Synthesis of magnetic chitosan supported metformin-Cu(II) complex as a recyclable catalyst for N-arylation of primary sulfonamides

Article abstract of DOI:10.1016/j.jorganchem.2021.121915

The application of chitosan, which has received much attention as a natural polymer and effective support, has many advantages such as biodegradability and biocompatibility. In this study, the immobilization of a copper complex on the magnetic chitosan bearing metformin ligand has been developed through immobilizing structurally defined metformin with long tail of (3-chloropropyl)trimethoxysilane (TMOS). The synthesized Fe₃O₄-chitosan@metformin-Cu(II) complex (Fe₃O₄-CS@Met-Cu(II)) was used as an effective, reusable and magnetic catalyst in the N-arylation of different derivatives of primary sulfonamides with arylboronic acids in ethanol. The primary sulfonamides were prepared from the reaction of sulfonyl chlorides with sodium cyanate in water under ultrasonic irradiation. Utilizing a wide variety of substrates in EtOH as a green solvent, high yields of the primary and secondary sulfonamides, easy work-up along with the excellent recovery and reusability of the catalyst, make this process a simple, economic and environmentally benign method. The synthesized Fe₃O₄-CS@Met-Cu(II) was characterized using various techniques such as XRD (X-ray diffraction), EDS (energy-dispersive X-ray spectroscopy), elemental mapping, TEM (transmission electron microscopy), FESEM (field emission scanning electron microscopy), VSM (vibrating sample magnetometer), ICP-MS (inductively coupled plasma mass spectroscopy), TGA (thermogravimetric analysis) and FT-IR (Fourier-transform infrared spectroscopy) analyses. The catalyst can be recycled and reused 5 times with no considerable loss of catalytic activity.

