Mesoporous silica nanoparticles in an efficient, solvent-free, green synthesis of acridinediones

Article abstract of DOI:10.1016/j.catcom.2014.11.015

Mesoporous silica nanoparticles (MSNs) are employed in an efficient, biocompatible and neutral catalytic green synthesis of acridinediones, through one-pot three-component reaction of dimedone with aromatic aldehydes, in the presence of a nitrogen source

Full text of DOI:10.1016/j.catcom.2014.11.015

Catalysis Communications 60 (2015) 100–104
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Short communication
Mesoporous silica nanoparticles in an efficient, solvent-free, green
synthesis of acridinediones
Zahra Nasresfahani, M.Z. Kassaee ⁎
Department of Chemistry, College of Sciences, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Mesoporous silica nanoparticles (MSNs) are employed in an efficient, biocompatible and neutral catalytic green
synthesis of acridinediones, through one-pot three-component reaction of dimedone with aromatic aldehydes, in
the presence of a nitrogen source (ammonium acetate or aromatic amines), under neat conditions. There are
several advantages for using MSNs in the current process such as good yield, easy catalysis, short reaction
time, easy work-up, and simplicity of operation.
Received 3 September 2014
Received in revised form 11 November 2014
Accepted 12 November 2014
Available online 20 November 2014
©
2014 Elsevier B.V. All rights reserved.
Keywords:
Acridinediones
Solvent-free conditions
Mesoporous silica nanoparticles
1
. Introduction
2. Experimental
Acridinediones have attracted keen interest of many researchers for
2.1. Preparation of mesoporous silica nanoparticles
their pharmaceutical implications including antimicrobial [1], antima-
larial [2], antitumor [3], antibacterial [4], and antifungal [5] activities.
They possess DNA binding properties and are used as drugs for cardio-
vascular diseases, such as angina pectoris [6], and hypertension [7].
Also, acridinediones are employed as DNA-intercalating anticancer
drugs [8]. Given the importance of such activities and properties, a num-
ber of methods for the synthesis of acridinedione derivatives have been
reported that employ various catalysts such as polyphosphoric acid [9],
cetyltrimethylammonium bromide (CTAB) [10], L-proline [11], zeolite
MSNs are prepared using the sol–gel method [25]. Briefly, 0.5 g of
CTAB and 0.14 g of NaOH are mixed in 240 mL deionized water. The so-
lution is stirred vigorously at 80 °C for 2 h, then 2.5 mL of TEOS is added,
and the reaction is continued for another 2 h. The as-prepared product
(MSNs-CTAB) is washed 3 times with ethanol and redispersed in
4 3
200 mL of ethanol containing 2 g of NH NO , at 80 °C. The remaining
mixture is refluxed for 6 h. In this process the CTAB template is re-
moved. The resulting precipitate is collected by centrifugation and
washed with ethanol repeatedly. Finally, it is dried under vacuum to
give MSNs product as a white powder.
[
12], N-propylsulfamic acid [13], ionic liquids [14], and microwave
irradiations [15]. They often suffer from long reaction times, harsh
conditions, toxicity, and difficulty in product separation. Hence, there
is still a great demand for simple, efficient, and green methods for
synthesis of acridinediones. MSNs have attracted considerable interest
in the life and materials science [16]. Their unique properties, such as
tunable and uniform diameter, tunable pore size, and high specific sur-
face area, make them versatile for a large range of applications in
drug delivery [17], MRI [18], cancer cell targeting [19], photodynamic
therapy [20], antireflective coatings [21], and catalysis [22–24]. A
number of recent reports on the functionalization of MSNs have given
several interesting systems for catalysis [22–24]. Here we report a
simple and efficient method for the synthesis of acridinediones using
MSNs as a green catalyst.
2.2. General procedure for the synthesis of acridinediones
A mixture of dimedone (2 mmol), aromatic aldehyde (1 mmol),
ammonium acetate or aromatic amine (1 mmol), and MSNs (10 mg)
is heated in an oil bath at 80 °C, under solvent free conditions. The reac-
tion process is monitored by TLC. The crude product is dissolved in hot
ethanol and then the catalyst is removed by filtration. The pure product
is obtained upon cooling the filtrate.
3. Results and discussion
Here we discuss characterizations of our MSNs through IR, XRD,
2
SEM, TEM and N adsorption–desorption analyses, followed by its em-
ployment as an efficient catalyst for the synthesis of acridinediones.
⁎
Corresponding author.
E-mail addresses: drkassaee@yahoo.com (Z. Nasresfahani), kassaeem@modares.ac.ir
−
1
In the FT-IR spectrum of MSNs, a band at about 1084 cm relates to
(M.Z. Kassaee).
the asymmetrical bonding stretch of Si\O. The broad absorption peak
http://dx.doi.org/10.1016/j.catcom.2014.11.015
566-7367/© 2014 Elsevier B.V. All rights reserved.
1

