Nanoparticles tungstophosphoric acid supported on polyamic acid: catalytic synthesis of 1,8-dioxo-decahydroacridines and bulky bis(1,8-dioxo-decahydroacridine)s

Article abstract of DOI:10.1007/s13738-016-0860-8

Tungstophosphoric acid nanoparticles supported on polyamic acid (TPA NPs/PAA) was prepared and employed as a catalyst for the facile selective synthesis of 1,8-dioxo-decahydroacridines and some bulky bis(1,8-dioxo-decahydroacridine)s via one-pot condensation of 5,5-dimethyl-1,3-cyclohexanedione and various aldehydes with aniline or ammonium acetate in ethanol–water solution. This catalyst was characterized by FT-IR, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), thermogravimetric analysis (TG), energy-dispersive X-ray analysis (EDAX), and inductively coupled plasma optical emission spectrometry (ICP-OES). The catalyst showed high thermal stability and good reusability. The products were isolated in high purity and the catalyst was easily separated in a simple workup and recycled several times without noticeable loss of activity under the described reaction conditions. The reaction is characterized by short reaction time, high efficiency, and mild reaction conditions.

Full text of DOI:10.1007/s13738-016-0860-8

J IRAN CHEM SOC
DOI 10.1007/s13738-016-0860-8
ORIGINAL PAPER
Nanoparticles tungstophosphoric acid supported on polyamic
acid: catalytic synthesis of 1,8‑dioxo‑decahydroacridines
and bulky bis(1,8‑dioxo‑decahydroacridine)s
Masoud Nasr‑Esfahani1 · Zahra Rafiee1 · Hassan Kashi1
Received: 16 October 2015 / Accepted: 9 April 2016
© Iranian Chemical Society 2016
Abstract Tungstophosphoric acid nanoparticles sup-
ported on polyamic acid (TPA NPs/PAA) was prepared
and employed as a catalyst for the facile selective synthesis
of 1,8-dioxo-decahydroacridines and some bulky bis(1,8-
dioxo-decahydroacridine)s via one-pot condensation of
5,5-dimethyl-1,3-cyclohexanedione and various aldehydes
with aniline or ammonium acetate in ethanol–water solu-
tion. This catalyst was characterized by FT-IR, X-ray dif-
fraction (XRD), field emission scanning electron micros-
copy (FESEM), transmission electron microscopy (TEM),
thermogravimetric analysis (TG), energy-dispersive X-ray
analysis (EDAX), and inductively coupled plasma optical
emission spectrometry (ICP-OES). The catalyst showed
high thermal stability and good reusability. The products
were isolated in high purity and the catalyst was easily sep-
arated in a simple workup and recycled several times with-
out noticeable loss of activity under the described reaction
conditions. The reaction is characterized by short reaction
time, high efficiency, and mild reaction conditions.
These compounds are polyfunctionalized 1,4-dihydropyri-
dines. They have a wide range of pharmacological prop-
erties, such as antitumor [1], antimalarial [2], antimicro-
bial [3], and fungicidal [4], and are prescribed as calcium
b-blockers [5]. Also, 9-arylacridines interact strongly with
topoisomerase-I (Topo-1) and act as anticancer agents
[6]. Bucricaine is used topically for surface anesthesia of
the eye and given by injection for infiltration anesthesia,
peripheral nerve block, and spinal anesthesia. Quinacrine
is also known as mepacrine. It acts as a gametocytocide.
It destroys the sexual erythrocytic forms of plasmodia and
acts as an antimalarial agent. Proflavine is found to be
active as bacteriostatic against many Gram-positive bac-
teria [7]. Amsacrine is an antineoplastic agent. It has been
used in acute lymphoblastic leukemia (Scheme 1) [8]. In
addition, 1,8-dioxo-decahydroacridines are used as laser
dyes [9, 10] and photoinitiators [11].
Multicomponent reactions of aldehydes, ammonium
acetate or amines and dimedone are used for the prepara-
tion of 1,8-dioxo-decahydroacridines in the presence of
various catalysts such as amberlyst-15 [12], ceric ammo-
nium nitrate (CAN) [13], Brønsted acidic imidazolium salts
[14], CeCl3·7H2O [15], 4-dodecylbenzenesulfonic acid
(DBSA) [16], 1,3-disulfonic acid imidazolium carboxylate
ionic liquids [17], FSG-Hf(NPf2)4 [18], [MIMPS]3PW12O40
[19], and protic pyridinium ionic liquid ([2-MPyH]OTf)
[20].
Keywords Heterogeneous catalyst · Bis(1,8-dioxo-
decahydroacridine) · Polyamic acid · Tungstophosphoric
acid · Nanoparticle · Supported catalyst
Introduction
Acridine derivatives, especially 1,8-dioxo-decahydroacr-
idine, are an important class of heterocyclic compounds.
