Oyster shell waste supported CuCl2 for aldehyde-alkyne-amine coupling reaction to propargylamines

Article abstract of DOI:10.1016/S1872-2067(14)60195-9

The development of an economic and simple heterogeneous oyster shell waste supported CuCl₂ catalyst for the aldehyde-alkyne-amine (A3) coupling reaction was reported. The waste oyster shell powder (OSP) supported CuCl₂ (OSP-CuCl

Full text of DOI:10.1016/S1872-2067(14)60195-9

Chinese Journal of Catalysis 35 (2014) 2006–2013
ava i l a b l e a t w w w. s c i e n c ed i r e c t . c o m
j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e /c h n j c
Article
Oyster shell waste supported CuCl2 for aldehyde‐alkyne‐amine
coupling reaction to propargylamines
Xingquan Xiong*, Huixin Chen, Rongjun Zhu
College of Materials Science and Engineering, Huaqiao University, Xiamen 361021, Fujian, China
A R T I C L E I N F O
A B S T R A C T
Article history:
The development of an economic and simple heterogeneous oyster shell waste supported CuCl2
catalyst for the aldehyde‐alkyne‐amine (A3) coupling reaction was reported. The waste oyster shell
powder (OSP) supported CuCl2 (OSP‐CuCl2) catalyst was prepared by a simple method from waste
OSPs and CuCl2, which was shown to be a highly active and recyclable catalyst for the A3‐coupling
reaction. A range of propargylamines were obtained in good to excellent yields (85%–97%) under
solvent‐free and microwave‐heated conditions. The OSP‐CuCl2 catalyst can be simply recovered by
filtration and reused for at least six runs. Propargylamine can be produced in 87% yield even when
the scale of the A3‐coupling reaction was increased to 150 mmol.
Received 8 June 2014
Accepted 17 July 2014
Published 20 December 2014
Keywords:
Propargylamine
A3‐coupling reaction
Oyster shell waste
Microwave irradiation
Green chemistry
© 2014, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
1. Introduction
most of these homogeneous catalytic systems suffer from the
problems of the difficult separation and recycling of the expen‐
Propargylamine derivatives are important materials in or‐
ganic synthesis, pharmaceutical chemistry and chemical engi‐
neering, with a structural motif that is found in many natural
products and drug molecules [1–4]. The synthesis of propar‐
gylamines is an important topic in modern synthetic chemistry.
Therefore, efforts have been made to develop efficient and
green strategies for this preparation. The most efficient, con‐
venient and reliable method for the production of propargyla‐
mines is the three component aldehyde‐alkyne‐amine coupling
(A3‐coupling) reaction [5]. The catalytic A3‐coupling reaction
gives water as the only byproduct. Gold salts [6,7], silver salts
[8,9]and other metal salts [10,11]have been used as homoge‐
neous catalysts to catalyze the A3‐coupling reaction. However,
sive or hazardous catalysts, and environmental pollution.
In order to overcome these drawbacks, the immobilization
of the metal salts on a solid support has been applied to the
A3‐coupling reaction, which allows the straightforward remov‐
al of the catalyst from the reaction mixture. Numerous methods
have been developed to immobilize metal salts on a large vari‐
ety of solid supports such as SiO2 [12], zeolite [13], tung‐
stophosphoric acid [14], polymers [15], and so on [16,17].
However, the disadvantages of these methods are the high
price of the catalyst, tedious and time consuming procedure of
catalyst preparation, and sensitivity of the Cu(I) compounds.
Thus, the development of an efficient and easily available solid
catalyst has been an interesting challenge. One way to improve
* Corresponding author. Tel/Fax: +86‐592‐6162225; E‐mail: xxqluli@hqu.edu.cn
This work was supported by the National Natural Science Foundation of China (21004024), the Province Natural Science Foundation of Fujian, China
(2011J01046), the Program for New Century Excellent Talents in University of Fujian Province (2012FJ‐NCET‐ZR03), the University Distinguished
Young Research Talent Training Program of Fujian Province (11FJPY02), and the Promotion Program for Young and Middle‐aged Teacher in Science
and Technology Research of Huaqiao University (ZQN‐YX103).
DOI: 10.1016/S1872‐2067(14)60195‐9 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 35, No. 12, December 2014

Xingquan Xiong et al. / Chinese Journal of Catalysis 35 (2014) 2006–2013
2007
synthesis efficiency and reduce the cost of the heterogeneous
catalyst is to use naturally available wastes as the support. A
number of recent studies have reported using bio‐wastes as the
support of catalysts, which would reduce the number of syn‐
thesis steps, cost and use of hazardous chemicals in the prepa‐
ration of heterogeneous catalysts [18].
microscopy/energy dispersive X‐ray spectroscopy (SEM/EDX)
used an Oxford instrument 7021. NMR spectra were acquired
in CDCl3 on a Bruker DMX‐400 spectrometer at 400 MHz for 1H
NMR. The chemical shifts are given in δ values from TMS as an
internal standard.
