Efficient and reusable ionic liquid stabilized magnetic cobalt nanoparticles as catalysts for aza- and thia-Michael reactions

Full text of DOI:10.1016/j.inoche.2015.01.027

Efficient and reusable ionic liquid stabilized magnetic cobalt nanoparticles as
catalysts for aza- and thia-Michael reactions
Manika Dewan, Arnab De, Subho Mozumdar
PII:
DOI:
Reference:
S1387-7003(15)00035-0
doi: 10.1016/j.inoche.2015.01.027
INOCHE 5864
To appear in:
Inorganic Chemistry Communications
Received date:
Revised date:
Accepted date:
11 November 2014
16 January 2015
18 January 2015
Please cite this article as: Manika Dewan, Arnab De, Subho Mozumdar, Efficient
and reusable ionic liquid stabilized magnetic cobalt nanoparticles as catalysts for
aza- and thia-Michael reactions, Inorganic Chemistry Communications (2015), doi:
10.1016/j.inoche.2015.01.027
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ACCEPTED MANUSCRIPT
Efficient and Reusable Ionic Liquid Stabilized Magnetic Cobalt Nanoparticles
as Catalysts for aza- and thia-Michael Reactions
Manika Dewan, Arnab De* and Subho Mozumdar#
Department of Chemistry, University of Delhi, Delhi-110007, India
* Department of Microbiology and Immunology, Columbia University, USA
Tel: +919810728438, #E-Mail: subhoscom@yahoo.co.in
Magnetic cobalt nanoparticles, stabilized using ionic liquid [bmim]BF4, have been used for
catalyzing aza- and thia- Michael reactions under environmentally benign conditions. The
catalyst has been efficiently recycled seven times for subsequent reactions by taking advantage
of their magnetic behavior and surface stabilization. The products were isolated in high yields in
short reaction times. The reaction proceeded under mild conditions at room temperature. TEM
analysis of particles, before and after completion of reaction, highlighted the recyclability of the
catalyst over multiple cycles of reaction.
R1
G
R1
[bmim]BF4-Co nanoparticles
+
X
G
R2
R2
G= CN, COMe, COOMe
X= SH or NH
Scheme 1.1: aza- and thia- Michael addition reaction catalyzed by [bmim]BF4 stabilized cobalt
nanoparticles
1

