Cu(II)-N-benzyl-amino-1H-tetrazole complex immobilized on magnetic chitosan as a highly effective nanocatalyst for C-N coupling reactions

Article abstract of DOI:10.1016/j.jorganchem.2021.121959

Herein, the synthesis of a novel catalytic nanosystem with high activity and easy recoverability through immobilization of Cu(II)-N-benzyl-amino-1H-tetrazole complex on magnetic chitosan (MCS-BAT-Cu(II)) is reported. The catalytic potential of MCS-BAT-Cu(II) catalyst has been assessed in C-N coupling reaction of 5-amino-1H-tetrazole with aryl halides. Various aryl iodides/bromides were successfully coupled using MCS-BAT-Cu(II) catalyst for the synthesis of 1-aryl-5-amino-1H-tetrazoles with excellent reaction yields. In addition, the magnetic catalyst was easily and effectively separated from the reaction mixture using an external magnet and reused five times without notable loss of catalytic activity.

Full text of DOI:10.1016/j.jorganchem.2021.121959

Journal of Organometallic Chemistry 950 (2021) 121959
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Cu(II)-N-benzyl-amino-1H-tetrazole complex immobilized on magnetic
chitosan as a highly effective nanocatalyst for C-N coupling reactions
a
b,∗
a,∗
Mohaddeseh Sajjadi , Mahmoud Nasrollahzadeh , Hossein Ghafuri
a
Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, 16846-13114, Iran
Department of Chemistry, Faculty of Science, University of Qom, PO Box 37185-359, Qom, Iran
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Herein, the synthesis of a novel catalytic nanosystem with high activity and easy recoverability through
immobilization of Cu(II)-N-benzyl-amino-1H-tetrazole complex on magnetic chitosan (MCS-BAT-Cu(II)) is
reported. The catalytic potential of MCS-BAT-Cu(II) catalyst has been assessed in C-N coupling reaction
of 5-amino-1H-tetrazole with aryl halides. Various aryl iodides/bromides were successfully coupled using
MCS-BAT-Cu(II) catalyst for the synthesis of 1-aryl-5-amino-1H-tetrazoles with excellent reaction yields.
In addition, the magnetic catalyst was easily and effectively separated from the reaction mixture using
an external magnet and reused five times without notable loss of catalytic activity.
Received 23 March 2021
Revised 2 June 2021
Accepted 18 June 2021
Available online 24 June 2021
Keywords:
MCS-BAT-Cu(II)
5
-Aminotetrazole
©
2021 Published by Elsevier B.V.
C-N coupling
Copper complex
Magnetic chitosan
5
-Amino-1H-tetrazole
1
. Introduction
and provided a recently expanding field of heterogeneous catal-
ysis. Tetrazoles, in particular aminotetrazoles, have been applied
as highly potent compounds in inorganic and/or organometallic
chemistry for the synthesis of coordination complexes [15–17],
metal organic frameworks (MOF) [18,19], coordination polymers
[20,21], and various (photo)catalysts [22,23] in organic chemistry.
They are a versatile starting material for multi-component reac-
tions, asymmetric syntheses [24–26], and catalysts for organic re-
actions [27–29].
Tetrazoles constitute a privileged class of heterocycles with at-
tractive characteristics such as a large number of nitrogen atoms,
high acidity, low basicity, maximum dipole moment, good stabil-
ity, high formation enthalpy, etc. These compounds are playing an
important role in medicinal/pharmacological chemistry, material
science, explosives/propellants, coordination chemistry [1–7], and
versatile scaffolds for the synthesis of N-containing compounds,
as well as being effective bioactive compounds, antihyperten-
sive drugs, peptidase inhibitors, anti-HIV and anticancer/antitumor
agents [8–10]. For instance, losartan and its analogues used as
antihypertensive drugs and/or the peptidase inhibitor CGS-26303
are the most significant drugs comprising tetrazole rings [9,11-13].
Furthermore, 1,5-disubstituted tetrazoles utilized as the bioisostere
The classical methods to synthesize tetrazoles, in particular
aminotetrazoles (Scheme 1), are based on the condensation of
nitriles, thioureas, cyanamides, imidoyl chlorides, carbodiimides,
and aminoiminomethanesulfonic acids with NaN . The reaction of
3
cyanamides with HN , the reaction of NaNO2 with aminoguani-
3
dine, thermal isomerization of 1-substituted aminotetrazoles in
melt state or boiling ethylene glycol, the reaction of various amines
with tetrazole comprising a leaving group in the 5th position, and
conversion of 1-aryltetrazoles to 1-arylaminotetrazoles via single
step ring opening and intramolecular cyclization processes using
organolithium reagents and NaN3 at -70 °C are some of the meth-
ods for the preparation of tetrazoles [30–34]. Due to their bene-
fits and applications, the development of more efficient methods
for preparing (amino)tetrazole scaffolds has received great atten-
tion. Each of the earlier methods has some drawbacks such as the
utilization of stoichiometric quantities of homogeneous catalysts,
moisture sensitive or harmful/expensive reagents, HN3 generation,
the formation of side products, low yields or tedious processes for
(
bioequivalent) of cis-amide bonds in peptides, show similar
physicochemical features and improved metabolic stability in liv-
ing organisms [14]. Generally, 5-substituted tetrazoles are widely
used in medicine, pharmacology, biochemistry, fine organic syn-
thesis, and in the industry as effective compounds in photography,
military, imaging chemicals, etc. [5].
Widespread applications of tetrazoles; especially in medicinal
and coordination chemistry, have attracted increasing attention
∗
Corresponding author:
E-mail addresses: mahmoudnasr81@gmail.com (M. Nasrollahzadeh),
ghafuri@iust.ac.ir (H. Ghafuri).
https://doi.org/10.1016/j.jorganchem.2021.121959
0
022-328X/© 2021 Published by Elsevier B.V.

