Rice-husk-supported FeCl3 nano-particles: Introduction of a mild, efficient and reusable catalyst for some of the multi-component reactions

Article abstract of DOI:10.1016/j.crci.2013.02.019

Rice-husk-supported FeCl₃ nano-particles (FeCl3-RiH) were prepared and used as an environmentally friendly catalyst in the synthesis of b-amino carbonyl compounds, 1,8- dioxo-octahydro xanthenes, and bis-indolyl methanes from simple and readily available precursor molecules.

Full text of DOI:10.1016/j.crci.2013.02.019

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CRAS2C-3725; No. of Pages 11
C. R. Chimie xxx (2013) xxx–xxx
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Full paper/Memoire
Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions
*
Farhad Shirini , Somayeh Akbari-Dadamahaleh, Ali Mohammad-Khah
Department of Chemistry, College of Science, University of Guilan, Rasht, 41335, Islamic Republic of Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
Rice-husk-supported FeCl3 nano-particles (FeCl3–RiH) were prepared and used as an
Received 11 January 2013
Accepted after revision 25 February 2013
Available online xxx
environmentally friendly catalyst in the synthesis of
b-amino carbonyl compounds, 1,8-
dioxo-octahydro xanthenes, and bis-indolyl methanes from simple and readily available
precursor molecules.
´
ß 2013 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Keywords:
FeCl3
Rice husk supported FeCl3 nanoparticles
b-amino carbonyl compounds (BAC)
1,8-dioxo-octahydro xanthenes (DOX)
Bis-indolyl methanes (BIM)
1. Introduction
xanthenes and bis-indolyl methanes from simple and
readily available precursor molecules. All of these com-
Recently, multi-component reactions (MCRs) have been
paid much attention by synthetic organic chemists from all
over the world because the building of architecturally
complex molecules with diverse ranges of complexity can
easily be achieved from available starting materials. In
most of the cases, a single product was obtained from three
or more different substrates by reacting in a well-defined
manner through MCRs. These time-efficient reactions are
environmentally benign and atom economic [1,2]. MCRs
are cost-effective since the expensive purification process-
es as well as the protection-deprotection steps are non-
existent [3]. The synthesis of heterocycles, using MCRs, is a
domain of classical carbonyl condensation chemistry.
One of the important goals in organic chemistry is the
development of new methodologies for the synthesis of
functionalized biologically active compounds with struc-
pounds have various medicinal and pharmaceutical
activities [4–8].
Among the various methods for the synthesis of
b-
amino carbonyl compounds, Mannich-type reaction con-
stitutes a method of choice in many cases due to its
versatility. Numerous versions of the Mannich reaction
have been developed to overcome the drawbacks associ-
ated with the classical Mannich reaction. One of the
efficient routes is to conduct a one-pot three-component
reaction of an aldehyde, an amine and a ketone with the
assistance of ultrasound irradiation [9], organic or mineral
acids, like proline [10], p-dodecyl benzene sulphonic acid
[11] and some Lewis acids (LA), like FeCl3 [12], Cu(OTf)2
[13], SbCl3 (10%) [14], Bi(OTf)3Á4H2O [15], and siloxy serine
organocatalysts [16]. Most of these methods, although
useful, suffer from drawbacks, such as long reaction time,
low yield, the use of toxic solvents, requirement of excess
of reagents/catalysts, laborious workup-procedures, and
harsh reaction conditions. Therefore, it is important to find
more convenient methods for the synthesis of these types
of compounds.
tural diversity, such as
b-amino carbonyl compounds,
* Corresponding author.
E-mail address: fshrini@gmail.com (F. Shirini).
