Cu-Ni bimetallic reusable catalyst for synthesis of propargylamines via multicomponent coupling reaction under solvent-free conditions

Article abstract of DOI:10.1039/c4ra06275b

A Cu-Ni bimetallic catalyst has been used as a reusable catalytic system for the multicomponent coupling reaction of aldehydes, phenylacetylene and secondary amines for the synthesis of propargylamines under solvent-free conditions. The reaction did not r

Full text of DOI:10.1039/c4ra06275b

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
Cu–Ni bimetallic reusable catalyst for synthesis of
propargylamines via multicomponent coupling
reaction under solvent-free conditions†
Cite this: RSC Adv., 2014, 4, 47958
Received 2nd July 2014
Accepted 15th September 2014
*
Suyog V. Katkar and R. V. Jayaram
DOI: 10.1039/c4ra06275b
www.rsc.org/advances
A Cu–Ni bimetallic catalyst has been used as a reusable catalytic
Inductive coupled plasma (ICP) analysis reveals bulk
system for the multicomponent coupling reaction of aldehydes, composition of Cu–Ni was Cu0.49Ni0.51 which was also similar to
phenylacetylene and secondary amines for the synthesis of prop- that of precursor solution. Scanning electron microscopy (SEM)
argylamines under solvent-free conditions. The reaction did not images Fig. 1(a and b) gives morphological information that the
require any other additives such as an inorganic base. The bimetallic Cu–Ni present in the form of irregular, dense particles with
catalyst displayed high activity and gives propargylamines in good to extremely broad size distribution (<200 nm to >400 nm). Large
excellent yields. This method provides a wide range of substrate particles are formed apparently due to agglomeration, as the
applicability. The catalyst could be magnetically separated and reused reaction in between metallic ions and sodium borohydride is
without loss in activity.
strongly exothermic.14 Energy dispersive X-ray analysis (EDAX),
(Fig. 2) shows 48.5% of Cu and 51.5% of Ni as the surface
composition, which is nearly the same as that of the bulk. XRD
(Fig. 3) pattern shows amorphous nature of catalyst.15
To develop an optimal catalytic system, various reaction
parameters were studied for the synthesis of 1a via a reaction of
benzaldehyde, morpholine and phenylacetylene at 90 ꢀC under
solvent-free conditions (Table 1). To assess the standing of Cu–
Ni bimetallic catalyst among other Cu based catalysts for
formation of corresponding propargylamine, for that some
comparative experiments were performed whereas for others
data is taken from literature (Table 1, entry 1–5) for this reaction
and Cu–Ni system was found to be the most effective (Table 1,
entry 9) and (Fig. 4).
Propargylamines are important synthetic intermediates for
synthesis of various nitrogen containing compounds such as
b-lactams, oxotremorine analogues, conrmationally restricted
peptides, and also they are components of bioactive compounds
or natural products.1 Traditionally, propargylamines are
synthesized by nucleophilic attack of lithium acetylides or
Grignard reagents, on imines.2 However, these reagents are
stoichiometric, moisture sensitive and require strictly
controlled reaction conditions. Propargylamines derivatives can
be also synthesised through a three component coupling of an
aldehyde, alkyne and amine.3,4 Recently various transition metal
catalysts such as Re,5 Hg2Cl2,6 Zr,7 Ag,8 Au,9 Cu,10 Ir11 and Cu/Ru
12
II have been explored for this synthesis. However, most of
these methods suffer from various disadvantages such as high
reaction temperatures, inert reaction conditions, expensive
catalytic systems.
Herein, we wish to report direct multicomponent coupling
reaction of aldehydes, phenylacetylene and secondary amine
under solvent-free conditions using Cu–Ni bimetallic catalyst
(Scheme 1). Cu–Ni bimetallic catalyst was prepared as per
reported method.13 Prepared catalyst was characterized by
various techniques such as ICP, XRD and SEM-EDAX.
Department of Chemistry, Institute of Chemical Technology (Deemed), Nathalal
Parekh Marg, Matunga, Mumbai 400 019, India. E-mail: rv.jayaram@ictmumbai.
edu.in; Fax: +91-2233611020; Tel: +91-2233612607
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra06275b
Scheme 1 Synthesis of propargylamines by Cu–Ni bimetallic catalyst.
47958 | RSC Adv., 2014, 4, 47958–47964
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
Fig. 2 EDAX of Cu–Ni bimetallic catalyst.
Fig. 3 XRD of Cu–Ni bimetallic catalyst.
Fig. 1 (a) & (b) SEM images of Cu–Ni bimetallic catalyst.
The optimum ratio of aldehyde, amine and alkyne was
(1.0 : 1.1 : 1.2 mmol). The multicomponent reaction carried
under identical conditions for long time but there was very low
self coupled product of phenylacetylene.
Cu–Ni bimetallic catalyst was recovered by simple magnetic
separation, aer completion of reaction. Ethyl acetate (10 mL)
was added, catalyst was collected by magnet (Fig. 5) and the
recovered catalyst showing consistent activity even aer h
cycle (Table 2, entry 5). Recovered catalyst aer h cycle was
characterized by SEM, ICP (Cu0.489Ni0.511), EDAX (Cu – 48.3% &
Ni – 51.7%) which is almost similar to freshly prepared catalyst
and XRD shows no signicant structural change and leaching of
metals in catalyst (Fig. 6, 7 and 8).
To assess substrate scope a number of structurally diverse
aldehydes, secondary amines and alkynes have been screened
for studying the generality as well as the efficacy of the present
Table 1 Synthesis of 1a using Cu-based catalystsa
Equivalent ratio
of reactants
Entry
Catalyst
wt%
Time (h)
%Yieldb
Reference
1
CuHAP
CuI
AgTPA
CuI in PEG as solvent
Si(CH2)3SO3$CuCl
Cu powder
Cu nano
Ni nano
Cu–Ni nano
20
1 : 1.2 : 1.3
1 : 1.2 : 1.5
1 : 1.2 : 1.3
1 : 1.2 : 1.5
1 : 1.2 : 1.5
1 : 1.1 : 1.2
1 : 1.1 : 1.2
1 : 1.1 : 1.2
1 : 1.1 : 1.2
6
1
6
12
16
3
3
3
80
98
80
85
54
37
75
NR
93
16a
16b
16c
16d
16e
TW
TW
TW
TW
2d
3
32c
30c
22c
50c
20
4d
5
6
7
8
20
20
20
9
3
a
This work (entries 6–9) reaction conditions: benzaldehyde (1.0 mmol), morpholine (1.1 mmol), phenylacetylene (1.2 mmol), catalyst (20 wt%)
b
c
d
heated at 90 ꢀC for 3 h. Isolated yields. For ready comparison mole ratio of catalyst was converted into wt%. Catalyst not recovered, NR –
no reaction, TW – this work.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 47958–47964 | 47959