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Scheme 1. Preparation of (aryl)aminotetrazoles using diverse methods.
the synthesis of catalysts and work-up, etc. Hence, it is important
to develop a more efficient and convenient technique to reduce
and/or eliminate the utilization and generation of hazardous com-
pounds [16,30,35].
is a natural cationic polysaccharide with excellent efficiency as a
support due to its biodegradability, biocompatibility, non-toxicity,
environmentally benign nature, and availability [41]. The fusion of
magnetic NPs and polysaccharides could afford one of the most in-
teresting kinds of nanomagnetic supports for simple recovery of
catalysts. Thus, the coating of CS about nanomagnetic core (MCS)
is a valuable approach.
[
2 + 3]-cycloaddition reactions using homogeneous catalysts
have turned into highly useful and synthetically attractive ap-
proaches for preparing tetrazoles [36]. Given the difficulties in
the recovery of homogeneous catalysts [29], more efficient, con-
venient, and newer routes to prepare tetrazole based heteroge-
neous catalysts/complexes need to be explored. There are numer-
ous reports/patents on the coordination of tetrazoles with various
transition metals (e.g. copper, palladium, platinum, iridium, etc.) in
the design or preparation and applications of the corresponding
chelate complexes [28,37-40]. Choosing a suitable (nano)catalyst to
fabricate these ligands and investigation of the more efficient tech-
niques for the preparation of tetrazole containing metal complexes
comprising a metal-nitrogen bond is of utmost significance. Fur-
thermore, transforming tetrazoles into valuable heterogeneous cat-
alysts extremely enhances sustainable economic development, as
exemplified by the increasing demand for the (nano)catalysts and
complexes using tetrazoles.
Transition metal catalyzed aryl C-N bond forming transforma-
tions are one of the most widely studied reactions in modern or-
ganic synthesis due to the importance of aromatic C-N bonds in
different areas such as e.g. natural products, coordination chem-
istry, agrochemicals, pharmaceuticals, heterocycles, conjugated
polymers and catalysis [42–46]. Nevertheless, many approaches
have been developed for C-N coupling or N-arylation reactions
between nitrogen based heterocycles and (pseudo)aryl halides to
form N-C bonds, most of which need pre-functionalization of or-
ganic compounds and/or Pd catalysts [45,47-50].
In the light of our endeavors in the synthesis of tetrazole
based heterogeneous complexes, in this study, we report here the
preparation of Cu(II)-N-benzyl-amino-1H-tetrazole complex sup-
ported on magnetic chitosan (MCS-BAT-Cu(II); Scheme 2) and
demonstrate its activity in the preparation of 1-aryl-5-amino-1H-
tetrazoles in high yield via N-arylation of unsubstituted 5-amino-
1H-tetrazole with aryl iodides/bromides in dioxane under nitrogen
atmosphere. Moreover, MCS-BAT-Cu(II) showed high recyclability
and was reused in five successive runs in C-N coupling reactions.
Several heterocycles containing embedded tetrazole ligands
have been applied for environmental applications via the syn-
thesis of heterogeneous nanocatalysts deploying diverse supports;
namely, polymers, Fe O @SiO nanoparticles (NPs), and other nat-
3
4
2
ural biomaterials [16,28,29]. Among diverse polymers, chitosan (CS)
2

