Caffeine gold complex supported on magnetic nanoparticles as a green and high turnover frequency catalyst for room temperature A3 coupling reaction in water

Article abstract of DOI:10.1002/aoc.4760

A new heterogeneous catalyst derived from gold (III) and supported on caffeine-coated magnetic nanoparticles, Fe₃O₄@Caff-Au, has been prepared and characterized using different techniques. This magnetic gold composite shows high catalytic activity in A³ coupling reactions of terminal alkynes, aldehydes and secondary amines. Using this green catalyst, propargylamines are obtained in high turnover frequency in short reaction times using water as solvent at room temperature. This stable and ready accessible catalyst can be easily recycled magnetically for at least nine consecutive runs without significant loss of activity and with slight aggregation of Au species.

Full text of DOI:10.1002/aoc.4760

Received: 17 September 2018
DOI: 10.1002/aoc.4760
Revised: 12 November 2018
Accepted: 17 November 2018
F U L L P A P E R
Caffeine gold complex supported on magnetic nanoparticles
as a green and high turnover frequency catalyst for room
temperature A3 coupling reaction in water
Mohammad Gholinejad1,2
| Mahmoud Afrasi1 | Carmen Najera3
1 Department of Chemistry, Institute for
Advanced Studies in Basic Sciences
(IASBS), Gavazang, Zanjan 45137‐66731,
Iran
2 Research Center for Basic Sciences &
Modern Technologies (RBST), Institute for
Advanced Studies in Basic Sciences
(IASBS), Zanjan 45137‐66731, Iran
3 Departamento de Química Orgánica and
Centro de Innovación en Química
Avanzada (ORFEO‐CINQA), Universidad
de Alicante, Apdo. 99, E‐03080 Alicante,
Spain
A new heterogeneous catalyst derived from gold (III) and supported on
caffeine‐coated magnetic nanoparticles, Fe3O4@Caff‐Au, has been prepared
and characterized using different techniques. This magnetic gold composite
shows high catalytic activity in A3 coupling reactions of terminal alkynes, alde-
hydes and secondary amines. Using this green catalyst, propargylamines are
obtained in high turnover frequency in short reaction times using water as sol-
vent at room temperature. This stable and ready accessible catalyst can be eas-
ily recycled magnetically for at least nine consecutive runs without significant
loss of activity and with slight aggregation of Au species.
KEYWORDS
A3 coupling, caffeine, Fe3O4, gold, turnover frequency
Correspondence
Mohammad Gholinejad, Department of
Chemistry, Institute for Advanced Studies
in Basic Sciences (IASBS), Gavazang,
Zanjan 45137‐66731, Iran.
Email: gholinejad@iasbs.ac.ir
Carmen Najera, Departamento de
Química Orgánica and Centro de
Innovación en Química Avanzada
(ORFEO‐CINQA), Universidad de
Alicante, Apdo. 99, E‐03080‐Alicante,
Spain.
Email: cnajera@ua.es
Funding information
University of Alicante, Grant/Award
Number: PROMETEOII/2014/017;
GeneralitatValenciana, Grant/Award
Number: PROMETEO2009/039; Fondo
Europeo de Desarrollo Regional (FEDER,
EU), Grant/Award Number: CTQ2016–
81797‐REDC; Spanish Ministerio de
Economía, Industria y Competitividad,
Agencia Estatal de Investigación (AEI),
Grant/Award Number: CTQ2016–76782‐
P; Spanish Ministerio de Economia y
Competitividad (MINECO), Grant/Award
Numbers: CTQ2014–51912‐REDC and
CTQ2013–43446‐P; Iran National Science
Foundation, Grant/Award Number:
Appl Organometal Chem. 2019;e4760.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4760

