N-Heterocyclic Carbene-Protected Ag Nanoparticles Immobilized on Polyacrylonitrile Fiber as Efficient Catalysts for a Three-Component Coupling Reaction

Article abstract of DOI:10.1002/asia.201800154

Metal nanoparticles (NPs) are routinely stabilized by the introduction of capping agents or their distribution on supports. In this context, we report the preparation and characterization of N-heterocyclic carbene (NHC)-stabilized silver NPs supported on

Full text of DOI:10.1002/asia.201800154

DOI: 10.1002/asia.201800154
Full Paper
Three-Component Coupling Reaction
N-Heterocyclic Carbene-Protected Ag Nanoparticles Immobilized
on Polyacrylonitrile Fiber as Efficient Catalysts for a Three-
Component Coupling Reaction
Jian Cao and Hongqi Tian*[a]
Abstract: Metal nanoparticles (NPs) are routinely stabilized
by the introduction of capping agents or their distribution
on supports. In this context, we report the preparation and
characterization of N-heterocyclic carbene (NHC)-stabilized
silver NPs supported on polyacrylonitrile fiber (PANF). As a
result, Ag loadings of up to 8% and particle sizes of 11.0Æ
3.2 nm were achieved. This novel nanocomposite catalyst
demonstrated high activity in addition to excellent stability
and reusability in the three-component reaction between al-
kynes, haloalkanes, and amines. In this system, the AgNPs
were stabilized by both a support effect and a ligand effect.
The unique NHC-protected AgNP structure and the PANF
support provide a synergistic effect in the deprotonation of
CspÀH bonds, with turnover numbers of up to 3500. This cat-
alyst was successfully recycled over eight runs without any
significant loss in activity, and with no significant aggrega-
tion of the AgNPs. Moreover, implementation of a flow
system with PANF-NHC@Ag as catalyst leads to an efficient
productivity of 57 mmolhÀ1.
lyst.[12] This novel NP catalyst efficiently catalyzed asymmetric
a-arylation reactions with up to 85% ee. Furthermore, Salor-
inne et al. described a bottom-up approach for the synthesis
of novel NHC-protected AuNPs by employing water-soluble
and pH-tunable NHCs,[13] whereas Ferry et al. employed biden-
tate hybrid NHC–thioether ligands to stabilize Pd and AuNPs
for use in various catalytic transformations.[14] However, despite
huge advances in this area, only a few examples of supported
NHC-NP systems have been reported, with one example in-
cluding an extensive characterization of an NHC-modified sup-
ported heterogeneous Ru/K-Al2O3 catalyst. The tunability of
Ru/K-Al2O3 by NHCs played an important role in a perfectly
chemoselective hydrogenation.[15]
Introduction
Metal nanoparticles (NPs) have attracted growing attention in
recent years owing to their unique properties compared with
those of their bulk counterparts.[1] These properties have re-
sulted in the application of NPs in a range of fields, including
drug research,[2] sensors,[3] and catalysis.[4,5] As such, the suc-
cessful preparation of metal NPs with small diameters is critical
for enhancing catalytic performances owing to the high
degree of dispersion and the nanosize effect of small parti-
cles.[6] The stabilization of such metal NPs is therefore essential,
and this is commonly achieved by the introduction of capping
agents[7] or by distribution of the metal NPs/clusters on sup-
ports.[4]
In the context of NPs, AgNPs are one of the most frequently
employed nanostructures, and have been used in a multitude
of applications, including catalysis, imaging, drug delivery, and
theragnostics.[16–18] However, only a few examples of NHC-func-
tionalized AgNPs have been described in the literature. For ex-
ample, in 2012, Yu et al. reported the stabilization of a AgNP
catalyst by a NHC polymer.[19] This novel nanoscale catalyst ex-
hibited an excellent activity in addition to good stability and
reusability for the carboxylation of terminal alkynes with CO2
at room temperature. These results therefore indicate that the
preparation of novel NHC-functionalized AgNPs could be of
particular importance in the context of nanochemistry.
To date, a wide range of capping agents have been reported
for the stabilization of metal NPs, with examples including
thiols, amines, disulfides, phosphines, and N-heterocyclic car-
benes (NHCs).[7–10] More specifically, the formation of coordina-
tion bonds between neutral and electron-rich NHCs and the
surfaces of metal NPs is crucial, as it allows the NPs to retain
their unique nanoscale properties.[11] In 2010, Ranganath et al.
reported a heterogeneous NHC-modified Fe3O4/PdNPs cata-
[a] Dr. J. Cao, Prof. H. Tian
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medi-
cine, Institute of Radiation Medicine
Chinese Academy of Medical Science and Peking Union Medical College,
Tianjin 300192 (China)
In general, NPs exhibit higher catalytic activities than their
bulk counterparts. However, owing to their reduced thermody-
namic stabilities,[1] modifications such as the addition of li-
gands and capping agents or the formation of core–shell type
particles have been examined to produce stable particles.[9] Un-
fortunately, the application of these modified catalysts often
E-mail: tianhongqi@irm-cams.ac.cn
Supporting information and the ORCID identification number(s) for the au-
thor(s) of this article can be found under:
https://doi.org/10.1002/asia.201800154.