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Scheme 2. MCS-BAT-Cu(II)-promoted preparation of substituted 5-amino-1H-tetrazoles.
Scheme 3. Preparation of N-benzyl-N-(3-bromophenyl)-5-amino-1H-tetrazole (3).
2. Experimental
2.3. Synthesis of N-benzyl-N-(3-bromophenyl)-5-amino-1H-tetrazole
3)
(
2
.1. Reagents and devices
A
mixture of N-benzyl-N-(3-bromophenyl)cyanamide (1.0
Commercially available reagents, materials, and solvents were
mmol), ZnBr2 (1.0 mmol), and NaN3 (1.5 mmol) in H O (20 mL)
2
utilized as received. CS with 85% de-acetylation degree, 50000-
0000 Da molecular weight (medium), solubility in 1% acetic acid
was stirred under reflux for 20 h (Scheme 3). Upon completion of
the reaction, as monitored using TLC, the solid residues obtained
were filtered from the reaction mixture, rinsed twice with water
(20.0 mL) and subsequently treated with 3 mL of 3.0 N HCl.
The as-prepared residue was purified/recrystallized with EtOH to
afford the desired pure products.
8
in the 80-mesh size was purchased from Nano Novin Polymer
company. FT-IR (Fourier transform infrared spectroscopy) spectra
were recorded by a Thermo Nicolet 370 FT-IR spectrometer using
KBr pellets. The NMR spectra were recorded on a Bruker spectrom-
eter (Avance DRX-400 MHz). XRD (X-ray diffraction) and VSM (vi-
brating sample magnetometer) measurements were validated by
Philips PW 1373 diffractometer (Cu Kα radiation = 0.15406 nm)
and SQUID magnetometer (Quantum Design MPMS 20XL) at 298 K,
respectively. The MCS-BAT-Cu(II) size and morphology were char-
acterized utilizing TEM (JEM-F200 JEOL) and FESEM (Cam scan
Mv2300). Energy Dispersive X-ray Spectroscopy (EDS) equipped in
FESEM (TESCAN MIRA3-XMU) was extensively applied to deter-
mine the chemical composition of the catalyst. The loading and
leaching of Cu were determined by inductively coupled plasma
mass spectrometry (ICP-MS, Perkin Elmer, Optima 8000).
2.4. Synthesis of MCS (4)
Fe3O4 NPs were fabricated via co-precipitation technique in ba-
sic media [52]. Next, a solution of CS (0.25 g) in acetic acid (1%
V/V, 50 mL) was prepared to which were added 2.0 g of as-
prepared Fe3O4 NPs at ambient temperature. The solution thus ob-
tained was stirred for 0.5 h, followed by the slow addition of NaOH
solution (1.0 M, 50 mL) and mechanically stirring the resulting so-
lution for another 0.5 h. Finally, the formed Fe3O4-CS was easily
collected using an external magnet and repeatedly washed with
twice-distilled water and ethanol, and dried in vacuo.
2
.2. Synthesis of N-benzyl-N-(3-bromophenyl)cyanamide (2)
2.5. Synthesis of N-benzyl-amino-1H-tetrazole-trimethoxysilane (5)
N-Benzyl-N-(3-bromophenyl)cyanamide (1) was synthesized
2.0
mmol
of
N-benzyl-N-(3-bromophenyl)-5-amino-1H-
(
Scheme 3) according to our recent report by N-benzylation of (3-
tetrazole (0.394 g) prepared and 2.0 mmol of TMOS [(3-
chloropropyl)trimethoxysilane)] were added to a flask containing
bromophenyl)cyanamide under ultrasonic irradiation [51].
3