In Fujian province, an enormous amount of oyster shell
wastes has been illegally disposed by oyster farms. Therefore,
the recycling of these is desirable. Oyster shell powder (OSP) has
been used widely as an additive in construction materials, ad‐
sorbent of heavy metal ions in sewage treatment and chicken
feed in chicken farms in order to reduce the amount of waste
oyster shells [19–21]. In addition, oyster shells have medicinal
value and have been used as a calcium source [22]. The main
component of oyster shells (>95%) is calcium carbonate.
Although OSPs are already widely used in other fields, their
application as support of heterogeneous catalysts is less well
understood. In addition, microwave (MW) irradiation has
proven to be a highly effective heating source for driving
chemical reactions in modern organic chemistry [23,24]. It was
found that MWs can accelerate the A3‐coupling reaction
[25,26].
In order to further improve the efficiency and practicability
of MW irradiation technology [27–30], we report here a simple,
green and scalable process for the synthesis of propargyla‐
mines from aldehydes, alkynes and amines catalyzed by a het‐
erogeneous OSP‐CuCl2 catalyst under microwave irradiation
and solvent‐free conditions. OSP‐CuCl2 is highly efficient, low
cost and easy to make. In addition, the catalyst was easily re‐
covered from the reaction mixture by filtration and was reusa‐
ble. This work is the first attempt to synthesize propargyla‐
mines using a catalyst composed of a bio‐waste material sup‐
port and CuCl2 in a one‐pot, three‐component and scalable
synthesis strategy. It not only produces useful propargylamines
at low cost, but also reduces waste and improves environmen‐
tal conditions.
2.2. Preparation of OSP‐CuCl2 and CaCO3‐CuCl2
In order to remove seaweeds and sands deposited on the
shell surface, the waste oyster shells were washed several
times in an ultrasonic cleaner and dried naturally. The oyster
shells were roughly crushed using a hammer then ground into
powder with a pestle and mortar and passed through a 100
mesh sieve. The OSPs were then dried at 100 °C for 2 h and
stored in a desiccator.
In a round‐bottom flask, OSPs (5.0 g) was mixed with CuCl2
(1.5 g, 0.011 mol) in deionized water (50 mL). The mixture was
stirred at room temperature for 8 h. The product was filtered
and washed with ethanol, ethyl acetate and water successively.
The catalyst was placed in a vacuum oven and dried overnight
at 50 °C. The CaCO3 supported CuCl2 catalyst was prepared by
the same procedure as described above. The two kinds of Cu(II)
heterogeneous catalysts are denoted as OSP‐CuCl2 and Ca‐
CO3‐CuCl2, respectively.
2.3. The A3‐coupling reactions
OSP‐CuCl2 and CaCO3‐CuCl2 were used for the preparation of
propargylamines by the A3‐coupling reaction of aldehydes,
amines and alkynes. In a typical procedure, to a mixture of al‐
dehyde (3.0 mmol), secondary amine (3.6 mmol) and alkyne
(3.6 mmol) was added OSP‐CuCl2 or CaCO3‐CuCl2 (10 mg) as
the catalyst. The mixture was stirred at 90 °C under MW irradi‐
ation (480 W) for 20 min. After complete conversion of the
aldehyde (determined by TLC analysis), the mixture was cooled
to room temperature and filtered, extracted with EtOAc, and
dried over anhydrous MgSO4. After evaporation of the solvent,
the crude product was obtained. Purification was performed by
silica gel flash column chromatography with a mixture of pe‐
troleum ether/ethyl acetate as eluent to afford the desired
propargylamines in good to excellent yields.
2. Experimental
2.1. Materials and instrumentation
Waste oyster shells used in this study was obtained from a
commercial oyster farm in Jimei district, Xiamen city, Fujian
province. All reagents and solvents were obtained from com‐
mercial sources and used without further purification. All the
A3‐coupling reactions were carried out in a commercial mi‐
crowave reactor (MAS‐II) manufactured by Sineo Microwave
Chemistry Technology (Shanghai) Co.
FT‐IR spectra were recorded using KBr on a Thermo Nicolet
iS10 FT‐IR spectrometer. OSP‐CuCl2 was analyzed by atomic
absorption spectrophotometry (AAS) using standard methods
with a Varian AA275 atomic absorption spectrophotometer
(USA). The crystallinity of OSP‐CuCl2 was characterized by XRD
on a Bruker D8 Advance (Germany) apparatus using Cu Kα ra‐
diation. The thermo gravimetric analyzer (TGA) was a TA in‐
strument (USA) DSC2910/SDT2960, and samples were heated
from 25 to 800 °C at 10 °C/min under N2. Scanning electron
2.4. Recycling and reuse of OSP‐CuCl2 and CaCO3‐CuCl2
After completion of the A3‐coupling reaction, OSP‐CuCl2 or
CaCO3‐CuCl2 was separated by simple filtration from the reac‐
tion system, and washed with water and ethanol. After drying
under vacuum at 60 °C for 1 h, the recycled catalyst was used
for the next run under the same conditions.
