in the synthesis of 1H-1,2,3,4-tetrazole

SALIMI AND ZAMANPOUR
13 of 14
FIGURE 13 FT-IR of Fe3O4/HT-NH2-CuII
in the synthesis of 1H-1,2,3,4-tetrazole a) First
run, b) recovered catalyst (fifth run)
1 mmol; sodium azide: 1.1 mmꢀol; triethyl orthoformate:
1.4 mmol; H2O as a solvent, 90 C]. As a result, the cata-
lyst was separated by an external magnet after the first
reaction condition was optimized via considering the
effect of different parameters, such as the amount of cata-
lyst, the reaction time, numerous solvents, and the
amount of solvent to achieve the highest conversion of
substrates.
ꢀ
run, washed using ethanol, and dried at 120 C under
vacuum oven, after which used for the subsequent suc-
cessive runs under similar circumstances (Figure 12). No
notable decrease of activity was observed, demonstrating
that the fact the applied catalyst is able and has great sta-
bility through the one-pot preparation of the
1-substituted 1H-1, 2, 3, 4-tetrazoles. Fe and Cu weren’t
detected in the reaction solutions based on ICP-AES eval-
uation via the hot filtration approach. After the solid-free
filtrates were subsequently stirred continuously under
optimized reaction conditions for its substrates as men-
tioned above, the results of 1-substituted 1H-1, 2, 3,
4-tetrazoles were significantly less than 5 percent after
12 hr.
ACKNOWLEDGEMENTS
We gratefully acknowledge the support of this work by
the University of Birjand.
ORCID
Mehri Salimi https://orcid.org/0000-0002-3956-3949
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How to cite this article: Salimi M, Zamanpour A.
Green synthesis of the 1-substituted 1H-1, 2, 3, 4-
tetrazoles over bifunctional catalyst based on
copper intercalated into Mg/Al hydrotalcite
modified magnetite nanoparticles. Appl
Organometal Chem. 2020;e5682. https://doi.org/10.
1002/aoc.5682