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
4
0.0 mL of EtOH and the mixture obtained was stirred/refluxed
3.2. Characterization of the catalyst
for 24 h at 70 °C. The obtained product was soluble in EtOH.
MCS-BAT-Cu(II) (7) catalyst was characterized by XRD, VSM, FE-
SEM, FT-IR, TEM, EDS, and ICP-MS analyses. The phase and crys-
talline nature of MCS-BAT-Cu(II) (7) were assessed by XRD analysis
2
.6. Synthesis of MCS-(CH ) -BAT (6)
2 3
MCS (0.5 g) was dispersed in 30.0 mL of EtOH for 0.5 h. Next,
(
Fig. 1a). As shown in Fig. 1a, the XRD spectrum of the catalyst dis-
played typical diffraction pattern at 2θ = 16.8°, 20.1°, 30.1°, 35.8°,
3.3°, 54.0°, 57.7° and 63.0°, which are assigned to [110], [111],
the soluble compound prepared in Section 2.5 was added drop-
wise to the mixture of dispersed aqueous MCS, followed by the
addition of 2.0 mmol of K CO (0.276 g) and mixing under reflux
4
2
3
[220], [311], [400], [422], [511] and [440] crystal planes of mag-
netic NPs, respectively (JCPDS file, File No. 19-0629). These peaks
for 24 h at 60 °C. After cooling, the resulting MCS-(CH ) -BAT was
2
3
collected by an external magnet, rinsed two times with EtOH and
distilled water, and dried to utilize as the magnetic support in the
coordination of Cu(II).
confirmed the successful preparation of Fe O4 particles. The pat-
3
terns at 2θ values of 43.5°, 50.3° and 74.7° can be assigned to [111],
[
200] and [220] crystal planes, respectively, in Cu cubic structure.
Fig. 1b depicts the FT-IR spectrum of MCS-BAT-Cu(II) (7). In the
2
.7. Synthesis of MCS-BAT-Cu(II) (7)
spectrum, characteristic adsorption peaks were observed at about
3
200-3400 cm 1 (-OH and/or -NH stretching), 2927 cm
−
−1
−1
(-CH
Finally, a solution of CuCl2 (0.25 g) was added to the obtained
−1
stretching), 1497 cm
(-NH bending vibration), 1405 cm
−1
(-C-H
MCS-(CH ) -BAT (0.5 g) in 25 mL of EtOH and the reaction mixture
2
3
stretching), and 1070 cm (-C-O-C stretching) [53,54]. The band at
405 cm 1 is ascribed to the CH OH stretching of the chitosan ma-
obtained was stirred at 75 °C for 24 h (Scheme 4). At the end of
this process, MCS-BAT-Cu(II) complex was collected utilizing an ex-
ternal magnet, washed with EtOH, and subsequently dried to check
its catalytic activity in N-arylation reactions.
−
1
2
−1
trix in Fe O -CS. Additionally, the band at 1634 cm is due to the
3
4
imine C=N stretching vibration modes, confirming the formation of
MCS supported copper(II)-tetrazole complex. In addition, the peak
at 630 cm 1 is attributed to the Fe-O stretching vibration of mag-
−
2
.8. General experimental procedure for C-N bond cross-coupling
netite NPs.
reactions
The elemental composition of MCS-BAT-Cu(II) (7) was stud-
ied by EDS analysis (Fig. 2a). The EDS spectrum of MCS-BAT-
Cu(II) (7) showed the presence of O, Fe, C, N, and Cl as well as
Cu elements (Fig. 2a) indicating the grafting of Cu(II)-N-benzyl-
N-(3-bromophenyl)-1H-tetrazole-5-amine on the surface of mag-
netic CS. The ‘N’ element in the complex could confirm the graft-
ing of N-benzyl-arylaminotetrazoles on magnetic NPs. Moreover,
the total content of copper in the MCS-BAT-Cu(II) (7) was de-
termined to be about 5.2 wt.% by ICP-MS measurement. Further-
more, Fig. 2b shows the FESEM images of MCS-BAT-Cu(II) (7). It
could be concluded that the surface of MCS is covered with Cu(II)-
N-benzyl-N-(3-bromophenyl)-5-amino-1H-tetrazole complex. Fur-
thermore, MCS-BAT-Cu(II) (7) has an average particle size in the
~13-21 nm range. The images indicated that the MCS-BAT-Cu(II) (7)
catalyst was fabricated (Fig. 2b).
An appropriate aryl halide (1.0 mmol), MCS-BAT-Cu(II) (0.05 g),
-amino-1H-tetrazole (1.0 mmol), K CO3 (1.5 mmol), and dioxane
5
2
(
5 mL) were stirred at 90 °C under N2 atmosphere for the ade-
quate time. When the reaction was complete, as monitored using
TLC, the mixture was cooled to ambient temperature, the magnetic
catalyst was removed from the mixture utilizing an external mag-
netic field and rinsed twice with water and EtOH and the product
was purified using ethyl acetate and aqueous EtOH. The obtained
tetrazoles were characterized by FT-IR and NMR.
3
. Results and discussion
.1. Synthesis of the catalyst
N-(3-Bromophenyl)cyanamide
3
(1)
were
and
N-benzyl-N-(3-
from 3-
The TEM analysis of MCS-BAT-Cu(II) (7) was performed for fur-
ther identification and the obtained TEM micrographs are depicted
in Fig. 3. The TEM micrographs displayed that Cu(II)-N-benzyl-
aminotetrazole complex were successfully immobilized/stabilized
on Fe3O4/chitosan and the average particle size was around
~18 nm.
bromophenyl)cyanamide
(2)
synthesized
bromoaniline according to Scheme 3. In continuation of our
recent works on various tetrazoles [4,6], the preparation of N-
benzyl-N-(3-bromophenyl)-5-amino-1H-tetrazole (3) in good yield
was performed through ZnBr -catalyzed [2 + 3]-cycloaddition of
2
(
2; Scheme 3) and NaN in H O under reflux conditions [16].
The magnetic property and magnetic hysteresis loop of the pro-
duced MCS-BAT-Cu(II) (7) were examined by VSM technique with
field sweeping in the -15000 to +15000 Oe range. According to
Fig. 3, the magnetization saturation (Ms) value of MCS-BAT-Cu(II)
3
2
MCS-(CH ) -BAT (6) was synthesized via functionalization of
2
3
MCS (4) with N-benzyl-amino-1H-tetrazole-trimethoxysilane (5),
followed by the incorporation of CuCl2 with the resulting MCS-
(7) was 50.0 emu g 1. Thus, the coordination of Cu(II)-N-benzyl-
−
(
CH ) -BAT (6) in EtOH under mild conditions to fabricate the
2 3
highly effective and magnetically separable MCS-BAT-Cu(II) (7)
aminotetrazole on the magnetic CS was verified by VSM analysis.
complex. The complex was prepared via a systematic sequence
Scheme 4). Firstly, the aqueous solution of Fe2 and Fe
added to the CS acidic solution at ambient temperature, followed
by the dropwise addition of NaOH to grow Fe O NPs on the
+
3+
was
3.3. Investigation of catalytic prowess of MCS-BAT-Cu(II) (7) in C-N
(
coupling reactions
3
4
chitosan cationic surface to prepare MCS (4) via a one pot co-
precipitation route. The obtained MCS (4) was dispersed for 30
min to form narrow black particles, followed by the reaction with
N-benzyl-amino-1H-tetrazole-trimethoxysilane (5) to prepare MCS-
The present work affords Cu(II)-N-benzyl-amino-1H-tetrazole
complex supported on magnetic chitosan as a novel heterogeneous
catalyst for C-N cross-coupling reactions. This catalytic system does
not require expensive, conventional, difficult to synthesize, and air
or moisture sensitive ligands. The MCS-BAT-Cu(II) (7) catalytic ac-
tivity was evaluated in the C-N coupling reaction of 5-amino-1H-
tetrazole with iodobenzene as a model reaction.
(
CH ) -N-benzyl-N-(3-bromophenyl)-5-amino-1H-tetrazole (6). Fi-
2 3
nally, MCS-BAT-Cu(II) (7) was fabricated via incorporation of MCS-
CH ) -BAT (6) with copper ions under reflux conditions. The cat-
(
2
3
alytic activity of MCS-BAT-Cu(II) catalyst was evaluated in the
preparation of various 1-aryl-5-amino-1H-tetrazoles through the
C-N cross-coupling of unsubstituted 5-aminotetrazole with aryl
halides at 90 °C.
To optimize the parameters of the reaction of 5-amino-1H-
tetrazole (1.0 mmol) with PhI (1.0 mmol) using MCS-BAT-Cu(II) (7),
the effects of various bases (1.5 mmol), solvents (5 mL) and cata-
lyst amount in the model coupling reaction were studied (Table 1).
4

