One-pot three-component Mannich reaction in water catalyzed by eco-friendly, hydrophobic and recyclable sulfonic acid based nanosilica (SBA-15-Ph-PrSO3H)

Article abstract of DOI:10.1039/c4ra05842a

A mild, effective and green method for the Mannich reaction of aromatic aldehydes, aromatic amines and ketones has been accomplished in good to excellent yields using hydrophobic SBA-15-Ph-PrSO₃H in water at room temperature. This new method consistently has the advantages of excellent yields, short reaction times, and non-toxic nature and reusability of the catalyst. Additionally, utilization of water as a green solvent, simple reaction conditions, isolation, and purification make this manipulation interesting from an environmental perspective. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra05842a

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One-pot three-component Mannich reaction
in water catalyzed by eco-friendly, hydrophobic
and recyclable sulfonic acid based nanosilica
(SBA-15-Ph-PrSO3H)
Cite this: RSC Adv., 2014, 4, 37941
*
Daryoush Zareyee and Hamidreza Alizadeh
A mild, effective and green method for the Mannich reaction of aromatic aldehydes, aromatic amines and
ketones has been accomplished in good to excellent yields using hydrophobic SBA-15-Ph-PrSO3H in water
at room temperature. This new method consistently has the advantages of excellent yields, short reaction
times, and non-toxic nature and reusability of the catalyst. Additionally, utilization of water as a green
solvent, simple reaction conditions, isolation, and purification make this manipulation interesting from an
environmental perspective.
Received 17th June 2014
Accepted 14th August 2014
DOI: 10.1039/c4ra05842a
www.rsc.org/advances
triates34,35 and chlorides,36 Brønsted acids,19,37–41 hydrochloric
acid,21 heteropoly acids42,43 and functionalized ionic liquid.44
Introduction
However, despite the diverse synthetic routes so far developed
for the Mannich reaction, a few one-pot procedures on the use
of unmodied aldehydes or ketones in water have been reported
in the literature. Furthermore, most of the reported Mannich
reactions in water have been carried out using silyl enol ether as
precursor,34–39 or performed in the presence of surfactants such
as sodium dodecyl sulfate.21,38–40 Unfortunately, normal-phase
separation is difficult during workup due to the formation of
emulsions because of the sodium dodecyl sulfate.
Additionally, it is very well known that green chemistry not
only requires the use of environmentally benign reagents and
solvents, but also the recovery and reuse of the catalyst. In this
regard, SBA is highly ordered mesoporous silica structured
The Mannich reaction is one of the most important carbon–
carbon bond forming reactions widely used in the synthesis of
various b-amino ketones, which are versatile synthetic building
blocks for the preparation of amino alcohols, peptides, lactams
and as precursors to synthesize amino acids and many nitrogen-
containing biologically important compounds.1–3 The Mannich
reaction relies on two as well as three component systems, but
the more desirable route is the use of a one-pot three-
component setup.4–6 Accordingly, the development of new
catalytic methods for one-pot three-component Mannich reac-
tion is of prime importance in organic synthesis. Mannich
reactions of aldehydes, ketones and amines have been realized
via Lewis acids,7–16 Lewis base,17 Brønsted acids18–23 and transi-
tion metal salts24–26 approaches. Despite the merits of
these methodologies, problems recycling and reusing of the
catalysts, toxic reagents and solvents, harsh reaction condi-
tions, toxicity or difficulty in product separation remain
concerns. Therefore, the search for new green methods is still
being actively pursued.
On the other hand, because of increasing concerns about
environmental effects, carrying out organic reactions in water
has become highly desirable in recent years.27–33 Apart from
being environmentally friendly, water possesses some unique
properties (such as being non-toxic, available in large quanti-
ties, cheap, non-ammable and non-hazardous) that are
different from other solvents, thus making it a very good reac-
tion medium for organic synthesis. The main catalysts reported
for Mannich reaction in water include Lewis acids such as
˚
materials (20–500 A). The unique physical properties of SBA and
SBA-based materials have made them highly desirable for their
applications. The large pore size allows for xation of large
active complexes, reduces diffusional restriction of reactants,
and enables reactions involving bulky molecules to take place.
The thicker pore walls make them more thermally and hydro-
thermally stable. Additionally, mesoporous materials contain-
ing sulfonic groups which combine a relatively high acid
strength with a large surface area and reactant accessibility, are
promising acid catalysts.45–48
As a continuation of our research work in using SBA-15-Ph-
PrSO3H as a heterogeneous, hydrophobic, and easily recyclable
catalyst in organic synthesis,49–52 and due to the numerous
advantages of using water as a solvent in organic reactions,
herein we wish to report an efficient and green procedure for the
synthesis of b-amino carbonyl compounds in water using SBA-
15-Ph-PrSO3H (Scheme 1).
Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr,
Iran. E-mail: zareyee@gmail.com; Fax: +98 123 214 5050; Tel: +98 123 214 5048
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results of Mannich reaction using hydrophilic catalyst SBA-15-
PrSO3H in water. To test the catalytic capabilities of SBA-15-
PrSO3H, the reaction of benzaldehyde, aniline and acetophe-
none was studied in the presence of 5 mol% SBA-15-PrSO3H in
water. As we expect, SBA-15-PrSO3H appeared to be much less
active than SBA-15-Ph-PrSO3H, affording 5% yield of the desired
b-amino carbonyl compound aer 4 h, while SBA-15-Ph-PrSO3H
gave 92% yield of the same product in 4 h. The greater reactivity
of SBA-15-Ph-PrSO3H is probably due to a synergistic effect
between sufficient hydrophobicity and acidity of siliceous
network. Furthermore, Mannich reaction is very sensitive to
reaction temperature. Although the high temperature could
improve the reaction rate and shorten the reaction time, but
favor side reactions. It was found that the room temperature
was an appropriate condition for Mannich reaction catalyzed
using SBA-15-Ph-PrSO3H.
Subsequently, on the basis of the optimization dosage of the
catalyst, studies focused on the application of SBA-15-Ph-
PrSO3H for different Mannich reactions of various electron-rich
and electron-poor benzaldehydes with different ketones and
amines in water at room temperature. As shown in Table 1, the
results reveal that the SBA-15-Ph-PrSO3H catalysis generally
results in good yields with aromatic aldehydes including those
carrying electron donating- or withdrawing substituents (Table
1, entries 1–6), even when moderately hindered aldehydes were
used (Table 1, entries 7–9), with the advantages of mild reaction
conditions and minimal environmental impact. The reaction
conditions were mild enough not to induce any damage to
moieties like methoxy group (Table 1, entries 10–13) which
oen undergo cleavage in the presence of strong acids or certain
Lewis acids. From the entries 14–16, it could be inferred that,
besides the aromatic ketones, aliphatic ketones could also be
employed to give good yields under the identical reaction
condition.
To show whether the reaction is actually proceeding in a
heterogeneous pathway or whether it is conducting through a
homogeneous manner, another reaction was performed, in
which the reactions of benzaldehyde, aniline and acetophenone
in the presence of SBA-15-Ph-PrSO3H was quenched aer 90
min and ltered off (ꢀ56% conversion). Then the residue was
then subjected to further reaction aer addition of water. We
found that no further catalytic activity was observed aer 3 h,
thus supporting the heterogeneous nature of the reaction.
Having established the viability of this reaction, it was then
decided to investigate reusability of the catalyst in the synthesis
of b-amino carbonyl from benzaldehyde, aniline and aceto-
phenone. Upon completion of the reaction, hot ethanol (30 mL)
was added to the reaction mixture. Aer decantation of
solvents, the fresh substrates and water were added. As shown
in Fig. 1, the recovered SBA-15-Ph-PrSO3H could be directly
reused in seven successive runs without signicant loss of
activity which clearly demonstrates the practical recyclability of
this catalyst. Moreover, the uniformity of highly ordered struc-
ture of SBA-15 aer seven times recovery is conrmed by TEM
images (Fig. 2).
Scheme 1 One-pot Mannich reaction of aldehydes, ketones and
amines catalyzed by SBA-15-Ph-PrSO3H in water at room
temperature.
Results and discussion
On the basis of the information obtained from our previous
studies,49–52 we anticipated that SBA-15-Ph-PrSO3H can be used
as an efficient catalyst for the promotion of the reactions which
need the use of an acidic catalyst to speed up. Additionally, as a
clean and cheap solvent, it is important to carry out Mannich-
type reaction in water for the environmental and economic
reasons. So, since the reactants were insoluble in water, we were
interested to investigate the applicability of this hydrophobic
catalyst in the Mannich reaction in water. Notably, introduction
of organosulfonic acid and hydrophobic phenyl groups into the
channels of SBA-15-Ph-PrSO3H was interesting since the
combination of both functionalities (acidic and hydrophobic)
allows the effectual reaction of organic substrates within the
hydrophobic channels of catalyst in water.
