Nanomagnetically modified sulfuric acid (γ-Fe2O 3@SiO2-OSO3H): An efficient, fast, and reusable catalyst for greener Paal-Knorr pyrrole synthesis

Article abstract of DOI:10.1007/s10562-014-1197-5

Paal-Knorr pyrrole synthesis was performed in the presence of superparamagnetic nanoparticles of modified sulfuric acid (γ-Fe ₂O₃@SiO₂-OSO₃H) as an efficient and magnetically separable catalyst. Recovery of the catalyst was simple using a magnet, allowing its reuse without significant loss of its catalytic activity (over five cycles).

Full text of DOI:10.1007/s10562-014-1197-5

Catal Lett
DOI 10.1007/s10562-014-1197-5
Nanomagnetically Modified Sulfuric Acid (c-Fe2O3@SiO2-
OSO3H): An Efficient, Fast, and Reusable Catalyst for Greener
Paal–Knorr Pyrrole Synthesis
•
Samaneh Cheraghi Dariush Saberi
•
Akbar Heydari
Received: 9 December 2013 / Accepted: 15 January 2014
Ó Springer Science+Business Media New York 2014
Abstract Paal–Knorr pyrrole synthesis was performed in
the presence of superparamagnetic nanoparticles of modi-
fied sulfuric acid (c-Fe2O3@SiO2-OSO3H) as an efficient
and magnetically separable catalyst. Recovery of the cat-
alyst was simple using a magnet, allowing its reuse without
significant loss of its catalytic activity (over five cycles).
[17], xanthan sulfuric acid [18], zirconium phosphonate [19],
and BiCl3/SiO2 [20]. Ultrasonic [21] or microwave irradia-
tion [22] method for this purpose has been reported too.
Recently deep eutectic solvents were used for the Paal–Knorr
reactions [23]. Apart from the high temperatures, prolonged
reaction times and tedious work-up, difficulty in separating
the catalyst from the reaction mixture as well as recycling of it
is the main disadvantage of almost all previously reported
methods. Thus, green, efficient, and easily recyclable cata-
lytic systems are still required for this reaction.
Keywords Superparamagnetic nanoparticles Á Paal–
Knorr pyrrole synthesis Á Sulfuric acid Á Magnetically
separable catalyst Á Reusability
With the appearance of magnetic nanoparticles and their
entrance into the catalyst field, the difficulty in separation of
catalyst from the reaction mixture was greatly improved.
Therefore the design of catalytic systems based on magnetic
nanoparticles became a hot topic in the field of organic syn-
thesis [24]. The main feature of magnetic nanoparticles is that
by applying an external magnetic field, they can be dispersed
or aggregated which allows for the facile separation and
recyclingofimmobilizedcatalystsonthenano-sizedsupports.
We have reported the preparation of c-Fe2O3@SiO2-
OSO3H and its application as a highly efficient and mag-
netically separable catalyst for the synthesis of aminoimi-
dazopyridine skeletons [25]. In continuation of our interest
in using magnetic nanoparticles as a catalyst support [26–
29], herein we report a green and environmentally benign
catalytic system based on a magnetic support for the
preparation of pyrrole derivatives via condensation reac-
tion of 2,5-hexanedione with amines.
1 Introduction
An important class of heterocyclic compounds are pyrroles.
They have different biological activity and show broad
applications in the field of medicine and drug [1, 2]. More-
over, the pyrrole moiety is found in many naturally occurring
compounds [3]. Although in recent years a variety of methods
have been developed for the synthesis of pyrroles, the Paal–
Knorr synthesis remains the most useful preparative method.
To date, numerous homogeneous and heterogeneous catalytic
system have been used to promote the reaction of 2,5-hex-
anedione with amines such as UO2(NO3)Á6H2O [4], Nano
sulfated zirconia [5], [HMIM]HSO4 ionic liquid [6], p-TSA
[7], SbCl3/SiO2 [8], K10 [9], montmorillonite KSF [10],
Sc(OTf)3 [11], Silica sulfuric acid [12], Bi(NO3)3ÁH2O [13],
Vitamin B1 [14], RuCl3 [15], PS/GaCl3 [16], SnCl2ÁH2O
S. Cheraghi Á D. Saberi Á A. Heydari (&)
Chemistry Department, Tarbiat Modares University,
P. O. Box 14155-4838, Tehran, Iran
2 Results and Discussion:
As shown in Scheme 1, the synthesis of 2,5-dimethyl-N-
phenyl pyrrole was chosen as our model reaction to opti-
mize the reaction conditions.
e-mail: heydar_a@modares.ac.ir
D. Saberi
e-mail: dariush.saberi@modares.ac.ir
123

