Nanomagnetically modified sulfuric acid (γ-Fe2O3@SiO2-OSO3H): An efficient, fast, and reusable green catalyst for the Ugi-like Groebke-Blackburn-Bienaymé three-component reaction under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2012.07.075

Superparamagnetic nanoparticles of modified sulfuric acid (γ-Fe₂O₃@SiO₂-OSO₃H) represent a straightforward and green catalyst for the rapid synthesis of aminoimidazopyridine skeletons via the Ugi-like Groebke-Blackburn-Bienaymé three-component reaction. The γ-Fe₂O₃@SiO₂-OSO₃H catalyst could be recovered and reused in five reaction cycles, giving a total TON = 453. The products were prepared under solvent-free conditions without any additives.

Full text of DOI:10.1016/j.tetlet.2012.07.075

Tetrahedron Letters 53 (2012) 5257–5260
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Nanomagnetically modified sulfuric acid ( -Fe2O3@SiO2-OSO3H): an efficient,
c
fast, and reusable green catalyst for the Ugi-like
Groebke-Blackburn-Bienaymé three-component reaction under solvent-free
conditions
Sadegh Rostamnia a, , Kamran Lamei a, Mohsen Mohammadquli b, Mehdi Sheykhan b, Akbar Heydari b
⇑
a Organic and Nano Group (ONG), Department of Chemistry, Faculty of Science, University of Maragheh, PO Box 55181-83111, Maragheh, Iran
b Department of Chemistry, Tarbiat Modares University, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Superparamagnetic nanoparticles of modified sulfuric acid (c-Fe2O3@SiO2-OSO3H) represent a straight-
forward and green catalyst for the rapid synthesis of aminoimidazopyridine skeletons via the Ugi-like
Received 11 April 2012
Revised 18 June 2012
Accepted 18 July 2012
Available online 27 July 2012
Groebke-Blackburn-Bienaymé three-component reaction. The -Fe2O3@SiO2-OSO3H catalyst could be
c
recovered and reused in five reaction cycles, giving a total TON = 453. The products were prepared under
solvent-free conditions without any additives.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Modified sulfuric acid
Magnetically recoverable nanocatalyst
Ugi-like multicomponent reaction
Encapsulated iron oxide nanoparticles
Green chemistry
The ‘greening’ of global chemical processes has became a major
issue in the chemical industry and biology both in terms of selec-
tion of reactions and for the study of solvent and catalyst effects.1
Solvent-free approaches show useful versatility and minimize the
formation of waste.2 On the other hand, the development of new
strategies for recycling catalysts, which minimizes the consump-
tion of auxiliary substances, energy, and time required in achieving
separations can result in significant economic and environmental
benefits.3
Much attention has been directed toward the fabrication of
magnetic nanoparticles because they have both fundamental and
practical values due to their potential applications in chemical
and materials science.4 The strategy of magnetic separation, taking
advantage of magnetic nanoparticles, is typically more effective
than filtration or centrifugation as it prevents loss of the catalyst.4,5
Magnetic separation of supermagnetic nanoparticles is simple,
economical, and promising for industrial applications. From both
economic and environmental viewpoints, organic reactions under
solvent-free conditions using recoverable catalysts have gained
significant attention.5,6
Combinatorial methods using multicomponent reactions
(MCRs) have been closely examined as a convenient solution for
the synthesis of diverse classes of compounds.7,8 Of pivotal impor-
tance in this area are the isocyanide-based MCRs such as the ver-
satile Ugi reactions.9 Aminoimidazo[1,2-a]pyridines, which
represent an important class of pharmaceutical compounds, exhi-
bit a wide spectrum of biological activities.9–11 Several isocya-
nide-based three-component reactions (3-CRs) have been
reported for the synthesis of these compounds by condensation
of an aldehyde, an isocyanide, and 2-aminoazine in the presence
of a Brønsted acid such as AcOH,12 HClO4,13 p-toluenesulfonic
acid,14 cellulose sulfuric acid,15 or Lewis acids such as Sc(OTf)3,16
MgCl2,17 SnCl2,18 ZrCl4,19 and ZnCl2 via the Groebke-Blackburn-
20
Bienaymé reaction (Scheme 1). However, many of these methods
suffer from drawbacks such as low yields of products, long reaction
times, harsh reactions conditions, tedious work-ups leading to the
generation of large amounts of toxic metal-containing waste, the
RHN
Mn+
N
or
H
N
R
N
C
Ph
Ph
NH2
O
conditions
N
N
⇑
Corresponding author. Tel.: +98 (421) 2274893; fax: +98 (421) 2276066.
N
E-mail
addresses:
rostamnia@maragheh.ac.ir,
srostamnia@gmail.com
(S. Rostamnia).
Scheme 1. Ugi-type Groebke-Blackburn-Bienaymé 3-CR.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.075

