One-pot multicomponent synthesis of N-sulfonyl amidines using magnetic separable nanoparticles-decorated N-heterocyclic carbene complex with copper

Article abstract of DOI:10.1007/s11164-021-04455-1

Magnetic separable nanoparticles-decorated N-heterocyclic carbene complex with copper (MNP[1-Methyl benzimidazole]NHC@Cu) has been prepared by covalent grafting of ionic liquid like 1-methyl benzimidazole unit on the surface of chlorofunctionalized Fe

Full text of DOI:10.1007/s11164-021-04455-1

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-021-04455-1
One‑pot multicomponent synthesis of N‑sulfonyl amidines
using magnetic separable nanoparticles‑decorated
N‑heterocyclic carbene complex with copper
Arvind Pawar1 · Shivanand Gajare2 · Audumbar Patil2 · Rajanikant Kurane2 ·
Gajanan Rashinkar2 · Suresh Patil1
Received: 8 November 2020 / Accepted: 29 March 2021
© The Author(s), under exclusive licence to Springer Nature B.V. 2021
Abstract
Magnetic separable nanoparticles-decorated N-heterocyclic carbene complex with
copper (MNP[1-Methyl benzimidazole]NHC@Cu) has been prepared by covalent
grafting of ionic liquid like 1-methyl benzimidazole unit on the surface of chloro-
functionalized Fe3O4 magnetic nanoparticles (MNPs) followed by metallation with
copper(I) iodide. MNP[1-Methyl benzimidazole]NHC@Cu complex has been char-
acterized by diferent techniques including Fourier transform infrared (FT-IR) spec-
troscopy, thermogravimetric analysis (TGA), energy-dispersive X-ray (EDX) analy-
sis, X-ray difraction (XRD), transmission electron microscopy (TEM) and vibrating
sample magnetometer (VSM). MNP[1-Methyl benzimidazole]NHC@Cu complex
was successfully implemented as heterogeneous catalyst in one-pot multicomponent
synthesis of N-sulfonyl amidines from phenylacetylene, tosyl azide and amines at
room temperature. Complex could be recycled six times without signifcant loss in
the yield of product.
* Suresh Patil
sanyujapatil@yahoo.com
Gajanan Rashinkar
gsr_chem@unishivaji.ac.in
1
Department of Chemistry, Padmabhushan Dr. Vasantraodada Patil College, Dist. Sangli,
Tasgaon, Maharashtra 416312, India
2
Department of Chemistry, Shivaji University, Kolhapur, Maharashtra 416004, India
Vol.:(0123456789)
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A. Pawar et al.
Graphic abstract
Keywords Magnetic separable nanoparticles · Multicomponent synthesis · Copper
iodide · N-sulfonyl amidines · Reusability
Introduction
From the last ten years, N-heterocyclic carbenes (NHCs) have been attracted to
researchers as powerful tools as ligand in organic chemistry and transition metal
(TM) catalysis with numerous applications in commercially important processes
[1–4]. NHCs are easily accessible, coordinative unsaturation, electron–rich, typ-
ical σ–donors and moderate π–acceptors, which sterically request structure for
complexation with transition metals. A huge nature of NHC‐TM structure is their
unremarkable unfaltering quality that is habitually referred to as one of the fun-
damental advances of these ligands over their phosphine accomplices [5–9]. They
are a fexible class of subordinate ligands that have gathered huge consideration
for their capacity to impact diferent C─C, C─N and C─O bond developments
in multicomponent reactions. In addition, they have remarkable properties such
as high activity and selectivity with increased stability toward air and moisture,
superior catalytic activities, ability to form stable metal complexes, adjustment of
electronic and steric parameters, ease of access to their azolium salt precursors
and tailor-made performance for specifc catalytic reactions [10–12]. In spite of
these properties, NHC-TM complexes have revealed the problem of contamina-
tion and recycling of catalyst during organic transformation due to their homo-
geneous nature [13]. To overcome these problems by replacing homogeneous
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One-pot multicomponent synthesis of N-sulfonyl amidines…
NHC-complexes with heterogeneous NHC-complexes with high area support
material, this gives realm from environmental pollution and economically favora-
ble [14]. Numbers of supporting materials have been reported with NHC-metal
complexes for variety of catalytic reaction in the organic synthesis [15–17].
However, despite tremendous advances, there is considerable scope for the fur-
ther development especially using magnetic nanoparticles (MNPs) as a support in
order to accomplish the aim of sustainable and environmentally benign processes.
MNPs have captivated their attention in the feld of catalysis due to their tech-
nology and chemical application [18, 19]. In recent years, eforts of the scientifc
community have been directed toward the synthesis of superparamagnetic nano-
particles for the design of magnetically retrievable nanocatalytic systems owing
to their exceptional physicochemical properties and rapid response to the applied
magnetic feld. Among that, Fe3O4 MNPs are robust, inexpensive, easy to pre-
pare, non-toxic, magnetically recoverable and can be reused multiple times for
several reaction cycles. Consequently, they have emerged as the viable alterna-
tives to existing solid-supported heterogeneous catalysts [20]. In addition, their
high surface region, superparamagnetism, simple surface change by utilizing
wanted functionalities and facile retrievability by external magnet have added
critical adaptability for such materials in task explicit catalytic systems [21, 22].