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results in facile NP aggregation and the formation of a deacti-
vated bulk mass, which in turn leads to poor activities and re-
usabilities. To address this issue, a combination of supports
and NPs may be considered a promising way forward. Indeed,
the ease of separation, the simple regeneration, and the high
stabilities of supported catalysts have spurred the develop-
ment of heterogeneous nanocatalysis, in addition to the direct
utilization of such catalysts in continuous-flow processes.[1,4,5]
To date, various support materials have been employed as
templates in the manufacture of metal NPs owing to the bene-
ficial synergistic properties of nanometal/polymer composites.
For example, Emam et al. reported a simple, green, and inex-
pensive one-pot method for the preparation of AgNPs, AuNPs,
and Ag-Au nano-alloys on a cellulosic solid support. In this
case, immobilization of the NP/bimetallic nanostructures pro-
duced a catalyst for the reduction of p-nitroaniline.[20] Further-
more, Liu et al. employed mesoporous SBA-15-supported
AgNPs as a catalyst system for an A3 coupling reaction.[21]
Recently, the use of fibers such as polyacrylonitrile fiber
(PANF), polypropylene fiber, and cotton fiber as support mate-
rials for adsorbents, metal ion sensors, and catalysts has been
reported.[22–27] Indeed, PANF is a particularly promising support
material owing to its inexpensive source, porous structure, and
good stability. Moreover, the PANF framework contains an
abundance of -CN groups, which can be easily functionalized
and immobilized with various moieties.[25,27] For example, previ-
ous studies have reported the immobilization of Ag complexes
to afford PANF-supported Ag complexes.[27] Thus, we herein
report a novel strategy for the synthesis of a sequence of
PANF-supported Ag nanoparticles (PANF-NHC@Ag) based on
the use of NaBH4 to reduce PANF-supported NHC-Ag com-
plexes (Scheme 1). The resulting PANF-NHC@Ag materials will
then be characterized, and their catalytic performances in the
three-component reaction between aldehydes, halomethanes,
and alkynes (AHA coupling) will be evaluated. This transforma-
tion is of particular interest, as the AHA coupling reaction is an
important approach in the synthesis of propargylamines,
which are recurrent moieties in biologically active compounds
and are also valuable intermediates in organic synthesis.[28–30]
Results and Discussion
Preparation and characterization of the fiber-supported
AgNPs
As outlined in Scheme 1, the preparation of PANF-NHC@Ag
was based on the reduction of a PANF-supported NHC-Ag
complex (PANF-NHC-Ag) by using NaBH4.[13] The first step in
this synthetic route involved the modification of PANF to give
the supported Ag complexes.[27] This was followed by reduc-
tion of the Ag complexes to yield the desired fiber-supported
AgNPs. To investigate the influence of the ligand, aminated
PANF coordinated with AgNO3 was also used as a precursor,
which was later reduced to produce amino-protected NPs
(PANF-Am@Ag). A detailed typical procedure for the prepara-
tion of these catalysts is given in the Supporting Information.
Following the successful preparation of PANF-NHC-Ag, the
extent of its modification was measured by calculating the
weight gain and by determining the concentration of metal
ions by inductively coupled plasma optical emission spectros-
copy (ICP-OES; Table S1 in the Supporting Information).[27] The
obtained PANF-NHC-Ag was then reduced, and the NP size
was controlled by tuning the reduction time and functionality
of PANF-NHC-Ag. To investigate the unique and attractive fea-
tures of the prepared NPs, transmission electron microscopy
(TEM) was employed to characterize the nanoscale structures
(see Figure 1). As shown in Figure 1a, nano-sized spherical Ag
particles with average diameters of 11.0Æ3.2 nm were success-
fully prepared and immobilized on the fiber surface. Upon
tuning the reduction time and the functionality (F), the NP size
could be varied from 11.0 nm (4–18 nm) to 44.5 nm (24–
52 nm; Figure 1). As indicated, upon increasing the functionali-
ty of the precursor, the formation of Ag clusters was promoted,
with aggregation of the AgNPs being observed at higher load-
ings. In addition, increased reduction times resulted in NP ag-
gregation (Figure 2). Under optimized conditions, AgNPs with
a loading of 8% (0.75 mmolgÀ1) and an average diameter of
11.0Æ3.2 nm were successfully prepared. However, upon ex-
amination of the obtained PANF-Am@Ag by TEM (Figure S1 in
the Supporting Information), few NPs were detected, thereby
demonstrating the importance of the NHC in stabilizing the
Scheme 1. Schematic illustration of the preparation of PANF-supported AgNP catalysts.