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GHOLINEJAD ET AL.
95844587; Institute for Advanced Studies
in Basic Sciences (IASBS) Research
Council, Zanjan University, Grant/Award
Number: 95844587
1 | INTRODUCTION
employed in Suzuki, Heck and Sonogashira reactions
under homogeneous conditions in aqueous media.[18]
However, to the best of our knowledge there has been
no report dealing with modification of any solid supports
with caffeine and its use in the design of heterogeneous
catalysts.
Propargylamines are useful synthetic intermediates in
organic synthesis, and are important building blocks in
natural products and therapeutic drug molecules.[19–27]
Some examples of pharmaceutically active compounds
having diverse propargylamine moieties are shown in
Scheme 1.[28–32]
Propargylamines traditionally were synthesized by the
stoichiometric reaction of lithium acetylides or Grignard
reagents with imine derivatives under inert reaction con-
ditions.[33–35] Nowadays, the most efficient and atom‐
economic process for the preparation of propargylamines
is the multicomponent transition metal‐catalyzed reac-
tion of aldehydes, alkynes and amines via metal C‐H
bond activations of terminal alkynes (A3 coupling reac-
tion).[36–40] Excellent progress in this area has been
reported by Wei and Li using homogeneous AuBr3 or
AuCl as the catalysts for C‐H bond activation in prepara-
tions of propargylamines.[41] Furthermore, after reporting
this procedure, various homogeneous gold catalysts have
been employed for this interesting reaction.[42–55] Despite
the high efficiency of the reported catalysts, in many
cases high catalyst loading and the expensive price of gold
considerably limit the versatility of these catalytic sys-
tems. Along this line, recently, different heterogeneous
gold[56–80] as well as magnetic catalysts[81–86] have been
applied for the A3 coupling reaction. Herein we report
Nowadays, the design of new heterogeneous catalysts
involving cheap, sustainable and eco‐friendly materials
with high efficiency and turnover frequency (TOF) is
important from a green chemistry standpoint.[1–3] In spite
of great success in the development of heterogeneous cat-
alysts, most of these catalysts suffer from separation prob-
lems and product contamination by the catalyst.
Recently, this problem has been solved using magnetic
nanoparticles (NPs), which are easily separated from the
reaction mixture by an external magnetic field. Among
the different magnetic materials, Fe3O4 NPs have differ-
ent properties, such as high surface area, high thermal
and mechanical stability, easy synthesis and magnetically
recovered, and have attracted great attention for design of
the catalysts. In order to use magnetic NPs as the catalyst
support, various ligands or polymers have been used for
its modification and also magnetic composites for the sta-
bilization of different transition metals.[4]
In the past two decades, different naturally occurring
materials have been employed for design of catalysts,[5–7]
as well as for the preparation of magnetic catalysts. Caf-
feine is a natural precursor widely consumed in bever-
ages, the most commonly used drug in the world, and
its analogues have recently drawn attention for their pos-
sible therapeutic applications as anticancer agents.[8,9]
Recently, the imidazole ring of caffeine has been used
as a N‐heterocyclic carbene precursor for the preparation
of gold (I),[10,11] silver,[12–14] Rh or Ir,[15] and Pt[16,17] com-
plexes, which showed interesting anticancer and biologi-
cal properties. Also, Pd complex of caffeine has been
SCHEME 1 Representative biologically active pharmacophores bearing propargylamines