Owing to these properties, they are widely used in synthetic chemistry [23].
Despite remarkable progress, research toward applications of Fe3O4 MNPs in the
synthesis of magnetically retrievable NHCs is still in its infancy and therefore
warrants immediate attention.
Amidines are privileged heterocyclic scafolds with wide range of pharma-
cological properties such as anticancer, antimalarial, antimicrobial, antitubercu-
lar, anti-infammatory, antioxidant, anticonvulsant and antihypertensive activi-
ties [24]. N-sulfonyl amidines are the important class of amidines that serve as
pharmacophores, synthetic intermediates and efcient coordinating ligands [25,
26]. Owing to their extraordinary properties, a number of new advanced bespoke
strategies have been developed [27–29] such as aerobic synthesis of N-sulfonyl
amidines by using cationic copper(I) complexes from terminal alkyne, sulfonyl
azide and amine [30], coupling of primary, secondary or tertiary amines and sul-
fonyl azides with terminal alkynes [31], chlorophosphite-mediated Beckmann
ligation of oximes and p-toluenesulfonyl azide [32], palladium-catalyzed sulfo-
nyl ynamide rearrangement in the presence of an amine [33], NaI-catalyzed con-
densation of sulfonamide and formamide [34]. Scrutiny of literature revealed that
Cu-catalyzed multi-component coupling between tosyl azide, phenyl acetylene
and amines represents most elegant protocol due to wide substrate scope, mild
reaction conditions and potential synthetic utility. Numbers of protocols have
been reported. However, there is a still scope for improvement, especially toward
developing a green procedure using magnetically retrievable catalyst.
Based on aforementioned discussion and in continuation of our studies related
to heterogeneous catalysis and multicomponent reaction [35–39], we report
herein preparation of magnetic separable nanoparticles-decorated N-heterocyclic
carbene complex with copper and its application in the synthesis of N-sulfonyl
amidines.
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A. Pawar et al.
Experimental section
General remarks
All reactions were carried out under air atmosphere in dried glassware. FT‐IR
spectra were measured with a Perkin-Elmer one FT‐IR spectrophotometer. The
samples were examined as KBr disks (~ 5% w/w). Raman spectroscopy was car-
ried out using a Bruker: RFS 27 spectrometer. The thermogravimetric analysis
(TGA) curves were obtained using instrument SDT Q600 V20.9 Build 20 in
the presence of static air at linear heating rate of 10 °C/minute from 25 °C to
1000 °C. Elemental analyses were performed in a PerkinElmer 2400, Series II,
CHNS/O analyzer and using an energy‐dispersive X‐ray spectroscopic facility
1
(Hitachi S 4800, Japan). H NMR and 13C NMR spectra were recorded with a
1
Bruker Avance (300 MHz for H NMR and 75 MHz for 13C NMR) spectrom-
eter using CDCl3 solvent and tetramethylsilane as an internal standard. Chemi-
cal shifts are expressed in parts per million (ppm), and coupling constants are
expressed in hertz (Hz). Mass spectra were recorded with a Shimadzu QP2010
gas chromatography–mass spectrometry (GC–MS). The materials were analyzed
by TEM using a PHILIPS CM 200 model with 20–200 kV accelerating voltages.
Melting points were determined using MEL‐TEMP capillary melting point appa-
ratus and are uncorrected. X-ray powder difraction (XRD) was taken using a
Bruker D2 Phaser. Magnetic measurements were performed on Lakeshore mag-
netometer, USA, Model 7407. Fe3O4 MNPs (1) [40], silica coated Fe3O4 MNPs
(2) [41] and all other chemicals were obtained from local suppliers and used
without further purifcation.
Preparation of 3‑chloropropyl‑modifed MNPs (3)
A mixture of silica-coated Fe3O4 MNPs (2) (10 g) and (3-chloropropyl)triethox-
ysilane (20 mL, 100 mmol) in dry xylene (100 mL) was refuxed in an oil bath.
After 24 h, the reaction mixture was cooled; product was isolated by magnetic
separation and washed with xylene (4 × 25 mL), methanol (4 × 25 mL), deionised
water (4 × 25 mL) and dried under vacuum at 50 °C for 12 h to aford 3-chloro-
propyl modifed MNPs (3). FTIR (KBr, thin flm): υ = 3408, 2925, 1099, 797,
699, 633, 583 cm−1.
Preparation of MNP[1‑Methyl benzimidazole]Cl (5)
A mixture of 3 (10.0 g) and 1-methyl benzimidazole (4) (6 g, 18 mmol) in dimeth-
ylformamide (50 mL) was heated at 80 °C in an oil bath. After 72 h, the solid was
separated by magnet, washed with MeOH (3 × 50 mL), CH2Cl2 (3 × 50 mL) and
dried under vacuum at 50 °C for 24 h to aford MNP[1-Methyl benzimidazole]Cl
(5).
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One-pot multicomponent synthesis of N-sulfonyl amidines…
IR (KBr, thin flm): υ=3428, 2925, 2860, 1654, 1642, 1457, 1387, 1093,
585 cm−1. CHNS elemental analysis observed: %C 13.42, %H 0.36, % N 4.78.
Loading: 0.36 mmol functional group per gram of 5.
