Carbon-based solid acid as an efficient and reusable catalyst for the synthesis of 1,8-dioxodecahydroacridines under solvent-free conditions

Article abstract of DOI:10.5012/bkcs.2011.32.7.2243

Carbon-based solid acid catalyst was found to be highly efficient, eco-friendly and recyclable heterogeneous catalyst for the multicomponent reaction of dimedone, aromatic aldehydes, and a nitrogen source (ammonium acetate or aromatic amines) under solven

Full text of DOI:10.5012/bkcs.2011.32.7.2243

Carbon-Based Solid Acid as an Efficient and Reusable Catalyst
Bull. Korean Chem. Soc. 2011, Vol. 32, No. 7 2243
DOI 10.5012/bkcs.2011.32.7.2243
Carbon-Based Solid Acid as an Efficient and Reusable Catalyst for the Synthesis
of 1,8-Dioxodecahydroacridines Under Solvent-Free Conditions
*
Abolghasem Davoodnia, Amir Khojastehnezhad, and Niloofar Tavakoli-Hoseini
*
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran. E-mail: adavoodnia@mshdiau.ac.ir
Received April 7, 2011, Accepted May 18, 2011
Carbon-based solid acid catalyst was found to be highly efficient, eco-friendly and recyclable heterogeneous
catalyst for the multicomponent reaction of dimedone, aromatic aldehydes, and a nitrogen source (ammonium
acetate or aromatic amines) under solvent-free conditions, giving rise to 1,8-dioxodecahydroacridines in high
yields. The present methodology offers several advantages, such as a simple procedure with an easy work-up,
short reaction times, high yields, and the absence of any volatile and hazardous organic solvents.
Key Words : Carbon-based solid acid, 1,8-Dioxodecahydroacridines, Solvent-free conditions
Introduction
Replacement of conventional toxic and pollutant Brønsted
and Lewis acid catalysts with environmentally benign and
reusable solid heterogeneous catalysts is an active area of
current research. Using solid acid catalysts have some
advantages such as ease of products separation, recycling of
the catalyst and environmental acceptability as compared to
Multicomponent reactions (MCRs) have emerged as
efficient and powerful tools in modern synthetic organic
chemistry because the synthesis of complex organic mole-
cules from simple and readily available substrates can be
achieved in a very fast and efficient manner without the
18
liquid acid catalyst. Carbon-based solid acid (CBSA)
1-4
isolation of any intermediate. In this type of reactions
catalyst has many advantages. It is insoluble in common
organic solvents, causes low corrosion, and shows environ-
mental acceptability. Also the products could be easily
separated from the reaction mixture and the catalyst is
recoverable without decreasing its activity. Therefore, it can
three or more components are reacted to form ideally one
product, which contains the essential parts of all the initial
reactants. MCRs contribute to the requirements of an
environmentally friendly process by reducing the number of
synthetic steps, energy consumption and waste production.
Therefore, developing new MCRs and improving known
MCRs are popular areas of research in current organic
chemistry.
19-22
be successfully used instead of sulfuric acid as catalyst.
To the best of our knowledge there are no examples on the
use of CBSAs as catalysts for the synthesis of 1,8-dioxo-
decahydroacridines.
1,4-Dihydropyridines (1,4-DHPs) are a common feature
of various bioactive compounds such as vasodilator, bron-
chodilator, anti-atherosclerotic, anti-cancer and anti-diabetic
Due to our interest in the synthesis of heterocyclic com-
23-26
pounds,
and in continuation of our previous works on the
27-35
applications of reusable catalysts in organic reactions,
herein we report the new efficient synthesis of 1,8-dioxo-
decahydroacridines using a CBSA as catalyst (Scheme 1).
5-8
agents. Also, a number of DHP derivatives are employed
as potential drug candidates for the treatment of congestive
9
heart failure. 1,8-Dioxodecahydroacridines and their deriv-
atives are polyfunctionalized 1,4-dihydropyridine derivatives
which have received less attention than other 1,4-dihydro-
pyridine derivatives. These compounds are generally synthe-
sized in a three-component cyclocondensation of dimedone,
aromatic aldehydes and ammonium acetate or amines in the
presence of several catalysts such as p-dodecylbenezene-
Experimental
All chemicals were available commercially and used with-
out additional purification. The catalyst was synthesized
according to the literature. Melting points were recorded on
an electrothermal type 9100 melting point apparatus. The IR
spectra were obtained using a 4300 Shimadzu spectrophoto-
10
sulfonic acid (DBSA), [B(C6F5)3], Proline, Amberlyst-
11
12
13 14
15, NH4Cl, and Brønsted acidic imidazolium salts.
15
1
meter as KBr disks. The H NMR (500 MHz) spectra were
Synthesis of these compounds by the classical Hantzsch's
16
procedure or reaction of aldoximes with dimedone, under
17
microwave irradiation have also been reported. However,
most of these reported procedures have disadvantages includ-
ing low yields, prolonged reaction time, toxic organic solvents
and harsh reaction conditions. Therefore, the development of
simple, efficient, high-yielding, and environmentally friend-
ly methods under mild conditions using new catalysts for the
synthesis of 1,8-dioxodecahydroacridines is still necessary.
Scheme 1. Synthesis of 1,8-dioxodecahydroacridines catalyzed by
CBSA.