GHOLINEJAD ET AL.
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for the first time the use of caffeine as a naturally occur-
ring and cheap compound for the modification of mag-
netic NPs and for the stabilization of gold metal. This
magnetic gold composite has been employed as an effi-
cient recoverable catalyst in the A3 coupling reaction of
aldehydes, amines and alkynes in water with low catalyst
loading at room temperature.
ammonia (6 mL) were added, and the resulting mixture
was stirred for 24 hr at room temperature. Produced
Fe3O4@SiO2 NPs were separated by an external magnet,
and washed with EtOH (3 × 10 mL) and dried in an oven
at 60°C.
2.4 | Synthesis of Iodo functionalized
magnetic NPs Fe3O4@SiO2@I
2 | EXPERIMENTAL
2.1 | General remarks
Fe3O4@SiO2 (1 g) were sonicated in dried toluene (20
mL) followed by dropwise addition of (3‐iodopropyl)
trimethoxysilane (4 mmol, 0.8 mL). The reaction mixture
was refluxed for 24 hr under argon atmosphere in dark
conditions. Then, the reaction mixture was subjected to
an external magnet, and the obtained solid was washed
with dichloromethane (3 × 10 mL), rinsed and dried
under vacuum at 60°C.
All materials were purchased from Sigma‐Aldrich, Across
and Merck Millipore. Reactions were monitored by gas
chromatography in a Varian CP‐3800 apparatus. 1H‐NMR
and 13C‐NMR spectra were recorded at 400 MHz and 100
MHz, respectively, on a Bruker Avance HD apparatus in
CDCl3. Chemical shifts are given on the δ‐scale in ppm,
and residual solvent peaks were used as internal stan-
dards. The transmission electron microscopy (TEM) and
scanning electron microscopy (SEM) mapping images
were captured with EOL JEM‐2010 and Hitachi S3000 N.
X‐ray photoelectron spectroscopy (XPS) analyses were per-
formed using a K‐Alpha spectrometer. The weight loss of
2.5 | Synthesis of caffeine‐functionalized
magnetic NPs
A mixture of 10 min sonicated Fe3O4@SiO2@I (1 g) in
dimethylformamide (DMF; 15 mL) and caffeine (10
mmol, 1.9 g) was added to an autoclave and heated for
48 hr at 150°C (solvothermal conditions). Then, the auto-
clave was allowed to cool to room temperature and the
solid was subjected to magnetic separation. The resulting
caffeine‐functionalized magnetic NPs were washed with
dichloromethane (3 × 10 mL) and ethanol (3 × 10 mL),
and dried under vacuum at 60°C.
samples was measured using
a thermogravimeter
NETZSCH STA 409 under an O2 flow rate of 20 mL
min−1 with a heating rate of 10°C min−1 from 30 to
800°C. Digital images of the samples were acquired with
Hitachi S4160 FE‐SEM apparatus operating at 20 kV. Fou-
rier transform‐infrared (FT‐IR) studies of samples were
performed using a FT‐IR spectrophotometer Bruker vector
22, by preparing their KBr pellets from 400 to 4000 cm−1
.
2.6 | Synthesis of the catalyst Fe3O4@Caff‐
Au
Magnetic measurements were performed using vibration‐
sample magnetometry, (MDK Co. Kashan, Iran) analysis.
Fe3O4@SiO2@Caff (1 g) was sonicated in H2O:CH3OH
(2:1, 12 mL) for 30 min at room temperature. Then, the
solution of NaAuCl4·2H2O (0.015 mmol, 6 mg) in water
(2 mL) was added slowly, and the mixture was stirred
for 24 hr at room temperature under argon atmosphere.
Then, the solid was separated with a magnet, washed
with water (2 × 10 mL) and ethanol (2 × 10 mL), and
dried in an oven at 60°C.
2.2 | Preparation of Fe3O4 NPs
FeCl3·6H2O (11.0 g) and FeCl2·4H2O (4.0 g) were dis-
solved in deionized water (250 mL), and the mixture
was stirred using a mechanical stirrer under an argon
atmosphere. To the resulting mixture, aqueous ammonia
(25%, 40 mL) was added slowly over 20 min, and the mix-
ture was stirred at 80°C for 4 hr. A black precipitate of
Fe3O4 was collected by using an external magnet and
washed with deionized water (3 × 20 mL) and ethanol
(3 × 20 mL), and finally dried under vacuum.
2.7 | General procedure for the synthesis
of propargylamines
To a 5‐mL flask, the catalyst (10 mg, 0.007 mol%), alde-
hyde (1 mmol), phenylacetylene (1.5 mmol), amine (1.5
mmol) and H2O (2 mL) were added, and mixture was
stirred at r.t. for 1 hr under argon atmosphere. The prog-
ress of the reactions was monitored by thin‐layer
2.3 | Preparation of Fe3O4@SiO2
Fe3O4 NPs (1 g) were sonicated in ethanol (200 mL) for
30 min. Then, tetraethyl orthosilicate (2 mL) and aqueous

