A novel mesoporous silica-grafted organocatalyst for the Michael addition reaction, synthesized via the click method

Article abstract of DOI:10.1039/c0gc00788a

An efficient and recyclable mesoporous silica-grafted bifunctional acid-base organocatalyst for the Michael addition of ketones to β-nitrostyrenes has been synthesized by click chemistry, affording the products with excellent diastereoselectivity. A remar

Full text of DOI:10.1039/c0gc00788a

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COMMUNICATION
A novel mesoporous silica-grafted organocatalyst for the Michael addition
reaction, synthesized via the click method†
Suman L. Jain,*a Arindam Modakb and Asim Bhaumik*b
Received 9th November 2010, Accepted 23rd December 2010
DOI: 10.1039/c0gc00788a
An efficient and recyclable mesoporous silica-grafted bi-
functional acid–base organocatalyst for the Michael ad-
Introduction
The utilization of organic compounds as catalysts, an area
dition of ketones to b-nitrostyrenes has been synthesized
termed ‘organocatalysis’,1 has become an area of tremendous
by click chemistry, affording the products with excellent
importance, and a significant amount of research has been
carried out in this direction in the last few years.2 Unlike
conventional metal-based catalysts, organocatalysts offer a
number of advantages, such as little or no activation, ease of
diastereoselectivity. A remarkable enhancement in the reac-
tion rates could be observed with respect to the correspond-
ing monofunctional organocatalyst.
functionalization, absence of the possibility of metal leaching,
reduced toxicity and simple reaction conditions. Therefore,
designing novel metal-free organocatalysts for organic reactions
is a key aspect of achieving the aim of sustainable chemical
synthesis.
aChemical Sciences Division, Indian Institute of Petroleum (Council of
Scientific & Industrial Research), Dehradun, 248005, India.
Immobilization of homogeneous catalysts is another impor-
tant goal, which helps in minimizing the environmental hazards
caused by homogeneous catalysts.3 Among various methods
such as ion exchange, physical adsorption, dipolar attraction
and covalent attachment of the species containing the active
sites to solid supports, the latter has been established as the
most efficient, since it prevents leaching, as well as enabling
better catalyst recycling.4 However, this approach often requires
multi-step reaction procedures, excess reagents and extreme
conditions, which causes decomposition of the catalyst or
ligand, either due to the properties of the inorganic support
or the harsh reaction conditions used for immobilization.
Ordered mesoporous materials5–8 synthesized in the presence
of supramolecular assemblies of surfactant molecules have been
utilized extensively as supports for immobilizing catalytically
active centers, due to their exceptionally high surface area and
tunable pore width, which favors easy diffusion of the substrate
E-mail: suman@iip.res.in; Fax: +91 135-2660202; Tel: +91 135-2525901
bDepartment of Materials Science, Indian Association for the Cultivation
of Science, Jadavpur, Kolkata, 700 032, India. E-mail: msab@iacs.res.in
† Experimental details: General: All commercially available substrates
and solvents were used as received. The melting points were deter-
mined in open-capillaries on a Buchi apparatus and are uncorrected.
The IR spectra were recorded on a Perkin-Elmer FT-IR X 1760
instrument. Elemental analyses were carried out using ASTM D-
3828 (Kjeldhal method). X-ray diffraction patterns were obtained by
a Bruker AXS D8 Advanced SWAX diffractometer using Cu Ka
(l = 0.15406 nm) radiation. Nitrogen adsorption–desorption isotherms
were obtained using a Bel Japan Inc. Belsorp-HP at 77 K. A JEOL
JEM 6700F field emission scanning electron microscope was used for
the determination of morphology of the particles. FT IR spectra of
these samples were recorded using a Nicolet MAGNA-FT IR 750
Spectrometer Series II. GC analyses were performed on Varian CP 3800
Gas Chromatograph for the identification of the reaction products.
