An efficient one-pot synthesis of 1, 8-dioxodecahydroacridines using silica-supported polyphosphoric acid (PPA-SiO2) under solvent-free conditions

Article abstract of DOI:10.1155/2012/214231

Silica gel-supported polyphosphoric acid (PPA-SiO₂) was found to be an efficient catalyst for the synthesis of 1, 8-dioxodecahydroacridines via one-pot three-component condensation of aryl aldehydes, dimedone, and ammonium acetate or 4-methyl a

Full text of DOI:10.1155/2012/214231

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(2), 504-509
An Efficient One-Pot Synthesis of
,8-Dioxodecahydroacridines Using
1
Silica-Supported Polyphosphoric Acid
(
PPA-SiO ) under Solvent-Free Conditions
2
§
,*
#
FARID MOEINPOUR and AMIR KHOJASTEHNEZHAD
§
Department of Chemistry
Islamic Azad University - Bandar Abbas Branch
Bandar Abbas 7915893144, Iran
#
Department of Chemistry,
Islamic Azad University - Mashhad Branch, Mashhad, Iran
f.moeinpour@gmail.com
Received 28 May 2011; Accepted 5 August 2011
Abstract: Silica gel–supported polyphosphoric acid (PPA-SiO ) was found to
2
be an efficient catalyst for the synthesis of 1,8-dioxodecahydroacridines via
one-pot three-component condensation of aryl aldehydes, dimedone, and
ammonium acetate or 4-methyl aniline in high yields, easy workup procedure
and short period of times. The catalyst was separated by simple filtration and
used in the reaction three times without any significant loss of its activity.
Keywords: Decahydroacridine, One-pot reaction, Solvent-free, Silica-supported polyphosphoric acid
(PPA-SiO2).
Introduction
The principles of green chemistry have been introduced to eliminate or reduce the use of
hazardous materials such as H SO or H PO in chemical processes. Cleaner technologies
2
4
3
4
could be possible by making use of environmentally friendly materials involving the use of
1
-3
solid acids. These catalysts have many advantages over liquid acid catalysts . Recently,
solid-supported reagents, such as silica gel-supported acids, have gained considerable
interest in organic synthesis because of their unique properties of the reagents such as high
efficiency due to more surface area, more stability and reusability, low toxicity, greater
4,5
selectivity and ease of handling . The 1,4-dihydropyridine (DHP) ring system is found in a
variety of compounds including dyes, organic materials and pharmaceuticals. Among the
pharmaceuticals, 1,4-dihydropyridines have been employed for the treatment of cardiovascular
6
diseases, such as, angina pectoris . 1,8-Dioxodecahydroacridines with a 1,4-dihydropyridine
parent moiety, have received less attention than other 1,4-dihydropyridine derivatives. These
compounds have been shown to have very high lasing efficiencies and used as

An Efficient One-Pot Synthesis of Solvent-Free Conditions 505
7
,8
photoinitiators . Very few methods are known in the literature for the synthesis of
acridinediones. The most straightforward synthesis of this compounds involve the three-
component condensation of an aldehyde, dimedone, and ammonium acetate or appropriate
9
amines in the presence of several catalysts such as p-dodecylbenezenesulfonic acid ,
1
0
11
12
13
14
Amberlyst-15 , [Hmim]TFA , Tris(pentafluorophenyl)borane , FeCl -SiO , Proline
,
3
2
1
5
16
17
Acidic Ionic Liquids , Brønsted acidic imidazolium salts , Zn(OAC) .2H O , Silica-
2
2
1
8
19
Bonded S-Sulfonic Acid and Ceric ammonium nitrate (CAN) . However, some of these
methodologies encounter some limitations, such as long reaction times, unsatisfactory
yields, harsh reaction conditions, expensive catalysts and tedious work-up procedure. Thus,
As part of our current studies on the development of new routes for the synthesis of organic
2
0,21
compounds using reusable catalysts
, in this context, we became interested to report a
simple, efficient and eco-friendly synthesis of 1,8-dioxodecahydroacridines via three-
component condensation of an aryl aldehyde, dimedone, and ammonium acetate or 4-methyl
aniline using silica-supported polyphosphoric acid (PPA-SiO ) as a reusable catalyst under
2
solvent free conditions (Scheme 1).
Scheme 1
Experimental
All chemicals were commercially available and used without further purification. All yields
refer to isolated products after purification. Products were characterized by comparison of
1
spectroscopic data (IR, H NMR spectra) and melting points with authentic samples. The
2
2
catalyst was synthesized according to the literature . Melting points were recorded on an
electrothermal type 9100 melting point apparatus. The IR spectra were obtained on a 4300
1
Shimadzu spectrophotometer as KBr disks. The H NMR (500 MHz) spectra were recorded
on Bruker DRX500 spectrometer in CDCl relative to TMS.
3
General procedure for the synthesis of 1,8-dioxodecahydroacridines using PPA-
SiO as catalyst
2
A mixture of dimedone 1 (2 mmol), aromatic aldehyde 2a-h (1 mmol), ammonium acetate
+
22
(
1 mmol) or 4-methyl aniline (1 mmol) and PPA-SiO (0.02 g, 0.0100 mmol H ) was
2
heated on the oil bath at 100 °C for 5-25 min. The reaction was monitored by TLC. After the
completion of the reaction, the reaction mixture was cooled to room temperature and hot
ethanol was added. The solid residue was dissolved in hot ethanol and filtered off. The crude
product was collected from the filtrate after cooling to room temperature and recrystallized
from ethanol to give compounds 3a-l in high yields. All of the 1,8-dioxodecahydroacridine