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GHOLINEJAD ET AL.
chromatography or 1H‐NMR. After completion of the
reaction, the crude products were extracted using ethyl
acetate (3 × 5 mL). Further purification was performed
by column chromatography on silica gel using hexane
and ethyl acetate as eluents. All products were known
the Si–O–Fe and bending vibration of the adsorbed water
on the surface, respectively, and also related peaks to the
Fe‐O bond between 460 and 630 cm−1 (Figure 1). On the
other hand, the FT‐IR spectra of Fe3O4@Caff‐Au indi-
cated two characteristic peaks of caffeine at 1617 and
1652 cm−1 related to C=O and C=N stretching bonds,
respectively[87] (Figure 1).
1
and charecterized by H‐NMR and 13C‐NMR.
Thermogravimetric analyses (TGA) of Fe3O4@SiO2,
Fe3O4@SiO2@I and Fe3O4@SiO2@Caff were studied
between 25 and 800°C (Figures S5–S7). Two small weight
losses in the Fe3O4@SiO2 material between 25–150°C and
120–800°C were related to the loss of physically absorbed
water and hydroxyl groups, respectively. TGA measure-
ments for Fe3O4@SiO2@I showed an increase in weight
loss between 150 and 800°C due to addition of an organic
group. Furthermore, the increase in weight loss in
Fe3O4@I@Caff confirmed the successful attachment of
caffeine to the magnetic material (Figure 2).
3 | RESULTS AND DISCUSSION
3.1 | Materials and characterization
Initially, magnetic NPs were prepared using the Massart
procedure without using any capping agent or surfactant.
The obtained Fe3O4 NPs were allowed to react with
tetraethyl orthosilicate under sol–gel process to give
core/shell Fe3O4 NPs (Fe3O4@SiO2) NPs. The presence
of silica shell around the magnetic NPs was further con-
firmed using TEM (Figure S1 in ESI).
Transmission electron microscopy images of
Fe3O4@Caff‐Au showed the presence of very uniform
and dispersed NPs (Figure 3). Furthermore, X‐ray diffrac-
tion of Fe3O4@Caff‐Au showed related peaks at 2θ values
In the next step, the Fe3O4@SiO2 NPs were treated
with (3‐iodopropyl) trimethoxysilane to afford iodo func-
tionalized magnetic NPs (Scheme 2) Fe3O4@SiO2@I.
Then, Fe3O4@SiO2@I was allowed to react with caffeine
in DMF under solvothermal conditions, achieving
Fe3O4@SiO2@Caff. In the final step, caffeine‐modified
magnetic NPs were treated with NaAuCl4·2H2O to pro-
duce magnetic NPs‐supported caffeine‐based gold (III)
complex. This material is referred to as Fe3O4@Caff‐Au
throughout the text of this article (Scheme 2). The con-
tent of the gold in the structure of the magnetic compos-
ite was determined by atomic absorption spectroscopy
(AAS) analysis to be 0.0075 mmol g−1
.
The structure of the prepared magnetic materials and
caffeine were studied by FT‐IR spectroscopy (Figures S2–
S4). In the case of Fe3O4@SiO2, the FT‐IR spectrum
showed peaks located at 1092 and 1636 cm−1 related to
FIGURE
1
Fourier transform‐infrared (FT‐IR) spectra of
Fe3O4@SiO2, Fe3O4@SiO2@Caff and caffeine
SCHEME 2 Preparation of Fe3O4@Caff‐Au