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Introduction
There are several reports of aza-and thia-Michael reactions that can be performed under mild
reaction conditions (normally at room temperature for a few minutes/hours). Catalysts employed
in such reactions include sulfated zirconia,1 silica-supported Lewis acids,2 polystyrene-sulfonic
acid,3 Si–Cu core–shell nanoparticles,4 ionic liquids5 and related acidic surfactants6,7 and
more recently by a ferrite-anchored glutathione catalyst.8 Uncatalysed intramolecular cyclization
of hydroxyl/amino chalcones as well as aza-Michael addition have also been reported to be
promoted in polyethylene glycol (PEG-400), but require relatively longer reaction times to
achieve reasonable yields.9 Supported metal catalysts such as Co(II) complex supported on SBA-
15 as reusable catalyst for aza- and thia- Michael reactions is highly efficient, but suffers from
reduced active surface sites on metal due to presence of chemically bound solid support.10
The longer reaction time in most of the recyclable heterogeneous catalysts mentioned above,
including nano-based catalysts and supported metal based catalysts is because of the low
catalytic surface area. Consequently, these catalysts suffer from reduced activity after one or two
cycles. Additionally, it is difficult to separate the catalyst.
Magnetic nano-materials have been used in the field of catalysis and other areas, such as
medicine, drug delivery and remediation.11,12 They can be easily synthesized and enhanced/tuned
by post-synthetic surface modifications.13 In view of their nano-size, the contact between
reactants and catalyst increases dramatically thus mimicking the homogeneous catalysts. They
offer an added advantage of being magnetically separable, thereby eliminating the requirement
of catalyst filtration after completion of the reaction.14 Additionally, magnetically recyclable
nanocatalysts have high catalytic activity and can be recycled easily.8
Green chemistry emphasizes the development of environmentally benign chemical processes and
technologies.15 In the past, Cerium (IV) ammonium nitrate has been used to catalyze aza-
Michael addition of amines to α,β-unsaturated electrophiles.16 Recently, it has been shown that
cobalt nanoparticles (Co NPs) can be used as catalysts offering great opportunities for a wide
range of applications in organic synthesis and chemical manufacturing processes. We
hypothesized that it may be possible to use ionic liquid stabilized magnetically recyclable cobalt
nanoparticles as catalyst for aza- Michael and thia- Michael addition reactions. The presence of a
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thin film of stabilizer i.e. hydrophilic room temperature ionic liquid [bmim]BF4 on the surface of
magnetic nanoparticles, would help to protect the catalytically active sites, allowing them to be
reused multiple times with negligible loss of activity.
Results and Discussion
Solventless catalysis of aza-and thia-Michael additions under mild conditions (at room
temperature and under atmospheric conditions) were carried out in the presence of magnetic
cobalt nanoparticles stabilized in ionic liquid. Products in quantitative yields were obtained
rapidly. When bare non-stabilized cobalt nanoparticles (in the absence of ionic liquids) was used,
1mole of phenylthiol reacted with 1mole of vinylmethylketone to give around ~8% yield in an
hour. Moreover, recyclability was a serious issue as particles underwent degradation after the
first cycle. However, when cobalt nanoparticles (30±5nm, 0.1mmole) stabilized with ionic liquid
[bmim]BF4 were isolated and used for the same Michael addition reaction, the yield achieved
was 95% in an hour. We postulate that ionic liquid formed a thin film providing electro-steric
stabilization which enhanced the catalytic properties and also prevented them from degradation.
A range of heteroatomic Michael donors (amines and thiols) were reacted with α,β-unsaturated
compounds (viz; acrylonitrile, methylvinylketone, methylacrylate and n-butylacrylate) (Scheme
1.1, Table 1.1 and Table 1.2) to obtain a series of aza- Michael and thia- Michael adducts
respectively. Secondary amines react faster than primary amines, as would be expected from
their higher nucleophilic character (Table 1.1; Entry 1.1.2 and Entry 1.1.6). On comparing
‘thia Michael reactions’ with ‘aza Michael additions’, thiols have a lower reaction time as they
are more nucleophilic than amines. (Table 1.1; Entry 1.1.1 and Table 1.2; Entry 1.2.1)
We also wanted to study the effect of particle size on catalytic efficiency. A reaction involving
1mmole of phenylthiol with 1mmole of methylacrylate (Table 1.2, Entry 1.2.3) was selected as
a model for further studies. We found that catalytic efficiency increased as expected as the
particle size decreased from a maximum value of 100nm to a lower value of 10nm. However,
below 10nm the catalytic efficiency was found to decrease. Figure 1.1 shows the trend of
catalytic activity as affected by the particle size. A decrease in the particle size causes an
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increase in the surface to volume ratio of the metal nanoparticles, increasing their catalytic
efficiency.
Catalyst concentration in the case of metal nanoparticle catalyzed reaction is another important
factor that was studied for cobalt nanoparticle catalyzed Michael additions. While studying the
effect of catalyst concentration on it’s efficiency, we found that the catalytic efficiency increased
with concentration upto 5mol%, after which it remained constant (Figure 1.2). Thus, ionic liquid
stabilized cobalt nanoparticles (of size 30±5 nm) could effectively catalyze when their
concentration was around 5mol%. The yield was not significantly affected by increasing catalyst
concentration beyond 5mol% (Figure 1.2).
Figure 1.3 and Figure 1.4 shows that magnetic cobalt nanoparticles could be easily extracted out
of the reaction mixture after catalyzing aza- Michael or thia- Michael addition with no loss in
their activity. Figure 1.4 demonstrates that the recycled particles could be used for eight
consequent runs of the same reaction with minimal loss of catalytic activity.
Conclusion
We have previously demonstrated the use of nanoparticles as catalysts in different organic
reactions and in drug delivery17-33. Here, we show that ionic liquid stabilized magnetic and
recyclable cobalt nanoparticles could be employed for upto seven runs in Michael addition
reaction with negligible loss in their activity.
General Procedure for preparation of [bmim]BF4 stabilized cobalt nanoparticles
In a typical procedure 0.01M CoCl2.6H2O in DMSO was taken in a round bottomed flask. The
reaction vessel was immersed in the water bath of an ultrasonicator operating at 33±3 kHz. Equal
volume of 0.05M sodium borohydride solution was added to the same solution drop wise.
Immediately after the reduction was over, 100µl of ionic liquid [bmim]BF4 was added as a
stabilizer to the reaction mixture so that the formed NPs could be immediately capped by electro-
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steric stabilization effects. Ionic liquid [bmim]BF4 stabilized, magnetic cobalt nanoparticles
prepared using chemical reduction method, were isolated by centrifuging at 4000 r.p.m. for 10
minutes. The isolated particles were washed once with ethanol and dried in vacuum for catalytic
purpose. These magnetic cobalt nanoparticles were characterized using DLS, TEM, SEM and
Electron diffraction, EDAX and VSM analysis techniques.
General Procedure for aza-Michael and thia- Michael Additions
1mmole of amine or thiol and 1mmole of activated α,β-unsaturated compound (Michael
acceptor) were stirred together in presence of 5mol% (0.1mmole) of stabilized cobalt
nanoparticles for an appropriate time (Scheme 1). Following the completion of the reaction as
indicated by TLC (Hexane: Ethyl acetate), dichloromethane was added to the reaction mixture
and the cobalt catalyst was recovered by applying a magnetic field and decanting rest of the
reaction mixture into another flask from where solvent was evaporated off and final product was
isolated. Further purification was carried out by column chromatography on silica gel using ethyl
acetate/ petroleum ether as eluent. Structural assignments of the products were done based on
their 1H NMR, 13C NMR and mass spectroscopic analysis.
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Table 1.1: Synthesis of aza-Michael adducts using recyclable cobalt nanoparticlesa.
Michael
Acceptor
Yield
(%)
Entry
1.1.1
Michael Donor
Productb
Time(min)
NH2
H
N
N
30
96
N
o
NH2
NH2
NH2
H
N
40
45
75
95
94
87
1.1.2
1.1.3
1.1.4
O
H
N
o
oMe
O
O
oMe
H
N
o
oBu
oBu
N
H
Me
N
N
N
Me
28
30
40
60
96
97
96
88
1.1.5
1.1.6
1.1.7
1.1.8
H
Me
N
o
N
Me
O
H
Me
o
o
N
N
oMe
Me
O
O
oMe
H
Me
N
N
oBu
N
Me
oBu
N
Me
Me
N
N
N
N
25
28
35
58
28
30
40
70
98
90
87
84
95
94
92
89
1.1.9
1.1.10
1.1.11
1.1.12
1.1.13
1.1.14
1.1.15
1.1.16
Me N
Me N
Me N
Me N
O
N H
N H
N H
N H
o
O
o
o
Me
Me
N
N
N
oMe
O
oMe
N
oBu
O
oBu
N
O
O
N
N
N H
o
N
O
N H
N H
N H
O
o
o
O
O
N
oMe
O
oMe
oBu
O
N
oBu
O
O
9