1631-0748/$ – see front matter ß 2013 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2013.02.019
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

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Xanthenes and their derivatives have received special
attention due to their diverse array of biological activities
such as anti-inflammatory, antibacterial and antiviral
activities [17–19]. In addition to this, they can be employed
as dyes [20], intracellular pH indicators [21], molecular
probes in chemical biology [22], and fluorescent materials
for the visualization of biomolecules [23]. There are several
reports in the literature for the synthesis of 3,3,6,6-
tetramethyl-1,8-dioxo-octahydro xanthene derivatives
employing aromatic aldehydes and dimedone; these
include p-TSA [24,25], sulfamic acid [26], molecular iodine
[27,28], heteropoly acid [29,30], silica sulfuric acid [31,32],
Amberlyst-15 [33], and wet cyanuric chloride [34]. Howev-
er, these methods suffer from one or more disadvantages
such as a long reaction time, low yield, the use of toxic
solvents, requirement of excess of reagents/catalysts,
laborious work-up procedures, and harsh reaction condi-
tions. Thus, the development of an environmentally benign
methodology for the synthesis of benzoxanthene deriva-
tives is in great demand.
Indoles and their derivatives have long been utilized as
antibiotics in the field of pharmaceuticals. Bis-indolyl
alkanes and their derivatives are more attractive com-
pounds as the bioactive metabolites of terrestrial and
marine origin [35]. The acid-catalyzed reaction of electron-
rich heterocyclic compounds with p-dimethylaminoben-
zaldehyde is known as the Ehrlich test [36] for p-electron
excessive heterocycles, such as pyrroles and indoles. The
analogous reaction of indoles with other aromatic or
aliphatic aldehydes and ketones produces azafulvenium
salts, which undergo the further addition with another
indole molecule to afford bis-indolyl methanes. Brønsted
[37,38] and Lewis acids [39] are both known to promote
this reaction. Recently, it was reported that the synthesis of
bis-indolyl methanes could be catalyzed by LiClO4 [40],
Ln(OTf)3 [41], PPh3ÁHClO4 [42], In(OTf)3 [43], montmoril-
lonite clay K-10 [44], etc., but the long reaction time (4–
10 h) and complicated operation limited their further
development. Despite the merits of these methodologies,
harsh reaction conditions, toxicity or difficulty in product
separation remain concerns. Therefore, the search for new
readily available green catalysts for this reaction is still
being actively pursued.
The above-mentioned disadvantages of the applica-
tion of the catalysts in the promotion of the synthesis
of
b-amino carbonyl compounds, 1,8-dioxo-octahydro
xanthenes and bis-indolyl methanes encouraged us to
use rice-husk-supported FeCl3 nano-particles as a new,
efficient and heterogeneous catalyst for the synthesis of
these types of compounds. All the reactions are
performed under mild reaction conditions in relatively
short reaction times in good to high yields (Scheme 1).
2. Experimental
2.1. Material
The chemicals were purchased from Fluka, Merck,
Aldrich and Southern Clay Products Chemical Companies.
The yields refer to the isolated products. The products were
Ar
O
A + B
(Table 1)
(Table 3)
NH
R1
R2
O
Ar
O
O
Ar
FeCl3-RiH
2C
+
O
H
Ar
2D
(Table 5)
HN
NH
X
X
O
O
C
NH2
X
X = H, Me
N
H
R1
O
R2
B
A
D
Scheme 1. Synthesis of
b-amino carbonyl compounds, 1,8-dioxo-octahydro xanthenes and bis-indolyl methanes in the presence of FeCl3–rice husk.
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

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F. Shirini et al. / C. R. Chimie xxx (2013) xxx–xxx
3
characterized by their physical constants, comparison with
authentic samples and IR and NMR spectroscopy. The
purity determination of the substrate and the reaction
monitoring were accomplished by TLC on silica gel
polygram SILG/UV 254 plates.
progress of the reaction was monitored by TLC. After
completion of the reaction (1 h), the reaction mixture was
diluted with EtOH (10 mL) and stirred for 15 min. The
catalyst was decanted and the crude product was
recrystallized with EtOH. The product was found to be
pure (91%) and no further purification was necessary.