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Scheme 4. Synthesis of MCS-BAT-Cu(II) (7) catalyst.
As illustrated in Table 1, the C-N coupling reaction was first car-
ried out without any catalyst at 90 °C (Entry 1), which resulted in
no coupling product formation. The optimum amount of the MCS-
BAT-Cu(II) (7) was 0.05 g (Table 1, entry 4). As shown in Table 1,
yields were observed using higher amounts of the MCS-BAT-Cu(II)
(Entry 14).
The effect of the substituent in the structure of tetrazole on the
catalytic activity was also examined. In order to evaluate the effi-
ciency of other catalysts in C-N cross-coupling reaction, the activity
the choice of the base (Na CO , NaOH, KOAc, NEt and K CO ) or
2
3
3
2
3
solvent (MeCN, toluene, EtOH, acetone, NMP, DMF, and dioxane) af-
fects the reaction. The best result could be obtained using dioxane
of Fe O @SiO -aminotet-Cu(II) (copper(II)-aminotetrazole complex
3 4 2
immobilized on silica coated Fe O ) catalytic system was investi-
3
4
and K CO3 as the solvent and base, respectively (Table 1, entry 10).
gated in a model reaction (entry 15). Fe O @SiO -aminotet-Cu(II)
3 4 2
2
As a result, other solvents such as DMF and toluene were found to
afford moderate yields in the coupling reaction (Table 1, entries 5,
was prepared according to our previous report (Fig. 4) [16]. Ac-
cording to Table 1, the nature of the substituent was not effective
and the product was obtained in good yield (entries 10 and 15).
The MCS-BAT-Cu(II)-catalyzed N-arylation of 5-amino-1H-
tetrazole with aryl iodides/bromides to prepare 1-aryl-5-amino-
1H-tetrazoles were carried out in dioxane at 90 °C under nitrogen
atmosphere. Various aryl halides containing either electron with-
6
). In addition, no organic co-solvents, surfactants, or ligands were
required. According to the results of the control experiment, ex-
cellent yield of coupling products was obtained when the reaction
conditions were as follows; catalyst amount: 0.05 g, base: K CO ,
2
3
solvent: dioxane, reaction temperature: 90 °C, reaction time: 4 h,
and under nitrogen atmosphere. No significant improvements in
drawing or donating groups (-H, -OMe, -Me, and -NO ) were
2
5