5258
S. Rostamnia et al. / Tetrahedron Letters 53 (2012) 5257–5260
OSO3H
OSO3H
HO3SO
O
O
O
OH
Fe(II)
+
(EtO)4Si
S
ClSO3H
γ-Fe2O3
calcination
Fe(III)
HO3SO
γ-Fe3O4
OSO3H
γ-Fe2
O @SiO
3
2
O3@SiO2-OSO3H
γ-Fe2
Figure 1. Schematic representation of the procedure for the synthesis of c-Fe2O3@SiO2-OSO3H nanoparticles and its SEM image.
Table 1
Table 4
One-pot synthesis of imidazo[1,2-a]pyridines 4
Study of the solvent and temperature on the model reaction. The bold values selected
as optimum value for next study
γ-Fe2O3@SiO2-OSO3H
Solvent
Temp (°C)
Time (h)
Yield (%)
O
N
(1mol%)
R
H2O
H2O
H2O
EtOH
EtOH
MeOH
CH2Cl2
Solvent-free
Solvent-free
Solvent-free
Solvent-free
rt
rt
50
rt
30
rt
rt
rt
35
rt
35
0.5
1
<10
13
20
<10
20
<10
<10
38
R'
N
C
Ar
Ar
H
solvent-free
35 oC
N
N
1
NH2
R
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
NHR'
4
2
3
a
Product
R
Ar
R0
Timeb (min)
Yieldc (%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
H
H
H
H
C6H5
c-Hex
c-Hex
c-Hex
c-Hex
tBu
c-Hex
c-Hex
c-Hex
c-Hex
tBu
60
45
45
45
60
70
60
60
60
60
70
60
92
94
94
93
90
87
90
90
88
86
85
86
4-NO2-C6H4
4-Cl-C6H4
3-NO2-C6H4
C6H5
64
58
92
1
6-CH3
6-CH3
6-CH3
6-CH3
6-CH3
5-CH3
5-CH3
C6H5
4-Cl-C6H4
3-NO2-C6H4
4-NO2-C6H4
4-NO2-C6H4
C6H5
Table 2
Optimization of the model reaction under solvent-free conditions. The bold values
selected as optimum value for next study
4j
4g
4k
c-Hex
c-Hex
Cat. (mol %)
Temp (°C)
Time (h)
Yield (%)
4-Cl-C6H4
0.5
0.5
1
1
1
1
2
2
2
35
35
rt
0.5
1
0.5
1
1
1
1
1
1
1
58
76
40
53
92
90
58
92
94
62
66
93
a
b
c
c-Hex (cyclohexyl).
Optimized time.
Isolated yield.
rt
35
45
rt
35
50
rt
of new synthetic methods for this purpose remains an attractive
goal.
3
5
5
rt
35
1
1
Recently, we developed methods for the synthesis of biologi-
cally interesting heterocycles via multicomponent reactions.21–28
The challenge in this field was developing efficient and rapid green
methods. Based on our earlier success in the preparation of mag-
netic nanoparticles as catalysts,6,21–23 combined with our achieve-
ments in this area, in this Letter, we present the results of an
extended investigation on the activity of the SO3H functionalized
Table 3
Recyclability study on the synthesis of model compound 4a
Runa
Yield% 4a
1
92
2
93
3
92
4
90
5
86b
magnetic nanocatalyst,21
c-Fe2O3@SiO2-OSO3H, as a green catalyst
a
in Ugi-like Groebke-Blackburn-Bienaymé reactions leading to the
formation of aminoimidazole derivatives without the requirement
for any solvent, salt, or additive. We have developed a synthetic
method for the preparation of 3-aminoimidazo[1,2-a]pyridines
via the three-component condensation of an aldehyde, 2-amino-
Time of the reaction was 60 min.
After 90 min.
b
requirement for an inert atmosphere, and the use of stoichiometric
or relatively expensive reagents.12–20 As a result, the development