Preparation of MNP[1‑Methyl benzimidazole]NHC@Cu (6)
A mixture of 5 (10.0 g), copper iodide (1.9 g, 10 mmol) and NaOtBu (0.096 g,
10 mmol) in THF (50 mL) was heated at 100 °C in an oil bath for 6 h. Afterward,
the mixture was separated by magnet, washed with the THF (3×50 mL) and dried
under vacuum at 50 °C for 24 h to aford MNP[1-Methyl benzimidazole]NHC@Cu
(6).
FT‐IR (KBr, thin flm): υ=3406, 2893, 2828, 1632, 1444, 1320, 1075, 586 cm−1;
Elemental analysis observed: %C 13.42, % O 45.51, % Fe 14.30, % Si 19.25, % N
4.78, % Cu 1.41, % I 0.97. Loading of Cu: 0.22 mmol functional group per gram of
6.
General method for synthesis of N‑sulfonylamidines
A mixture of phenylacetylene (1 mmol), tosyl azide (1 mmol), amine (1.2 mmol),
and MNP[1-Methyl benzimidazole]NHC@Cu (6) (50 mg) in THF solvent (5 ml)
was stirred at room temperature. After completion of the reaction as monitored by
the TLC, the complex 6 was removed by magnetic separation. Evaporation of sol-
vent in vacuuo followed by column chromatography over silica gel using petroleum
ether/ethyl acetate (8:2) aforded pure products.
NMR data of synthesized compounds:
1
(1) N1, N1-Dimethyl-2-phenyl-N2-tosylacetamidine (Table 3, product (10a): H
NMR (CDCl3, 400 MHz): δ 7.82 (d, J=8.4 Hz, 2H) 7.29–7.14 (m, 7H), 4.42 (s,
2H), 3.11 (s, 3H), 2.92 (s, 3H), 2.38 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz):
δ 166.7, 145.6, 142.1, 141.1, 136.2, 131.8, 129.7, 128.9,127.2, 124.6, 63.5, 41.8,
21.8 ppm.
(2) N1, N1-Diisopropyl-2-phenyl-N2-tosylacetamidine (Table 3, product (10b):
1H NMR (CDCl3, 300 MHz): δ 7.84 (d, J=7.2 Hz, 2H), 7.27–7.22 (m, 7H), 4.42
(s, 2H), 4.03–3.99 (m, 1H), 4.46 (s, 1H), 2.40 (s, 3H), 1.40 (d, J=6 Hz, 6H), 0.84
(d, J=6 Hz, 6H), ppm; 13C NMR (CDCl3, 75 MHz): δ 163.4, 141.6, 141.5, 134.9,
129.0, 128.8, 127.9, 126.7, 126.2, 50.4, 48.0, 38.47, 21.4, 19.8 ppm.
1
(3) N1, N1-Diethyl-2-phenyl-N2-tosylacetamidine (Table 3, product (10c): H
NMR (CDCl3, 300 MHz): δ 7.78 (d, J=6.6 Hz, 2H), 7.27–7.13 (m, 7H), 4.39 (s,
2H), 3.51 (q, 2H), 3.22 (q, 2H), 2.37 (s, 3H), 1.16 (t, J=6.9, 6.9 Hz, 3H), 0.96 (t,
J=6.9, 6.9 Hz, 3H) ppm; 13C NMR (CDCl3, 75 MHz): 164.5, 141.6, 141.2, 134.3,
129.0, 128.8, 127.8, 126.7, 126.2, 43.4, 43.2, 36.5, 21.4, 13.4, 11.8 ppm.
(4) N1-Methyl-N1-phenyl-N2-(4-methylbenzensulfonyl)-2-phenylacetamidine
1
(Table 3, product (10d): H NMR (CDCl3, 400 MHz): δ 7.88 (d, J=8.0 Hz, 2H),
7.28–7.20 (m, 5H), 7.11–7.08 (m, 3H), 6.83–6.77 (m, 4H), 4.25 (s, 2H), 3.34 (s, 3H),
1 3

A. Pawar et al.
2.42 (s, 3H) ppm; 13C NMR (CDCl3, 75 MHz): 164.4, 142.6, 142.4, 141.5, 133.7,
129.6, 129.4, 128.9, 128.3, 127.4, 126.9, 126.6, 41.6, 35.5, 21.4 ppm.
1
(5) N1,N1-Triphenyl-N2-tosylacetamidine (Table 3, product (10e): H NMR
(CDCl3, 400 MHz): 8.03 (d, J=8.4 Hz, 2H), 7.85–7.42 (m, 13H), 6.75 (d, 4H), 4.52
(s, 2H), δ 2.45 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz): 165.2, 142.3, 139.5,
131.9, 128.1, 128.5, 127.8, 127.4, 126.9, 126.5, 36.9, 21.6 ppm.
1
(6) 2-phenyl-N,N-dipropyl-N’-tosylacetamidine (Table 3, product (10f): H
NMR (CDCl3, 300 MHz): δ 7.76 (d, J=7.8 Hz, 2H), 7.29–7.18 (m, 7H), 4.45 (s,
2H), 3.42 (t, J=7.5 Hz, 7.2 Hz, 2H), 3.12 (t, J=7.8 Hz, 7.5 Hz, 2H), 2.40 (s, 3H),
1.65 (t, J=7.2 Hz, 6.9 Hz, 2H), 1.42–1.26 (m, 2H), 0.89–0.75 (m, 6H) ppm; 13C
NMR (CDCl3, 75 MHz): δ 164.7, 141.4, 141.2, 134.4, 128.9, 128.8, 127.9, 126.8,
126.2, 50.7, 50.5, 36.7, 21.6, 21.4, 20.0, 11.3, 11.1 ppm.