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Fig. 1. (a) XRD pattern and (b) FT-IR spectrum of MCS-BAT-Cu(II) (7).
Table 1
Optimization of N-arylation of iodobenzene with 5-amino-1H-tetrazole using MCS-BAT-Cu(II).a
Entry
MCS-BAT-Cu(II) (7) (g)
MCS-BAT-Cu(II) (0.0)
MCS-BAT-Cu(II) (0.01)
MCS-BAT-Cu(II) (0.01)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.05)
MCS-BAT-Cu(II) (0.07)
Fe3O4@SiO2-aminotet-Cu(II) (0.05)
Solvent
MeCN
Base
Yieldb (%)
0.0
0.0
18
1
2
3
4
5
6
7
8
9
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
K2CO3
Et3N
MeCN
Acetone
Acetone
DMF
29
78
Toluene
Ethanol
NMP
62
0.0
44
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
61
1
1
1
1
1
1
0
1
2
3
4
5
92
0.0
58
KOAc
NaOH
K2CO3
K2CO3
28
92
91
a
Reaction conditions: 5-amino-1H-tetrazole (1.0 mmol), phenyl iodide (1.0 mmol), base (1.5
mmol), solvent (5.0 mL), 90 °C, 4 h, N2 atmosphere.
b
Isolated yield.
6