S. Rostamnia et al. / Tetrahedron Letters 53 (2012) 5257–5260
5259
γ-Fe2O3@SiO2-OSO3H
N
S
S
N
(1 mol%)
O
NH2
N
C
solvent-free
35 oC, 1 h
N
3
6
2
5
87%
NHCyHex
Scheme 2. The use of
c
-Fe2O3@SiO2-OSO3H for the synthesis of aminoimidazothiazole 6.
To demonstrate the diversity of the
c
-Fe2O3@SiO2-OSO3H nano-
catalyst and to expand the scope of the process, the optimized con-
ditions were applied to a series of substrates 1, 2, and 3 as shown in
Table 4.
OSO3H
N
2
4
Ar
N
Solid Acid
The catalytic activity of
c-Fe2O3@SiO2-OSO3H in the Ugi-like
NR
Groebke-Blackburn-Bienaymé three-component synthesis of an
aminoimidazothiazole was also studied under the optimized con-
ditions. The yield of the designed product 6 was 87% after 1 h
(Scheme 2).
Although we have not established the exact mechanism for this
reaction in the presence of c-Fe2O3@SiO2-OSO3H in an experimental
manner, a possible explanation for the synthesis of 3-aminoimi-
dazo[1,2-a]pyridines 4, based on an isocyanide-based multicompo-
nent reaction12–20,30–32 is proposed in Scheme 3.
SiO2
γ-Fe2O3
H
O3SO
=
N
N
OSO3
H
O
C
Ar
N
1
Ar
R
3
In summary, covalent functionalization of sulfuric acid onto
H2O
O3SO
H
N
N
magnetic
c-Fe2O3@SiO2 nanoparticles has successfully been
achieved. An extensive and systematic study identified
c
-Fe2O3@-
Ar
SiO2-OSO3H as a heterogeneous, green, and reusable catalyst for
the synthesis of aminoimidazopyridines via an Ugi-like (isocya-
nide-based) three-component reaction. A variety of annulated ami-
noimidazoles are accessible under mild conditions using this
method. This rapid, green method in which the catalyst can be
recycled might serve as an interesting alternative to other
synthetic methods. The aminoimidazole products are of potential
synthetic and pharmaceutical interest.
Scheme 3. A plausible mechanism for the Ugi-like MCR using
c-Fe2O3@SiO2-
OSO3H.
pyridine, and an isocyanide using SO3H-functionalized magnetic
iron oxide as the catalyst.
The maghemite nanoparticles (c-Fe2O3, Fig. 1) were synthesized
by a chemical co-precipitation technique using ferric and ferrous
ions.21–23 Based on our previous reports,6,21–23 coating a layer of
Acknowledgment
silica on the surface of the c-Fe2O3 nanoparticles and then func-
We gratefully acknowledge funding support from the Univer-
sity of Maragheh.
tionalization of the iron oxide with a sulfonic acid group were
achieved by treatment with tetraethyl orthosilicate [(EtO)4Si,
TEOS] followed by chlorosulfonic acid (0.60 mmol gꢀ1 –SO3H load-
ing, see Supplementary data).
Supplementary data
In order to investigate the catalytic activity and application of
c
-Fe2O3@SiO2-OSO3H in the Ugi-like multicomponent synthesis
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012. 07.
075.
of imidazopyridines,4,29 we examined its efficiency in a model
reaction between 2-aminopyridine, benzaldehyde, and cyclohexyl
isocyanide. Due to the fact that the solvent may play an important
role in this process, various solvents were screened. The model
reaction was examined in methanol, ethanol, and water using 2%
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c
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