1
(7) N1, N1-dibutyl-2-phenyl- N2-tosylacetamidine (Table 3, product (10 g): H
NMR (CDCl3, 300 MHz): δ 7.78 (d, J=8, 4, 2H), 7.29–7.15 (m, 7H), 4.42 (s, 2H),
3.43 (t, J=8.1 Hz, 7.5, 2H), 3.11 (t, J=8.1 Hz, 7.8, 2H), 2.44 (s, 3H), 1.36–1.14 (m,
8H), 0.91–0.80 (m, 6H) ppm; 13C NMR (CDCl3, 75 MHz): δ 164.6, 141.5, 141.5,
134.5, 128.9, 128.8, 127.9, 126.7, 126.2, 49.0, 48.7, 36.9, 30.4, 28.7, 21.3, 20.2,
19.9, 13.6, 13.5 ppm.
(8) N1-Isopropyl-N2-(4-methylbenzensulfonyl)-2-phenylacetamidine (Table 3,
product (10 h): 1H NMR (CDCl3, 400 MHz): δ 7.83 (d, J=10.4 Hz, 2H), 7.86–7.18
(m, 7H), 4.98 (s, 1H), 4.27 (s, 2H), 4.14–4.05 (m, 1H), 2.42 (s, 3H), 1.00 (d,
J=6.4 Hz, 6H) ppm; 13C NMR (CDCl3, 75 MHz): δ 165.4, 141.7, 140.7, 133.3,
129.6, 129.3, 128.2, 126.5, 42.2, 38.5, 21.4, 21.0 ppm.
(9) N1-benzyl-N2-(4-methylbenzenesulfonyl)-2-phenylacetamidine (Table 3,
1
product (10i): H NMR (CDCl3, 300 MHz): δ 7.76 (d, J=7.9 Hz, 2H), 7.55–7.31
(m, 10H), 7.29–7.27 (m, 2H), 5.43 (t, 1H), 4.23 (s, 2H), 4.17 (d, 2H), 2.39 (s, 3H)
ppm; 13C NMR (CDCl3, 75 MHz): δ 165.4, 141.4, 138.8, 134.3, 131.9, 130.4, 129.8,
129.4, 128.9, 128.2, 127.5, 126.4, 43.8, 39.7, 20.6 ppm.
1
(10) N1,N1-dinonyl-2-phenyl-N2-tosylacetamidine (Table 3, product (10j): H
NMR (CDCl3, 400 MHz): δ 7.78 (d, J=8.4 Hz, 2H) 7.27–7.14 (m, 7H), 4.39 (s,
2H), 3.39 (t, J=7.6, 8.0 Hz, 2H), 3.0 (t, J=8.0, 8.0 Hz, 2H), 2.38 (s, 3H), 1.58 (s,
5H), 1.32–1.21 (m, 25H), 0.91–0.86 (m, 6H) ppm; 13C NMR (CDCl3, 75 MHz): δ
165.1, 141.9, 141.2, 135.8, 129.7, 129.1, 127.8, 126.5, 125.8, 50.2, 49.7, 36.2, 31.8,
30.2, 29.1, 28.7, 27.8, 26.4, 26.1, 22.7, 21.7, 13.8 ppm.
(11) (Z)-2-(4-nitrophenyl)-1-(piperidin-1-yl)-N-tosylethanimine (Table 3,
1
product (10 k): H NMR (CDCl3, 400 MHz): δ 7.79 (d, J=8.4 Hz, 2H) 7.26–7.15
(m, 6H), 4.41 (s, 2H), 2.9 (t, 4H), 1.53 (qu, 4H), 1.21 (qu, 2H), 2.38 (s, 3H), ppm;
13C NMR (CDCl3, 75 MHz): δ 164.0, 145.4, 143.6, 143.4, 141.1, 130.4, 130.1,
130.0, 128.2, 121.0, 130.0, 128.2, 120.0, 45.1, 37.7, 26.0, 25.6, 26.0, 24.3 ppm.
Results and discussion
The preparation of magnetic separable nanoparticles-decorated N-heterocyclic
carbene complex with copper is outlined in Scheme 1. Initially, Fe3O4 MNPs (1)
was synthesized by co-precipitations method and coated with silica layer by using
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One-pot multicomponent synthesis of N-sulfonyl amidines…
Fe3O4
MNPs
MNPs (1)
TEOS
Fe3O4
MNPs
Silica coated MNPs (2)
OEt
Xylene, 110 oC
EtO Si
Cl
24 h
OEt
(3-Chloropropyl)triethoxy silane
O
O
O
Fe3O4
MNPs
Si
Cl
3-Chloropropyl modified MNPs (3)
CH3
N
N
O
DMF, 80 C
72 h
1-Methyl benzimidazole (4)
O
O
O
CH3
Cl
Fe3O4
MNPs
Si
N
N
MNP[1-Methyl benzimidazole]Cl (5)
CuI, NaOt-Bu
THF
I
Cu
O
O
O
CH3
Fe3O4
MNPs
Si
N
N
MNP[1-Methyl benzimidazole]NHC@Cu (6)
Scheme 1 Preparation of MNP[1-Methyl benzimidazole]NHC@Cu (6)
TEOS (tetraethyl ortho silicate) aforded silica coated MNPs (2) through sol–gel
method [40, 41] which on further treatment with (3‐chloropropyl)triethoxysilane
aforded 3-chloropropyl modifed MNPs (3). The synthetically fertile chloro group
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A. Pawar et al.