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0.24 nm can be clearly observed, which can be attributed to
the lattice spacings of the (111) planes of the AgNPs.[31]
The modified fibers were then analyzed by scanning elec-
tron microscopy (SEM) to examine both the general morpholo-
gy and the microscopic fine structure. As shown in Figure 3,
Figure 3. Scanning electron microscopy: (a) PANF; (b) PANF-Am@Ag;
(c) PANF-NHC@Ag; and (d) PANF-NHC@Ag after eight catalytic runs.
the prepared PANF-NHC@Ag and PANF-Am@Ag exhibited
greater thicknesses and surface coarseness than PANF itself. In
addition, following reduction by NaBH4, Ag nanoparticles were
found on the PANF-NHC@Ag surface. Subsequently, energy dis-
persive spectroscopy (EDS) was utilized to characterize the
PANF-NHC@Ag catalyst. As shown in Figure 4a, peaks corre-
sponding to C, N, O, and Ag were observed in the EDS spec-
trum, thereby confirming that the AgNPs were immobilized on
the fiber surface. In addition, examination of the prepared
PANF-NHC@Ag by energy-dispersive X-ray elemental mapping
(Figures 4b–g) showed the highly dispersed AgNPs in the
PANF matrix as bright spots. The dispersion of N, C, and O
over the fiber surface was also confirmed by elemental map-
ping.
Figure 1. Typical TEM images of PANF-NHC@Ag: (a) F=0.75 mmolgÀ1, reduc-
tion for 6 h; (b) F=0.75 mmolgÀ1, reduction for 12 h; (c) F=1.1 mmolgÀ1, re-
duction for 6 h; (d) F=1.1 mmolgÀ1, reduction for 12 h; and
(e) F=0.75 mmolgÀ1, reduction for 6 h.
Analysis of the original PANF by X-ray diffraction (XRD, Fig-
ure 5a) showed an intense reflection peak at 2q=178 attribut-
ed to the (100) diffraction of the hexagonal lattice, which is
constructed through the parallel tight packing of the molecu-
lar rods. This confirms that intermolecular repulsions between
the CN groups of PANF result in the formation of a rod-like
conformation.[32] In the case of PANF-NHC@Ag (Figure 5c), four
additional peaks at 2q=38.5, 44.3, 64.5, and 77.18 were as-
cribed to the (111), (200), (220), and (311) planes, respective-
ly,[21] which correspond to the face-centered cubic (fcc) struc-
ture of the AgNPs (JCPDS No. 00-004-0783). This result there-
fore confirms that Ag complexes were successfully transformed
into AgNPs through reduction by using NaBH4, and that these
NPs were subsequently deposited on the PANF surface.
X-ray photoelectron spectroscopy (XPS) was then utilized to
examine both the chelating mechanism and the elemental
composition. The full survey spectrum of PANF-NHC@Ag (Fig-
ure 6a) shows principal energy levels for O1s, N1s, Ag3d, and
C1s at 536.10, 403.26, 374.02, 368.03, and 287.34 eV.[31] In addi-
tion, the high-resolution XPS spectrum (Figure 6b) shows the
typical doublet (resulting from spin-orbital splitting) for an
electron on a 3d level of Ag. Furthermore, the high-resolution
Figure 2. Control of NP size by tuning the reduction time and functionality
of PANF-NHC-Ag.
AgNPs. Furthermore, the high-resolution transmission electron
microscopy (HRTEM) image of PANF-NHC@Ag is shown in Fig-
ure 1e, where lattice fringes with spacings of approximately
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Figure 4. (a) EDS spectrum for PANF-NHC@Ag, (b) SEM image, and (c)–
(g) energy-dispersive X-ray elemental mapping images for PANF-NHC@Ag.
Figure 6. XPS spectra: (a) survey scan of PANF-NHC@Ag, and (b) high-resolu-
tion XPS narrow scan of Ag3d (I, PANF-NHC-Ag; II, PANF-NHC@Ag; III, PANF-
NHC@Ag after eight runs).
at 368.03 and 374.02 eV (Figure 6b-II), which corresponded to
Ag3d3/2 and 3d5/2, respectively, and were attributed to the Ag
nanoparticles.[31] The Ag3d peak for the recycled supported
NPs is also shown (Figure 6b-III), which demonstrates that Ag0
was the dominant form of Ag following catalyst recycling.
Solid-state 13C NMR spectroscopy (Figure 7) was employed
to confirm the proposed PANF framework and the incorpora-
tion of the NHC moiety. As indicated, the pure PANF material
produced signals at 29.7, 122.1, and 172.5 ppm corresponding
to the backbone carbon atoms, the cyano carbon atoms, and
the ester carbonyl carbon atoms (Figure 7a).[34,35] As expected,
following amination, the signal corresponding to the ester car-
bonyl carbon atom disappears, and a new signal originating
from the amide carbon atom appears at approximately
174.5 ppm. In addition, strong carbon signals corresponding to
the NHC moieties can be seen at 137.0 and 130.1 ppm (Fig-
ure 7d), with long reduction times leading to the disappear-
ance of the NHC structure (Figure 7c). As the NHC moiety sta-
bilizes the NPs, longer reduction times result in the formation
of bigger particles through aggregation (Figure 2).
Figure 5. XRD patterns of the fiber samples: (a) PANF; (b) PANF-NHC-Ag;
(c) PANF-NHC@Ag; and (d) PANF-NHC@Ag, after eight catalytic runs.