Full text of DOI:10.1016/j.jorganchem.2021.121915

Journal of Organometallic Chemistry 948 (2021) 121915
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis of magnetic chitosan supported metformin-Cu(II) complex
as a recyclable catalyst for N-arylation of primary sulfonamides
Mahmoud Nasrollahzadeh∗, Zahra Nezafat, Khatereh Pakzad, Fatemeh Ahmadpoor
Department of Chemistry, Faculty of Science, University of Qom, Qom 37185-359, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The application of chitosan, which has received much attention as a natural polymer and effective sup-
port, has many advantages such as biodegradability and biocompatibility. In this study, the immobiliza-
tion of a copper complex on the magnetic chitosan bearing metformin ligand has been developed through
immobilizing structurally defined metformin with long tail of (3-chloropropyl)trimethoxysilane (TMOS).
The synthesized Fe3O4-chitosan@metformin-Cu(II) complex (Fe3O4-CS@Met-Cu(II)) was used as an effec-
tive, reusable and magnetic catalyst in the N-arylation of different derivatives of primary sulfonamides
with arylboronic acids in ethanol. The primary sulfonamides were prepared from the reaction of sulfonyl
chlorides with sodium cyanate in water under ultrasonic irradiation. Utilizing a wide variety of substrates
in EtOH as a green solvent, high yields of the primary and secondary sulfonamides, easy work-up along
with the excellent recovery and reusability of the catalyst, make this process a simple, economic and
environmentally benign method. The synthesized Fe3O4-CS@Met-Cu(II) was characterized using various
techniques such as XRD (X-ray diffraction), EDS (energy-dispersive X-ray spectroscopy), elemental map-
ping, TEM (transmission electron microscopy), FESEM (field emission scanning electron microscopy), VSM
(vibrating sample magnetometer), ICP-MS (inductively coupled plasma mass spectroscopy), TGA (thermo-
gravimetric analysis) and FT-IR (Fourier-transform infrared spectroscopy) analyses. The catalyst can be
recycled and reused 5 times with no considerable loss of catalytic activity.
Received 25 February 2021
Revised 17 May 2021
Accepted 30 May 2021
Available online 4 June 2021
Keywords:
Sulfonamide
N-Arylation
Chitosan supported Cu(II) complex
Magnetic catalyst
Arylboronic acid
© 2021 Elsevier B.V. All rights reserved.
1. Introduction
include high cost and toxicity. Therefore, researchers have tried
to develop more efficient, cost effective, low toxicity and environ-
Sulfonamides are a vital group of pharmaceutical compounds
with an extensive spectrum of biological applications. In addition,
they are applied as useful intermediates in organic synthesis. Sul-
fonamides with medicinal properties have various medicinal appli-
cations such as anticonvulsants and HIV protease inhibitors. Gen-
erally, sulfonamides are prepared via the reaction of sulfonyl chlo-
rides with amine derivatives. Nevertheless, sulfonyl chlorides have
some drawbacks, such as difficulty of handling and inappropriate-
ness for long term storage. Only some of them are commercially
available due to their instability [1–5].
mentally friendly catalysts for the synthesis of N-aryl sulfonamides.
Copper based catalysts have been extremely effective for the syn-
thesis of N-aryl sulfonamides from boronic acids and various pri-
mary sulfonamide derivatives. Copper based catalysts have some
advantages, including high yield, low cost and non-toxic character
[13–18].
Among various catalytic systems, heterogeneous catalysts are
highly attractive for researchers because they have many advan-
tages, the most important of which is the simple separation of the
catalyst from the reaction mixture [19–22]. Therefore, one of the
most important challenges in the preparation heterogeneous cat-
alysts is the selection of the right support for the functionaliza-
tion of metal nanoparticles (NPs) or complexes [23]. There are het-
erogeneous compounds, which are applied as efficient supports for
the heterogenization of homogeneous catalysts via the decoration
of homogeneous organometallic complexes, metal or metal oxide
NPs on the their surface [24]. Different suitable supports must be
used to synthesize heterogeneous catalysts such as graphene, nat-
ural and synthetic polymers [13,25–27], silicon dioxide, iron ox-
Usually, direct approaches are taken for the effective synthesis
of N-aryl sulfonamides using various compounds such as aryl silox-
anes, halides, boronic acids, etc., under diverse catalytic systems
[6–10]. The use of palladium based catalysts is a known method
for the synthesis of N-aryl sulfonamides [11,12]. The use of these
catalysts is associated with problems; the most important of which
∗
Corresponding author.
E-mail address: mahmoudnasr81@gmail.com (M. Nasrollahzadeh).
https://doi.org/10.1016/j.jorganchem.2021.121915
0022-328X/© 2021 Elsevier B.V. All rights reserved.