in 3 allowed attachment of ionic liquid like group on the surface of MNPs through
quaternization with 1-methyl benzimidazole (4) to yield azolium salt precursor acro-
nymed as MNP[1-Methyl benzimidazole]Cl (5). Finally, the complexation of 5 with
copper iodide by using NaOtBu as base aforded the magnetic separable nanoparti-
cles-decorated N-heterocyclic carbene complex with copper acronymed as MNP[1-
Methyl benzimidazole]NHC@Cu (6).
Fourier transform infrared (FT‐IR) spectroscopy was employed to monitor reac-
tions involved in the preparation of MNP[1-Methyl benzimidazole]NHC@Cu
(6). The FT-IR spectrum of Fe3O4 MNPs (1) displayed Fe–O stretching band at
583 cm−1. The formation of silica coated Fe3O4 MNPs (2) was confrmed by FT-IR
peaks at 796, 959 and 1099 cm−1 attributed to Si–O–Si symmetric, Si–O symmet-
ric and Si–O–Si asymmetric stretching modes, respectively [42]. The FT-IR spec-
trum of 3-chloropropyl MNPs (3) displayed characteristic peaks at 3408 cm−1 (O–H
stretching), 2925 cm−1 (C–H stretching vibration of propyl group), 1099 cm−1 (Si–O
stretching) (Fig. 1a) [43]. The quaternization of 3 with 4 was realized by appear-
ance of three prominent peaks at 1654 cm−1 (C=N stretching vibration), 1642 cm−1
(C=C stretching vibration) and 1387 cm−1 (C–N stretching) suggesting the forma-
tion of 5 (Fig. 1b) [44]. Finally, the formation 6 was confrmed by a strong intense
band of N–C–N strengthening in the range 1340–1500 cm−1 as a result coordination
of NHC carbon ligand with copper metal ion as well as shifting of characteristic IR
absorption peaks to lower frequency values (Fig. 1c) [45, 46].
The thermal stability profles of bare Fe3O4 MNPs (1) and MNP[1-Methyl ben-
zimidazole]NHC@Cu (6) were investigated by TGA analysis over the temperature
range of 25–1000 ºC at a heating rate of 10 ºC/min (Fig. 2). In both cases, initial
Fig. 1 FT-IR spectra of a 3-chloropropyl-modifed MNPs (3); b MNP[1-Methyl benzimidazole]Cl (5);
c MNP[1-Methyl benzimidazole]NHC@Cu (6); d reused MNP[1-Methyl benzimidazole]NHC@Cu (6)
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One-pot multicomponent synthesis of N-sulfonyl amidines…
Fig. 2 TGA curves of bare Fe3O4 MNPs (1) and MNP[1-Methyl benzimidazole]NHC@Cu (6)
weight loss of 3.68% up to 102 ºC and 4.96% up to 111 ºC, respectively, for 1 and 6
is due to evaporation of physically adsorbed water. TGA curve of bare Fe3O4 MNPs
(1) displayed no signifcant weight loss from 111 to 800 ºC which indicates that
presence of only iron oxides and no any organic moiety attached on the surface
of MNPs. In TGA curve of 6, the second weight loss was observed 8.79% in the
range of 102–502 ºC attributed to loss of surface bound organic scafolds by thermal
decomposition such as (3-chrolopropyl)triethoxy silane and 1-methyl benzimida-
zole. The steep weight loss of 15.67% at 700 °C displayed thermal decomposition of
copper iodide and major weight loss ascribed to residual silica and metallic oxides
which possess high thermal stability.
The CHNS analysis of Compound [MNP-methylbenzimi]Cl (5) revealed that
nitrogen-containing 1-methylbenzimidazole loading was 0.36 mol functional group
per gram of 5. The energy-dispersive X-ray (EDX) analysis of MNP[1-Methyl ben-
zimidazole]NHC@Cu (6) displayed oxygen and iron as the major elements which
are attributed to magnetic nanoparticle core of Fe3O4. In addition, 6 displayed minor
peaks for silicon, nitrogen and iodine (Fig. 3). The presence of copper in its respec-
tive energy position also suggests the formation of complex 6. The EDX analysis
revealed loading of 0.22 mmol of Cu per gram of 6.
The crystalline material structure and retention of Fe3O4MNPs in MNP[1-Methyl
benzimidazole]NHC@Cu (6) were investigated by X-ray difraction (XRD) analysis.