5
0ꢀ FARID MOEINPOUR et al.
derivatives are known and were identified by comparison of their physical and spectroscopic
8,16,17,23,24
data (IR, NMR) with those of authentic samples
.
1
Selected physical and HNMR data of the products
3
,3,6,6-Tetramethyl-9-(4-chlorophenyl)-1,2,3,4,5,6,7,8-octahydroacridine-1,8-dione (3)
1
m.p. 299 – 301 °C ; H NMR (CDCl , 500 MHz): δ 0.96 (s, 6H, 2CH ), 1.09 (s, 6H, 2CH );
3
3
3
2
.16 (d, J ＝16 Hz, 2H, H-2a,7b), 2.27 (d, J ＝16 Hz, 2H,H-2a',7b'), 2.28 (d, J ＝16.5 Hz,
H-4c,5d), 2.35 (d, J ＝16.5 Hz, H-4c',5d'), 5.06 (s, 1H, H-9), 7.07 (brs, 1H, NH), 7.17 (d, J
8.3 Hz, 2H, ArH), 7.29 (d, J ＝ 8.3 Hz, 2H, ArH).
＝
3
,3,6,6-Tetramethyl-9-(4-nitrophenyl)-1,2,3,4,5,6,7,8-octahydroacridine-1,8-dione (8)
o
1
m.p 286-288 C H NMR (500 MHz, CDCl ) δ: 0.85 (s, 6H, 2Me), 1.01 (s, 6H, 2Me), 1.96
3
(
d, J＝16.5 Hz, 2H, H-2a,7b),2.23 (d, J＝16.5 Hz, 2H, H-2a',7b'), 2.33 (d, J＝16.5 Hz,2H,
H-4c,5d), 2.52 (d, J＝16.5 Hz, 2H, H-4c',5d'), 4.90(s, 1H, H-9), 7.5 (d, J＝8.5 Hz, 2H, ArH),
.1 (d, J＝8.5 Hz, 2H, ArH), 6.1 (brs, 1H, NH).
8
3,3,6,6-Tetramethyl-1,8-dioxo-9-(4-chlorophenyl)-10-(4-methylphenyl)-decahydro-
acridine (10)
1
m.p. 270-271°C; H NMR (500 MHz, CDCl ): δ 0.80(s, 6H,), 0.94 (s, 6H), 1.83 (d, J = 17.4
3
Hz, 2H), 2.05–2.21 (m, 6H), 2.49(s, 3H), 5.23 (s, 1H), 7.08 (d, J = 8.4 Hz, 2H), 7.21 (d, J =
7
.6 Hz, 2H),7.36 (t, J = 8.4 Hz, 4H).
Recycling of the catalyst
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 100 °C
under vacuum for 2 h and reused for the similar reaction. As it is shown in Figure 1, the
catalyst could be reused at least three times without significant loss of activity.
91
89
87
100
80
60
40
20
0
1
2
3
Reaction cycles
Figure 1
Results and Discussion
To optimize the reaction conditions, the reaction of benzaldehyde (1 mmol), dimedone
2 mmol), and ammonium acetate (1 mmol) in the presence of PPA-SiO (0.02 g) was
(
2
selected as a model. The reaction was carried out in various solvents and under solvent-free
conditions. As shown in Table 1, in comparison to conventional methods, the yields of the
reaction under solvent-free conditions are greater and the reaction time is shorter. The
shortest time and best yield were achieved at 100 °C. Next, to found the optimum quantity