However, many of these methods suffer from disadvan-
tages such as long reaction times, toxic organic solvents,
unsatisfactory yields, and expensive catalysts. Thus, the
development of simple, efficient, and high-yielding meth-
ods using new catalysts for the synthesis of these com-
pounds would be highly desirable. In recent years, nano-
catalysts such as ZnO nanoparticles [21], nano titanium
dioxide [22], sulfonic acid-functionalized nanoporous silica
* Masoud Nasr-Esfahani
manas@yu.ac.ir
1
Department of Chemistry, Yasouj University,
Yasouj 75918-74831, Iran
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J IRAN CHEM SOC
Scheme 1 Representative drugs
with acridine constitutional
formula
Scheme 2 Synthesis of
1,8-dioxo-decahydroacridines
(SBA-Pr-SO3H) [23], and Fe3O4 nanoparticles [24] have
been used for the synthesis of 1,8-dioxo-decahydroacrid-
ines. Also the use of Fe2O3@SiO2‐PW has been reported
for the synthesis of acridines, but no selectivity has been
observed [25].
The major drawbacks of heteropoly acids are extreme
water solubility, hard recovery, and recycling which limit
their practical applications. The utilization of heteropoly
acids supported on polymer as heterogeneous catalysts in
organic synthesis seems to be one of the most attractive
ways to avoid the above-mentioned problems. They are
referred to as environmentally benign catalysts because
of their non-polluting properties [26]. In general, heterop-
oly acids supported on polymer offer higher surface area,
high atom efficiency, easy product purification, and simple
reusability.
In continuation of our interest in the application of het-
erogeneous catalysts to the development of synthetic meth-
ods [27–31], herein we report a simple and highly efficient
route for the synthesis of 1,8-dioxo-decahydroacridines
using tungstophosphoric acid nanoparticles supported on
polyamic acid (TPA/PAA) as a recoverable catalyst with
high catalytic activity under reflux conditions in ethanol–
water as solvent (Schemes 2, 3).
voltage. Thermal degradation of polymers was carried
out in the range 28–800 °C at a heating rate of 10 °C/min
under nitrogen atmosphere using a thermogravimetric ana-
lyzer-TG-209 F3, Netzsch, Germany. Optical rotation was
obtained with the Jasco p-1030 polarimeter. The morphol-
ogy of the polymer and catalyst was observed using field
emission scanning electron microscopy (FE-SEM) (KYKY-
EM-3200) and the X-ray diffraction (XRD) patterns of the
polymer and catalyst were recorded using an XRD (Bruker,
D8 Advance, Rheinstetten, Germany) with a copper target
at 40 kV and 35 mA and Cu Kα (λ = 1.54 Ǻ) in the range
of 10°–80° at the speed of 0.05°/min. Transmission electron
microscopy was recorded using a Zeiss-EM10C operated
at a 100 kV accelerating voltage. The inductively coupled
plasma optical emission spectrometry (ICP-OES) spectra
were recorded using an ICP-OES-730-Varian instrument.
The melting points were determined using an electrother-
mal digital melting point apparatus and are uncorrected.
Reaction courses and product mixtures were monitored by
thin-layer chromatography (TLC).
Synthesis of polymer
To a 50 mL three-necked round-bottomed flask equipped
with a high-power electromagnetic stirrer and N2 inlet,
3,5-diamino-1,2,4-triazole (11, 0.500 g, 5.05 mmol)
and freshly distilled NMP (4 mL) were added. A clear
diamine solution was formed after stirring for 5 min.
Then, 3,3′,4,4′-benzophenonetetracarboxylic dianhydride
(BTDA) 10 (1.100 g, 5.05 mmol) was added immediately,
followed by additional NMP (2 mL) to adjust the solid con-
tent of the mixture to be 20 wt%. The mixture was stirred
at room temperature for 24 h to afford an almost color-
less, highly viscous solution. The inherent viscosity of the
resulting PAA was 0.75 dl g−1, which was measured in
Experimental
Chemicals were purchased from Merck or Aldrich. IR
spectra were recorded from KBr discs on a JASCO FT-IR-
680. NMR spectra were taken with a Bruker 400 MHz
Ultrashield spectrometer at 400 MHz (1H) and 100 MHz
(13C) using CDCl3 or DMSO-d6 as a solvent. Energy-dis-
persive X-ray spectroscopy analyses (EDAX) were carried
out on a PHILIPS XL30, operated at a 20 kV accelerating
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J IRAN CHEM SOC
Scheme 3 Selective synthesis
of 1,8-dioxo-decahydroacrid-
ines and bis(1,8-dioxo-decahy-
droacridine)s from dialdehyde,
amine, and dimedone with
different molar ratios
Scheme 4 Synthesis of polyamic acid (PAA)
DMF at a concentration of 0.5 g dl−1 at 25 °C (Scheme 4)
[32].
pH of effluent water was neutralized. The resulting solid
was titrated with sodium hydroxide solution and the sup-
ported acid was determined to be 98 %. Thus, with respect
to the initial amount of polymer and acid, the catalyst was
30 % w/w from heteropoly acid relative to polyamic acid.