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Scheme 1. Preparation of chitosan via deacetylation of chitin.
Scheme 2. Synthesis of primary sulfonamides.
ide, MCM-41, poly(vinylidene fluoride), aluminum oxide, boehmite,
SBA-15, etc. [28–36]. Among various supports, Fe3O4 NPs are ap-
plied in electronic devices and biomedicine and as catalysts in dif-
ferent kinds of organic reactions due to their non-toxicity and su-
perparamagnetic behavior, which allows their easy separation from
the reaction media [37–39].
(De-acetylation degree: 85%, molecular weight: 50000-80000 Da
(medium), particle dimension: powder with a mesh size of 80 (sol-
uble in 1% acetic acid) was obtained from Nano Novin Polymer
Co. The as-synthesized Fe3O4 NPs supplied by Iran’s Pishgaman-
e Nano Mavad Co. were spherically shaped with particle sizes of
approximately 20 nm. The synthesized compounds were charac-
terized using FT-IR, NMR, XRD, TEM, TGA/DTG, VSM, EDS, ele-
mental mapping, ICP-MS and FESEM. FT-IR and NMR spectra were
recorded using Perkin-Elmer 781 and Bruker Avance DRX400 in-
struments, respectively. The magnetic property of the prepared
complex was studied using VSM (Meghnatis Daghigh Kavir Co.) at
298 K . TEM and FESEM analyses were applied to evaluate the mor-
phology of the catalyst using Philips CM120 and Cam scan Mv2300
instruments, respectively. XRD was conducted in the 2θ range of
Presently, the use of natural polymers as efficient supports has
received much attention. Among various biopolymers, chitosan has
been very attractive [40–45]. Chitosan is a linear natural polymer
glucosamine units, which is prepared from deacetylation of chitin
in an alkaline environment (Scheme 1). Chitin is obtained from
the exoskeleton of squids, crabs and shrimps. Chitosan has some
advantages, including biodegradability, non-toxicity, biocompatibil-
ity, accessibility and pharmacological properties [46,47]. Chitosan
is applied in various fields such as medicine and pharmacy due
to its many benefits. It has biological properties such as antifun-
gal, antibacterial, antioxidant and antitumor. In addition, chitosan
is used as a suitable support for the preparation of various het-
erogeneous catalysts due to the suitable functional groups in its
structure [48–51].
˚
10-80° using a Philips PW 1373 diffractometer (Cu Kα = 1.5406 A).
TGA experiments were performed in the air flow at a heating rate
of 10°/min using a TG 209F3 NETZSCH instrument. The elemental
contents of the catalysts were determined by inductively coupled
plasma optical emission spectrometry (ICP-MS, Perkin Elmer, Op-
tima 8000)
Nowadays, metal complexes have received much attention in
various applications; especially in catalysis. Among the various
atoms, nitrogen is the most widely used electron donor in ligand
systems [52]. Metformin (Met) is one of the compounds used as an
effective ligand [53–55].
2.2. Synthesis of Fe3O4-Chitosan
Fe3O4-Chitosan (Fe3O4-CS) was synthesized according to a liter-
ature method [56]. For this purpose, 0.25 g of CS in was dissolved
50 mL of 1% acetic acid (V/V), followed by the addition of 2 g of
Fe3O4 NPs and stirring for 0.5 h. In the final step, 50 mL of NaOH
solution (1.0 M) were added slowly. The prepared Fe3O4-CS was
collected by an external magnet.
In the present work, first, the synthesis of primary sulfon-
amides using sulfonyl chlorides and sodium cyanate under ultra-
sonic irradiation is reported (Scheme 2). Chitosan has then been
used an efficient, novel and green support for the synthesis of a
magnetic heterogeneous catalyst. In this regard, the metformin-
copper(II) complex was immobilized on the Fe3O4-CS surface using
(3-chloropropyl)trimethoxysilane (TMOS) (Scheme 3). The synthe-
sized Fe3O4-CS@Met-Cu(II) was used in the N-arylation of primary
sulfonamides as a novel and magnetic catalyst using arylboronic
acids in ethanol solvent (Scheme 4).
2.3. Synthesis of Fe3O4-Chitosan@Metformin-Cu(II) complex
Firstly, 5 mmol of metformin were added to 5 mmol of (3-
chloropropyl)trimethoxysilane in EtOH (60 mL) and the mixture
thus obtained was stirred under reflux conditions for 24 h (So-
lution A). Afterwards, 1.5 g of Fe3O4-CS in 70 mL of ethanol was
subjected to ultrasonication for 20 min. 5 mmol of K2CO3 were
then added dropwise into the mixture of Fe3O4-CS and solution
A, which was then refluxed for 24 h. Finally, the desired Fe3O4-
CS@Met was collected using an external magnet, washed with
ethanol, and dried at 60 °C in a vacuum oven for 12 h. In the next
step, 1 g of the prepared Fe3O4-CS@Met in the previous step and
2. Experimental
2.1. Tools and reagents
All chemicals were purchased from the Merck and Aldrich
Chemical Co. and used with no additional purification. Chitosan
2