2244 Bull. Korean Chem. Soc. 2011, Vol. 32, No. 7
Abolghasem Davoodnia et al.
Results and Discussion
recorded with a Bruker DRX500 spectrometer.
Preparation of CBSA. The CBSA was prepared accord-
19
ing to the reported procedure by Hara and co-workers.
The one-pot synthesis of 1,8-dioxodecahydroacridines was
achieved by the three-component condensation of dime-
done, aromatic aldehydes, and ammonium acetate or aromatic
amines in the presence of CBSA as a heterogeneous catalyst
(Scheme 1). CBSA was prepared according to the literature
Naphthalene (20 g) was heated in concentrated sulfuric acid
(> 96%, 200 mL) at 250 °C under a flow of N2. After heating
for 15 h, excess sulfuric acid was removed from the dark
brown tar by vacuum distillation at 250 °C for 5 h, which
resulted in a black solid. The solid was then ground to a
powder and was washed repeatedly in boiling water until
impurities such as sulfate ions were no longer detected in the
wash water. The density of the SO3H group was measured
using NaOH (0.01 mol/L) as titrant by acid-base potentio-
metric titration. The amount of SO3H attached to the poly-
cyclic aromatic carbon was 2.79 mmol/g.
19
procedure. At first, the synthesis of compound 4a was
selected as a model reaction to optimize the reaction condi-
tions. The reaction was carried out by heating a mixture of
dimedone (2 mmol), benzaldehyde (1 mmol), and ammo-
nium acetate (1 mmol) under various conditions.
The efficiency of the reaction is affected mainly by the
amount of CBSA (Table 1). No product was obtained in the
absence of the catalyst even after 180 min (entry 1) indicat-
ing that the catalyst is necessary for the reaction. Increasing
the amount of the catalyst increased the yield of the product
4a. The optimal amount of CBSA was 0.03 g (entry 4);
increasing the amount of the catalyst beyond this value did
not increase the yield noticeably (entries 5, 6).
General Procedure for the Synthesis of 1,8-Dioxodeca-
hydroacridines 4a-p Catalyzed by CBSA. A mixture of
dimedone 1 (2 mmol), aromatic aldehyde 2 (1 mmol),
ammonium acetate or aromatic amines 3 (1 mmol), and
CBSA (0.03 g) was heated in the oil bath at 100 °C for 15-40
min. During the procedure, the reaction was monitored by
TLC. Upon completion, the reaction mixture was cooled to
room temperature and hot ethanol was added. The catalyst
was insoluble in hot ethanol and it could therefore be
recycled by a simple filtration. The product was then
collected from the filtrate after cooling to room temperature
and recrystallized from ethanol to give compounds 4a-p in
high yields.
Furthermore, the reaction was carried out in different solv-