Ag XPS spectrum of PANF-NHC-Ag contained two peaks at
368.35 and 374.28 eV (Figure 6b-I), which corresponded to
Ag3d3/2 and 3d5/2, respectively, and which can be attributed to
the NHC-Ag complex.[33] Following reduction, the high-resolu-
tion Ag XPS spectrum of PANF-NHC@Ag contained two peaks
The utilization of porous materials as the NP support also
allows the generation of specific adsorption sites for reaction
substrates.[4] Thus, nitrogen adsorption/desorption isotherms
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cobalt,[44] AgI,[45] and AuNPs[46] were also employed as catalysts
in the AHA coupling reaction. In addition, the deprotonation
of CspÀH bonds by AgNPs has been reported.[19,47] However,
the development of a new highly efficient and environmentally
friendly AgNP catalytic system for the AHA coupling reaction is
still desirable.
Thus, we initially investigated the catalytic performance of
PANF-NHC@Ag in the AHA coupling reaction, by employing di-
chloromethane, phenylacetylene, and pyrrolidine as the model
reactants. Optimization of the feed ratio for the terminal
alkyne, dihalomethane, and amine components gave a ratio of
1.0:1.2:1.2. Typically, enhanced activities were found for organ-
ic bases such as triethylamine and 1,8-diazabicyclo[5.4.0]un-
dec-7-ene (DBU), likely owing to their superior solubility over
inorganic bases in this AHA coupling reaction (Table S3 in the
Supporting Information). We also performed the coupling reac-
tion by using Na2CO3, NaHCO3, and Cs2CO3, and yields in the
range 70–82% were obtained in the presence of these inor-
ganic bases (Table S3 in the Supporting Information, entries 3–
5). In addition, this novel system typically yielded good per-
formances in a range of common organic solvents. More spe-
cifically, the highest propargylamine yield was obtained in tolu-
ene, whereas other solvents, such as dimethyl sulfoxide, tetra-
hydrofuran, CH3CN, and CH2Cl2, afforded moderate to good
yields (Table S3 in the Supporting Information, entries 6–9). In-
terestingly, in the absence of solvent, PANF-NHC@Ag gave an
excellent yield of 86% (Table S3 in the Supporting Information,
entry 10). As sustainability is a significant concern in the chemi-
cal industry, the neat reaction is preferable, as it allows the as-
sembly of complex compounds without the requirement for
solvents. Furthermore, the reported AgNP-catalyzed reaction
was carried out smoothly at 258C, and proceeded at lower
temperatures compared with previously reported AHA reac-
tions.[45,46,48]
Figure 7. Solid-state 13C NMR spectra for (a) PANF, (b) PANF-Am@Ag,
(c) PANF-NHC@Ag following a long reduction time, and (d) PANF-NHC@Ag.
were performed on PANF before and after modification to
characterize its porosity and surface area (see Table S2 in the
Supporting Information). Following the grafting of ethylenedia-
mine, the PANF surface area decreased to 33.1 m2 gÀ1. In con-
trast, upon grafting of the NHC derivatives, the surface area in-
creased to 55.1 m2 gÀ1, with subsequent chemical reduction
giving a further increase to 73.4 m2 gÀ1 owing to the formation
of AgNPs. As nanoscale pores were observed for the modified
fibers, the porous materials were utilized as a NP support con-
taining specific adsorption and active sites.
The detailed nucleation process for the formation of NPs
from reaction solutions has been previously described by a
two-step model.[36] More specifically, the formation of NPs can
be considered as a chemical reaction that produces solid
AgNPs from solvated Ag0 precursor atoms. As such, the indi-
vidual nucleation and growth steps can be adapted and de-
signed by tuning the concentration of Ag0, thereby allowing a
controlled synthesis of AgNPs through application of the ap-
propriate parameters (Figure 2). Indeed, a number of studies
have reported that the nucleation process is critical in improv-
ing the catalytic performance of NPs.[2] In the case of our
system, nucleation occurs on the PANF surface. As the precur-
sor PANF-NHC-Ag is hydrophilic, it is easily reduced to Ag0 by
NaBH4,[17] whereas the NHC moiety stabilizes the AgNPs owing
to its electron-donating properties.[7,9] Moreover, in the nuclea-
tion stage, Ag0 aggregates with other Ag0 atoms in close prox-
imity owing to its immobilization on the PANF framework.
With the optimized conditions in hand, the substrate scope
of the AHA coupling reaction was investigated (Table 1). Di-
chloromethane, dibromomethane, diiodomethane, and dibro-
momethylbenzene all produced good results (Table S3 in the
Supporting Information, entries 11 and 12, and Table 1, 4b),
and excellent yields were achieved when using cyclic, hetero-
cyclic, and acyclic aliphatic amines as the substrates (Table 1,
4a, 4l, and 4d). Interestingly, AHA coupling products were
also isolated when primary amines were used as substrates
(Table 1, 4m and 4n).
To investigate the leaching of AgNPs, a filtration experiment
was carried out to determine whether the AHA reaction was
catalyzed in a heterogeneous or homogeneous manner.[49]
After allowing the reaction to proceed for 0.5 h, the PANF-
NHC@Ag catalyst was removed from the reaction mixture by
filtration. The reaction mixture was then allowed to stir for a
further 1.5 h in the absence of the fiber catalyst, but no further
increase in conversion was observed. In addition, the Ag con-
tent in the clear filtrate was <1.0 ppm (as determined by ICP-
OES), which confirms the stability of the supported catalyst.