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Scheme 3. Schematic representation of the synthesis of Fe3O4-CS@Met-Cu(II).
Scheme 4. N-Arylation of primary sulfonamides by phenylboronic acids using
Fe3O4-CS@Met-Cu(II).
0.5 g of CuCl2.2H2O were stirred under reflux conditions in 70 mL
of ethanol for 24 h. Upon completion of the reaction, the synthe-
sized magnetic catalyst was collected using a magnet, washed with
ethanol, and dried (Scheme 3).
2.4. Synthesis of primary sulfonamides
10 mmol of sodium cyanate (NaOCN), 10 mmol of sulfonyl chlo-
ride, and 50 mL of distilled water were irradiated in an ultrasonic
bath for 20 min. After completion of the reaction (monitored using
TLC), the mixture was cooled and the pure white needle-shaped
crystals were filtered [57].
Fig. 1. XRD pattern of Fe3O4-CS@Met-Cu(II).
2.5. N-Arylation of primary sulfonamides using Fe3O4-CS@Met-Cu(II)
Fig. 1 displays the XRD analysis of Fe3O4-CS@Met-Cu(II) mag-
netic nanocatalyst. The peaks with 2θ values of 30.3°, 35.9°, 43.4°,
54.0°, 57.3°, 63.2°, and 73.95 planes of the cubic Fe3O4 (JCPDS 19-
0629) confirm the presence of Fe3O4 NPs [21].
catalyst
A 50 mL flask was filled with 0.5 mmol of primary sulfonamide,
0.5 mmol of arylboronic acid, 0.7 mmol of trimethylamine (Et3N),
0.02 g of Fe3O4-CS@Met-Cu(II), and 7 mL of ethanol and the mix-
ture thus obtained was stirred at reflux for the appropriate time
(monitored using TLC). When the reaction was over, the reaction
mixture was cooled and the catalyst was collected using an exter-
nal magnet. After evaporation of ethanol, the solid residue was pu-
rified by recrystallization from ethyl acetate and n-hexane to yield
the appropriate product. The melting points of products matched
those reported in our previous work and literature values [13,57].
EDS spectrum and elemental mapping were applied to study
the chemical composition of the Fe3O4-CS@Met and Fe3O4-
CS@Met-Cu(II) (Fig. 2 (a, b)). As shown in Fig. 2a, the presence
of Fe, N, Si, O, and C elements in the Fe3O4-CS@Met structure is
verified using EDS and elemental mapping analyses. As displayed
in Fig. 2a, copper is not observed in the Fe3O4-CS@Met elemen-
tal mapping. According to the EDS and elemental mapping of the
Fe3O4-CS@Met-Cu(II), the presence of Fe, N, Si, O, Cu and C were
confirmed in the structure of Fe3O4-CS@Met-Cu(II) (Fig. 2b). The
content of the Cu within Fe3O4-CS@Met-Cu(II), as determined us-
ing ICP-MS, was 9.1 wt. %.
3. Results and discussion
FESEM and TEM analyses illustrated the morphology and parti-
cle size of Fe3O4-CS@Met-Cu(II) (Fig. 3). The results of FE-SEM dis-
play the spherical shape and uniform distribution of the particles
in the nanometer range. The shape and size of the particles were
investigated using TEM analysis (Fig. 3). As shown in Fig. 3, the
morphology of the magnetic nanocatalyst is spherical, the average
3.1. Fe3O4-CS@Met-Cu(II) characterization
The synthesized Fe3O4-CS@Met-Cu(II) magnetic nanocatalyst
was characterized using XRD, EDS, elemental mapping, FESEM,
TEM, VSM, ICP-MS, TGA/DTG, and FT-IR spectroscopy.
3

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Fig. 2. EDS spectra and elemental mapping of (a) Fe3O4-CS@Met and (b) Fe3O4-CS@Met-Cu(II).
4

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Fig. 2. Continued
diameter is about 13 nm and some nanoparticle aggregations are
observed.
netic. Magnetic property is the most important advantage of this
catalytic system, which causes easy separation from the reaction
mixture using an external magnet.
Magnetic behavior of the Fe3O4-CS@Met-Cu(II) was studied by
VSM analysis (Fig. 4). As shown in Fig. 4, the amount of magneti-
zation saturation of Fe3O4-CS@Met-Cu(II) is about 30 emu/g. As a
result, VSM analysis shows that the nanocatalyst is superparamag-
The synthesized Fe3O4-CS@Met-Cu(II) catalyst was character-
ized using FT-IR spectroscopy (Fig. 4). As shown in Fig. 4, the peaks
at 3200-3500 and 580 cm−1 are related to NH or OH groups of
5