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Fig. 2. (a) EDS spectrum and (b) FESEM images of MCS-BAT-Cu(II) (7) catalyst.
converted to 1-aryl-5-amino-1H-tetrazoles in 72-92% yields within
-8 h and the results are shown in Table 2. It was found that
the two I groups, 1,4-diiodobenzene (Table 2, entry 7) interest-
ingly afforded the double addition product. In order to optimize
the synthesis of 1,4-phenylene-bis(1H-tetrazol-5-amine) (Table 2,
entry 7), an additional experiment was conducted using excess
3
the presence of electron withdrawing groups in the aryl halides
promoted the Cu(II)-catalyzed N-arylation reactions with less re-
activity compared to those bearing electron donating substituents
and resulted in lower product yields [46]. Generally, the aryl
halides with electron donating substituents (-OMe, and -Me) were
more reactive than those with electron withdrawing substituents
5-amino-1H-tetrazole (2.0 mmol), catalyst (0.1 g), and K CO (3.0
2
3
mmol).
A plausible mechanism is represented in Scheme 5, wherein the
C-N coupling reaction of aryl halides with 5-amino-1H-tetrazole
using the base leads to the formation of 1-aryl-5-amino-1H-
tetrazoles. In the first step, intermediate (A) is formed by the ox-
idative addition of the aryl halide to the catalyst (ArCuX). The re-
action between the deprotonated aminotetrazole with the interme-
diate (A) is then followed by a nucleophilic attack in the presence
of the base. Finally, the formation of the desired product and the
regeneration of Cu catalyst occur via a reductive elimination stage
[46,55].
(
-NO ) in the preparation of arylaminotetrazoles (Table 2, entries
2
2
-5,9). For example, 4-iodonitrobenzene and 4-bromonitrobenzene
(
Table 2, entries 6,10) resulted in lower yields in longer coupling
reaction times. As shown in Table 2, aryl iodides containing elec-
tron donating groups (entries 2-5) reacted at 90 °C after 3-4.5 h,
while the species containing the NO - electron withdrawing group
2
(
entry 6) requires higher reaction time (7 h). The results revealed
that the coupling reactions of aryl iodides proceeded smoothly
with high reaction yields in the presence of MCS-BAT-Cu(II) (7)
compared with those of aryl bromides. Due to the presence of
After purification, the desired products were characterized by
1H NMR, 13C NMR, and FT-IR spectra [16,30,56]. The disappear-
7

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Fig. 3. TEM images and magnetization curve of MCS-BAT-Cu(II) (7) catalyst.
Fig. 4. Structure of Fe3O4@SiO2-aminotet-Cu(II).
ance of N-H stretching of the aminotetrazole ring and the pres-
ence of two NH2 stretching signals in the FT-IR spectra provided
clear evidence for the preparation of substituted aminotetrazoles
3.4. Catalyst recyclability
Recyclability/reusability is one of the significant properties of a
catalytic (nano)system from practical, commercial, industrial, and
economic aspects. Therefore, the reusability of MCS-BAT-Cu(II) (7)
for the preparation of substituted tetrazoles was tested in C-N
bond cross-coupling of 5-amino-1H-tetrazole with iodobenzene.
The catalyst could be simply collected from the reaction mixture
by an external magnet, rinsed twice with EtOH, and dried at 70 °C
(
Fig. 5). The 1H NMR spectrum of unsubstituted 5-amino-1H-
tetrazole showed two NH peaks corresponding to the NH2 and NH
groups while the 1HNMR spectrum of the substituted aminotetra-
zoles (Fig. 6a) indicated the appearance of one NH2 signal (6.6-7
ppm). Furthermore, the 13C NMR spectrum of the pure products
(
Fig. 6b) showed one peak for the carbon of the tetrazole ring at
45-160 ppm.
th
1
for 9 h for further catalytic runs. After the 5 run, MCS-BAT-Cu(II)
8