Z. Nasresfahani, M.Z. Kassaee / Catalysis Communications 60 (2015) 100–104
101
Fig. 1. FT-IR spectrum of our fabricated mesoporous silica nanoparticles (MSNs).
Fig. 2. XRD pattern (a), and SEM image (b) of the mesoporous silica nanoparticles (MSNs).

102
Z. Nasresfahani, M.Z. Kassaee / Catalysis Communications 60 (2015) 100–104
Table 1
Solvent effects on the preparation of acridinediones over the mesoporous silica nanopar-
ticles (MSNs).
Entry
Solvent
Temperature
Yield (%)a
Time (min)
1
2
3
4
5
CH
CH
CH
CH
3
3
3
3
CH
COCH
COOCH
CN
2
OH
Reflux
Reflux
Reflux
Reflux
80 °C
80
75
85
60
90
60
60
60
60
10
3
2 3
CH
Solvent free
a
Isolated yield.
nearly coincides with the adsorption one, which reveals reversible
nitrogen adsorption inside the mesopores.
Our synthesized MSNs are tested as the catalyst in the synthesis
of acridinediones, where the yield increases possibly due to the
higher surface area of MSNs, as well as the presence of reactive OH
groups on the surface and particularly inside of its pores. Hence,
our effort to develop an efficient and environmentally benign
methodology for the synthesis of acridinediones focuses initially on
the three-component cyclocondensation of dimedones with benzal-
dehyde and ammonium acetate as a model reaction. We evaluate
Fig. 3. The TEM image of mesoporous silica nanoparticles (MSNs).
the effect of different solvents such as CH
3 2 3 2 3
CH OH, CH COOCH CH ,
CH COCH , and CH CN, along with solvent-free conditions on the
3
3
3
within the range of 3000–3750 cm− is ascribed to the O\H stretching
1
reaction rate under similar circumstances. A solvent-free conditions af-
fords products in higher yield with shorter reaction time (Table 1).
Next, we probe different amounts of the catalyst (5-20 mg). The opti-
mum yield of the product is obtained when 10 mg of MSNs is used
−1
−1
vibration of the silanol groups. Peaks at 2854 cm and 2923 cm cor-
respond to C\H stretching which disappear after complete removal of
CTAB surfactants (Fig. 1).
The XRD pattern of the synthesized catalyst is performed from
.0°(2θ) to 80.0° (2θ), where a very prominent broad peak corre-
(Table 2).
2
To evaluate the scope of this catalytic transformation, the optimized
sponds to the formation of a hexagonal array of pores (Fig. 2a). Uni-
form and spherical morphology of MSNs is confirmed by SEM images
with an average size of 39–70 nm (Fig. 2b), TEM image display
rather monodispersed spherical MSNs with a mean diameter of
reaction conditions are subsequently applied to the reaction of dimedone
with a variety of different aromatic aldehydes in the presence of an
ammonium acetate or aromatic amine (Scheme 1).
A wide range of aromatic aldehydes, bearing either electron-
donating or electron-withdrawing substituent, react successfully to
give the corresponding acridinedione products in high yields, over
short reaction times (Table 3). The MSNs seem to be a selective catalyst,
since only syntheses involving the reaction of aryl aldehydes produce
the corresponding acridinediones. No reaction is observed when
aliphatic aldehydes (including butyraldehyde and crotonaldehyde) or
ketones (including acetophenone and 4-methoxyacetophenone) are
used.
1
10 ± 10 nm (Fig. 3).
The total surface area and average pore diameter of MSNs are
analyzed by N adsorption and desorption measurements. In effect,
2
the specific surface area, pore volume and average pore diameter
are calculated via Brunauer–Emmett–Teller (BET) method [26]
(
2
Fig. 4). N adsorption–desorption measurement for the MSNs dem-
onstrates a Type IV isotherm, which is characteristic of mesoporous
materials. The sharp inflection over a narrow relative pressure rang-
ing from 0.18 to 0.29 indicates that capillary condensation occurs in
the mesopores and illustrates that MSNs have uniform pores. Further
evidence for this is the fact that desorption branch of the isotherm
Based on our data, we suggest a plausible mechanism for the synthe-
sis of acridinediones using MSNs (Scheme 2).
Our mesoporous catalyst is repeatedly used in the same reaction
showing no change in its catalytic activity. The relation between
the number of cycles of the reaction and the catalytic activity, in
terms of yield of the product, imply that the MSNs can be recycled
and reused for at least four times without losing much of its activity
(
Fig. 5).
To further evaluate the overall utility of the current methodolo-
gy, we compare our results with those of the other methods report-
ed for the synthesis of acridinediones. This comparison is shown
in (Table 4). It is clear from the data that our method reduces the
reaction times significantly and provides higher yields of the
products.
Table 2
Effect of catalyst amount on the synthesis of acridinediones.
Entry
Catalyst (mg)
Time (min)
Yield (%)a
1
2
3
4
5
10
15
20
20
10
15
15
85
90
90
90
a
Fig. 4. Adsorption–desorption isotherms of N
2
mesoporous silica nanoparticles (MSNs).
Isolated yield.