2.5. Spectroscopic data of propargylamines
4‐(1,3‐diphenylprop‐2‐ynyl)morpholine. IR (KBr, νmax
,
cm–1): 3059 (m), 2956 (s), 2852 (s), 2750 (m), 2690 (w), 2222
(w), 1680 (w), 1559 (m), 1489 (s), 1450 (s), 1317 (s), 1114 (s),
1001 (s), 758 (s), 696 (s). 1H NMR (400 MHz, CDCl3): δ = 7.67
(d, J = 7.4 Hz, 2H), 7.57–7.49 (m, 2H), 7.41–7.27 (m, 6H), 4.83 (s,

2008
Xingquan Xiong et al. / Chinese Journal of Catalysis 35 (2014) 2006–2013
1H), 3.63–3.87 (m, 4H), 2.62–2.78 (m, 4H).
1452 (m), 1375 (m), 1267 (s), 1103 (s), 1020 (m), 952 (m), 709
(s), 609 (w). 1H NMR (400 MHz, CDCl3): δ = 8.09–8.02 (m, 2H),
7.56–7.44 (m, 3H), 4.95 (s, 2H), 3.47 (s, 2H), 2.60–2.50 (m, 4H),
1.06–0.98 (2s, 6H).
4‐(1‐(furan‐2‐yl)‐3‐phenylprop‐2‐ynyl)morpholine. IR (KBr,
ν
max, cm–1): 3117 (w), 3057 (w), 2956 (s), 2854 (s), 2752 (w),
2690 (w), 2225 (w), 1597 (m), 1494 (m), 1450 (m), 1315 (m),
1112 (s), 1006 (m), 922 (m), 752 (s). 1H NMR (400 MHz,
CDCl3): δ = 7.62–7.28 (m, 6H), 6.64–6.31 (m, 2H), 4.91 (s, 1H),
3.89–3.70 (m, 4H), 2.79–2.59 (m, 4H).
3. Results and discussion
4‐(1‐(4‐chlorophenyl)‐3‐phenylprop‐2‐ynyl)morpholine. IR
(KBr, νmax, cm–1): 3057 (m), 2956 (s), 2854 (s), 2222 (w), 1597
(m), 1487 (s), 1450 (s), 1315 (s), 1114 (s), 1006 (s), 856 (m),
756 (m), 692 (m). 1H NMR (400 MHz, CDCl3): δ = 7.67–7.49 (m,
4H), 7.37 (d, J = 6.4 Hz, 5H), 4.79 (s, 1H), 3.90–3.72 (m, 4H),
2.81–2.62 (m, 4H).
4‐(1‐(4‐methoxyphenyl)‐3‐phenylprop‐2‐ynyl)morpholine.
IR (KBr, νmax, cm–1): 3055, 2999 (w), 2928 (w), 2820 (w), 1606
(m), 1508 (m), 1319 (m), 1249 (m), 844 (m), 763 (m). 1H NMR
(400 MHz, CDCl3): δ = 7.60–7.49 (m, 4H), 7.38–7.32 (m, 3H),
6.93 (d, J = 8.7 Hz, 2H), 4.76 (s, 1H), 3.84 (s, 3H), 3.76 (s, 4H),
2.65 (s, 4H).
4‐(3‐phenylprop‐2‐ynyl)morpholine. IR (KBr, νmax, cm–1):
3057 (m), 2958 (s), 2920 (s), 2854 (s), 2814 (s), 2235 (w),
1559 (w), 1489 (m), 1448 (s), 1323 (s), 1118 (s), 1006 (m), 758
(m), 692 (m). 1H NMR (400 MHz, CDCl3): δ = 7.55–7.41 (m, 2H),
7.30 (dd, J = 8.6, 5.0 Hz, 3H), 3.86–3.73 (m, 4H), 3.52 (s, 2H),
2.71–2.60 (m, 4H).
3.1. Catalyst characterization results
FT‐IR spectroscopy is a technique that provides valuable
information on OSP‐CuCl2 and CaCO3‐CuCl2. Figure 1 shows the
FT‐IR spectra of the OSPs, CaCO3, OSP‐CuCl2 and CaCO3‐CuCl2
samples. As can be seen from Fig. 1, CuCl2 deposition onto the
OSPs resulted in slight lowering shifts of the characteristic ab‐
sorption, i.e., the peak at 1429 cm–1 was shifted to 1425 cm–1. In
addition, the –CO32– bending vibration absorption peaks at 878
and 712 cm–1 were shifted to lower wavenumber at 877 and
711 cm–1 after the complexing of CuCl2 with OSPs. The slight
shifts of the peaks of OSP‐CuCl2 can be attributed to the chela‐
tion of CuCl2 with biological molecules such as chitin and pro‐
teins on the surface of OSPs. Compared to OSPs, when CaCO3
was complexed with CuCl2, the –CO32– stretching peak at 1423
cm–1 was shifted to the lower wavenumber at 1421 cm–1. Fur‐
thermore, the –CO32– bending vibration peaks at 713 cm–1 were
shifted to the lower wave number at 711 cm–1 after the deposi‐
tion of CuCl2. The lower frequency of the above peak indicated
the physical adsorption of CuCl2 by CaCO3.