An Efficient One-Pot Synthesis of Solvent-Free Conditions 50ꢁ
of PPA-SiO , the reaction of benzaldehyde, dimedone and ammonium acetate was carried
2
out under the previously mentioned conditions using different quantities of catalyst at
1
00 °C. The use of 0.02 g of catalyst resulted in the highest yield in 10 min.
Table 1. Synthesis of 1,8-dioxodecahydroacridine 3a in the presence of PPA-SiO (0.02 g,
2
+
22
0
.0100 mmol H ) in different solvents and optimization of temperature in solvent-free
conditions.
a
Entry
Solvent
MeOH
EtOH
Temperature, °C
Time, min
300
300
300
300
110
10
Yield, %
Trace
82
1
2
3
4
5
7
8
64
78
81
100
70
80
CH CN
85
72
62
75
92
93
3
H O
2
Solvent-free
Solvent-free
Solvent-free
Solvent-free
100
120
10
10
9
a
The yields were calculated based on benzaldehyde and refer to the pure isolated product.
Thus, we prepared a range of 1,8-dioxodecahydroacridines under the optimized reaction
conditions. In all cases, aromatic aldehydes with substituents carrying either electron-
donating or electron-withdrawing groups reacted successfully and gave the expected
products in excellent yields and short reaction times. The kind of aldehyde has no significant
effect on the reaction. The results are shown in Table 2. It was indicated that both electron
rich and electron deficient aldehydes reacted well, mostly leading to high yields of products.
+
22
Table 2. Preparation of 1,8-dioxodecahydroacridines using PPA-SiO (0.02 g, 0.010 mmol H )
as catalyst .
2
a
b
Time
min
c
M.p., °C
Found Reported
Entry
Ar
R'
Products
Yield
2
3
1
2
3
4
5
6
7
8
9
C H
6
H
3a
3b
3c
3d
3e
3f
10
10
5
93 192-195 (190-192)
95 239-242 (241-243)
92 300-302 (299-301)
5
1
1
7
7
4-BrC H
H
6
4
4-ClC H
H
6
4
4
8
2-ClC H
H
18
14
18
13
5
90 220-222 (221-223)
6
2
4
4-OCH C H
4
H
89 270-272 (270-272)
90 269-271 (190-192)
3
6
8
4-CH C H
4
H
3
6
1
7
7
6
6
6
6
3-NO C H
H
H
3g
3h
3i
88 288-291 (288-290)
94 286-289 (286-288)
87 260-263 (260-262)
90 270-271 (269-271)
88 280-282 (281-283)
93 285-287 (283-284)
2
6
4
4
1
1
1
1
1
4-NO C H
2
6
C H
6
4-CH C H
25
18
25
24
5
3
6
4
4
4
4
1
1
1
0
1
2
4-ClC H
4-CH C H
3j
6
4
3
6
4-OCH C H 4-CH C H
3k
3l
3
6
4
3
6
3-NO C H
4-CH C H
3 6
2
6
4
a
+ 22 b
The amount of PPA-SiO as a catalyst was chosen (0.020 g, 0.010 mmol H )
. All products were
2
1
characterized by use of H NMR and IR spectral data, and comparison of their melting points with
c
those of authentic samples. Isolated yields.

5
0ꢂ FARID MOEINPOUR et al.
The catalyst also showed excellent reusability in these reactions. The catalyst was
recovered in excellent yields (91, 89 and 87% in Figure 1) and used in the reactions three
times; it showed the same activity as fresh catalyst without any significant loss of its
activity.
To show merit of the present work in comparison with reported results in the literature,
1
2
10
we compared results of PPA-SiO with tris(pentaflurophenyl)borane , Amberlyst-15 ,
2
14
19
16
proline , ceric ammonium nitrate (CAN) and brønsted acidic imidazolium salts as
catalysts in the reaction of benzaldehyde, dimedone and ammonium acetate. As shown in
Table 3, PPA-SiO can act as high efficiency catalyst with fast time and high yields of the
2
obtained products.
1
2
Table 3. Comparison results of PPA-SiO with tris(pentaflurophenyl)borane , Amberlyst-
1
2
10
14
19
16
5 , proline , ceric ammonium nitrate (CAN) and brønsted acidic imidazolium salts as
catalysts in the reaction of benzaldehyde, dimedone, and ammonium acetate.
Entry
Catalyst
Tris(pentaflurophenyl)borane
Amberlyst-15
Time/min
168
Yield%
80
1
2
3
4
5
6
240
300
240
240
81
98
98
85
L - proline
Ceric ammonium nitrate (CAN)
Brønsted acidic imidazolium salts
PPA-SiO2
10
93
Conclusion
In conclusion, we have reported a new simple catalytic method for the synthesis of 1,8-
dioxodecahydroacridines by one-pot condensation reaction of aryl aldehydes, dimedone, and
ammonium acetate or 4-methyl aniline using PPA-SiO as an efficient, reusable and green
2
heterogeneous catalyst under solvent-free conditions. The catalyst can be recycled after a
simple work-up and reused at least three runs without appreciable reduction in its catalytic
activity. High yields, short reaction times, easy work-up and absence of any volatile and
hazardous organic solvents are some advantages of this approach.
Acknowledgment
The authors are thankful to the Islamic Azad University-Bandar Abbas Branch Research
Council for partial financial support.
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