2.2. Instrumentation
2.7. Synthesis of bis-indolyl methanes: a typical procedure
The IR spectra were run on
a PerkinElmer bio-
spectrometer and a Bruker Vector 22. The 1H NMR
(400 MHz) and 13C NMR (100 MHz) spectra were run on a
Bruker AvanceiII-400 spectrometer in CDCl3 using TMS as
A mixture of rice-husk-supported FeCl3 nano-particles
(0.15 g), benzaldehyde (1 mmol) and indole and/or 2-
methylindole (2 mmol) in EtOH (1 mL) was heated at 80 8C.
The progress of the reaction was monitored by TLC. After
completion of the reaction, the reaction mixture was
diluted with EtOH (10 mL) and stirred for 10 min. The
catalyst was decanted and the crude product was
recrystallized from EtOH/H2O (3:1 mL). The product was
found to be pure (92%) and no further purification
was needed.
an internal reference (
d in ppm). Microanalyses were
performed on a Perkin-Elmer 240-B microanalyzer. The
melting points were recorded on a Bu¨ chi B-545 appara-
tus in open capillary tubes. The characterization of rice
husk (RiH) was obtained using scanning electron
microscopy (SEM-Philips XL30) with field emission
gun and energy-dispersive spectroscopy (EDS). Prior to
placing into the microscope, the RiH particles were
coated with gold under vacuum (SCD 005 sputter coater,
Bal-Tec, Swiss) and examined at an acceleration voltage
of 17 kV.
2.8. Spectral data for new compounds
2.8.1. 3-(4-bromophenyl)-1-phenyl-3-
(phenylamino)propan-1-one (Table 1, entry 4)
2.3. Preparation of rice husk [45]
IR (KBr), 3400, 3020, 1662 cmÀ1 1H NMR (400 MHz,
;
TMS, CDCl3), 3.48 (m, 2 H), 4.60 (br, 1H), 5.00 (m, 1H), 6.57
(s, 2H), 6.72 (s, 1H), 7.13 (s, 2H), 7.37–7.60 (m, 8 H), 7.93 (s,
2H). 13C NMR (400 MHz, TMS, CDCl3): 46.08, 54.22, 113.87,
118.10, 121.08, 128.20, 128.23, 128.79, 129.18, 131.93,
133.62, 136.55, 142.09, 146.69, 197.90.
The rice samples (named as Hassani) were obtained
from Rasht (Guilan Province) in the north of Iran. RiH was
obtained from a local mill, washed several times with
distilled water to remove any adhering materials and dried
at room temperature for 48 h. The dried RiH was smashed
and sieved (80–170 mesh size), washed with distilled
water and dried at 110 8C for 4 h.
2.8.2. 3-(4-bromophenylamino)-1,3-diphenylpropan-1-one
(Table 1, entry 5)
IR (KBr) 3375, 3010, 1660 cmÀ1;1H NMR (400 MHz, TMS,
CDCl3), 2.43 (s, 3H), 3.36–3.42 (dd, J1 = 8.00 Hz, J2 = 16.00 Hz,
1H), 3.47–3.52 (dd, J1 = 4.40 Hz, J2 = 16.00 Hz, 1H), 4.69 (br,
1H), 4.95 (m, 1H), 6.44–6.460 (d, 8.40 Hz, 2H), 7.17–7.19 (d,
8.40 Hz, 2H), 7.26 (s, 3H), 7.34–7.37 (t, 7.20 Hz, 2H), 7.43–
7.44 (d, 7.20 Hz, 2H), 7.82–7.84 (d, 7.60 Hz, 2H), 7.84–7.86
(d, J = 7.60, 2H), 13C NMR (400 MHz, TMS, CDCl3), 21.70,
46.12, 54.93, 109.47, 115.45, 126.28, 127.49, 128.36, 128.92,
129.44, 131.79, 134.14, 142.55, 144.51, 146.06, 197.80.