GHOLINEJAD ET AL.
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FIGURE 2 Thermogravimetric analysis (TGA) diagrams of
Fe3O4@SiO2, Fe3O4@SiO2@I and Fe3O4@SiO2@Caff
of 30.3°, 35.6°, 43.2°, 53.4°, 57.4° and 62.8°, corresponding
to (210), (311), (400), (422), (511) and (440) planes of
Fe3O4 (Figure S8).[88] On the basis of the half‐width of
the (311) reflection (Figure S8), the average crystallite size
(~6.8 nm) was calculated using the Debye–Scherer
equation.[89]
Also, SEM‐Map and overlay map images confirmed
the presence of C, N and Au, which are uniformly distrib-
uted in the structure (Figures 4 and 5).
Furthermore, energy‐dispersive X‐ray (EDX) analysis
showed the presence of different elements such as Au,
N, Si, Fe and C in the structure of Fe3O4@Caff‐Au
(Figure 6).
The structure of Fe3O4@Caff‐Au was also studied
using XPS in N, Si, Au and Fe regions. XPS results
showed three main binding energy peaks at 709.8, 723.5
eV that are related to Fe (II) form, and peaks at 711.9
and 725.1 eV corresponding to Fe 2p3/2 and Fe 2p1/2,
respectively, related to Fe (III) species. It should be noted
that other satellite peaks at 716.9 eV and 730.1 eV are
related to Fe3+ in the Fe2O3 phase, indicating partial oxi-
dation of Fe3O4. The XPS spectra in N 1s showed two
peaks at 400 and 402 eV, which are attributed to the neu-
tral amine and positively charged quaternary nitrogen
species, respectively.[90,91] The XPS of the Si 2p showed
the presence of binding energy peaks at 102.9 eV and
103.7 eV, which are related to O‐Si‐C or O‐Si‐O bonds,
respectively.[92] Finally, XPS spectra for the Au4f region
revealed a doublet peak at 85.9 and 89.9 related to Au
(III) species[93,94] (Figure 7).
FIGURE 3 Transmission electron microscopy (TEM) images of
Fe3O4@Caff‐Au at different magnifications
modification of magnetic NPs during the preparation
steps of Fe3O4@Caff‐Au. It is worth mentioning that all
magnetic materials showed zero coercivity and rema-
nence on the magnetization loop, which confirmed their
superparamagnetic properties and the easy separation of
compound by an external magnetic field (Figure 8).
The superparamagnetic behavior of Fe3O4@Caff‐Au
was studied using magnetization curves of Fe3O4 NPs,
Fe3O4@SiO2@I and Fe3O4@Caff‐Au (Figure 8). The
results indicated a decrease of magnetization values in
the Fe3O4@SiO2@I and Fe3O4@Caff‐Au materials in
comparison to Fe3O4 NPs, indicating the successful
3.2 | Catalytic performance
Initially, the reaction of benzaldehyde with piperidine
and phenyl acetylene in water was selected as a model
reaction, and the effects of different factors such as

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GHOLINEJAD ET AL.
FIGURE 4 (a) Scanning electron microscopy (SEM) and map images of Fe3O4@Caff‐Au; (b) C; (c) N; and (d) Au
FIGURE 6 Energy‐dispersive X‐ray (EDX) spectrum of the
Fe3O4@Caff‐Au
FIGURE 5 Overlay map image of Fe3O4@Caff‐Au
mol% of catalyst was employed, the yield decreased to
73% (Table 1, entry 6). As we obtained excellent results
using water as green solvent, we did not study the effi-
ciency of the presented catalyst in other organic solvents.
Therefore, a loading of 0.007 mol% of catalyst, room tem-
perature and water were selected as the optimized reac-
tion conditions. To study whether cationic gold species
are working as actual catalysts using Fe3O4@Caff‐Au,
catalyst loading and reaction temperature were studied.
Using 0.05 and 0.025 mol% of catalyst at 50°C, the reac-
tion took place quantitatively in 1 hr (Table 1, entries 1
and 2). By lowering the reaction temperature to 25°C
and using 0.025 mol% catalyst quantitative yield was also
obtained (Table 1, entry 3). Lowering catalyst loading to
0.01 and 0.007 mol% afforded 100 and 99% yield, respec-
tively (Table 1, entries 4 and 5). However, when 0.005