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Table 2
MCS-BAT-Cu(II)-catalyzed C-N cross-coupling reaction of 5-amino-1H-tetrazole with various aryl
halides.aa
Yieldb (%)
92
TON
TOF (h
5622
−1
)
Entry
1
Aryl halide
Product
Time (h)
4
22488
2
3
3
4
93
92
22732
22488
7577
5622
4
5
4.5
4.5
90
89
21999
21755
4888
4834
6
7
8
9
7
82
88
84
86
72
20043
10755
20532
21021
17599
2863
1434
3422
3503
2199
7.5
6
6
1
0
8
a
Reaction conditions: MCS-BAT-Cu(II) (0.05 g), aryl halide (1.0 mmol), 5-amino-1H-tetrazole (1.0
mmol), K2CO3 (1.5 mmol), Dioxane (5.0 mL), 90°C, nitrogen atmosphere.
b
Isolated yield.
Fig. 5. FT-IR spectrum of 1-(4-methylphenyl)-5-amino-1H-tetrazole.
9

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Fig. 6. (a) 1H NMR and (b) 13 C NMR spectra of 1-(4-methylphenyl)-5-amino-1H-tetrazole.
(
(
7) can be reused with a minor decrease in the catalytic prowess
analysis of the resulting solution of the coupling reaction and less
than 0.1% of the total content of Cu was observed.
Fig. 7). As depicted in Fig. 7, the magnetic catalyst presented ex-
cellent product yields even after the 5th reaction sequence. The
XRD analysis of the recycled catalyst (after five cycles) revealed
that the recycled MCS-BAT-Cu(II) (7) complex had the same peaks
as the fresh catalyst (Fig. 8). To check the heterogeneity of the re-
cycled catalyst, the leaching phenomenon was examined by ICP-MS
4. Conclusion
In summary, we report the C-N bond cross-coupling of 5-
amino-1H-tetrazole with aryl halides by a novel heterogeneous
copper complex (Cu(II)-N-benzyl-amino-1H-tetrazole) on Fe O -
3
4
10

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Scheme 5. Proposed mechanism for the N-arylation reaction using MCS-BAT-Cu(II) (7).
Fig. 7. Recycling performance of MCS-BAT-Cu(II) (7) in N-arylation of 5-amino-1H-tetrazole with iodobenzene.
chitosan as a stabilizer/support. The synthesized MCS-BAT-Cu(II)
signed catalytic nanosystem showed advantages such as easy re-
cycling, high stability, long life, good dispersibility, facile work-up,
and high catalytic activity within short reaction times. The efficacy
of the developed catalytic system (MCS-BAT-Cu(II)) is superior to
those of other catalytic systems in terms of reaction time, yield,
work-up, and amount of catalyst. Furthermore, the good struc-
tural characteristics of MCS-supported copper(II)-tetrazole complex
make it potentially useful in other catalytic transformations.
catalyst was characterized by various techniques such as XRD, FT-
IR, EDS, VSM, FESEM, TEM, and ICP-MS. Efficient preparation of
1
-aryl-5-amino-1H-tetrazole derivatives was carried out in excel-
lent yields. The present work reports an unprecedented instance of
aminotetrazole grafted on magnetic chitosan as a magnetically re-
coverable catalyst, which could be recycled/reused five times with-
out any noticeable changes in the reaction time and yield. The de-
11

M. Sajjadi, M. Nasrollahzadeh and H. Ghafuri
Journal of Organometallic Chemistry 950 (2021) 121959
Fig. 8. XRD pattern of reused MCS-BAT-Cu(II) catalyst after fifth recycle.
Declaration of Competing Interest
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The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared to
influence the work reported in this paper.
[
15] L. Zeisel, N. Szimhardt, M.H.H. Wurzenberger, T.M. Klapötke, J. Stierstorfer,
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2
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The supports presented by the Iran University of Science and
Technology and the University of Qom is appreciated.
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