The crystalline phases of OSP‐CuCl2 and CaCO3‐CuCl2 were
characterized by XRD. The XRD patterns are shown in Fig. 2.
The XRD patterns of OSP‐CuCl2 and CaCO3‐CuCl2 showed char‐
acteristic reflections at 2θ = 23.28°, 29.24°, 36.40°, 39.26°,
43.25°, 47.74°, and 48.73° corresponding to the (012), (104),
(110), (113), (202), (024), and (116) planes of calcite (JCPDS
72‐1652). The XRD patterns also showed the characteristic
reflection for CuCl2 at 2θ = 32.2° corresponding to the (201)
plane of the cubic CuCl2 crystal. The results indicated that
OSP‐CuCl2 and CaCO3‐CuCl2 catalysts were prepared success‐
fully.
N,N‐diethyl‐3‐phenylprop‐2‐yn‐1‐amine. IR (KBr, νmax
,
cm–1): 3057 (w), 2970 (s), 2818 (m), 2225 (w), 1597 (w), 1487
(m), 1458 (m), 1379 (m), 1321 (m), 1201 (w), 1064 (m), 758
(m), 692 (m). 1H NMR (400 MHz, CDCl3): δ = 7.52–7.39 (m, 2H),
7.36–7.31 (m, 3H), 3.67 (s, 2H), 2.80–2.60 (m, 4H), 1.15–1.13
(2s, 6H).
N‐butyl‐N‐(3‐phenylprop‐2‐ynyl)butan‐1‐amine. IR (KBr,
ν
max, cm–1): 3059 (w), 2955 (s), 2866 (m), 2818 (m), 1597 (w),
1462 (m), 1371 (m), 1321 (m), 1089 (m), 947 (m), 754 (m),
1
692 (m). H NMR (400 MHz, CDCl3): δ = 7.50–7.42 (m, 2H),
7.38–7.28 (m, 3H), 3.65 (s, 2H), 2.61–2.51 (m, 4H), 1.55–1.50
(m, 4H), 1.44–1.32 (m, 4H), 1.01–0.97 (2s, 6H).
4‐(4‐(4‐methoxyphenoxy)but‐2‐ynyl)morpholine. IR (KBr,
ν
max, cm–1): 3049 (w), 2920 (s), 2854 (s), 2025 (w), 1595 (w),
To characterize the thermal behavior of OSP‐CuCl2 and Ca‐
1506 (s), 1454 (s), 1373 (s), 1290 (m), 1215 (m), 1114 (m),
1010 (s), 827 (m), 711 (m), 524 (w). 1H NMR (400 MHz, CDCl3):
δ = 6.89–6.82 (m, 4H), 4.65 (s, 2H), 3.74 (s, 3H), 3.73–3.64 (m,
4H), 3.29 (d, J = 1.6 Hz, 2H), 2.56–2.43 (m, 4H).
CaCO3-CuCl2
712
875
N,N‐diethyl‐4‐(4‐methoxyphenoxy)but‐2‐yn‐1‐amine.
IR
1421
OSP-CuCl2
(KBr, νmax, cm–1): 3049 (w), 2968 (s), 2827 (s), 2256 (w), 1595
(w), 1506 (w), 1458 (m), 1377 (m), 1317 (m), 1213 (s), 1101
(m), 1037 (s), 825 (m), 746 (w). 1H NMR (400 MHz, CDCl3): δ =
6.95–6.89 (m, 2H), 6.87–6.80 (m, 2H), 4.66 (s, 2H), 3.76 (s, 3H),
3.45 (s, 2H), 2.56–2.45 (m, 4H), 1.04–0.98 (2s, 6H).
4‐morpholinobut‐2‐ynyl benzoate. IR (KBr, νmax, cm–1): 3066
(w), 2924 (m), 2856 (m), 2237 (w), 1724 (s), 1595 (m), 1448
(m), 1371 (m), 1267 (m), 1112 (m), 1008 (m), 862 (m), 796
(m), 567 (w). 1H NMR (400 MHz, CDCl3): δ = 8.13–7.98 (m, 2H),
7.59–7.46 (m, 2H), 4.97 (s, 2H), 3.80–3.69 (m, 4H), 3.35 (s, 2H),
2.62–2.52 (m, 4H).
711
877
1425
1423
CaCO3
OSPs
712
875
712
878
1429
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm1)
4‐(diethylamino)but‐2‐ynyl benzoate. IR (KBr, νmax, cm–1):
3066 (w), 2970 (w), 2820 (w), 2270 (w), 1726 (s), 1595 (m),
Fig. 1. FT‐IR spectra of OSPs, CaCO3, OSP‐CuCl2, and CaCO3‐CuCl2.