View Article Online
RSC Advances
Communication
Fig. 4 Concentration vs time plot for the formation of propragylamin.
Fig. 6 SEM image of recovered catalyst after 5th cycle.
Fig. 5 (a) Cu–Ni bimetallic catalyst suspended in ethyl acetate after
completion of reaction; (b) Cu–Ni bimetallic catalyst was collected
using a magnet.
Table 2 Recyclability of the Cu–Ni catalyst for the synthesis of 1aa
Run
Time (h)
Yieldb [%]
Fig. 7 EDAX of recovered catalyst after 5th cycle.
1
2
3
4
5
3
3
3
3
3
93
91
89
86
85
a
Reaction conditions: benzaldehyde (1.0 mmol), morpholine (1.1
mmol), phenylacetyline (1.2 mmol), catalyst (20 wt%), heated at 90 ꢀC.
b
Isolated yields.
procedure and results are summarized in Table 3. The different
aldehydes aromatic, heteroaromatic and aliphatic were found
to undergo these reactions afforded good to excellent yield
(Table 3, entries 1–18). Benzaldehyde gave excellent yield in this
reaction condition (Table 3, entry 1). In case of benzaldehydes
with electron donating group such as methyl, methoxy and
hydroxyl gives lower yield as compare to unsubstituted benzal-
dehyde and benzaldehyde with electron-withdrawing group
such as cyano (Table 3, entries 2–5 and 7).
Fig. 8 XRD of recovered catalyst after 5th cycle.
Reaction proceeded equally smooth in case of hetero-
aromatic aldehydes such as 2-thiophenecarboxaldehyde, 2-fur-
ancarboxaldehyde and 4-pyridinecarboxaldehyde to afford
respective propargylamines in best yields (Table 3, entries 9–11
and 14). The aliphatic aldehyde such as heptaldehyde and
butyraldehyde were reacted smoothly with morpholine and
piperidine respectively gives afford the corresponding deriva-
tives in very good yields (Table 3, entries 8 and 15). There was
not much difference in yield when we compare secondary
amines such as morpholine, piperidine and dibutylamine
(Table 3, entries 1, 12 and 16). Sterically hindered aldehyde such
as 1-naphthaldehyde with piperidine also gives corresponding
47960 | RSC Adv., 2014, 4, 47958–47964
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
Table 3 One pot synthesis of propargylamines using Cu–Ni bimetallic catalysta
Entry
1
Aldehyde
Amine
Acetylene
Product
Time (h)
3.0
Isolated yieldb,c (%)
93
2
3
4
5
4.0
3.5
3.0
3.5
80
83
85
78
6
7
3.0
3.0
85
90
8
9
4.0
3.0
78
95
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 47958–47964 | 47961