S. Cheraghi et al.
O
NH2
Generally speaking, different derivatives of aniline and
benzyl amine were well coupled with 2,5-hexanedione to
give the corresponding pyrrole. Among these derivatives,
4-methoxy benzyl amine was the fastest response (Table 2,
entry 8). In contrast, for chlorinated aniline derivatives the
reaction time was longest (Table 2, entries 9 and 10). The
reaction conditions were also used to di-amino substrates,
in giving bipyrrole compounds in good yields (Table 2,
entries 11–14 and 16).
-
γ
-
Fe
H
O
SiO OSO3
@
2
3
2
+
N
O
solvent-free
60 C
O
,
Scheme 1 Synthesis of 2,5-dimethyl-N-phenyl pyrrole
The first reaction was performed in CH2Cl2 as solvent,
in the presence of 20 mg of catalyst, and at room tem-
perature. After 10 h of reaction time, only 40 % of product
was found (Table 1, entry 1). To improve the efficiency of
the reaction, first, the solvent effect was investigated. To
this end, some organic solvents as well as solvent-free
conditions was examined (Table 1, entries 2–5) and as can
be seen in this table, in solvent-free condition the reaction
proceeded more efficiently than with other solvents. By
increasing the amount of the catalyst to 30 mg, no differ-
ence was made in the reaction yield. On the contrary, the
reduction in catalyst loading to 10 mg gave rise to a sig-
nificant drop of yield (Table 1, entries 6 and 7). Finally, the
role of the temperature was probed. It was observed that
increasing the temperature to 60 °C enhances the yield by a
significant amount. By elevating the temperature up to
80 °C, the yield remained unchanged (Table 1, entries 8
and 9). After passing 24 h of reaction time in the absence
of catalyst, a 90 % efficiency was obtained which it indi-
cates that the presence of catalyst is essential for increasing
the reaction rate (Table 1, entry 10).
The reusability of the catalyst was also tested in the
reaction between 2,5-hexanedione and aniline. When the
stirring was stopped, CH2Cl2 was add to the reaction. Then,
the catalyst was adsorbed onto the surface of the stir bar.
The nanoparticles were then washed with H2O and Et2O
respectively, air-dried and used directly for the next reac-
tion without further purification. The c-Fe2O3@SiO2-
OSO3H nanoparticles could be recovered and reused five
times without any significant loss of catalytic activity
(Fig. 1).
3 Experimental
3.1 Catalyst Preparation
The maghemite (c-Fe2O3) nanoparticle was synthesized by
a chemical co-precipitation technique of ferric and ferrous
ions in alkali solution [25c]. FeCl2Á4H2O (1.99 g) and
anhydrous FeCl3 (3.25 g) were dissolved in water (20 mL)
separately, followed by the two iron salt solutions being
mixed under vigorous stirring (800 rpm). A NH4OH solu-
tion (0.6 M, 200 mL) was then added to the stirring mixture
at room temperature, immediately followed by the addition
of a concentrated NH4OH solution (25 %, w/w, 30 mL) to
maintain the reaction pH between 11 and 12. The resulting
black dispersion was continuously stirred for 1 h at room
temperature and then heated to reflux for 1 h to yield a
brown dispersion. The magnetic nanoparticles were then
purified by a repeated centrifugation (3,000–6,000 rpm,
20 min), decantation, and redispersion cycle three times,
until a stable brown magnetic dispersion (pH 9.4) was
obtained. Coating of a layer of silica on the surface of the
c-Fe2O3 nanoparticles was achieved by premixing (ultrasonic)
a dispersion of the purified nanoparticles (8.5 %, w/w,
20 mL) obtained previously with methanol (80 mL) for 1 h
at 40 °C. Concentrated ammonia solution as added, and the
resulting mixture was stirred at 40 °C for 30 min. Subse-
quently, tetraethyl orthosilicate (TEOS, 1.0 mL) was
charged to the reaction vessel, and the mixture was contin-
uously stirred at 40 °C for 24 h. The silica-coated nano-
particles were collected by a permanent magnet, followed
by washing three times with EtOH, diethyl ether and drying
at 100 °C in vacuum for 24 h.
Therefore, the optimum conditions for this reaction were
as follows: 20 mg of catalyst at 60 °C under solvent-free
condition. Having established optimum conditions, a series
of pyrroles was synthesized by reacting various amines
with 2,5-hexanedione in the presence of c-Fe2O3@SiO2-
OSO3H in order to showcase the broad scope and gener-
ality of this method.
Table 1 Results of screening the conditions
Entry
Solvent
Catalyst
(mg)
Temp.
(°C)
Time
(h)
Yield
(%)a
1
2
CH2Cl2
20
20
20
20
20
30
10
20
20
–
r.t
r.t
r.t
r.t
r.t
r.t
r.t
60
80
60
10
10
10
10
5
40
55
20
25
70
70
50
90
90
90
CH3OH
3
n-Hexane
4
Toluene
5
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
6
5
7
5
8
3
9
3
10
24
Reaction conditions: 2,5-hexanedione (0.5 mmol), aniline (1 mmol)
a
Isolated yield
123