IR (KBr, cm−1): 3320, 3064, 2925, 1785, 1727, 1589,
1450, 1346, 1292, 1098, 1065, 980, 836, 634.
[α]2D0 = +38.4° (c = 0.005 g/mL, DMF); IR (KBr,
cm−1): 3490, 3064, 2925, 1785, 1589, 1450, 1346, 1292,
1182, 917, 856, 798.
Preparation of TPA NPs/PAA
Polyamic acid (5 g) in 10 mL of DMF was stirred at 50 °C.
Tungstophosphoric acid (1.5 g) was dissolved in deionized
water and impregnated dropwise into the mixture and was
stirred for 0.5 h at 50 °C and 24 h at room temperature.
After evaporating the solvent under reduced pressure, a
brown solid was obtained. The solid was washed with dis-
tilled water and filtered. This work was repeated until the
Synthesis of N‑butyl‑N‑phenylaniline
In a round-bottom flask, 1-bromobutane (2.74 g, 0.02 mol),
diphenylamine (2.014 g, 0.012 mol), and sodium hydrox-
ide (4.0 g, 0.1005 mol) were added in dimethylsulfoxide
(30 mL), followed by heating at 110 °C for 12 h. After
cooling to room temperature the resulting mixture was
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J IRAN CHEM SOC
extracted with ethyl acetate/water. The solvent was evap-
orated and the resulting crude liquid was purified by col-
umn chromatography on neutral alumina using hexane as
solvent to give a colorless liquid with a yield of 80.2 %.
1H·NMR (CDCl3), δ (ppm): 7.27–7.23 (4H, m, Ar–H),
6.98–6.96 (4H, m, Ar–H), 6.94–6.92 (2H, m, Ar–H), 3.61
(2H, t, J = 8.0 Hz, N–CH2), 1.44–1.42 (2H, m, CH2), 1.31–
1.29 (2H, m, CH2), 0.89 (3H, t, J = 7.0 Hz, CH3).
J = 16.3 Hz), 2.16 (4H, s, 2×CH2), 1.56–1.48 (2H, m,
CH2), 1.34–1.26 (2H, m, CH2), 1.10 (6H, s, 2×CH3),
1.00 (6H, s, 2×CH3), 0.90 (3H, t, J = 3.5 Hz); 13C NMR
(100 MHz, CDCl3) δ (ppm): 194.22 (C=O), 191.05 (–
C=O, aldehyde), 149.54 (C=C), 152.14, 148.65, 138.12,
130.85, 128.76, 127.29, 119.62, 113.81 (Ar–C), 112.80
(C=C), 50.12 (2×CH2), 46.16 (CH2), 40.86 (2×CH2),
39.71 (CH), 31.85 (2×C(CH3)2), 29.09 (CH2), 28.03
(4×CH3), 20.07 (CH2), 13.85 (CH3).
Synthesis of 4,4′‑(butylazanediyl)dibenzaldehyde (5)
9,9′-((Butylazanediyl)bis(1,4-phenylene))bis(3,3,6,6-
tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-
dione) (7): Yellow solid: m.p. 231–233 °C; IR (KBr,
cm−1): 3278, 3072, 2956, 2869, 1631, 1612, 1506, 1486,
1222; 1H·NMR (400 MHz, DMSO-d6) δ (ppm): 8.81
(2H, s, NH), 7.12 (4H, d, J = 8.5 Hz, Ar–H), 6.73 (4H,
d, J = 8.5 Hz, Ar–H), 5.03 (2H, s, 2×CH), 3.70 (2H, t,
J = 6.5 Hz, N–CH2), 2.33 (4H, d, 2×CH2, J = 18.0 Hz),
2.21 (4H, d, 2×CH2, J = 16.3 Hz), 2.06 (8H, s, 4×CH2),
1.54–1.51 (2H, m, CH2), 1.29–1.24 (2H, m, CH2), 1.09
(12H, s, 4×CH3), 1.00 (12H, s, 4×CH3), 0.88 (3H, t,
J = 5.5 Hz); 13C·NMR (100 MHz, CDCl3) δ (ppm): 198.68
(C=O), 151.39 (C=C), 147.07, 128.43, 120.26, 119.96
(Ar–C), 115.19 (C=C), 60.42 (4×CH2), 58.50 (CH2),
50.79 (4×CH2), 32.74 (2×CH), 29.43 (4×C(CH3)2), 27.33
(CH2), 21.08 (8×CH3), 18.45 (CH2), 14.14 (CH3).