View Article Online
RSC Advances
Communication
Table 3 (Contd.)
Entry
Aldehyde
Amine
Acetylene
Product
Time (h)
3.0
Isolated yieldb,c (%)
10
93
11
12
2.5
3.0
90
90
13
14
3.5
3.5
82
88
15
16
3.5
3.5
85
85
17
18
3.0
3.0
87
85
47962 | RSC Adv., 2014, 4, 47958–47964
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
Table 3 (Contd.)
Entry
Aldehyde
Amine
Acetylene
Product
Time (h)
Isolated yieldb,c (%)
19
4.5
No Reaction
a
Reaction conditions: aldehyde (1.0 mmol), amine (1.1 mmol), alkyne (1.2 mmol), catalyst (20 wt%), heat at 90 ꢀC. b Isolated yield. c The product
were identied by GC-MS.
propargylamines in good yield (Table 3, entry 13). As expected,
aliphatic alkynes such as 4-pentyne-1-ol gave high yield (Table 3,
entry 17). Electron rich substituted aromatic alkyne such as 4-
methyl phenylacetylene smoothly reacted with benzaldehyde
and pipyridine, gave good yield, there was no reaction in case of
electron poor phenylacetylene such as 4-nitro phenyleacetylene
(Table 3, entries 18 and 19).
It has been proposed that the multicomponent reaction
proceeds through the terminal C–H bond activation of the
alkyne by the Cu-based catalyst.17–20 The copper acetylide
intermediate generated, reacts with the iminium ion formed by
the reaction of the aldehyde and the amine to yield the corre-
sponding propargylamines, water and Cu–Ni catalyst. Thus
regenerated Cu–Ni bimetallic catalyst further in the reaction
and completes the catalytic cycle.
U. Hacksell, J. Org. Chem., 1994, 59, 1139; (d) M. Miura,
M. Enna, K. Okuro and M. Nomura, J. Org. Chem., 1995,
60, 4999; (e) T. Naota, H. Takaya and S. I. Murahashi,
Chem. Rev., 1998, 98, 2599.
4 (a) L. Zani and C. Bolm, Chem. Commun., 2006, 4263; (b)
C. Wei, Z. Li and C. Li, Synlett, 2004, 1472.
5 Y. Kuninobu, Y. Inoue and K. Takai, Chem. Lett., 2006, 35,
1376.
6 P. Li and L. Wang, Chin. J. Chem., 2005, 23, 1076.
7 (a) J. F. Traverse, A. H. Hoveyda and M. L. Snapper, Org. Lett.,
2003, 5, 3273; (b) L. C. Akullian, M. L. Snapper and
A. H. Hoveyda, Angew. Chem., Int. Ed., 2003, 42, 4244.
8 (a) C. Wei, Z. Li and C. J. Li, Org. Lett., 2003, 5, 4473; (b) Z. Li,
C. Wei, L. Chen, R. S. Varma and C. J. Li, Tetrahedron Lett.,
2004, 45, 2443; (c) K. M. Reddy, N. S. Babu, P. S. S. Prasad
and N. Lingaiah, Tetrahedron Lett., 2006, 47, 7563; (d)
R. Maggi, A. Bello, C. Oro, G. Sartori and L. Soldi,
Tetrahedron, 2008, 64, 1435; (e) P. Li, L. Wang, Y. Zhang
and M. Wang, Tetrahedron Lett., 2008, 49, 6650.
Conclusions
In conclusion a Cu–Ni bimetallic catalyst was explored for the
multicomponent coupling of aldehyde, secondary amine and
alkyne by C–H bond activation under solvent-free conditions.
While most of the reported methods required an inert atmo-
sphere, the present methodology does not require any special
operating conditions, thus making procedure simple. Good
yields, mild reaction conditions and solvent-free protocol are
advantages of this method. Besides, catalyst recovery was ach-
ieved using a magnetic separation.
9 (a) C. Wei, Z. Li and C. J. Li, J. Am. Chem. Soc., 2003, 125,
9584; (b) V. K. Y. Lo, Y. Liu, M. K. Wong and C. M. Che,
Org. Lett., 2006, 8, 529.
10 (a) C. Wei and C. J. Li, J. Am. Chem. Soc., 2002, 124, 5638; (b)
H. Z. S. Syeda, R. Halder, S. S. Karla, J. Das and J. Iqbal,
Tetrahedron Lett., 2002, 43, 6485; (c) N. Gommermann,
C. Koradin, K. Polborn and P. Knochel, Angew. Chem., Int.
Ed., 2003, 42, 5763; (d) L. Shi, Y. Q. Tu, M. Wang,
F. M. Zhang and C. A. Fan, Org. Lett., 2004, 6, 1001; (e)
B. M. Choudary, C. Sridhar, M. L. Kantam and B. Sreedhar,
Tetrahedron Lett., 2004, 45, 7319; (f) S. B. Park and
H. Alper, Chem. Commun., 2005, 1315; (g) B. Sreedhar,
P. S. Reddy, B. V. Prakash and A. Ravindra, Tetrahedron
Lett., 2005, 46, 7019; (h) P. Likhar, S. Roy, M. Roy,
M. S. Subhas, M. L. Kantam and R. L. De, Synlett, 2007,
2301; (i) M. K. Patil, M. Keller, B. M. Reddy, P. Pale and
J. Sommer, Eur. J. Org. Chem., 2008, 4440.
Notes and references
1 E. Ramu, R. Varala, N. Sreelatha and S. R. Adapa, Tetrahedron
Lett., 2007, 48, 7184.
2 (a) J. Montgomery, Acc. Chem. Res., 2000, 33, 467; (b) I. Marek,
Tetrahedron, 2005, 61, 11309; (c) J. Zhu and H. Bienayme,
Multi-component reactions, Wiley-VCH, Weinheim, 2005; (d)
A. Domling and I. Ugi, Angew. Chem., Int. Ed., 2000, 39, 3168.
3 (a) M. Konishi, H. Ohkuma, T. Tsuno, T. Oki, G. D. VanDuyne
and J. Clardy, J. Am. Chem. Soc., 1990, 112, 3715; (b)
M. A. Huffman, N. Yasuda, A. E. DeCamp and
E. J. J. Grabowski, J. Org. Chem., 1995, 60, 1590; (c)
A. Jenmalm, W. Berts, Y. L. Li, K. Luthman, I. Csoregh and
11 (a) C. Fischer and E. M. Carreira, Org. Lett., 2001, 3, 4319; (b)
S. Sakaguchi, T. Kubo and Y. Ishii, Angew. Chem., Int. Ed.,
2001, 40, 2534; (c) S. Sakaguchi, T. Mizuta, M. Furuwan,
T. Kubo and Y. Ishii, Chem. Commun., 2004, 1638.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 47958–47964 | 47963