Xingquan Xiong et al. / Chinese Journal of Catalysis 35 (2014) 2006–2013
2009
100
90
(1)
(2)
CaCO3-CuCl2
80
70
OSP-CuCl2
60
50
20
30
40
50
2 /(o )
60
70
80
100 200 300 400 500 600 700
Temperature (oC)
Fig. 2. XRD patterns of OSP-CuCl2 and CaCO3-CuCl2.
Fig. 3. TGA curves of CaCO3‐CuCl2 (1) and OSP‐CuCl2 (2).
CO3‐CuCl2, TGA was performed under a N2 atmosphere. Figure
3 gives the TGA curves from room temperature to 800 °C. As
can be seen in Fig. 3, calcination of the CaCO3‐CuCl2 started at
590 °C and was at 730 °C. The mass of CaCO3‐CuCl2 during the
calcination under the N2 atmosphere decreased by 37% be‐
cause of the decomposition of CaCO3 (Fig. 3(1)). OSP‐CuCl2 ex‐
hibited a slow mass loss at 100 °C with 0.4% mass loss, which
was attributed to the removal of adsorbed water (Fig. 3(2)). An
obvious mass loss (9.2%) from 100 to 590 °C was observed,
which was assigned to the decomposition of chitin and protein
molecules in the OSPs. OSP‐CuCl2 did not show any obvious
mass loss between room temperature and 200 °C, which indi‐
cated that the OSP‐CuCl2 catalyst was thermally stability below
200 °C.
Cu was detected on OSPs and CaCO3 by SEM/EDX analysis.
Figure 4 shows typical SEM/EDX images of the Cu(II) element
from OSP‐CuCl2 and CaCO3‐CuCl2. Fig. 4(a) and (c) showed that
CuCl2 was uniformly coated onto the OSPs and CaCO3. Fig. 4(a)
and (b) show that the OSP‐CuCl2 catalyst can be reused for at
least six consecutive runs without any decrease in the CuCl2 on
the recycled OSP‐CuCl2 catalyst. However, Fig. 4(c) and (d)
showed that the CuCl2 of the recycled CaCO3‐CuCl2 catalyst after
six cycles was obviously lower than on the fresh catalyst. The
difference of the Cu element after six cycles between OSP‐CuCl2
and CaCO3‐CuCl2 can be explained by the biomolecules on the
OSP particle surface, such as chitin and proteins, which play an
important role in the chelation of CuCl2. Therefore, the
OSP‐CuCl2 catalyst has better stability.
3.2. Screening of the copper catalysts
In order to determine the best catalyst for the A3‐coupling
reaction, the catalytic activities of different copper salts and
supported copper salt catalysts were examined with a model
reaction using benzaldehyde, phenylacetylene and morpholine
under solvent‐free conditions at 90 °C. The results are summa‐
rized in Table 1.
When OSPs was used as the catalyst, the A3‐coupling reac‐
tion did not give any product (entry 1). When the A3‐coupling
reaction was carried out using homogeneous copper catalysts
such as CuSO4·5H2O, CuBr, and CuCl2 for 20 min at 90 °C under
MW irradiation, 4‐(1,3‐diphenylprop‐2‐ynyl)morpholine was
obtained in 87%, 87%, and 83% isolated yield, respectively
(entries 2–4). However, these homogeneous copper catalysts
could not be reused. In order to recycle the copper salts, sup‐
ported catalysts such as OSP‐CuSO4, OSP‐Cu(OAc)2, Ca‐
CO3‐CuCl2, OSP‐CuBr, and OSP‐CuCl2 were employed as a het‐
erogeneous catalyst. The results showed that when the reaction
was carried out using OSP‐CuSO4, OSP‐Cu(OAc)2, CaCO3‐CuCl2,
and OSP‐CuBr as the catalyst for 20 min at 90 °C under MW
irradiation, the desired product was obtained in good to excel‐
lent yields of 81%, 89%, 88%, and 92%, respectively (entries
5–8). OSP‐CuCl2 was the most effective catalyst in terms of the
isolated yield of the corresponding product (96%, entry 9).
Under a conventional heating condition, we investigated the
activity of the catalysts for the formation of 4‐(1,3‐diphe‐
nylprop‐2‐ynyl)morpholine at 90 °C. After 240 min, when sup‐
a
b
c
b
(a)
(b)
(c)
(d)
b
b
100 μm
100 μm
100 μm
100 μm
Fig. 4. SEM/EDX images of CuCl2 dispersion on OSP‐CuCl2 (a), OSP‐CuCl2 recycled six times (b), CaCO3‐CuCl2 (c), and CaCO3‐CuCl2 recycled six times
(d).

2010
Xingquan Xiong et al. / Chinese Journal of Catalysis 35 (2014) 2006–2013
and afforded the product in excellent yield (96%, entry 7).
Table 1
Therefore, the following A3‐coupling reactions were carried
out under solvent‐free condition to avoid the use of a volatile
organic solvent to reduce environmental pollution.
Copper salt catalysts in the three‐component A3‐coupling reaction of
benzaldehyde, phenylacetylene, and morpholine.