The recyclability of the PANF-NHC@Ag catalyst was then in-
vestigated. Following the recovery of PANF-NHC@Ag from the
reaction mixture by filtration, it was reused in the subsequent
Catalytic activity of the supported catalysts in the three-
component coupling reaction
The formation of CÀC bonds by the deprotonation of CspÀH is
one of the most versatile and graceful manipulations in organ-
ic chemistry. In this context, in 2010, an Au-catalyzed AHA cou-
pling reaction was reported by Aguilar et al. for the efficient
synthesis of propargylamines.[37] In this reaction, the CspÀH and
CÀhalogen bonds are activated by AuNPs to form new CÀC
and CÀN bonds. Later, copper salts,[38–41] In2O3 NPs,[42] FeIII,[43]
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and the thermal properties of the fibers were investigated by
thermogravimetry (TG) and differential scanning calorimetry
(DSC; Figure S2 in the Supporting Information). In the case of
PANF-NHC@Ag, it was observed that no significant degrada-
tion occurred below 2008C. Upon decreasing the catalyst load-
ing to 0.01% and allowing the reaction to proceed for 72 h, a
35% yield was obtained, along with an unprecedented turn-
over number (TON) of 3500. A mercury droplet test was con-
ducted. The conversion did not change after the addition of
mercury as a heterogeneous catalysis poison.[11]
Table 1. Three-component coupling reactions catalyzed by PANF-
NHC@Ag.[a]
In this study, Ag particles were immobilized on the fiber sur-
face to prevent their aggregation. Indeed, owing to the highly
disperse nature and thermal stability of the AgNPs, they exhib-
ited superior performances in the AHA reaction compared with
Ag complexes and Ag salts.[45] In addition, the incorporation of
a support for the NPs inhibited particle growth and aggrega-
tion,[1,5] with the modified PANF promoting NP generation
while also protecting against aggregation. Furthermore, their
adequate dispersion on the fiber surface could be attributed
to chemical reduction by NaBH4 as opposed to the use of tra-
ditional thermal decomposition methods during NP formation.
Moreover, the NHC moieties act as protecting groups to pre-
vent aggregation of the fine AgNPs.[9,13] It should also be
noted that a low yield was obtained when PANF-Am@Ag was
employed as the catalyst in this transformation (Table S3 in the
Supporting Information, entry 2).
Catalytic mechanism of the supported catalysts in the three-
component coupling reaction
A plausible reaction mechanism for the PANF-NHC@Ag-cata-
lyzed AHA reaction is outlined in Scheme 2, where two poten-
tial pathways are suggested. In path A, the dihalomethane sub-
strate interacts with the metal–alkynyl complex to give a prop-
argylhalide intermediate, which further interacts with the
amine substrate to yield the desired product. In path B, the di-
halomethane interacts with the amine to produce an iminium
ion intermediate, which reacts with the metal–alkynyl complex
to afford the desired product. Indeed, previous literature sug-
gested that path A dominates in copper-catalyzed reactions,[39]
whereas path B dominates in iron-[43] and gold[37]-catalyzed re-
actions. Based on these reports and on our experimental re-
sults, the three-component coupling reaction was considered
to follow path B. According to this mechanism, methanimini-
um chloride is initially formed by the reaction of the amine
with CH2Cl2. The corresponding propargylamine can then be
obtained quantitatively from this isolated intermediate[45]
through its reaction with the silver acetylide.
[a] Reaction conditions: haloalkanes (1.2 mmol), amines (1.2 mmol), al-
kynes (1.0 mmol), PANF-NHC@Ag (1 mol%, calculated based on Ag), DBU
(2.0 mmol), 258C. [b] X=Cl. [c] X=Br.
run for the synthesis of 4a. After eight consecutive cycles, the
yield of 4a was maintained at 81% (Figure 8a). The catalyst re-
cyclability in the reactions employing CH2Br2 and dibromome-
thylbenzene as substrates was also investigated (Figures 8b,c),
Flow chemistry
Continuous-flow microreactors and their application in chemi-
cal syntheses can be considered an effective alternative strat-
egy to conventional batch-based regimes.[50–53] With the above
promising results in hand, the high stability (Figure S2 in the
Supporting Information) and excellent catalytic activity exhibit-
ed by PANF-NHC@Ag indicate its potential as a suitable cata-
Figure 8. Reusability of PANF-NHC@Ag in the synthesis of 4a and 4b.
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Scheme 2. Proposed mechanism for the AgNP-catalyzed AHA reaction.
lyst for application in continuous-flow processes. Thus, in the
context of this study, we employed an experimental setup con-
sisting of a silicone column (100 mm length, 4.6 mm inner di-
ameter) and a peristaltic pump (Figure 9). The fiber was cooled
yield of >85% at the end of this period. Furthermore, waste
production was notably minimized by this flow process, and a
long catalyst life time of 24 h was achieved as a result of mini-
mal exposure to air or humidity.[52] In comparison with other
reported catalytic systems for the AHA reaction, PANF-
NHC@Ag is superior because of its high catalytic activity, its ex-
cellent reusability, and its suitability for application in the ab-
sence of solvent (Table 2).