2.4. Preparation of the catalyst (FeCl3–rice husk) [45]
The catalyst was prepared by impregnation of RiH
(50 g) with a solution of anhydrous FeCl3 (0.053 mol,
8.62 g) in acetone. The solvent was evaporated under
reduced pressure and the catalyst was heated at 120 8C for
8 h to give FeCl3–RiH (58 g).
2.5. Synthesis of
procedure
b-amino carbonyl compounds: a typical
2.8.3. 3-(3-chlorophenylamino)-1,3-diphenylpropan-1-one
(Table 1, entry 9)
A
mixture of benzaldehyde (1.0 mmol), aniline
IR (KBr) 3375, 3005, 1668 cmÀ1;1H NMR (400 MHz,
TMS, CDCl3), 3.42–3.48 (dd, J1 = 7.60 Hz, J2 = 16.20 Hz, 1H),
3.51–3.56 (dd, J1 = 4.80 Hz, J2 = 16.01 Hz, 1H), 4.77 (br, 1H),
4.99–5.02 (dd, J1 = 4.80 Hz, J2 = 7.60 Hz, 1H), 6.58 (s, 1H)
6.64–6.66 (d, 7.60 Hz, 1H), 7.26–7.28 (d, 7.20 Hz, 1H),
7.35–7.39 (t, 7.60 Hz, 2H), 7.44–7.46 (d, 7.60 Hz, 1H), 7.48–
7.50 (d, 7.60 Hz, 2H),7.58–7.62 (t, 7.20 Hz, 2H), 7.92–7.94
(d, J = 7.60, 2H),13C NMR (400 MHz, TMS, CDCl3), 46.13,
54.64, 111.96, 113.61, 117.70, 126.29, 127.58, 128.23,
128.77, 128.96, 130.11, 133.58, 134.82, 136.59, 142.36,
148.18, 198.12.
(1.0 mmol), acetophenone (1.1 mmol), and FeCl3–RiH
(0.04 g) was stirred in anhydrous EtOH (3 mL) at room
temperature for 8 h. The reaction was monitored by TLC.
Upon completion, CH2Cl2 was added and the catalyst was
separated by filtration. The solution was concentrated
under reduced pressure. The solid residue was washed
with hot EtOH and dried to afford the requested product in
95% yield.
2.6. Synthesis of 1,8-dioxo-octahydro xanthenes: a typical
procedure
2.8.4. 3-(4-bromophenylamino)-3-phenyl-1-p-tolylpropan-
1-one (Table 1, entry 11)
A mixture of rice-husk-supported FeCl3 nano-particles
(0.2 g), benzaldehyde (1 mmol) and dimedone (2 mmol)
was heated at 100 8C in the absence of the solvent. The
IR (KBr) 3380, 3020, 1680 cmÀ1 1H NMR (400 MHz,
;
TMS, CDCl3), 3.41–3.47 (dd, J1 = 7.60 Hz, J2 = 16.20 Hz, 1H),
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

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Table 1
Preparation of
b-amino carbonyl compounds promoted FeCl3–rice husk.
Entry
1
Product
Time (h)
8
Yield (%)a,b
95
m.p. (8C) (Found)
m.p. (8C) (Lit.)
Reference
[46]
164–166
169–171
O
O
HN
HN
2
12
96
100–101
119–120
[46]
Cl
3
14
94
144–146
150–152
[47]
O
O
HN
HN
OCH3
4
13
95
127–129
–
–
Br
Br
5
13
92
180–182
–
–
O
O
O
O
HN
HN
HN
HN
6
7
8
8
10
14
94
96
92
160–162
167–168
185–187
170–171
170–171
184–186
[46]
[46]
[46]
CH3
Cl
NO
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

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Table 1 (Continued )
Entry
9
Product
Time (h)
13
Yield (%)a,b
92
m.p. (8C) (Found)
m.p. (8C) (Lit.)