O
O
O
Cu catalyst
N
H
+
+
3.4. One‐pot three‐component synthesis of propargylamines
free of solvent
90oC
N
H
To expand the scope of the A3‐coupling reaction, various
alkynes, aldehydes and amines were used as starting substrate.
Under the optimized conditions, the A3‐coupling reaction was
performed in air under MW irradiation with OSP‐CuCl2 as cata‐
lyst. The results are summarized in Table 3. Both aromatic and
aliphatic aldehydes, including those bearing functional groups
such as alkoxy and chloro substitutions, underwent the
A3‐coupling reaction smoothly to provide the corresponding
propargylamines in good to excellent yields (85%–97%, entries
1–11). Different amines also have an effect on the reaction.
Excellent yields were observed when a cyclic amine, such as
morpholine, was used (entries 1–5, 8, and 10). Lower yields
were observed when a chain amine, such as dibutylamine and
diethylamine, was used (entries 7 and 11). In addition, we ex‐
amined the effect of functional alkynes with electron‐donating
and electron‐withdrawing groups, such as 1‐methoxy‐4‐(prop‐
2‐ynyloxy)benzene and prop‐2‐ynyl benzoate. As can be seen
in Table 3, both electron‐donating and electron‐withdrawing
substituted aromatic alkynes gave good to excellent yields
(89%–95%, entries 8–11).
MW irradiation
Conventional heating
Entry
Catalyst
OSPs
CuSO4·5H2O
CuBr
Time (min) Yielda (%) Time (min) Yielda (%)
1
2
3
4
5
6
7
8
9
20
20
0
87
240
240
240
240
240
240
240
240
240
0
67
90
84
80
79
86
90
94
20
87
CuCl2
20
83
OSP‐CuSO4
OSP‐Cu(OAc)2
CaCO3‐CuCl2
OSP‐CuBr
OSP‐CuCl2
20
81
20
89
20
88
20
20(20)b
92
96(11)b
Reaction conditions: benzaldehyde (3 mmol), alkyne (3.6 mmol),
amines (3.6 mmol), catalyst (0.01 g), MW 480 W, 20 min.
a Isolated yields. b Conventional heating.
ported CuCl2, CaCO3‐CuCl2, and OSP‐CuCl2, were used as cata‐
lyst, the yields of propargylamines were 86% and 94%, respec‐
tively (Table 1). In addition, when OSPs‐CuCl2 was used as cat‐
alyst, the reaction gave only 11% yield after 20 min under a
conventional heating condition. This showed that MW irradia‐
tion dramatically accelerated the reaction rate of the A3‐cou‐
pling reaction.
Table 3
OSP‐CuCl2 catalyzed A3‐coupling reaction.
3.3. Screening of the solvent
O
H
Isolated
yield (%)
R1
N
Entry
1
R4
O
R5
R2
O
R3
The solvent plays an important role in the A3‐coupling reac‐
tion. To check the solvent effect on the outcome of the
A3‐coupling, the model reaction was performed with OSP‐CuCl2
in various solvents such as MeOH, acetonitrile, DMF, toluene,
DMSO, and H2O at 100 °C (Table 2).
96
NH
CHO
2
3
4
5
94
95
94
97
O
O
O
NH
NH
NH
CHO
CHO
As shown in Table 2, DMF was the best solvent (96%, entry
5), while toluene afforded a lower yield (67%, entry 3). Good
yields of the desired propargylamine were obtained when the
reaction was performed in acetonitrile and DMSO (80% and
87%, entries 2 and 4) and moderate results were observed
when the reaction was carried out in MeOH and H2O (76% and
79%, entries 1 and 6). More important was that the model re‐
action also occurred efficiently under solvent‐free condition,
O
O
CHO
HCHO
O
NH
6
7
HCHO
HCHO
91
85
N
H
HN
O
Table 2
Screening of solvent for the one pot synthesis of propargylamines.
8
HCHO
95
H3CO
H3CO
O
O
NH
NH
Entry
Solvent
MeOH
MeCN
toluene
DMSO
DMF
Isolated yield (%)
9
HCHO
HCHO
90
93
1
2
3
4
5
6
7
76
80
67
87
96
79
96
N
H
10
O
O
O
11
HCHO
89
O
N
H
H2O
—
O
Reaction conditions: aldehyde (3 mmol), alkyne (3.6 mmol), amines
(3.6 mmol), catalyst (0.01 g), MW 480 W, 20 min.
Reaction conditions: benzaldehyde (3 mmol), alkyne (3.6 mmol),
amines (3.6 mmol), catalyst (0.01 g), MW 480 W, 20 min.

Xingquan Xiong et al. / Chinese Journal of Catalysis 35 (2014) 2006–2013
2011
3.5. Reuse of OSP‐CuCl2 and CaCO3‐CuCl2
Table 4
Scale‐up synthesis of the A3‐coupling reaction.