The well indexing of all the peaks in difractogram to the JCPDS card No. 86–1339
agreed retention of single-phase inverse spinel structure of Fe3O4 nanocore with
high phase purity and crystallinity (Fig. 4). The characteristic peaks at 2θ values of
30.12°, 35.25°, 44.07°, 57.61°, 62.37°, 71.03° and 87.13° being assigned to the (2
2 0), (3 1 1), (4 0 0), (5 5 1), (4 4 0), (6 2 0) and (6 4 2) crystallographic planes of
Fe3O4 nanocore, respectively, were observed in XRD pattern. The most intense peak
is observed for (3 1 1) plane at 2θ value 35.25°. The broad peaks at 2θ from 21° to
1 3

A. Pawar et al.
Fig. 3 EDX spectrum of MNP[1-Methyl benzimidazole]NHC@Cu (6)
Fig. 4 XRD of MNP[1-Methyl benzimidazole]NHC@Cu (6) (black); XRD of reused MNP[1-Methyl
benzimidazole]NHC@Cu (6) (blue)
32° of the XRD pattern are assigned to the silica phase. The crystallite size calcu-
lated with respect to most intense peak by using Scherrer equation was found to be
51.6 nm. The XRD analysis revealed preservation of crystallographic structure of
Fe3O4 MNPs (1) in 6 even after multi-step functionalization.
The surface morphology of MNP[1-Methyl benzimidazole]NHC@Cu (6)
was studied by transmission electron microscopy (TEM). The TEM micrographs
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One-pot multicomponent synthesis of N-sulfonyl amidines…
Fig. 5 TEM images of a,b MNP[1-Methyl benzimidazole]NHC@Cu (6); c nanoparticle shows lat-
tice fringe width; d-e reused MNP[1-Methyl benzimidazole]NHC@Cu (6); f SAED pattern of MNP[1-
Methyl benzimidazole]NHC@Cu (6)
displayed granules with spherical shape and non-smooth surface. Moreover, TEM
images show embedded dark Fe3O4 nanocores surrounded by gray shell (Fig. 5a, b)
[47]. The average nanoparticle size of 6 was found to be 10 nm with a lattice fringe
width distance of d(311) =2.5182 ̊A, which reveals the formation of perfect crystal
structure (Fig. 5c). The selected-area electron difraction (SAED) pattern exhibited
four strong difraction rings which were assigned to the (3 1 1), (4 0 0), (3 3 1) and
(4 2 2) bright dotted with ring pattern persuade the polycrystalline nature of Fe3O4
MNPs (1) (Fig. 5d).
The magnetic properties of bare Fe3O4 MNPs (1) and MNP[1-Methyl benzimida-
zole]NHC@Cu (6) were evaluated by magnetic hysteresis loops at room temperature
using vibrating sample magnetometer (VSM) shown in Fig. 6. The saturation mag-
netization (Ms) values for bare Fe3O4 MNPs (1) and 6 were found to be 53 emug−1
(Fig. 6a) and 30 emug−1 (Fig. 6b), respectively. The saturation magnetization value
of 6 exhibited comparatively low. This quenching of Ms value is ascribed due to sur-
face functionalization [48]. However, magnetization exhibited by 6 was sufcient to
enough for efective separation by external magnet.
In order to optimize the reaction conditions, a model reaction between phe-
nyl acetylene (7; 1.0 mmol), tosyl azide (8; 1.0 mmol) and dimethylamine (9a;
1.2 mmol) in the presence of MNP[1-Methyl benzimidazole]NHC@Cu (6) was car-
ried out at room temperature for the synthesis of N-sulfonyl amidines (Scheme 2).
1 3

A. Pawar et al.
Fig. 6 a Magnetic curve (VSM) of bare Fe3O4 MNPs (1), b magnetic curve (VSM) of MNP[1-Methyl
benzimidazole]NHC@Cu (6)
R
N
O
S
O
MNP[1-Methyl benzimidazole]NHC@Cu (6)
R1
O
(50mg)
N3
R
R1
N
H
N
+
+
THF(5mL), RT
S
O
10(a-j)
9(a-j)
7
8
Scheme 2 MNP[1-Methyl benzimidazole]NHC@Cu (6) catalyzed synthesis of N-sulfonylamidines
1 3

One-pot multicomponent synthesis of N-sulfonyl amidines…
Table 1 Optimization of solvent in synthesis of N-sulfonyl amidines a, b
Entry
Solvent
Time (min)
Yield (%)
TON
TOF (h−1
)
1
2
3
4
5
6
7
8
Water
DCM
THF
CHCl3
Ethanol
Methanol
Toluene
1,4-Dioxane
2880
260
50
220
240
235
290
560
35
71
94
40
55
60
45
40
3181
6454
8545
3636
5000
5454
4090
3636
66
1490
10,295
993
1250
1394
846
389
Bold text indicate that it is a outstanding results compared to other entries
a
Reaction condition:: phenyl acetylene (1.0 mmol), tosyl azide (1.0 mmol), dimethylamine (1.2 mmol),
solvent (5 mL)
b Isolated yields after chromatography
Initially, the efect of various solvents on the model reaction was investigated in the
presence of 6 at room temperature (Table 1). The reaction aforded poor yield of
10a in water (Table 1, entry 1), whereas better yields were obtained in polar aprotic
solvents such as dichloromethane (DCM), tetrahydrofuran (THF) (Table 1, entries
2–3). Further, moderate yield of 10a was obtained in non-polar solvent such as chlo-
roform toluene and 1–4 dioxane (Table 1, entry 4, 7 and 8). Moreover, moderate
yields were achieved in polar protic solvents like methanol and ethanol (Table 1,
entries 5–6). Among all the screened solvents, THF furnished the highest yield 10a
(Table 1, entry 3). Therefore, THF was chosen as the solvent for further studies.