Table 2. Different catalytic systems for the AHA coupling reaction.
Catalyst
T [8C]/t [h]
Solvent
Reusability
Ref.
AuNPs
CuCl
CuCl
CuI
nano In2O3
FeCl3
50/24
25/36
60/24
80/18
65/16
100/12
80/24
120/12
65/24
25/2
CH2Cl2
CH3CN
CH3CN
CH3CN
DMSO
CH3CN
CH3CN
dioxane
CH3CN
neat
–
–
–
–
3
–
–
–
3
10
37
38
39
41
42
43
44
45
CoBr2
AgOAc
Au/CeO2
PANF-NHC@Ag
46
this work
Figure 9. Schematic representation of the continuous-flow process.
with liquid nitrogen and ground into particles of approximate-
ly 1–5 mm diameter. The silicone column was operated with a
PANF-NHC@Ag loading of 1.0 g (functionality=0.75 mmolgÀ1).
A stock solution containing the substituted alkyne 1 (1.0 mol),
dihalomethane 2 (5 mol), amine 3 (1.2 mol), and DBU (1.0 mol)
was pumped into the continuous-flow device at 258C, with an
optimized flow rate of 0.5 mLminÀ1 giving a yield of 95%. The
retention time for this reaction was 3.3 min and a productivity
of 4a of 57 mmolhÀ1 was achieved. In addition, the experi-
ment time was set at 24 h when the reagent solution was con-
tinuously injected into the system. This resulted in an instant
Conclusions
We herein reported the preparation and characterization of N-
heterocyclic carbene (NHC)-stabilized silver nanoparticles (NPs)
supported on polyacrylonitrile fiber (PANF) and the subsequent
application of the immobilized NPs as catalysts for the efficient
synthesis of propargylamines. The particle size of the AgNPs
was successfully tuned by varying the functionalities and the
reduction time to yield AgNPs with a loading of 8% and an
average diameter of 11.0Æ3.2 nm. Essentially, the cooperative
effect between the PANF support and the NHC ligand stabi-
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purified by flash chromatography on silica gel (eluent: hexane/
ethyl acetate=4:1, v/v) to give the corresponding propargylamine.
lized the AgNPs to prevent aggregation, and the resulting
PANF-NHC@Ag catalyst exhibited a high activity for the three-
component reaction between aldehydes, halomethanes, and
alkynes (AHA coupling), which proceeded smoothly in the ab-
sence of solvents. Furthermore, the PANF-NHC@Ag catalyst
particles could be easily recovered by simple filtration and
were reusable over eight cycles. Under the reaction conditions
employed, the AgNP catalyst exhibited no loss in activity and
no leaching of Ag into the reaction solution was observed.
These observations are of particular importance as they led to
the development of a stabilized metal NP catalyst system suita-
ble for application in continuous-flow processes.
Acknowledgments
This work was supported by the innovation team funding
(1649) from the Institute of Radiation Medicine, Chinese Acade-
my of Medical Sciences & Peking Union Medical College, the
Fundamental Research Fund for CAMS&PUMC (2016ZX310199),
the CAMS Innovation Fund for Medical Science (CIFMS, 2017-
I2M-3-019) from the Chinese Academy of Medical Sciences &
Peking Union Medical College, and Tianjin Major Scientific and
Technological Special Project for Significant New Drugs Devel-
opments (17ZXXYSY00090).
Experimental Section
General experimental information (materials, characterization, and
measurements), characterization of the products, and additional
tables and figures are provided in the Supporting Information.
Conflict of interest
The authors declare no conflict of interest.
Typical procedure for preparation of PANF-NHC-Ag
[1] R. J. White, R. Luque, V. L. Budarin, J. H. Clark, D. J. Macquarrie, Chem.
Soc. Rev. 2009, 38, 481.
Dried PANF (5.0 g), deionized water (50 mL), and ethylenediamine
(100 mL) was introduced into a 250 mL three-neck flask. The sus-
pension was heated to reflux for 2 h. Next, the modified PANF was
filtered out and washed with deionized water at 70–808C until the
pH of the washed water was 7. Then, the modified fiber was dried
overnight under vacuum at 608C to give the aminated PANF. The
weight gain of aminated PANF was 16.2% (functionality:
2.1 mmolgÀ1).
[2] L. Rizzello, P. P. Pompa, Chem. Soc. Rev. 2014, 43, 1501.
[3] X. Hu, S. Dong, J. Mater. Chem. 2008, 18, 1279.
[4] F. Meemken, A. Baiker, Chem. Rev. 2017, 117, 11522.
[5] P. Munnik, P. E. de Jongh, K. P. de Jong, Chem. Rev. 2015, 115, 6687.
[6] Y. Sun, Chem. Soc. Rev. 2013, 42, 2497.
[7] B. L. Cushing, V. L. Kolesnichenko, C. J. O’Connor, Chem. Rev. 2004, 104,
3893.
[8] L. S. Ott, R. G. Finke, Coord. Chem. Rev. 2007, 251, 1075.