The separation and recovery of a heterogeneous catalyst is
an important step in the preparation of fine chemicals. To
achieve both environmental and economic benefits, the lifetime
of OSP‐CuCl2 and its reusability are important considerations
for practical applications, especially for the A3‐coupling reac‐
tion performed on a large scale. To clarify this issue, a set of
experiments for the synthesis of 4‐(1,3‐diphenylprop‐2‐
ynyl)morpholine from benzaldehyde, phenylacetylene and
morpholine with OSP‐CuCl2 and CaCO3‐CuCl2 as catalyst were
performed. The results are shown in Fig. 5. The results indicat‐
ed that there were noticeable drops in the product yields over
OSP‐CuCl2 after 6 cycles (from 96% to 81%), suggesting that
CuCl2 leaching occurred for the heterogeneous OSP‐CuCl2 cata‐
lyst. Moreover, the A3‐coupling reaction catalyzed by Ca‐
CO3‐CuCl2 gave increasingly low yields (only 68% after 6 cy‐
cles). The copper(II) content of the OSP‐CuCl2 catalyst after 6
cycles was 6.17% as detected by AAS, which was lower than on
the fresh OSP‐CuCl2 (9.38%). AAS analysis showed that the
copper(II) content in CaCO3‐CuCl2 obviously decreased from
10.21% to 2.57% after 6 cycles. An obvious conclusion can be
drawn that the obvious difference in catalytic activity after 6
cycles between OSP‐CuCl2 and CaCO3‐CuCl2 was caused by the
chitin and protein molecules on the OSP surface, which played
an important role in the chelation of CuCl2. Thus, this makes
OSP‐CuCl2 more stable and the preferred catalyst.
Entry
1
2
3
4
Scale (mmol)
Isolated product (g) Isolated yield (%)
3
30
60
150
30
30
0.5
5.1
96
90
89
87
89
87
83
70
10.0
24.4
5.0
5a
6b
7c
8d
4.9
4.7
3.9
30
30
a Catalyst recycled from entry 2 and used for second run. b Third run.
c Fourth run. d Fifth run.
Meanwhile, the recovery and reuse of OSP‐CuCl2 was also in‐
vestigated. The recovered catalyst exhibited good activity for
up to five consecutive cycles. When the scale of the reaction
was 30 mmol, the catalyst can be recycled and reused at least
five times and still maintained a moderate yield (70%, entry 8).
3.7. Proposed mechanism of A3 coupling reaction
On the basis of the above results, a proposed reaction
mechanism for the A3 coupling reaction catalyzed by OSP‐CuCl2
under microwave-heated conditions is illustrated in Fig. 6. The
initial step is activation of the terminal alkyne by the OSP‐CuCl2
catalyst under MW irradiation to afford the corresponding
copper‐alkylidine complex on the OSPs support. Then, the
copper acetylide intermediate reacted with iminium ion (gen‐
erated in situ from the corresponding aldehyde and amine) to
give the desired propargylamine, with the OSP‐CuCl2 catalyst
being regenerated for a further cycle of reactions.
3.6. Scale‐up synthesis of propargylamines
To demonstrate the potential of this method for production
purposes, the scale‐up synthesis of propargylamines was in‐
vestigated with N,N‐diethyl‐3‐phenylprop‐2‐yn‐1‐amine as a
model reaction. The results are summarized in Table 4. The
A3‐coupling reaction between formaldehyde, phenylacetylene
and diethylamine proceeded successfully and the product was
obtained in good yields almost comparable to those in the small
scale reactions. The results of scale‐up experiments showed
that when the scale of the reaction was 150 mmol, the yield of
purified N,N‐diethyl‐3‐phenylprop‐2‐yn‐1‐amine was 87%.
4. Conclusions
We successfully developed a bio‐waste OSP‐based compo‐
site with CuCl2 as a heterogeneous catalyst for the scale‐up
synthesis of propargylamines by a one‐pot three‐component
A3‐coupling reaction of aldehydes, amines and alkynes under
MW irradiation. A wide range of functional groups could be
tolerated under the reaction conditions. The A3‐coupling reac‐
R1
100
H
R3
R2
R4
H
(1)
(2)
90
80
70
60
50
N
R1
Iminium ion
OH-
Microwave
C-H alkyne activation
Microwave
=CuCl2
OSPs-CuCl2
O
H
N
R3
R2
R4
R2
H
R3 R4
1
2
3
4
5
6
R1
Cycles
+
H2O
Fig. 5. Reusability of OSP‐CuCl2 (1) and CaCO3‐CuCl2 (2) in benzalde‐
hyde, phenylacetylene, and morpholine as starting materials under MW
irradiation.
Fig. 6. Proposed mechanism for the A3 coupling reaction catalyzed by
OSP‐CuCl2.

2012
Xingquan Xiong et al. / Chinese Journal of Catalysis 35 (2014) 2006–2013
Graphical Abstract
Chin. J. Catal., 2014, 35: 2006–2013 doi: 10.1016/S1872‐2067(14)60195‐9
Oyster shell waste supported CuCl2 for aldehyde‐alkyne‐amine
coupling reaction to propargylamines
Xingquan Xiong*, Huixin Chen, Rongjun Zhu
Huaqiao University
OSPs
CuCl2
Oyster shell wastes
R1
R4
R2
R5
N
20 minutes
OSPs-CuCl2
+
O
11 examples
One-pot, MW
OSP‐CuCl2 is a highly efficient, low cost and reusable catalyst for the syn‐
thesis of propargylamines in good to excellent yields under micro‐
wave‐heated conditions. The propargylamine yield was 87% even when
the reaction scale was increased to 150 mmol.