Preparation of azide-functionalized SBA-15 (SBA-N3):10a 3-
Chloroproyl-functionalized mesoporous silica (1 g) was added to
the saturated solution of sodium azide (50 mL) in dry DMF. The
resulting mixture was stirred at 90 ◦C for 3 h. The material was filtered
off and soxhlet-extracted in ethanol for 24 h. The obtained material
was dried at 60 ◦C for 12 h. Elemental analysis (%):N, 2.18; C, 1.92; H,
1.21 Loading: 0.52 mmol N3 g-1 as determined by the value of nitrogen
content and TGA analysis. Immobilization of the three ponytailed
compound 2 to the silica support by click reaction: Stirring of the mixture
containing SBA-N3 3 (2 g. 0.52 mmol g-1), three ponytailed compound 2
(0.15 g, 0.5 mmol), CuI (5 mol%), triethylamine (0.25 ml, excess 5 mmol)
in dry DMF (15 ml) under nitrogen for 24 h at room temperature
to yield silica immobilized three ponytailed material 4. The prepared
material 4 was thoroughly washed with DMF, dichloromethane and
dried under vacuum. To check the Cu-coordination with triazole
moieties, we performed Cu-analysis by ICP-AES – no copper was
observed, indicating the absence of copper and thus precluding its
role in the catalytic reaction. Elemental analysis of compound 4 gave
N (1.85%); C (5.2%); H (1.12%). Heating of 3 with 4-aminopyridine
in a 1 : 1 molar ratio in DMF for 5–6 h gave a quantitative yield of
silica-immobilized pyridinium salts 1. Elemental analysis (%): N, 1.69,
C, 3.75, Cu, 0. Loading: 0.11 mmol g-1 as determined by the value of
nitrogen content in elemental analysis. General experimental procedure
for Michael addition: To a mixture of nitroalkenes (0.5 mmol) and
catalyst 1 (0.05 mmol, 10 mol%) was added ketone (2.5 mmol), and the
resulting suspension was vigorously stirred at 40–50 ◦C. The progress
of the reaction was monitored by TLC (silica gel). After completion,
the catalyst was separated by filtration, washed with CH2Cl2, dried
and used as such for subsequent runs. The combined organic layer was
dried over anhydrous Na2SO4, concentrated under reduced pressure,
and purified by flash column chromatography. The isolated yields of the
products are mentioned in Table 1. The diastereoselectivity (syn/anti
ratio) of the products was determined by GC analysis.
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and product molecules during the reaction. Thus, organic
catalytically active centers can be grafted onto functionalized
mesoporous surfaces through covalent bonding, potentially
opening up applications of these organic–inorganic hybrid
materials in catalytic reactions.
[3+2] Azide–alkyne cycloaddition,9 termed the ‘click’ reaction
due to its simplicity, fidelity, high conversion, absence of side
products and mild reaction conditions, has proven to be an
efficient approach for the assembly of functionalized organic
molecules. Recent work has described many applications of this
approach in the field of bioactive molecules/supported reagents
and catalysts,10 but there are relatively few reports from the field
of organocatalysis.11
Fig. 1 Mesoporous silica-supported organocatalysts 1.
of ketones to aryl-substituted nitroolefins. Excellent yields and
high diastereoselectivities of nitroalkanes are obtained, under
mild solventless reaction conditions.
Results and discussion
The Michael addition of ketone nucleophiles to b-nitroolefins
represents an important transformation, since the resulting g-
nitro ketones are valuable synthons in the synthesis of highly
useful building blocks in organic synthesis.12 Organocatalytic
approaches, in particular immobilization of organocatalysts, are
gaining ever-increasing interest due to the continuously growing
demand for green chemical synthesis. In this context, Tuchman-
Shukrona13 reported a bifunctional organocatalyst, possessing
both acidic (H-bond donating) and basic (nucleophilic) moieties
for Michael addition. Alza et al.14 reported a highly selective
polystyrene-supported organocatalyst for Michael additions.
However, this method involves a multistep catalyst synthesis,
longer reaction times and the use of additives. Zhao et al.15
describes the use of silica-supported pyrrolidine-triazoles pre-
pared by click chemistry for the Michael addition of ketones to
nitroolefins. However, the time-consuming multistep synthetic
procedure and the long reaction times (72 h) certainly provide
scope for developing an efficient organocatalyst for this reaction.
In this paper we wish to report a novel silica-supported bi-
functional acid–base organocatalyst 1 (Fig. 1), synthesised using
click chemistry, which efficiently catalyzes the Michael addition
Catalyst preparation and characterization
The synthetic pathway for the preparation of silica-supported
organocatalyst 1 is shown in Scheme 1. 3-Azidopropyl-
functionalized mesoporous silica 3 (4 mol%), prepared following
the literature procedure,10a was used as the support. The other
coupling partner 2 was readily prepared by the reaction of
3,4,5-trihydroxybenzyl chloridewith propargyl bromide under
basic conditions. Subsequently, the Cu(I)-catalyzed [3+2] cy-
cloaddition of azido-functionalized mesoporous silica support
3 with 2 (‘click’ conditions) resulted in the formation of silica-
supported organocatalyst 4. The loading of catalyst 4 was found
to be 0.15 mmol g-1, as determined by the nitrogen content
(1.85%) in the elemental analysis. Subsequently, the reaction
of 4 with 4-aminopyridine in a 1 : 1 molar ratio readily gave
mesoporous silica-supported organocatalyst 1. The possibility
of the synthesis of dimeric species during this step (Scheme 1)
could not be ruled out completely. Therefore, the heterogeneous
material synthesized for use in catalytic reactions may be a
mixture of monomeric and dimeric formst.