A control reaction was carried out in which model reaction was carried out using
Fe3O4 MNPs (1) and MNP[1-Methyl benzimimidazole]Cl (5). The reaction could
not be initiated by using 1 and 5 in spite of using high quantities (up to 200 mg),
indicating that they were inefective as catalysts for the projected reaction (Table 2,
entry 1–2). Next, the efect of catalyst loading was investigated on the model reac-
tion. In the presence 10 mg (0.0022 mmol) and 20 mg (0.0044 mmol) of 6, low
amount of corresponding product, viz. N1,N1-Dimethyl-2-phenyl-N2-tosylaceta-
midine (10a), was formed even after prolonged reaction time (Table 2, entry 3–4).
Gratifyingly, when the amount of catalyst was increased from 30 mg (0.0066 mmol)
to 50 mg (0.011 mmol), the yield of 10a was elevated up to 94% (Table 2, entry
5–7). However, no substantial alteration has been occurred in the yield of product
and reaction time using quantities beyond 50 mg up to 200 mg (Table 2, entries
8–10). Thus, 50 mg of 6 was selected as optimal catalyst loading for further studies.
1 3

A. Pawar et al.
Table 2 Optimization of catalyst loading in synthesis of N-sulfonyl amidines a
Entry
Catalyst
Amount of
Time (minute)
Yieldb (%)
TON
TOF (h−1
)
catalyst (mg)
1
2
Fe3O4 MNPs (1)
MNP[1-Methyl
benzimidazole]
Cl (5)
MNP[1-Methyl
benzimidazole]
NHC@Cu (6)
6
6
6
6
6
6
6
200
200
2880
2880
–
–
–
–
–
–
3
10
110
48
21,818
11,992
4
5
6
7
8
9
10
20
30
40
50
100
150
200
90
80
65
50
45
40
40
73
89
91
94
94
95
95
16,390
13,484
10,340
8545
4272
2878
11,060
10,138
9574
10,295
5696
4361
3271
2159
Bold text indicate that it is a outstanding results compared to other entries
a
Reaction condition: phenyl acetylene (1.0 mmol), tosyl azide (1.0 mmol), dimethylamine (1.2 mmol),
THF (5 mL) at RT
b Isolated yields after chromatography
With the optimal reaction conditions in hands, the scope and generality of the
methodology were illustrated for one-pot multicomponent reaction using phe-
nylacetylene (7), tosyl azide (8) and variety of amines (9). The results are sum-
marized in Table 3. In all the cases, reactions proceeded smoothly afording the
desired N-sulfonyl amidines in good to excellent yields. It is worth mentioning
that amines with aliphatic chain furnished better yield than aromatic amines
(Table 3, entry 10a–c and 10f–g). Primary amines also efciently reacted with
phenylacetylene, and tosyl azide gives corresponding good yield (Table 3, entry
10 h–j). The reactions were clean and high yielding without generation of any
side product.
A plausible mechanism of N-sulfonyl amidines synthesis from phenyl acetylene,
tosyl azide and amines using MNP[1-Methyl benzimidazole]NHC@Cu (6) is out-
lined in Scheme 3. Initially, 6 interacts with phenylacetylene (7) through hydrogen
bonding to aford copper acetylide intermediate (I). Further, addition of tosyl azide
(8) to intermediate (I) to forms copper triazolyl intermediate (II). In the next step,
the formed intermediate (II) subsequently discharges N2 and produces ketenimine
1 3

One-pot multicomponent synthesis of N-sulfonyl amidines…
Table 3 MNP[1-Methyl benzimidazole]NHC@Cu (6) catalyzed synthesis of N-sulfonyl amidines a
1 3

A. Pawar et al.
Table 3 (continued)
a
Reaction condition: Phenyl acetylene (1.0 mmol), tosyl azide (1.0 mmol), substituted amines
(1.2 mmol), solvent THF (5 mL); MNP[1-Methyl benzimidazole]NHC@Cu (6) (50 mg); b Isolated yields
after chromatography
intermediate (III). Finally, attack of substituted amine (9) takes place on intermedi-
ate (III) which furnishes the desired N-sulfonyl amidines (10a–j) [49, 50].
To ascertain whether the reactions are truly heterogeneous, leaching studies
were performed by analyzing the reaction fltrate after the recovery of MNP[1-
Methyl benzimidazole]NHC@Cu (6) by using atomic absorption spectroscopy
(AAS). Further, the hot fltration test was carried out to confrm heterogeneous
nature of MNP[1-Methyl benzimidazole]NHC@Cu (6) by using the model reac-
tion. In this test, a mixture of 6 (50 mg), phenylacetylene (7a; 1.0 mmol), tosyl
azide (8a; 1.0 mmol) and dimethylamine (9a; 1.0 mmol) in THF (5 mL) was
heated at 70 ºC. The 6 was separated from the hot reaction mixture when 50%
conversion was accomplished (GC). The reaction was continued with the fltrate
for further 6 h. There was no increase in the yield of the product beyond 50%
even after 6 h confrming the heterogeneous nature of 6.