R3
Up to 97% yields
6 cycles
150 mmol scale
R1
R2
R4
R3
R5
Free of solvent
+
H
N
2008: 4440
tion was carried out at a relatively low temperature, in a short‐
[14] Reddy K M, Babu N S, Suryanarayana I, Prasad P S S, Lingaiah N.
Tetrahedron Lett, 2006, 47: 7563
[15] Salam N, Kundu S K, Roy A S, Mondal P, Roy S, Bhaumik A, Islam S
K M. Catal Sci Technol, 2013, 3: 3303
[16] Yang J, Li P H, Wang L. Catal Commun, 2012, 27: 58.
[17] Salam N, Sinha A, Roy A S, Mondal P, Jana N R, Islam S K M. RSC
Adv, 2014, 4: 10001
[18] Smith S M, Oopathum C, Weeramongkhonlert V, Smith C B,
Chaveanghong S, Ketwong P, Boonyuen S. Bioresour Technol,
2013, 143: 686
er reaction time, and in air without a solvent under MW irradi‐
ation, and gave good to excellent yields. Propargylamine was
obtained in 87% yield when the scale of the A3‐coupling reac‐
tion was increased to 150 mmol. The OSP‐CuCl2 catalyst was
easily recovered from the reaction mixture by filtration and
could be reused at least six times. The catalyst not only pro‐
duced useful propargylamines at low cost, but also reduced
waste and improved environmental conditions.
References
[19] Kuo W T, Wang H Y, Shu C Y, Su D S. Constr Build Mater, 2013, 46:
128
[20] Hsu T C. J Hazard Mater, 2009, 171: 995
[21] Yang C R, Ko T H, Lin Y C, Lee S Z, Chang Y F, Hsueh H T. Environ
Chem Lett, 2013, 11: 33
[1] Zani L, Bolm C. Chem Commun, 2006: 4263
[2] Konishi M, Ohkuma H, Tsuno T, Oki T, VanDuyne G D, Clardy J. J
Am Chem Soc, 1990, 112: 3715
[22] Tsugawa N, Okano T, Higashino R, Kimura T, Oshio Y, Teraoka Y,
Igarashi C, Ezawa I, Kobayashi T. Biol Pharm Bull, 1995, 18: 677
[23] Lidstrom P, Tierney J, Wathey B, Westman J. Tetrahedron, 2001,
57: 9225
[3] Hu T S, Tannert R, Arndt H D, Waldmann H. Chem Commun, 2007:
3942
[4] Jeon H B, Lee Y, Qiao C, Huang H, Sayre L M. Bioorg Med Chem,
2003, 11: 4631
[24] Xiong X Q, Cai L, Tang Z K. Chin J Org Chem, 2012, 32: 1410
[25] Shi L, Tu Y Q, Wang M, Zhang F M, Fan C A. Org Lett, 2004, 6:
1001
[26] Bariwal J B, Ermolat’ev D S, Van der Eycken E V. Chem Eur J, 2010,
16: 3281
[5] Peshkov V A, Pereshivko O P, Van der Eycken E V. Chem Soc Rev,
2012, 41: 3790
[6] Zhang X, Corma A. Angew Chem Int Ed, 2008, 47: 4358
[7] Layek K, Chakravarti R, Kantam M L, Maheswaran H, Vinu A. Green
Chem, 2011, 13: 2878
[27] Xiong X Q, Chen H X, Zhu R J. Catal Commun, 2014, 2014, 54: 94
[28] Xiong X Q, Cai L. Catal Sci Technol, 2013, 3: 1301
[29] Xiong X Q, Chen H X, Tang Z K, Jiang Y B. RSC Adv, 2014, 4: 9830
[30] Xiong X Q, Cai L, Jiang Y B, Han Q. ACS Sustainable Chem Eng, 2014,
2: 765
[8] Maggi R, Bello A, Oro C, Sartori G, Soldi L. Tetrahedron, 2008, 64:
1435
[9] Jeganathan M, Dhakshinamoorthy A, Pitchumani K. ACS Sustaina‐
ble Chem Eng, 2014, 2: 781
[10] Chen W W, Nguyen R V, Li C J. Tetrahedron Lett, 2009, 50: 2895
[11] Eagalapati N P, Rajack A, Murthy Y L N. J Mol Catal A, 2014, 381:
126
[12] Karimi B, Gholinejad M, Khorasani M. Chem Commun, 2012, 48:
8961
Page numbers refer to the contents in the print version, which include
both the English and Chinese versions of the paper. The online version
only has the English version. The pages with the Chinese version are only
available in the print version.
[13] Patil M K, Keller M, Reddy B M, Pale P, Sommer J. Eur J Org Chem,