Z. Nasresfahani, M.Z. Kassaee / Catalysis Communications 60 (2015) 100–104
103
Scheme 1. Synthesis of acridinediones catalyzed by the mesoporous silica nanoparticles (MSNs).
Table 3
Catalytic synthesis of acridinediones derivatives over MSNs in solvent-free conditions.
Entry
Aldehyde
Ph
Amine
Yield (%)a
Time (min)
m.p (°C)
m.p (°C) [Lit]
1
2
3
4
5
6
7
5
8
9
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
Ph
4
OAc
4
OAc
4
OAc
4
OAc
4
OAc
4
OAc
4
OAc
4
OAc
4
OAc
4
OAc
4
OAc
4
OAc
90
83
85
93
87
92
82
85
88
84
93
95
88
85
92
86
83
87
85
86
10
10
15
10
20
25
15
20
30
15
10
20
15
20
25
20
20
10
15
15
275–277
294–295
220–224
290–293
320–325
290–295
280–285
290–300
270–280
212–217
230–235
313–316
235–238
270–275
285–290
252–257
280–283
287–290
263–265
250–253
258–260 [27]
290–300 [27]
221–223 [28]
294–296 [27]
318–320 [27]
302–304 [29]
284–286 [30]
301–302 [29]
278–280 [29]
–
4-Cl-C
2-Cl-C
6
H
H
4
6
4
2 6 4
3-NO -C H
4-Me-C
2-OH-C
4-OH-C
6
H
6
H
6
H
4
4
4
2-OMe-C
4-OMe-C
6
H
H
4
6
4
2-OH-3-OMe-C
5-Br-2-OH-C
4-Br-C
4-Cl-C
3-NO -C
6
H
4
10
11
14
15
16
13
17
18
19
20
6
H
4
–
6
H
4
312–315 [27]
243–245 [10]
272–274 [10]
291–293 [10]
260–262 [29]
281–283 [10]
292–294 [31]
269–271 [31]
254–256 [32]
6 4
H
2
6
H
4
Ph
Ph
4-OMe-C
Ph
6
H
4
4-Me-C
4-Me-C
4-Me-C
4-Me-C
Ph
6
H
6
H
6
H
6
H
4
4
4
4
3-NO
2 6 4
-C H
4-Me-C
6 4
H
4-Cl-C
Ph
6 4
H
a
Isolated yield.
Scheme 2. A plausible mechanism for catalytic synthesis of acridinediones over mesoporous silica nanoparticles (MSNs).

104
Z. Nasresfahani, M.Z. Kassaee / Catalysis Communications 60 (2015) 100–104
1
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