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Fig. 3. FESEM and TEM images of Fe3O4-CS@Met-Cu(II).
ture. Furthermore, the peaks in 1090 and 790 cm−1 are related to
–
chitosan and Fe O groups of Fe3O4 NPs, respectively, which con-
firms the presence of magnetic nanoparticles and chitosan. In ad-
dition, the peaks in the range of 1640-1690 cm−1 are related to
=
–
Si O in the structure of TMOS.
Thermogravimetric analysis (TGA) and differential thermal anal-
C
N, confirming the presence of metformin in the catalyst struc-
ysis (DTA) tests in airflow (40 mL/min) at
a heating rate of
10 °C/min on an autonomic TGA-DTG were performed from 25 °C
6

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Fig. 4. (a) Magnetization curves and (b) FT-IR spectrum of the Fe3O4-CS@Met-Cu(II).
Scheme 5. Proposed mechanism for synthesis of primary sulfonamides.
stage after 600 °C corresponds to the decomposition of the synthe-
sized Fe3O4-CS@Met-Cu(II).
3.2. Ultrasound-mediated synthesis of primary sulfonamides
Primary sulfonamides were synthesized via the reaction of
sodium cyanate (10 mmol) and aryl sulfonyl chlorides (10 mmol) in
H2O (50 mL) as the solvent under ultrasonic irradiation for 20 min
(Table 1). The proposed mechanism is displayed in Table 1. As pre-
sented in Scheme 5, water has been used as a solvent and nu-
cleophile [57]. Since stoichiometric quantities of the substrates are
used up after the reaction is complete, there are no substrates left
and the only side product formed is NaCl salt.
3.3. N-Arylation of primary sulfonamides
Fig. 5. TGA-DTG analysis of (a) Fe3O4-CS@Met and (b) Fe3O4-CS@Met-Cu(II).
Fe3O4-CS@Met-Cu(II) was applied as a magnetic nanocatalyst
for N-arylation of primary sulfonamides with arylboronic acids in
ethanol under reflux conditions. The reaction conditions for N-
arylation of p-toluenesulfonamide (p-TsNH2) using PhB(OH)2 were
optimized using different amounts of catalyst and bases in ethanol
(Table 2). In the absence of catalyst or base in the reaction, no re-
action takes place (Table 2, entries 1 and 2). The results indicate
that the presence of Fe3O4-CS@Met-Cu(II) and the base is required
for N-arylation of sulfonamides. Among the various bases used in
the reaction, trimethylamine (Et3N) was found the best (Table 2,
to 700 °C. Fig. 5 (a, b) shows the comparative weight losses
of Fe3O4-CS@Met and Fe3O4-CS@Met-Cu(II), respectively. For both
samples, the loss of weight was observed at temperatures below
200 °C due to the release of water and other organic solvents in
the structure. In addition, in both cases, the weight loss observed
at 200-500 °C was related to the decomposition of chitosan and
metformin ligand. As displayed in Fig. 5b, the final decomposition
7