Reference
–
130–132
–
Cl
O
HN
O
10
8
91
125–127
131–132
[48]
HN
H3C
11
10
95
145–147
–
–
O
HN
H3C
m.p.: melting point.
a
Isolated yield.
b
Products were characterized by their physical constants and comparison with authentic samples [46–48].
3.50–3.55 (dd, J1 = 4.80 Hz, J2 = 16.20 Hz, 1H), 4.67 (br, 1H),
4.96–5.00 (dd, J1 = 4.80 Hz, J2 = 7.60 Hz, 1H), 6.58 (s, 1H)
6.65–6.67 (d, 8.80 Hz, 2H), 7.17–7.19 (d, 8.80 Hz, 2H),
7.25–7.27 (d, 7.60 Hz, 3H), 7.34–7.37 (t, 7.60 Hz, 2H), 7.42–
7.44 (d, 7.20 Hz, 2H),7.60 (t, 7.60 Hz, 1H), 7.92–7.94 (d,
J = 7.20, 2H),13C NMR (400 MHz, TMS, CDCl3), 46.20, 54.82,
109.54, 115.45, 126.29, 127.54, 128.21, 128.76, 128.93,
131.81, 133.57, 136.59, 142.43, 146.00, 198.17.
catalyst at room temperature proceeded with the highest
yield.
Furthermore, the Mannich reaction was very sensitive
to the reaction temperature. High temperatures could
improve the reaction rate and shorten the reaction time,
but favor side reactions and the oxygenolysis of aldehyde
and amine. It was found that the room temperature was an
appropriate condition for the Mannich reaction catalyzed
by FeCl3–RiH (Scheme 2).
3. Results and discussions
After optimization of the reaction conditions and in
order to show the generality of the method, we used the
optimized conditions for the synthesis of different types of
Very recently, we have reported the preparation of the
rice-husk-supported FeCl3 nano-particles and its applica-
bility in the promotion of the acylation of aldehydes and
deprotection of the obtained 1,1-diacetates [45]. In
continuation of this study, we have found that this reagent
b
-amino carbonyl compounds. Our investigations clarified
that various aromatic aldehydes and amines bearing
different substitutes, such as OMe, Me, Br and Cl, were
all suitable for the reactions.
is also efficiently able to catalyze the synthesis of
b
-amino
In order to show the merit of the catalyst, we have
compared the results obtained from the reaction of
acetophenone, benzaldehydes, and aniline in the presence
of FeCl3–RiH with some of the other catalysts for the
similar reaction (Table 3). LAs, such as [C6H11N(CH2
carbonyl compounds, 1,8-dioxo-octahydro xanthenes, and
bis-indolyl methanes. All the reactions are performed
under mild reaction conditions in good to high yields
(Table 1).
First of all, we have tried to study the Mannich reaction
using FeCl3–RiH as the catalyst. For obtaining the best
amounts of the catalyst, an optimization study was
performed using the reaction of benzaldehyde, acetophe-
none and aniline as a model reaction in the presence of
varying amounts of the catalyst [FeCl3–RiH] under differ-
ent conditions, including various solvents (DMF, CH3CN,
DCM, H2O, and EtOH) at room temperature. We found that
absolute EtOH was the best choice among the solvents. The
reaction failed to yield any products in DCM or H2O and the
yields in CH3CN and DMF were very poor. The results
showed that the reaction using 0.04 g of absolute EtOH as a
CHO
NH2
+
O
HN
RiH-FeCl3 (0.04 g)
anhydrous EtOH, r. t.
1 (mmol)
1 (mmol)
O
1.1 (mmol)
Scheme 2. Mannich reaction catalyzed by FeCl3–rice husk.
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

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Table 2
Comparison of the effect of the catalysts on the preparation of 1,3-diphenyl-3-(phenylamino)propan-1-one (a).