Scheme 1 Synthesis of organocatalyst 1.
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Table 1 Michael addition reactions under different reaction
The powder X-ray diffraction pattern for mesoporous silica-
supported organocatalyst 1 is shown in Fig. S1†. This reveals
that the organocatalyst has a highly ordered 2D-hexagonal
mesophase, with three strong reflections corresponding to the
(100), (110) and (200) planes.7 The unit cell parameter (a0)
for this functionalized organocatalyst was ca. 11.1 nm. All the
samples retained their mesostructures after the immobilization
of the organocatalyst at the mesopore surface by the three func-
tionalization reactions shown in Scheme 1. The N2 adsorption–
desorption isotherms of 1 are shown in Fig. S2†. These
isotherms, classified as type IV, are characteristic of materials
with large mesopores.8 A sharp increase in N2 uptake for
adsorption is observed at P/P0 = 0.6–0.76, together with a large
hysteresis, characteristic of a SBA-15 type material.8j The pore
size distribution of these samples was estimated by employing
the NLDFT method (inset of Fig. S2), suggesting a peak pore
width of ca. 4.35 nm. A considerably smaller pore width of 1
relative to the SBA-15 host suggested functionalization on the
internal pore surface. The BET surface area of immobilized
catalyst was 336 m2 g-1, and the pore volume was 0.5 cm3 g-1.
The FE SEM image of 1 is shown in Fig. S3†. This figure
indicates that the material is mainly composed of bar-like
particles 1–1.5 nm long. Some fine particles of diameter 0.1 nm
can also be seen. The small particle size of our immobilized
catalyst could be helpful for easy diffusion of reagents during
the catalytic reactions. The covalent bonding in 1 was evident
from the FTIR spectroscopic result, wherein a remarkable
reduction in the intensity of the frequency of the azido band
(ca. 2100 cm-1) was observed (Fig. S4†). The presence of Si–
OH stretching at ca. 956 cm-1 in this FTIR spectrum due to
the surface silanol groups of the mesoporous support further
supports the immobilization of organocatalyst 1. The loading of
the organocatalysts was found to be 0.11 mmol g-1, as calculated
by the nitrogen content (1.69%) obtained by elemental analysis
(considering the predominant formation of 1a).16
conditionsa
Entry Solvent Catalyst
T (◦C) Yield (%)b dr (syn/anti)c
1
2
3
4
5
6
7
8
CH3CN 1
40
40
40
40
40
40
40
86
Trace
20
65
98
—
82
30
75
82 : 12
—
96 : 4
95 : 5
97 : 3
—
95 : 5
96 : 4
94 : 6
95 : 5
97 : 3
CHCl3
Toluene
H2O
—
—
—
1
1
1
1
3
4
—
4-Aminopyridine 40
9
10
11
—
—
—
5
6
1
40
40
25
92
68
a Reaction conditions: cyclohexanone (2.5 mmol), b-nitrostyrene
(0.5 mmol), catalyst (10 mol%), 24 h. b Isolated yields. c Calculated by
1H NMR.
the catalytic activity of the silica-supported monofunctional
organocatalyst 4 was found to be poorer than catalyst 1 under
similar reaction conditions (Table 1, entries 6 and 7). Similarly,
the use of the homogeneous catalyst 4-aminopyridine afforded
a very poor yield of the desired product (Table 1, entry 8). An
immobilized organocatalyst 5 prepared by the reaction of 4-
aminopyridine with 3-chloropropyl SBA-15 was also found to
be a poor catalyst for this reaction (Table 1, entry 9).
We also synthesized the SBA-supported free amine 6 by
treating 1 with a solution of Na2CO3, and studied its catalytic
activity. The prepared material showed slightly lower catalytic
activity than 1 under similar reaction conditions (Table 1, entry
10). These findings established the superiority of the catalyst 1,
which benefits from the triazole rings being present on its surface
due to the click reaction. The reaction was mainly dependent
on the base used, the yield of the product increasing with the
amount of the base, as presented in Table 1 (entries 5, 7, 8 and
10). Moreover, no reaction occurred between cyclohexanone and
b-nitrostyrene in the absence of any base. As shown in Table 1
(entries 5 and 10) the effect of the protonated species (catalyst 1
vs. 6) was found to be minor, and provided comparable yields of
product (98 vs. 92%, respectively). A◦lso, the reaction was found
to be slow at room temperature, 40 C being optimum for this
reaction (Table 1, entry 11).
Catalytic activity for Michael addition
The catalytic efficiency of the organocatalyst 1 was examined
for the Michael addition of ketones 7 to b-nitrostyrenes 8 under
solvent-free conditions (Scheme 2).