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aReaction condition: 1mmole of amine 1mmole of activated α, β-unsaturated compound (Michael acceptor) stirred
together in presence of 5mol% of stabilized cobalt nanoparticles b Isolated products characterized using FT-IR, TLC,
1H and 13C NMR
10

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Table 1.2: Synthesis of thia–Michael adducts using recyclable cobalt nanoparticlesa
Yield
(%)
Michael
Donor
Michael
Acceptor
Time
(min)
Entry
1.2.1
Productb
SH
S
N
20
35
45
65
98
96
95
85
95
93
92
80
N
o
SH
SH
SH
SH
S
S
1.2.2
1.2.3
1.2.4
1.2.5
1.2.6
1.2.7
1.2.8
O
OMe
oBu
N
o
oMe
O
S
o
oBu
N
O
S
25
40
CH3
SH
CH3
S
o
O
CH3
SH
CH3
S
OMe
o
o
50
90
O
O
oMe
oBu
CH3
SH
CH3
S
oBu
CH3
CH3
aReaction conditions: 1mmole of thiol and 1mmole of activated α, β-unsaturated compound (Michael acceptor)
b
stirred together in presence of 5mol% of stabilized cobalt nanoparticles. Isolated products characterized using FT-
IR, TLC, 1H and 13C NMR
11

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Figure 1.1: Optimization of size of cobalt nanoparticles over Michael addition reaction.a
aReaction condition: 1mmole of phenylthiol and 1mmole of methylacrylate stirred together in presence of 5 mole%
cobalt nanoparticles for one hour at room temperature and atmospheric pressure. bIsolated pure products
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Figure 1.2: Optimization of concentration of cobalt nanoparticles for Michael addition reaction.a
aReaction condition: 1mmole of phenylthiol and 1mmole of methylacrylate stirred together in presence of cobalt
b
nanoparticles (30±5 nm) for one hour at room temperature and atmospheric pressure. Isolated pure products
13

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Figure 1.3: Reaction mixturea (a) before and (b) after separation of magnetic catalyst by applying
external magnetic field.
aReaction condition: 1mmole of phenylthiol and 1mmole of methylacrylate stirred together in presence of cobalt
nanoparticles (30±5 nm) for one hour at room temperature and atmospheric pressure.
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Figure 1.4: Recyclability of cobalt nanoparticles for Michael addition reaction.a
aReaction condition: 1mmole of phenylthiol and 1mmole of methylacrylate stirred together in presence of cobalt
nanoparticles (30±5 nm, 5mol%) for one hour at room temperature and atmospheric pressure.
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Graphical abstract
Magnetic cobalt nanoparticles, stabilized using ionic liquid [bmim]BF4, have been used for
catalyzing aza- and thia- Michael reactions under environmentally benign conditions. The
catalyst has been efficiently recycled seven times for subsequent reactions by taking advantage
of their magnetic behavior and surface stabilization. The products were isolated in high yields in
short reaction times. The reaction proceeded under mild conditions at room temperature. TEM
analysis of particles, before and after completion of reaction, highlighted the recyclability of the
catalyst over multiple cycles of reaction.
R1
G
R1
[bmim]BF4-Co nanoparticles
+
X
G
R2
R2
G= CN, COMe, COOMe
X= SH or NH
16

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Highlights
1. Magnetic cobalt nanoparticles used to catalyze aza- and thia- Michael reactions.
2. Reaction carried out in environmentally benign conditions at room temperature.
3. Products isolated in high yields, in short reaction times.
4. Catalyst efficiently recycled seven times.
17