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Table 1
Synthesis of primary sulfonamides.
Entry
Substrate
Product
Yield (%)a
Melting point (°C)
Melting point (°C) [lit.]
1
2
3
98
95
94
136-138
140-144
150-151
136-140 [58]
140-144 [Aldrich]
149-152 [Aldrich]
4
90
95
179-181
164-166
178-180 [Aldrich]
163-167 [Aldrich]
5
a
Isolated yield.
Table 2
Optimization of the reaction conditions.a
methylbenzensulfonamides, as summarized in Table 4. Fe3O4-
CS@Met-Cu(II) nanocatalyst was observed to be an efficient cata-
lyst due to the reasonable reaction time, ease of operation, sim-
plicity of simple work-up protocol, and reaction conditions. In ad-
dition, compared to other catalysts, Fe3O4-CS@Met-Cu(II) nanocat-
alyst can be easily separated from the reaction mixture by a mag-
net and reused in several consecutive cycles.
Entry
Fe3O4-CS@Met-Cu(II) (g)
Base
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
9
0.0
-
40
40
50
30
50
55
25
35
20
0.0
0.0
75
86
70
83
85
75
95
0.0
Et3N
0.01
0.01
0.01
0.015
0.02
0.02
0.02
K2CO3
Et3N
Na2CO3
K2CO3
K2CO3
Na2CO3
Et3N
3.4 Possible mechanism for N-arylation of primary sul-
fonamides A catalytic cycle mechanism is proposed for the N-
arylation reaction of primary sulfonamides using Fe3O4-CS@Met-
Cu(II) in the presence of Et3N as an appropriate base (Scheme 6).
As observed in Scheme 6, the oxidative addition reaction of the
catalyst occurs in the first stage, leading to the formation of an in-
termediate (a). In the second stage, the reaction occurs between
deprotonated primary sulfonamides and intermediate (a) by nucle-
ophilic attack. Finally, the formation of the desired product and the
regeneration of the catalyst are carried out by a reductive elimina-
tion stage.
a
Reaction conditions: Phenylboronic acid (0.5 mmol), p-TsNH2 (0.5 mmol),
base (0.7 mmol), catalyst, ethanol (7 mL), reflux.
b
Isolated yield.
entry 9). The product yield increased when the catalyst amount
increased to 0.01 g. According to the results, the optimal amount
of the catalyst is 0.02 g (Table 2, entry 9). On the other hand, de-
creasing the catalyst loading will cause the reaction to be incom-
plete (Table 2, entry 4).
3.4. Reusability of Fe3O4-CS@Met-Cu(II)
After optimizing the reaction conditions, various primary sul-
fonamides with electron withdrawing and donating groups and
a wide range of arylboronic acids were examined to synthesize
the secondary sulfonamides (Table 3). In all cases, the products
were synthesized in high yields. The results indicate that ortho-
substituted arylboronic acids react slowly compared to para iso-
mers (Table 3, entries 3 and 6). However, electronic effects do not
play much of a role in the product yields.
One of the most important features of a catalyst is the ability to
recycle and reuse it. The recyclability of the Fe3O4-CS@Met-Cu(II)
was studied in a model reaction of p-TsNH2 and phenylboronic
acid in the presence of Et3N as an effective base in EtOH solvent.
When the reaction was complete, the catalyst was removed from
the reaction mixture using a magnet and reused in the next cycles.
The synthesized magnetic catalyst can be applied 5 times with no
considerable loss of catalytic performance (Fig. 6). Fig. 7 displays
the FT-IR, XRD, and VSM analyses of the recycled catalyst. As ob-
served in Fig. 7a, in contrast to the fresh catalyst, the FT-IR spec-
The melting points of all the products were recorded and com-
pared with those of authentic samples [13]. The FT-IR and 1HNMR
spectra also confirm the structure of products (Figure S1-S3, see
Supporting Information). The appearance of the two strong and
sharp absorption bands in the structure of primary sulfonamides
(NH2 stretching bands) and the disappearance of one absorption
band (NH stretching vibration) confirm the formation of the sec-
ondary sulfonamides (Figure S1).
=
trum of the recycled catalyst has all the peaks related to C N, NH
–
–
or OH, Fe O, and Si O groups, in 1640-1690, 3200-3500, 580, and
1090 and 790 cm−1 respectively. According to Fig. 7b, the XRD
,
pattern of the recycled catalyst shows the same peaks as in the
fresh catalyst. Moreover, copper leaching investigation of the cat-
alyst after the recycling tests by ICP-MS analysis was found to be
negligible (~0.1%). In addition, Fig. 7c shows the VSM analysis of
The efficacy and capability of our catalyst were compared
with those of some reported catalysts in N-arylation of 4-
8

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Table 3
a
N-Arylation of primary sulfonamides with arylboronic acids in ethanol.
Entry
R
R’
Product
Time (min)
Yield (%)b
Melting point (°C) (lit. m.p. [Ref.]).
TON
TOF (min−1
)
1
2
4-Me
4-Me
H
20
35
95
91
100-103 (102-103 [59])
113-114 (112-114 [60])
33181
31784
1659
4-OMe
908
3
4
4-Me
4-Me
2-Me
4-Cl
50
30
90
90
107-109 (105-107 [59])
118-122 (118-119 [59])
31435
31435
628
1047
5
6
H
H
H
30
35
90
90
109-111 (110 [Aldrich])
120-122 (117-119 [61])
31435
31435
1047
898
4-Me
7
8
H
4-OMe
35
30
89
91
97-100 (93-94.5 [62])
102-104 (104-105 [59])
31086
31784
888
4-Cl
H
1059
9
4-Cl
2-Me
50
40
87
106-110 (-)
30387
607
10
11
4-Cl
4-Cl
4-Me
90
88
84-86 ([commercial])
31435
30736
785
768
4-OMe
40
140-144 (141-142 [59])
(continued on next page)
9