[9] M. J. MacLeod, J. A. Johnson, J. Am. Chem. Soc. 2015, 137, 7974.
[10] N. Mçller, A. Ruehling, S. Lamping, T. Hellwig, C. Fallnich, B. J. Ravoo, F.
Glorius, Angew. Chem. Int. Ed. 2017, 56, 4356; Angew. Chem. 2017, 129,
4421.
[11] A. Rꢁhling, K. Schaepe, L. Rakers, B. Vonhçren, P. Tegeder, B. J. Ravoo, F.
Glorius, Angew. Chem. Int. Ed. 2016, 55, 5856; Angew. Chem. 2016, 128,
5950.
[12] K. V. S. Ranganath, J. Kloesges, A. H. Schꢂfer, F. Glorius, Angew. Chem.
Int. Ed. 2010, 49, 7786; Angew. Chem. 2010, 122, 7952.
[13] K. Salorinne, R. W. Y. Man, M. Taki, M. Nambo, C. M. Crudden, C.-H. Li,
C. M. Crudden, Angew. Chem. Int. Ed. 2017, 56, 6198; Angew. Chem.
2017, 129, 6294.
The NHC-Ag complex ([N-benzyl-N’-(methoxycarbonyl methyl)imi-
dazolin-2-ylidene]silver chloride) was prepared as described in the
Supporting Information. To a solution of NHC-Ag complex (3.2 g,
9.5 mmol) in CH3CN (75 mL), ethylenediamine-aminated PANF
(2.0 g, functionality: 2.1 mmolgÀ1) was added, and the suspension
was stirred at reflux for 4 h. The modified fiber was then filtered
and washed with CH3CN in a Soxhlet extractor for 24 h. Then, the
modified fiber was dried under vacuum to give PANF-NHC-Ag
(2.7 g, weight gain: 35%, Ag carbene functionality: 0.75 mmolgÀ1).
The functionalities of PANF can be tuned by feed ratio and reaction
time (Table S1 in the Supporting Information).
[14] A. Ferry, K. Schaepe, P. Tegeder, C. Richter, K. M. Chepiga, B. J. Ravoo, F.
Glorius, ACS Catal. 2015, 5, 5414.
Typical procedure for preparation of PANF-NHC@Ag
[15] J. B. Ernst, S. Muratsugu, F. Wang, M. Tada, F. Glorius, J. Am. Chem. Soc.
2016, 138, 10718.
[16] V. K. Sharma, R. A. Yngard, Y. Lin, Adv. Colloid Interface Sci. 2009, 145, 83.
[17] M. A. Bhosale, B. M. Bhanage, Curr. Org. Chem. 2015, 19, 708.
[18] X.-Y. Dong, Z.-W. Gao, K.-F. Yang, W.-Q. Zhang, L.-W. Xu, Catal. Sci. Tech-
nol. 2015, 5, 2554.
[19] D. Yu, M. X. Tan, Y. Zhang, Adv. Synth. Catal. 2012, 354, 969.
[20] H. E. Emam, M. M. El-Zawahry, H. B. Ahmed, Carbohydr. Polym. 2017,
166, 1.
[21] G.-P. Yong, D. Tian, H.-W. Tong, S.-M. Liu, J. Mol. Catal. A: Chem. 2010,
323, 40.
A mixture of PANF-NHC-Ag (1.3 g, functionality: 0.75 mmolgÀ1) and
NaOH (0.2 g) were added to deionized water (10 mL). Then, aque-
ous NaBH4 solution (100 mL, 0.1m) was added under vigorous stir-
ring. The reaction mixture was stirred for 6 h. The modified fiber
was filtered out and washed with deionized water and EtOH, then
dried under vacuum at 608C for 12 h to afford the PANF-NHC@Ag
(1.2 g).
General procedure of the AHA reaction catalyzed by PANF-
NHC@Ag
[22] J.-W. Lee, T. Mayer-Gall, K. Opwis, C. E. Song, J. S. Gutmann, B. List, Sci-
ence 2013, 341, 1225.
[23] Y. Wang, R. Qu, F. Pan, X. Jia, C. Sun, C. Ji, Y. Zhang, K. An, Y. Mu, Chem.
Eng. J. 2017, 317, 187.
[24] M. Monier, I. M. Kenawy, M. A. Hashem, Carbohydr. Polym. 2014, 106, 49.
[25] X. Xing, H. Yang, M. Tao, W. Zhang, J. Hazard. Mater. 2015, 297, 207.
[26] D.-G. Yu, J. Zhou, N. P. Chatterton, Y. Li, J. Huang, X. Wang, Int. J.
Nanomed. 2012, 7, 5725.
[27] J. Cao, G. Xu, P. Li, M. Tao, W. Zhang, ACS Sustainable Chem. Eng. 2017,
5, 3438.