1 3

One-pot multicomponent synthesis of N-sulfonyl amidines…
R
N
I
R1
O
Cu
O
O
O
N
CH3
Fe3O4
MNPs
S
O
Si
N
N
Product (10a-j)
(7)
MNP[1-Methyl benzimidazole]NHC@Cu (6)
H
R
R1
N
..
(9)
O
S
Cu
N
N
O
O
O
CH3
C
Fe3O4
MNPs
Si
N
O
C
Cu
N
O
CH3
Fe3O4
MNPs
O
O
Si
N
Copper acetylide intermediate (I)
Ketenimine intermediate (III)
O
N
N3
N
O
S
N
S
O
-N2
O
(8)
Cu
N
O
CH3
Fe3O4
O
Si
N
MNPs
O
Copper-triazolyl intermediate (II)
Scheme 3 A plausible mechanism for the MNP[1-Methyl benzimidazole]NHC@Cu (6) catalyzed syn-
thesis of N-sulfonyl amidines
Fig. 7 Reusability of MNP[1-Methyl benzimidazole]NHC@Cu (6) in the synthesis of N-sulfonyl ami-
dines
1 3

A. Pawar et al.
From the green chemistry point of view, recovery and recyclability of the sup-
ported catalyst are an unavoidable parameter for industrial and commercial scale
that must be tackled for any catalytic process. Thus, the recovery and reusability
of MNP[1-Methyl benzimidazole]NHC@Cu (6) are investigated by employing
model reaction (Fig. 7). In brief, after reaction was completed, the 6 was iso-
lated from reaction mixture by magnet. The complex 6 was washed with copious
amount THF to remove organics wedded in the catalyst sites and dried under vac-
uum at room temperature. The amounts of necessary reactants were recalculated
on the basis recovered catalyst. The recovered catalyst could be reused for six
times without signifcant decrease in the yield of the products. Further, the stabil-
ity of recycled catalyst was studied by FT-IR spectroscopy, EDX, XRD and TEM
analysis of 6. It is noteworthy to mention that the FT-IR (Fig. 1d) spectrum of
reused 6 still retains the prominent peak pattern of the 6. The EDX mapping of 6
after six catalytic cycles confrmed the integrity of the recycled catalyst. Moreo-
ver, TEM analysis of fresh (Fig. 5 a–c) and reused 6 (Fig. 5 d–e) designates that
morphology is preserved even after six successive runs. The results of FT-IR,
EDX, XRD and TEM analysis of fresh and reused 6 confrmed that the structural
rigidity and main characteristics of complex remain conserved, demonstrating
stability of 6 after six consecutive runs.
To demonstrate the importance of MNP[1-Methyl benzimidazole]NHC@Cu
(6) in comparison with other reported methods, we have summarized previous
report for synthesis of N-sulfonyl amidines in Table 4. The comparison of results
clearly persuades that 6 is a superior catalyst in terms of catalyst loading and
reaction time as compared to the reported catalyst.
Table 4 Comparison of diferent catalyst for synthesis of 10b
Sr.No Catalyst
Quantity
Solvent
Temperature Time Yield (%) Reference
(min)
1
2
3
4
5
6
7
8
9
[Cu(Triaz)2]BF4
1 mol%
5 mol%
4.17 mol% THF
10 mol%
10 mol%
Solvent free RT
Toluene 70 ºC
270
1800 98
80
720
120
120
120
720
180
96
[30]
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
Cu(OTf)2
Cu-Scolecite
CuI
RT
89
89
90
89
82
89
93
THF
THF
25 ºC
RT
CuI
MOF−Cu2I2(BTTP4) 2.4 mol% THF
CuI
CuI
RT
10 mol%
10 mol%
5 mol%
THF
RT
THF
RT
Cu
CH3CN
25 ºC
@C
10
Present work
MNP[1-Methyl benzi-
midazole]NHC@
Cu (6)
50 mg
THF
RT
55
93
–
Bold text indicate that it is a outstanding results compared to other entries
1 3

One-pot multicomponent synthesis of N-sulfonyl amidines…
Conclusion
In conclusion, we have reported a magnetic separable nanoparticles-decorated
N-heterocyclic carbene complex with copper acronymed as MNP[1-Methyl ben-
zimidazole]NHC@Cu (6). The catalyst 6 was thoroughly characterized by FT-IR
spectroscopy, XRD, TEM, TGA, EDX, CHNS and VSM analysis. MNP[1-Methyl
benzimidazole]NHC@Cu (6) was successfully employed as a heterogeneous cata-
lyst with outstanding activity in multicomponent reaction of phenylacetylene, tosyl
azide and variety of amines for the synthesis of N-sulfonyl amidines. The protocol
ofers several striking advantages such as good yields, simple work up procedure,
short reaction time, magnetically separable and efcient recyclability of the catalyst.
Supplementary Information The online version contains supplementary material available at https://doi.
org/10.1007/s11164-021-04455-1.
Acknowledgements We gratefully acknowledge Indian Institute of Bombay (IITB), North-Estern Hill
University Shillong (NEHU), Indian Institute of Technology, Madras (IITM), for providing spectral facil-
ities and Central Facility Centre (CFC) Shivaji University Kolhapur for providing quantitative spectral
analysis.
Declaration
Confict of interest The authors declare no confict of interest.
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