Entry
Catalyst
Time (h)
Yield (%)a
Reference
1
2
3
4
5
6
7
8
9
[C6H11N(CH2C6H4)2SbOSO2CF3] (5 mol%)
Montmorillonite K10 (10%)
FeCl3 (10%)
24
20
20
15
20
20
20
8
65
[49]
35
[11]
0
[9]
SbCl3 (10%)
60
[11]
Phenyl phosphonic acid (10%)
Phenyl phosphonic acid/SiO2 (10%)
Cu–silicate (10%)
40
[11]
45
[11]
40
[11]
FeCl3–RiH
95
This work
This work
RiH
20
90 (imine)
a
Isolated yields.
Ph
O
Ph
O
O
Ph
Ph
O
O
FeCl3-RiH (0.15 g)
EtOH, 80 C
FeCl3-RiH (0.2 g)
Solvent-free, 100 C
+
+
O
O
N
H
H
H
HN
NH
(1 mmol)
(2 mmol)
(1 mmol)
(2 mmol)
Scheme 4. Synthesis of bis-indolyl methanes catalyzed by FeCl3–rice
Scheme 3. Synthesis of 1,8-dioxo-octahydro xanthenes catalyzed by
husk.
FeCl3–rice husk.
C6H4)2SbOSO2CF3], FeCl3, SbCl3, phenyl phosphonic acid
and phenyl phosphonic acid/SiO2 promoted the reaction in
0–65% yields after 15–20 h (Table 3, entries 1, 3–6). Under
the same conditions, Cu–silicate and montmorillonite K-10
After successful synthesis of a series of b-amino
carbonyl compounds, in good yields, we turned our
attention toward the synthesis of 3,3,6,6-tetramethyl-
1,8-dioxo-octahydro xanthenes by the condensation of
aldehydes and 5,5-dimethyl-1,3-cyclohexadione (dime-
done) (Table 2) First of all and in an optimized procedure,
with respect to the solvent, catalyst concentration,
temperature, and time, the condensation of 4-chloroben-
zaldehyde (1 mmol), and dimedone (2.1 mmol) was
investigated in the presence of FeCl3–RiH as the catalyst.
Our investigations clarified that the best result can be
obtained in the absence of solvent at 100 8C using 0.2 g of
FeCl3–RiH (Scheme 3).
gave b-amino carbonyl compounds in 40% yield after 20 h
and 35% yield after 20 h, respectively (Table 3, entries 2 and
7). However, among the catalysts studied for this reaction,
FeCl3–RiH was found to be the most effective one for this
transformation, since it resulted in the highest conversion
into the desired product (Table 3, entry 8). It is very
important to note that the same reaction in the presence of
RiH produces the corresponding imine, even after pro-
longed reaction times (Table 3, entry 9).
N
H
O
O
2
O
R NH
2
R3
R1
R1
R4
FeCl
OH
O
O
R1
R1
R
-RiH
3
FeCl
-RiH
3
O
H
O
R
O
-FeCl -RiH
FeCl
-RiH
3
R4
3
R1
O
R
O
R2
-H2O
R2
R
O
R1
R1
-H2O
O
HN
NH
O
R1
R1
FeCl -RiH
3
O
R4
R
R1
R1
R3
R1
-FeCl
3
R3
-RiH
(Table 3)
FeCl
-RiH
NH
3
OH
R
H
R
N
-H2O
-FeCl
H
-RiH
HN
NH
3
Scheme 5. A plausible mechanism for the synthesis of
b-amino carbonyl compounds, 1,8-dioxo-octahydro xanthenes, and bis-indolyl methanes in the
presence of FeCl3–rice rusk.
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

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7
Table 3
Solvent-free synthesis of 1,8-dioxo-octahydro xanthenes in the presence of FeCl3–rice husk.
a,b
Entry
1
Product
Time (h)
1
Yield (%)
91
m.p. (8C) (Found)
m.p. (8C) (Lit.)