ents and under solvent-free conditions. As shown in Table 2,
the yields of the reaction under solvent-free conditions were
greater and the reaction times were generally shorter than the
conventional methods. The best result was obtained at 100
ºC for 20 min under solvent-free conditions. Increasing the
reaction time or temperature did not improve the yield.
Recycling and Reusing of the Catalyst. Due to the fact
that the catalyst was insoluble in hot ethanol, it could
therefore be recycled by a simple filtration. The separated
catalyst was washed with ethanol, dried at 60 °C under
vacuum for 1 h and was reused in another reaction. The
catalyst could be used at least three times without significant
loss of activity.
Table 1. Effect of the amounts of CBSA on the model reaction
Entry
Catalyst (g)
Time (min)
Yield (%)
1
2
3
4
5
6
None
0.01
0.02
0.03
0.05
0.10
180
30
30
20
20
40
None
65
84
1
Selected H NMR Data.
93
3,3,6,6-Tetramethyl-1,8-dioxo-9-(4-chlorophenyl)-deca-
hydroacridine (4d): (500 MHz, CDCl3) δ 1.00 (s, 6H,
2Me), 1.12 (s, 6H, 2Me), 2.19 (d, J = 16.3 Hz, 2H), 2.27
(d, J = 16.3 Hz, 2H), 2.29 (d, J = 16.7 Hz, 2H), 2.41 (d,
J = 16.7 Hz, 2H), 5.07 (s, 1H, CH), 6.68 (s br., 1H, NH),
7.19 (d, J = 8.4 Hz, 2H, arom-H), 7.30 (d, J = 8.4 Hz, 2H,
arom-H).
93
95
Reaction conditions: dimedone (2 mmol), benzaldehyde (1 mmol), and
ammonium acetate (1 mmol) at 100 °C. Isolated yields.
Table 2. Synthesis of compound 4a in the presence of CBSA (0.03
g) in different solvents
3,3,6,6-Tetramethyl-1,8-dioxo-9-(4-nitrophenyl)-deca-
hydroacridine (4h): (500 MHz, CDCl3) δ 1.00 (s, 6H,
2Me), 1.14 (s, 6H, 2Me), 2.19 (d, J = 16.5 Hz, 2H), 2.28
(d, J = 16.5 Hz, 2H), 2.32 (d, J = 16.7 Hz, 2H), 2.46 (d,
J = 16.7 Hz, 2H), 5.19 (s, 1H, CH), 6.12 (s br., 1H, NH),
7.54 (d, J = 8.7 Hz, 2H, arom-H), 8.10 (d, J = 8.7 Hz, 2H,
arom-H).
Entry
Solvent
Temperature (°C) Time (h) Yield (%)
1
2
EtOH
MeOH
Reflux
Reflux
Reflux
Reflux
Reflux
70
5
85
75
5
3
H O
5
72
4
CH CN
5
65
5
CH Cl
5
Trace
62
3,3,6,6-Tetramethyl-1,8-dioxo-9-(4-chlorophenyl)-10-
(4-methylphenyl)-decahydroacridine (4l): (500 MHz,
CDCl3) δ 0.83 (s, 6H, 2Me), 0.97 (s, 6H, 2Me), 1.86 (d, J =
17.4 Hz, 2H), 2.09 (d, J = 17.4 Hz, 2H), 2.15 (d, J = 16.5 Hz,
2H), 2.22 (d, J = 16.5 Hz, 2H), 2.52 (s, 3H, Me), 5.27 (s, 1H,
CH), 7.11 (d, J = 8.3 Hz, 2H, arom-H), 7.24 (d, J = 8.3 Hz,
2H, arom-H), 7.37 (d, J = 8.7 Hz, 2H, arom-H), 7.39 (d, J =
8.7 Hz, 2H, arom-H).
6
Solvent-Free
Solvent-Free
Solvent-Free
Solvent-Free
Solvent-Free
Solvent-Free
30 (min)
30 (min)
20 (min)
20 (min)
20 (min)
20 (min)
7
80
75
8
90
83
9
100
93
10
11
110
93
120
94
Reaction conditions: dimedone (2 mmol), benzaldehyde (1 mmol), and
ammonium acetate (1 mmol). Isolated yields.