GHOLINEJAD ET AL.
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FIGURE 7 X‐ray photoelectron
spectra (XPS) of Fe3O4@Caff‐Au at: (a) Fe
2p; (b) N 1s; (c) Si 2p; and (d) Au 4f
regions
yields, respectively. In addition, reaction of heterocyclic
3‐thiophenecarbaldehyde with piperidine and 2‐
thiophenecarbaldehyde
with
morpholine
and
phenylacetylene were performed efficiently giving 95%
and 91% yields, respectively (Table 2, entries 16 and 17).
Also, 3‐pyridinecarboxaldehyde reacted effectively with
piperidine or pyrrolidine and phenylacetylene affording
92–95% yields, respectively (Table 2, entries 18 and 19).
Reactions of 1‐octyne as aliphatic alkyne with benzalde-
hyde and piperidine and also heptanal as an aliphatic
aldehyde with phenylacetylene and piperidine proceeded
well, and products were obtained in 83–91% yields,
respectively (Table 2, entries 20 and 21). Different amines
such as piperidine, morpholine, pyrrolidine and
dimethylamine reacted in the A3 coupling reaction suc-
cessfully affording desired products in excellent yields.
FIGURE 8 Magnetization curves for Fe3O4 nanoparticles (NPs),
Fe3O4@SiO2@I NPs, Fe3O4@Caff‐Au and reused Fe3O4@Caff‐Au
we prepared a reduced Fe3O4@Caff‐Au sample by
treating it with an excess of NaBH4. Results indicated that
using this new catalyst, a very low yield for the model
reaction was obtained (Table 1, entry 7).
3.3 | Recycling of the catalyst
We studied the recycling properties of the catalyst in the
reaction of benzaldehyde, piperidine and phenylacetylene
under the optimized reaction conditions. For this pur-
pose, after 1 hr reaction time the catalyst was separated
by an external magnet, the recovered material was
washed with diethyl ether and then used in another batch
of the reaction. The following experiments showed that
the catalyst was successfully recovered and reused for
nine consecutive runs with a very small decrease in activ-
ity. However, in the 10th run the yield of the reaction
decreased to 70% (Figure 9). The leaching content of Au
species in each recycling step was investigated by AAS
Using the above optimized reaction conditions, this
catalyst was then explored for A3 coupling reaction of
variety aldehydes, amines and alkynes (Table 2). The
results indicated excellent yields and TOFs were observed
for various aromatic aldehydes containing electron‐
deficient groups (Table 2, entries 2–7), as well as alde-
hydes having electron‐donating groups (Table 2, entries
8–13) within 1 hr. The reactions of 1‐naphthaldehyde
(Table 2, entry 14) and biphenyl‐4‐carboxaldehyde
(Table 2, entry 15) with piperidine and phenylacetylene
proceeded very well affording 91% and 90% isolated

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GHOLINEJAD ET AL.
TABLE 1 Optimization of the reaction conditions for the reaction of benzaldehyde, piperidine and phenylacetylene catalyzed by
Fe3O4@Caff‐Aua
Entry
Solvent
Cat (mol%)
Temp (°C)
Yield (%)b
1
2
3
4
5
6
7
H2O
H2O
H2O
H2O
H2O
H2O
H2O
0.05
50
100
100
100
100
99
0.025
0.025
0.01
50
r.t.
r.t.
r.t.
r.t.
r.t.
0.007
0.005
0.007
73
34
aReaction conditions: benzaldehyde (0.5 mmol), piperidine (0.75 mmol), phenylacetylene (0.75 mmol), H2O (2 mL) and catalyst (see column).
bYields were determined by 1H‐NMR.
TABLE 2 Reactions of different aldehydes, amines and alkynes in the presence of Fe3O4@Caff‐Aua
(1)
(2)
(3)
96%
[13714]b
90%
[12857]b
92%
[13142]b
(4)
85%
[12142]b
(5)
95%
[13571]b
(6)
93%
[13285]b
(7)
95%
[13571]b
(8)
92%
[13142]b
(9)
95%
[13571]b
(Continues)

GHOLINEJAD ET AL.
9 of 13
TABLE 2 (Continued)
(1)
(2)
(3)
96%
[13714]b
90%
[12857]b
92%
[13142]b
(10)
(11)
(12)
91%
[13000]b
90%
[12857]b
83%
[11857]b
(13)
92%
[13142]b
(14)
91%
[13000]b
(15)
90%c
[4285]b
(18)
92%
[13142]b
(16)
95%
[13571]b
(17)
91%
[13000]b
(19)
95%
[13571]b
(21)
91%c
[13000]b
(20)
83%c
[11857]b
(Continues)