Under a nitrogen atmosphere, the PANF-NHC@Ag catalyst (26 mg,
containing Ag 0.01 mmol), alkyne 1 (1.0 mmol, 1.0 equiv), haloal-
kane 2 (1.2 mmol, 1.2 equiv), amine 3 (1.2 mmol, 1.2 equiv), and
DBU (2.0 mmol) were added to a three-neck flask. The mixture was
stirred at 258C for 3 h. After the reaction was completed as indicat-
ed by thin layer chromatography (TLC), the reaction mixture was
filtered. The catalyst was washed with CH3CN for recycling. The
combined organics were then concentrated, and the residue was
[28] A. A. Boulton, B. A. Davis, D. A. Durden, L. E. Dyck, A. V. Juorio, X.-M. Li,
I. A. Paterson, P. H. Yu, Drug Dev. Res. 1997, 42, 150.
&
&
Chem. Asian J. 2018, 00, 0 – 0
www.chemasianj.org
8
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
[29] S. Nag, G. Kettschau, T. Heinrich, A. Varrone, L. Lehmann, B. Gulyas, A.
Thiele, ꢃ. Keller, C. Halldin, Bioorg. Med. Chem. 2013, 21, 186.
[30] V. A. Peshkov, O. P. Pereshivko, E. V. Van der Eycken, Chem. Soc. Rev.
2012, 41, 3790.
[31] Z. Dong, X. Le, X. Li, W. Zhang, C. Dong, J. Ma, Appl. Catal. B 2014, 158–
159, 129.
[32] S. M. Badawy, A. M. Dessouki, J. Phys. Chem. B 2003, 107, 11273.
[33] C. Satheeshkumar, J.-Y. Park, D.-C. Jeong, S. G. Song, J. Lee, C. Song, RSC
Adv. 2015, 5, 60892.
[34] A. S. El-Khouly, E. Kenawy, A. A. Safaan, Y. Takahashi, Y. A. Hafiz, K. Sono-
moto, T. Zendo, Carbohydr. Polym. 2011, 83, 346.
[44] Y. Tang, T. Xiao, L. Zhou, Tetrahedron Lett. 2012, 53, 6199.
[45] X. Chen, T. Chen, Y. Zhou, C.-T. Au, L.-B. Han, S.-F. Yin, Org. Biomol.
Chem. 2014, 12, 247.
[46] A. Berrichi, R. Bachir, M. Benabdallah, N. Choukchou-Braham, Tetrahe-
dron Lett. 2015, 56, 1302.
[47] M. Yu, Y. Wang, W. Sun, X. Yao, Adv. Synth. Catal. 2012, 354, 71.
[48] V. S. Rawat, T. Bathini, S. Govardan, B. Sreedhar, Org. Biomol. Chem.
2014, 12, 6725.
[49] Y.-B. Huang, M. Shen, X. Wang, P.-C. Shi, H. Li, R. Cao, J. Catal. 2015, 330,
452.
[50] J. C. Pastre, D. L. Browne, S. V. Ley, Chem. Soc. Rev. 2013, 42, 8849.
[51] J. Britton, C. L. Raston, Chem. Soc. Rev. 2017, 46, 1250.
[52] D. Cambiꢄ, C. Bottecchia, N. J. W. Straathof, V. Hessel, T. Noꢅl, Chem. Rev.
2016, 116, 10276.
[35] X. Liu, W. Chen, Y.-l. Hong, S. Yuan, S. Kuroki, T. Miyoshi, Macromolecules
2015, 48, 5300.
[36] D. Erdemir, A. Y. Lee, A. S. Myerson, Acc. Chem. Res. 2009, 42, 621.
[37] D. Aguilar, M. Contel, E. P. Urriolabeitia, Chem. Eur. J. 2010, 16, 9287.
[38] Z. Lin, D. Yu, Y. Zhang, Tetrahedron Lett. 2011, 52, 4967.
[39] D. Yu, Y. Zhang, Adv. Synth. Catal. 2011, 353, 163.
[40] B. R. Buckley, A. N. Khan, H. Heaney, Chem. Eur. J. 2012, 18, 3855.
[41] Z. Lin, D. Yu, Y. N. Sum, Y. Zhang, ChemSusChem 2012, 5, 625.
[42] M. Rahman, A. K. Bagdi, A. Majee, A. Hajra, Tetrahedron Lett. 2011, 52,
4437.
[53] M. B. Plutschack, B. Pieber, K. Gilmore, P. H. Seeberger, Chem. Rev. 2017,
117, 11796.
Manuscript received: January 29, 2018
Revised manuscript received: April 2, 2018
Version of record online: && &&, 0000
[43] J. Gao, Q.-W. Song, L.-N. He, Z.-Z. Yang, X.-Y. Dou, Chem. Commun. 2012,
48, 2024.
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FULL PAPER
Three-Component Coupling Reaction
Jian Cao, Hongqi Tian*
&& – &&
N-Heterocyclic Carbene-Protected Ag
Nanoparticles Immobilized on
Polyacrylonitrile Fiber as Efficient
Catalysts for a Three-Component
Coupling Reaction
Carbenes for coupling: N-heterocyclic
carbene (NHC)-stabilized silver nanopar-
ticles (NPs) supported on polyacrylonit-
rile fiber (PANF). As a result, Ag loadings
of up to 8% and particle sizes of
nanocomposite catalyst demonstrated
high activity in addition to excellent sta-
bility and reusability in the three-com-
ponent reaction between alkynes, hal-
oalkanes, and amines.
11.0Æ3.2 nm were achieved. This novel
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