Reference
[50]
201–202
203–205
O
O
O
O
2
1
95
232–234
230–232
[50]
Cl
O
O
3
1.5
94
240–241
240–241
[50]
Br
O
O
O
O
O
F
4
1
92
220–221
223–224
[50]
O
O
O
O
5
1.5
91
242–244
241–243
[51]
OCH3
O
6
1.5
92
217–220
221–223
[51]
NO2
O
O
O
O
7
1.5
91
190–191
190–192
[51]
Br
O
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

G Model
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8
F. Shirini et al. / C. R. Chimie xxx (2013) xxx–xxx
Table 3 (Continued )
a,b
Entry
8
Product
Time (h)
1.
Yield (%)
94
m.p. (8C) (Found)
m.p. (8C) (Lit.)
Reference
[51]
163–165
167–168
O2N
O
O
O
9
1.5
89
165–166
162–164
[52]
H3CO
O
O
O
O
O
10
1.25
91
226–229
226–228
[51]
Cl
O
m.p.: melting point.
a
Isolated yield.
b
Products were characterized by their physical constants and comparison with authentic samples [50–52].
After optimization of the reaction conditions and in
order to show the applicability of the proposed method,
different types of aldehydes were subjected to the same
reaction and the results are presented in Table 3.
It is noteworthy that the electronic properties of the
group on the aldehydes’ aromatic ring have a delicate
effect on reaction times. As shown in Table 3, the aromatic
aldehydes containing electron-withdrawing groups
showed relatively similar reactivity to those containing
electron-donating groups.
The advantages of FeCl3–RiH over the reported
catalysts for the synthesis of 3,3,6,6-tetramethyl-1,8-
dioxo-octahydroxanthene derivative of 4-chlorobenzal-
dehyde are shown in Table 4. It is noteworthy that some of
the previously reported methods require longer reaction
times.
FeCl3–RiH. We have found that the best results can be
obtained in EtOH at 80 8C using 0.15 g of FeCl3–RiH
(Scheme 4).
Encouraged by this successful result, we studied
various aldehydes under optimized conditions to better
understand the scope and generality of this simple
procedure. A series of aromatic aldehydes underwent an
electrophilic substitution reaction with indole and 2-
methyl indole to afford a wide range of substituted bis-
indolyl methanes, in good to excellent yields. This
method is equally effective for aldehydes bearing
electron-withdrawing or -donating groups in the aro-
matic rings (Scheme 5, Table 5).
In addition, this procedure is superior, compared to the
literature data, with respect to the catalyst, solvent and
eco-friendliness (Table 6).
After this study, we were interested in studying the
applicability of FeCl3–RiH in the promotion of the synthesis
of bis-indolyl methanes via the condensation of aldehydes
with indoles. In this study and in order to optimize the
reaction conditions, the condensation of 4-chlorobenzal-
dehyde and indole was investigated in the presence of
A plausible mechanism for the synthesis of b-amino
carbonyl compounds, 1,8-dioxo-octahydro xanthenes and
bis-indolyl methanes in the presence of FeCl3–RiH is
shown in Scheme 5. Presumably, FeCl3–RiH acts as a LA to
catalyze the nucleophilic attack on the carbonyl group of
the aldehyde.
Table 4
Comparison of the results obtained from the synthesis of 1,8-dioxo-octahydro xanthenes from 4-chlorobenzaldehyde and dimedone in the presence of
various catalysts.
Entry
Catalyst
Time (h)
Yield (%)a
Reference
1
2
3
5
FeCl3Á6H2O in [bmim][BF4] at 80 8C
Cellulose sulfonic acid
TMSCl
7
5
8
1
93
[53]
94
[54]
74.3
95
[55]
FeCl3–RiH
This work
a
Isolated yields.
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

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F. Shirini et al. / C. R. Chimie xxx (2013) xxx–xxx
9
Table 5
Synthesis of bis-indolyl methanes in the presence of FeCl3–rice husk as the catalyst.