To establish the generality of the protocol, we carried out
the Michael addition reaction of a variety of ketones 7 and b-
nitroalkenes 8 in the presence of catalyst 1 (10 mol%) at room
temperature under similar conditions. The results of these exper-
iments are presented in Table 2. Aromatic b-nitroalkenes, sub-
stituted with either electron-donating or electron-withdrawing
groups, reacted efficiently with cyclic ketones, and provided good
product yields with high diastereoselectivities (syn/anti > 85 : 1).
In contrast, the reaction of aliphatic nitroalkenes (Table 2, entry
11) was found to be very slow, yielding only trace amounts of the
product along with unidentified by-products. Among the cyclic
ketones used, cyclohexanone was found to be more reactive than
cyclopentanone. However, aliphatic ketones such as acetone
(Table 1, entry 10) gave comparable results to cyclohexanone
under the reaction conditions used.
Scheme 2 Michael addition reaction.
Initially, organocatalyst 1 (10 mol%, 0.05 mmol) was added
to a mixture of cyclohexanone (2.5 mmol) and b-nitrostyrene
(0.5 mmol), and the resulting mixture stirred vigorously at 40 ◦C
under solventless conditions. The reaction was found to proceed
efficiently, and afforded an excellent yield (98%) of the Michael
adduct, with high diastereoselectivity towards the syn-adduct
(syn/anti ratio 97 : 3). It is interesting to note that adding a
solvent (acetonitrile, toluene, dichloromethane, water) had an
adverse effect, giving a poor yield of product (Table 1, entries
1–4). When mesoporous silica support 3 was used, no reaction
between cyclohexanone and b-nitrostyrene occurred, whereas
In order to establish the recyclability of the catalyst 1, the
reaction of cyclohexanone and b-nitrostyrene were studied
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Table 2 Michael addition using catalyst 1a
Entry
1
Ketone 7
Nitroalkene 8
Product 9
Time (h)
24
Yield (%)b
98
dr (syn/anti)c
97 : 3
2
20
99
98 : 2
3
4
20
24
98
88
99 : 1
96 : 4
5
6
24
30
84
92
98 : 2
92 : 8
7
30
97
99 : 1
8
9
20
24
72
65
87 : 13
88 : 12
10
11
18
60
94
—
—
Trace
a Reaction conditions: nitroalkene (0.5 mmol), ketone (2.5 mmol), catalyst (10 mol%, 0.05 mmol) at 40 ◦C. b Isolated yield. c Determined by GC.
d Using acetonitrile (5 ml) as solvent. e Using 4 as the catalyst.
under similar reaction conditions. After completion of the
reaction, the catalyst was separated by filtration, washed with
dichloromethane, dried at room temperature and reused in five
additional experiments. In all cases, silica-supported organocat-
alyst 1 exhibited consistent catalytic activity and provided
similar product yields with high diastereoselectivity, establishing
the recycling and reusability of the catalyst without further
activation or adding further catalyst (Table 3). Furthermore,
to check the leaching of the organic group from the support, the
supported catalyst 1 was added to dichloromethane and stirred
at room temperature for 24 h. The catalyst was then separated
by filtration, and the filtrate treated with cyclohexanone and
b-nitrostyrene for 2 days at room temperature. No reaction
occurred, establishing that no leaching had taken place during
the course of the reaction, and therefore the reaction was truly
heterogeneous in nature.
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Table 3 Recycling studies of silica-supported catalyst 1 in the Michael
reaction of cyclohexanone with b-nitrostyrene
Enantioselective Organocatalysis, Wiley-VCH, Weinheim, Germany,
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Run
Yield (%)
dr (syn/anti)
1
2
3
4
5
6
98
98
98
96
97
97
97 : 3
97 : 3
96 : 4
97 : 3
95 : 5
97 : 3
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Conclusions
In summary, we have developed a novel mesoporous silica-
grafted bifunctional acid–base organocatalyst 1 using an azide–
alkyne click reaction. This organocatalyst showed excellent
catalytic activity for the Michael reaction of ketones to ni-
troolefins, affording high yields with excellent diastereoselec-
tivities. Organocatalyst 1 was found not only to be superior
to the corresponding monofunctional organocatalyst, but also
enhanced the reaction rates significantly as a result of the triazole
moieties being present. The ease of catalyst synthesis, efficient
recycling, and mild reaction conditions are other key advantages
of this methodology.
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Acknowledgements
We thank the referee for their valuable suggestions in the
discussion of the results of this study.
Notes and references
14 E. Alza and M. A. Pericas, Adv. Synth. Catal., 2009, 351, 3051.
15 Y.-B. Zhao, L.-W. Zhang, L.-Y. Wu, X. Zhong, R. Lia and J.-T. Ma,
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16 The calculated loading of the organocatalyst 1 on the mesoporous
silica starting from the azido-functionalized support (0.52 mmol g-1)
was found to be 0.15 mmol g-1.
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