At the outset, for obtaining the optimum reaction condi-
tions, in the initial catalytic activity experiment, a reaction was
carried out using 1 mmol benzaldehyde, 1 mmol aniline, 1
mmol acetophenone and 1 mol% catalyst. These were stirred at
ambient temperature in water. Interestingly, 35% of the related
b-amino carbonyl compound was obtained aer 8 h. Consid-
erable improvement was observed in the yield of the related
product when amount of catalyst increased to 3 mol% (68%
yield aer 6 h) and 5 mol% (92% yield aer 4 h). Besides,
increasing the quantity of catalyst to 7 mol% did not improve
the result to a greater extent. To illustrate the efficiency of the
catalyst, the same reaction was also carried out in the absence of
the catalyst. The reaction was not performed aer a long reac-
tion time. These results indicate that the presence of 5 mol% of
this hydrophobic catalyst is necessary to produce the b-amino
carbonyl compounds in good yields. Then, in order to show the
effect of surface hydrophobicity of the catalyst, we compared the
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Table 1 Synthesis of different b-amino carbonyl compounds in water at room temperature using SBA-15-Ph-PrSO3H as catalyst
Entry
Aldehyde (R1)
Amine (R2)
Ketone (R3)
Product
Time (h)
Yielda (%)
1
4
92
2
3
4
5
6
7
8
9
3.5
92
90
89
90
90
88
90
83
4
4
4
6
6
6
6
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Table 1 (Contd.)
Entry
10
Aldehyde (R1)
Amine (R2)
Ketone (R3)
Product
Time (h)
3.5
Yielda (%)
94
11
12
13
7
7
7
90
89
85
14
15
4
4
91
92
16
5
90
a
Isolated yields.
resulting mixture was ltered to recover the catalyst, and the
ltrate was evaporated off the solvent to give the crude product.
The analytical sample was obtained by recrystallization of crude
product from ethanol. Spectroscopic data for selected examples
listed below.
Experimental section
General procedure for the preparation of b-amino carbonyl
compounds
To the mixture of aldehyde (1 mmol), ketone (1 mmol) and
amine (1 mmol) in 3 mL of water, SBA-15-Ph-PrSO3H (0.03 g, 5
mol%) was added. The mixture was stirred at room temperature
for appropriate time indicated in Table 1 until the reaction was
completed as monitored by thin-layer chromatography. The
1
(Entry 2). H NMR (400 MHz; CDCl3): dH ¼ 2.34 (s, 3H), 3.48–
3.60 (m, 2H), 5.01 (t, 3J ¼ 8 Hz, 1H), 6.64–6.66 (d, 3J ¼ 8 Hz, 2H), 6.73
(t, 3J ¼ 8 Hz, 1H), 7.11–7.20 (m, 3H), 7.35–7.37 (d, 3J ¼ 8.4 Hz, 2H),
7.45–7.49 (t, 2H), 7.57–7.61 (m, 1H), 7.93–7.99 (d, 3J ¼ 8.4 Hz, 2H).
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54.3, 55.3, 114.3, 115.0, 122.4, 127.4, 128.2, 128.7, 128.9, 133.5,
134.4, 136.6, 145.6, 158.8, 198.3.
Conclusions
In conclusion, at room temperature, the direct Mannich reac-
tion of a variety of aromatic aldehydes, anilines and ketones in a
three-component reaction in aqueous media was efficiently
catalyzed by SBA-15-Ph-Pr-SO3H with dual functionality
comprised of both hydrophobicity and acidity properties. The
high yield, reusability of catalyst, operational simplicity and
using water make the present method as potentially green and
useful method in organic synthesis.
Fig. 1 Recyclability of the catalyst SBA-15-Ph-PrSO3H for the Man-
nich reaction of benzaldehyde, aniline and acetophenone after 4 h.
Acknowledgements
The authors acknowledge the Islamic Azad University of
Qaemshahr Research Councils for support of this work.
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1
(Entry 10). H NMR (400 MHz; CDCl3): dH ¼ 3.50–3.58 (m,
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Hz, 2H), 7.57–7.61 (t, 3J ¼ 7.2 Hz, 1H), 7.92–7.94 (t, 3J ¼ 7.2 Hz,
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136.7, 158.9, 198.4.
1
(Entry 11). H NMR (400 MHz; CDCl3): dH ¼ 3.38–3.52 (m,
2H), 3.80 (s, 3H), 4.59 (br, s, 1H), 4.92–4.94 (t, 3J ¼ 6.8 Hz, 1H),
3
6.48–6.51 (d of d, J ¼ 4 Hz, 2H), 6.86–6.89 (m, 2H), 7.03–7.06
(m, 2H), 7.28–7.35 (m, 2H), 7.45–7.49 (m, 2H), 7.57–7.61 (m,
1H), 7.91–7.93 (m, 2H), 13C NMR (100 MHz, CDCl3): dC ¼ 46.3,
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