Nanomagnetically Modified Sulfuric Acid
Table 2 Preparation of various
pyrroles in the presence of
c-Fe2O3@SiO2-OSO3H
Entry
Amine
Product
Time(h)
3
Yield(%)a
90
NH2
N
1
2
3
4
NH2
N
3
3
3
88
89
90
NH2
MeO
N
MeO
NH2
N
NH2
Br
N
5
3
78
Br
NH2
N
6
7
5
80
88
NH2
N
0.5
NH2
N
8
15 min
80
MeO
MeO
Cl
Cl
NH2
N
9
12
12
78
78
NH2
N
10
Cl
Cl
NH2
NH2
N
NH2
11
12
3
3
75
70
N
N
NH2
N
NH2
N
N
N
13
14
3
4
72
60
H2N
H2N
N
NH2
N
NH2
15
16
2
2
90
90
Reaction conditions: 2,
5-hexanedione (0.5 mmol),
amine (1 mmol), catalyst
(20 mg), 60 °C
H2N
N
N
NH2
a
Isolated yield
Chlorosulfonic acid (1 g) was added drop-wise at
room temperature (over 15 min) to a suspension of 1 g
c-Fe2O3@SiO2 in Et2O (50 mL) while dispersed by sonica-
tion. The mixture was stirred for 5 h and then concentrated
and the residue was washed three times with Et2O, air-
dried to obtain c-Fe2O3@SiO2-OSO3H. The loading of
impregnated acid measured by back titration
(0.60 mmol g-1).
123

S. Cheraghi et al.
2925, 2855, 1650, 1572, 1518, 1407, 1343, 1038; 1H NMR
(250 MHz, CDCl3) d 2.11(s, 6H, 2CH3), 5.03 (s, 2H, CH2),
5.89 (s, 2H, pyrrolics), 6.24 (d, 1H, J = 7.0 Hz, CH of
3
Ar), 7.10–7.21 (m, 2H, 2CH of Ar), 7.37 (d, 1H,
3J = 7.25 Hz, CH of Ar); MS (EI, 70 eV): m/z (%) = 219
(M?, 22), 125 (50), 91 (100).
3.2.1.4 1-(4-Chlorophenyl)-2,5-dimethyl-1H-pyrrole
(Table 2, entry 10) Isolated yield = 78 %; yellow oil;
IR cm-1: 2925, 2880, 1653, 1490, 1405, 1349, 1092, 1016;
1H NMR (250 MHz,CDCl3) d 2.17 (s, 6H, 2CH3), 5.01
(s, 2H, CH2), 5.92 (s, 2H, pyrrolics), 6.85 (d, 2H,
3J = 8.25 Hz, 2CH of Ar), 7.30 (d, 2H, 3J = 8.50 Hz, CH
of Ar); MS (EI, 70 eV): m/z (%) = 219 (M?, 67), 127 (85),
89.(100).
Fig. 1 Reusability of the c-Fe2O3@SiO2-OSO3H catalyst in the
synthesis of 2,5-dimethyl-N-phenyl pyrrole. Reaction time 3 h
3.2 General Procedure for the Synthesis of Pyrroles
To a solution of amine (1 mmol) and 2,5-hexanedione
(0.5 mmol) at 60 °C, c-Fe2O3@SiO2-OSO3H (20 mg) was
added. The mixture was allowed to stirring at this tem-
perature for a period time specified in Table 2. The reac-
tion was monitored by TLC (8:1 hexane/EtOAc). After
completion of the reaction, 10 mL CH2Cl2 was added and
catalyst was removed by using an external magnet. Evap-
oration of the solvent under reduced pressure gave the
products. Further purification was achieved by thin layer
chromatography using n-hexane/EtOAc as the solvent
system to afford the pyrroles. For all known pyrroles, the
spectral data matched that reported in the literature, while
for the new pyrroles, the spectral data was consistent with
the anticipated product.
4 Conclusion
In conclusion, we have shown that sulfonic acid supported
on magnetite nanoparticles can act as a novel, effective and
heterogeneous catalyst for the one-pot synthesis of pyrroles
from commercially available starting materials. Various
amines were condensed with 2,5-hexanedione to give the
corresponding products in high yields. Recovery of the
catalyst was simple using a magnet, allowing its reuse
without significant loss of its catalytic activity (over five
cycles).
Acknowledgments The authors would like to acknowledge finan-
cial support provided by Tarbiat Modares University for carrying out
this research.
3.2.1 Spectral Data for New Compounds:
3.2.1.1 1-(3,4-Dimethylphenyl)-2,5-dimethyl-1H-pyrrole
(Table 2, entry 4) Isolated yield = 90 %; yellow oil; IR
cm-1: 2924, 2859, 1614, 1506, 1452, 1411, 1340, 1020; 1H
NMR (250 MHz,CDCl3) d 2.01(s,6H, 2CH3), 2.28 (s, 3H,
CH3), 2.30 (s, 3H, CH3) 5.87 (s, 2H, pyrrolics), 6.91 (s, 1H,
CH of Ar), 6.91–6.96 (m, 2H, 2CH of Ar), 7.18 (d, 1H,
3J = 7.7 Hz, CH of Ar); MS (EI, 70 eV): m/z (%) = 199
(M?, 100), 143 (7), 83.(34).
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123

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