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Table 3 (continued)
Entry
R
R’
Product
Time (min)
Yield (%)b
Melting point (°C) (lit. m.p. [Ref.]).
TON
TOF (min−1
)
12
4-Br
H
H
70
90
80
75
115-117 (116-117 [63])
27942
26196
349
291
13
4-NO2
134-137 (135-136 [59])
a
Reaction conditions: Arylboronic acid (0.5 mmol), sulfonamide (0.5 mmol), Et3N (0.7 mmol), Fe3O4-CS@Met-Cu(II) (0.02 g), EtOH (7 mL), reflux.
Isolated yield.
b
Table 4
Comparison of Fe3O4-CS@Met-Cu(II) nanocatalyst with other reported catalysts in the N-arylation of 4-methylbenzensulfonamides.
Entry
Catalyst
Substrate
Reaction condition
Time
Yield (%)a
Ref.
1
2
3
4
5
6
7
Cu(OAc)2
Phenylboronic acid
Phenyl bromide
Phenyl iodide
Dry isopropanol, K2CO3, 90 °C in a sealed tube
K2CO3, microwave heating
DMF, K3PO4
12 h
3 h
-
65
70
95
95
97
50
95
[8]
CuI
[10]
[14]
[57]
[18]
[64]
CuI/N-methylglycine
Cu-zeolite NPs
Mn/Cu cocatalyzed
Cu(OAc)2.H2O
Fe3O4-CS@Met-Cu(II)
Phenylboronic acid
Phenyl iodide
K2CO3, H2O, reflux
3 h
24 h
-
CuI, MnF2, DMEDA, KOH, H2O, 60 °C
Anhyd. MeOH, reflux
Phenylboronic acid
Phenylboronic acid
Et3N, EtOH, reflux
20 min
This work
a
Isolated yield.
Scheme 6. Proposed mechanism for N-arylation of primary sulfonamides.
10

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Fig. 6. Reusability of Fe3O4-CS@Met-Cu(II) in N-arylation of p-TsNH2.
Fig. 7. (a) FT-IR, (b) XRD, and (c) VSM analysis of the recycled catalyst.
the recycled catalyst, which indicates that the recycled catalyst has
significant magnetic properties.
(Fe3O4-CS@Met-Cu(II)) has then been synthesized and applied in
the N-arylation of different primary sulfonamides with arylboronic
acids in ethanol under reflux conditions. In this study, chitosan
was applied as an efficient, natural, and novel support to synthe-
size a heterogeneous catalyst. Fe3O4-CS@Met-Cu(II) was character-
ized using different analytical methods including XRD, TEM, FE-
SEM, EDS, elemental mapping, VSM, ICP-MS, TGA/DTG, and FT-IR.
The experimental results show the high catalytic performance of
4. Conclusion
In conclusion, a green and easy technique has been developed
for the preparation of primary sulfonamides under ultrasonic irra-
diation. An efficient and magnetic nanocatalyst based on chitosan
11

M. Nasrollahzadeh, Z. Nezafat, K. Pakzad et al.
Journal of Organometallic Chemistry 948 (2021) 121915
Fe3O4-CS@Met-Cu(II) and the formation of the products in high
yields. Finally, Fe3O4-CS@Met-Cu(II) can be recycled 5 times with-
out any important reduction in its performance, which shows its
high stability.
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Declaration of Competing Interest
[22] M. Nasrollahzadeh, S.M. Sajadi, Preparation of Pd/Fe3O4 nanoparticles by use
of Euphorbia stracheyi Boiss root extract: a magnetically recoverable catalyst
for one-pot reductive amination of aldehydes at room temperature, J. Colloid
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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.
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