Entry
1
Product
Time (min)
15
Yield (%)a,b
m.p. (8C) (Found)
m.p. (8C)
(Lit.)
Reference
[56]
92
144–145
149–150
HN
NH
2
10
96
75–77
76–77
[56]
Cl
HN
NH
3
40
92
183–185
185–187
[56]
OCH3
HN
NH
4
30
95
222–224
217–220
[56]
NO2
HN
NH
5
45
90
127–128
123–125
[57]
OH
HN
NH
6
10
94
89–91
93–94
[56]
CH3
HN
NH
NH
7
50
91
219–221
221–224
[58]
O2N
HN
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

G Model
CRAS2C-3725; No. of Pages 11
10
F. Shirini et al. / C. R. Chimie xxx (2013) xxx–xxx
Table 5 (Continued )
Entry
Product
Time (min)
40
Yield (%)a,b
93
m.p. (8C) (Found)
m.p. (8C)
(Lit.)
Reference
[56]
8
75–76
70–71
Cl
NH
HN
9
20
95
201–203
198–202
[58]
HN
NH
10
20
90
101–103
98–99
[56]
NH
NH
11
14
94
243–245
247–248
[56]
HN
NH
12
11
97
247–248
186–188
[58]
Cl
NH
HN
13
15
95
248–250
240–242
[59]
NO2
HN
NH
NH
14
30
90
209–211
237–239
[60]
OH
HN
m.p.: melting point.
a
Isolated yield.
b
Products were characterized by their physical constants and comparison with authentic samples [56–60].
Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019

G Model
CRAS2C-3725; No. of Pages 11
F. Shirini et al. / C. R. Chimie xxx (2013) xxx–xxx
11
Table 6
Comparison of the results obtained from the synthesis of bis-indolyl methane from benzaldehyde and indole in the presence of various catalysts.
Entry
Catalyst
Time (min)
Yield (%)a
Reference
1
2
3
4
5
6
[bmim]BF4
270
90
90
98
72
89
–
[61]
FeCl3Á6H2O (5 mol %) in [omim]PF6
[62]
I2
10
[63]
Mg(HSO4)2
Silica sulfuric acid
FeCl3–RiH
360
120
15
[64]
[64]
92
This work
a
Isolated yields.
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4. Conclusions
In summary, we have developed an environmentally
friendly protocol, allowing high yields in mild conditions, for
the three-component synthesis of
pounds 1,8-dioxo-octahydro xanthenes and bis-indolyl
methanes catalyzed by FeCl3–RiH. This method offers
several advantages compared to those reported in literature:
b-amino carbonyl com-
ꢀ
ꢀ
ꢀ
mild and highly efficient catalyst activity;
cost efficiency of the catalyst;
avoidance of the troublesome preparation of the enol
derivatives and of the pre-formed imines;
wide substrate scope;
ease of product isolation/purification, making it a useful
and attractive strategy for the synthesis of the above-
mentioned products.
ꢀ
ꢀ
´
[38] (a) R. Sanz, D. Miguel, J.M. Alvarez-Gutie´rrez, F. Rodrı´guez, Synlett 7
(2008) 975;
Acknowledgments
(b) R. Sanz, D. Miguel, A. Martı´nez, M. Gohain, P. Garcı´a-Garcı´a, M.A.
´
Ferna´ndez-Rodrı´guez, E. Alvarez, F. Rodrı´guez, Eur. J. Org. Chem. 36
We are thankful to the University of Guilan Research
Council for the partial support of this work.
(2010) 7027.
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Please cite this article in press as: Shirini F, et al. Rice-husk-supported FeCl3 nano-particles: Introduction of a mild,
efficient and reusable catalyst for some of the multi-component reactions. C. R. Chimie (2013), http://dx.doi.org/
10.1016/j.crci.2013.02.019