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GHOLINEJAD ET AL.
TABLE 2 (Continued)
(1)
(2)
(3)
96%
[13714]b
90%
[12857]b
92%
[13142]b
(24)
(22)
96%
[13714]b
96%
[13714]b
(23)
92%
[13142]b
aReaction conditions: aldehyde (1 mmol), amine (1.5 mmol), alkyne (1.5 mmol), H2O (2 mL) and catalyst (10 mg containing 0.007 mol% Au). Isolated yields.
b[TOF] values [(mol product/mol catalyst)/time of reaction (hr)].
cReaction time: 3 hr.
FIGURE
9
Recycling of the catalyst for the reaction of
benzaldehyde, piperidine and phenylacetylene
(Table S1). The results indicated that 15% of Au was
leached up to run 9. However, in run 10, 30% leaching
was observed indicating that leaching of Au may be
responsible for the decrease in catalytic activity during
the recycling of the catalyst.
FIGURE 10 Transmission electron microscopy (TEM) images of
the reused catalyst after 10 runs
Transmission electron microscopy images of the
reused catalyst after 10 runs showed that the catalyst
structure and presence of almost uniform NPs were pre-
served (Figure 10).
Furthermore, overlay map image of the reused cata-
lyst after 10 runs showed the presence of N, and mostly
uniform and slightly aggregate Au species (Figure 11).

GHOLINEJAD ET AL.
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4 | CONCLUSION
In conclusion, we prepared a new catalyst comprising Au
(III) supported on caffeine‐modified magnetic NPs with a
simple method, and characterized it using different tech-
niques. This catalyst exhibits excellent catalytic efficiency
in the A3 coupling reaction of various aldehydes with dif-
ferent amines and alkynes in water. Using this new cata-
lyst, high TOF was obtained under low catalyst loading
and short reaction times at room temperature. The cata-
lyst was recovered and recycled magnetically, and reused
for nine consecutive runs with a very small decrease in
activity.
FIGURE 11 Overlay map image of reused Fe3O4@Caff‐Au after
ASSOCIATED CONTENT
10 runs
Supporting Information1 H‐NMR and 13C‐NMR of
propargylamines, the TEM images of Fe3O4@SiO2, XRD
pattern of Fe3O4@Caff‐Au, original FTIRs, and TGAs
spectra
3.4 | Comparison of catalytic activity
ACKNOWLEDGEMENTS
Comparison data about the catalytic activity of
Fe3O4@Caff‐Au with some other supported gold catalysts
in the A3 coupling reaction of 4‐methylbenzaldehyde,
piperidine and phenylacetylene as a common substrate
(Table 3) showed a higher catalytic efficiency of the pre-
sented catalyst (Fe3O4@Caff‐Au).
The authors are grateful to Institute for Advanced Studies
in Basic Sciences (IASBS) Research Council, Zanjan Uni-
versity and Iran National Science Foundation (INSF‐
Grant No. 95844587) for support of this work. The
authors are also thankful to the Spanish Ministerio de
TABLE 3 Comparative catalytic activity of Fe3O4@Caff‐Au with other reported Au catalysts in a A3 coupling reaction
Catalyst
T (°C)
T (hr)
Au (mol%)
Yield (%)
[53]
Au38 (SC2H4Ph)24
[56]
80
5
0.01
3
84
92
90
83
95
75
83
63
81
88
90
95
LDH‐AuCl4
[59]
60
5
Au/CeO2
100
75
6
0.12
10
Au NPs[60]
12
18
24
8
MNP@PILAu[62]
Au@HS‐MCM[66]
60
1
80
2
NP@Au/NNN‐pincer[71]
Fe3O4@Au[95]
85
0.07
10
100
100
60
24
24
11
24
1
NAP‐Mg‐Au(0)[76]
Au@PMO‐IL[78]
0.04
0.2
0.07
0.007
Bent@Im@Au[96]
50
Fe3O4@Caff‐Au [this work]
r.t.

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GHOLINEJAD ET AL.
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