View Article Online
RSC Advances
Communication
12 S. Sakaguchi, T. Mizuta, M. Furuwan, T. Kubo and Y. Ishii,
(d) Q. Zhang, et al., App. Organometal. Chem., 2010, 24, 809;
(e) B. Shreedhar, et al., Tetrahedron let., 2007, 48, 7882.
Chem. Commun., 2002, 268.
13 X. Wang, C. Chen, Y. Chang and H. Liu, J. Hazard. Mater., 17 A. Jahangeer, K. V. Ramanuachary, S. E. Loand and
2009, 161, 815.
14 Y. Chen, Catal.Today, 1998, 44, 3.
A. K. Ganguli, Colloids Surf., A, 2008, 331, 206.
18 C. Wei, Z. Li and C. Li, Org. Lett., 2003, 5, 4473.
15 A. S. Burange, S. R. Kale and R. V. Jayaram, Tetrahedron Lett., 19 Z. Li, C. Wei, L. Chen, R. S. Varma and C. J. Li, Tetrahedron
2012, 53, 2989. Lett., 2004, 45, 2443.
16 (a) B. M. Choudary, et al., Tetrahedron Lett., 2004, 45, 7319; 20 L. Shi, Y. Q. Tu, M. Wang, F. M. Zhang and C. A. Fan, Org.
(b) B. Shreedhar, et al., Tetrahedon Lett., 2005, 46, 7019; (c)
K. Mohan Reddy, et al., Tetrahedron Lett., 2006, 47, 7563;
Lett., 2004, 6, 1001.
47964 | RSC Adv., 2014, 4, 47958–47964
This journal is © The Royal Society of Chemistry 2014