Carbon-Based Solid Acid as an Efficient and Reusable Catalyst
Bull. Korean Chem. Soc. 2011, Vol. 32, No. 7 2245
Table 3. Preparation of 1,8-dioxodecahydroacridines 4a-p using CBSA (0.03 g) as catalyst
mp (ºC)
Reported
Entry
Ar
R
Products
Time (min)
Yields (%)
Found
1
C H
H
20
93
192-195
190-192
2
4-BrC H
H
25
90
239-242
241-243
3
2-ClC H
H
30
90
220-222
221-223
4
4-ClC H
H
15
90
300-302
299-301
5
6
7
4-MeC H
4-MeOC H
3-O NC H
H
H
H
35
30
25
86
88
85
269-271
270-272
288-291
269-270
270-272
288-290

2246 Bull. Korean Chem. Soc. 2011, Vol. 32, No. 7
Table 3. Continued
Abolghasem Davoodnia et al.
mp (ºC)
Entry
Ar
R
Products
Time (min)
Yields (%)
Found
Reported
8
4-O NC H
H
15
92
286-289
286-288
9
C H
C H
30
84
252-255
254-256
10
C H
4-MeC H
35
85
260-263
260-262
11
4-ClC H
4-MeOC H
30
88
250-252
251-252
12
4-ClC H
4-MeC H
30
88
270-271
269-271
13
4-MeOC H
C H
40
81
220-222
220-222

Carbon-Based Solid Acid as an Efficient and Reusable Catalyst
Bull. Korean Chem. Soc. 2011, Vol. 32, No. 7 2247
Table 3. Contiued
mp (ºC)
Entry
Ar
R
Products
Time (min)
Yields (%)
Found
Reported
14
4-MeOC H
4-MeC H
40
35
35
86
280-282
281-283
15
4-MeC H
4-MeOC H
86
238-240
238-241
16
3-O NC H
4-MeC H
85
285-287
283-284
17
4-ClC H
4-ClC H
45
80
232-233
230-232
18
3-O NC H
4-ClC H
50
84
169-171
170-172
Reaction conditions: dimedone (2 mmol), aromatic aldehyde (1 mmol), and ammonium acetate or aromatic amine (1 mmol) at 100 ºC under solvent-
free conditions. All the products were characterized by IR spectral data and comparision of their melting points with those of authentic samples. Also,
the structures of some products were confirmed by H NMR spectral data. Isolated yields.
Subsequently, therefore, all reactions were carried out at 100
ºC in the presence of CBSA (0.03 g) under solvent-free
conditions.
a wide variety of 1,8-dioxodecahydroacridines and the
obtained results are summarized in Table 3. Aromatic amines
substituted with electron-donating group or none reacted
successfully with dimedone and a wide range of aromatic
aldehydes bearing both electron-donating and electron-with-
Using these optimized reaction conditions, the scope and
efficiency of this approach was explored for the synthesis of

2248 Bull. Korean Chem. Soc. 2011, Vol. 32, No. 7
Abolghasem Davoodnia et al.
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purpose, the same model reaction was again studied under
optimized conditions. After the completion of the reaction,
the reaction mixture was cooled to room temperature, and
hot ethanol was added. The catalyst was separated by simple
filtration, dried at 60 °C under vacuum for 1 h, and reused
for a similar reaction. As shown in Figure 1, the catalyst
could be reused at least three times without significant loss
of activity.
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In conclusion, we have reported a simple new catalytic
method for the synthesis of 1,8-dioxodecahydroacridines by
one-pot three-component reaction of dimedone, aromatic
aldehydes, and ammonium acetate or aromatic amines using
CBSA as an efficient, reusable, and green heterogeneous
catalyst. The catalyst can be recycled after a simple work-up,
and used at least three times without substantial reduction in
its catalytic activity. High yields, short reaction times and
easy work-up are just a few of the advantages of this proce-
dure.
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Acknowledgments. The authors are thankful to Islamic
Azad University, Mashhad Branch for financial support.
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