Under N2 atmosphere at 0 °C, freshly distilled POCl3
(23.1 mL, 25 eq.) was added dropwise to DMF (17.6 mL,
23 eq) and then stirred for 1 h. Then, N-butyl-N-phenylani-
line (2.230 g, 9.9 mmol) was added to this solution, and the
resulting mixture was stirred for 4 h at 95 °C. After cooling
to room temperature, the mixture was poured into a beaker
containing ice cubes and basified with 4 M NaOH. The
resulting mixture was extracted with EA/brine. After evap-
orating the organic solvent, the crude product was purified
by column chromatography on neutral alumina using a
mixture of ethylacetate/n-hexane (1:4, v/v), to give a pale
1
green liquid (2.5 g, yield = 90 %). H·NMR (CDCl3), δ
(ppm): 9.85 (2H, s, CHO), 7.78 (4H, d, J = 8.4 Hz, Ar–H),
7.13 (4H, d, J = 8.4 Hz, Ar–H), 3.82 (2H, t, J = 8.0 Hz,
N–CH2), 1.45–1.41 (2H, m, CH2), 1.30–1.26 (2H, m, CH2),
0.85 (3H, t, J = 6.5 Hz, CH3).
4-(Butyl(4-(3,3,6,6-tetramethyl-1,8-dioxo-10-phe-
nyl-1,2,3,4,5,6,7,8,9,10-decahydroacridin-9-yl)phenyl)
amino)benzaldehyde (8): Orange solid; mp: 106–109 °C;
[α]2D0 = +71.5° (c = 0.033 g/mL, CHCl3); IR (KBr, cm−1):
2956, 2923, 2869, 1718, 1642, 1592, 1508, 1448, 1249; 1H
NMR (400 MHz, CDCl3) δ (ppm): 9.74 (1H, s, CHO), 7.66
(2H, d, J = 8.8 Hz, Ar–H), 7.38–7.17 (4H, m, Ar–H), 7.12
(1H, d, J = 5.5 Hz, Ar–H), 6.96 (2H, d, J = 8.5 Hz, Ar–H),
6.88 (2H, d, J = 8.6 Hz, Ar–H), 6.70 (2H, d, J = 8.5 Hz,
Ar–H), 5.49 (1H, s, CH), 3.71 (1H, t, J = 7.6 Hz, N–
CH2), 3.62 (1H, t, J = 7.6 Hz, N–CH2), 2.45 (2H, d,
J = 13.4 Hz, CH2), 2.38 (2H, d, J = 16.0 Hz, CH2), 2.26
(4H, s, 2×CH2), 1.39–1.33 (2H, m, CH2), 1.28–1.24 (2H,
m, CH2), 1.14 (6H, s, 2×CH3), 1.11 (6H, s, 2×CH3), 0.94
(3H, t, J = 6.7 Hz, CH3); 13C·NMR (100 MHz, CDCl3) δ
(ppm): 190.23 (C=O), 189.28 (–C=O, aldehyde), 160.02
(C=C), 145.93, 131.79, 130.16, 129.42, 128.51, 127.59,
127.20, 125.62, 123.84, 120.51, 115.73, 115.15 (Ar–C),
113.25 (C=C), 50.33 (2×CH2), 47.08 (CH2), 46.47
(2×CH2), 43.76 (CH), 31.37 (2×C(CH3)2), 29.75 (CH2),
27.38 (4×CH3), 20.31 (CH2), 13.96 (CH3).
General procedure for the synthesis
of 1,8‑dioxo‑decahydroacridine
In a 25 mL flask, a mixture of aldehyde (1 mmol),
5,5-dimethyl-1,3-cyclohexanedione (2 mmol), amine
(1 mmol) and nanoparticles TPA/PAA (30 wt%, 0.04 g)
was refluxed in ethanol–water (2 mL, v/v = 1) for 0.5–1 h.
After completion of the reaction as monitored by TLC,
because the heterogeneous catalyst was insoluble in etha-
nol–water, it was removed by filtration and the solution
was cooled to room temperature and the pure product was
crystallized in EtOH to form crystals. The removed catalyst
was washed with ethanol and dried prior to reuse in subse-
quent reactions.
4-(Butyl(4-(3,3,6,6-tetramethyl-1,8-dioxo-1,2,3,4,
5,6,7,8,9,10-decahydroacridin-9-yl)phenyl)amino)benzal-
dehyde (6): Cream solid; mp: 161–163 °C; [α]2D0 = +109.2°
(c = 0.021 g/mL, CHCl3); IR (KBr, cm−1): 3282, 3066,
2956, 2871, 1683, 1643, 1608, 1484, 1220; 1H·NMR
(400 MHz, DMSO-d6) δ (ppm): 9.71 (1H, s, CHO), 8.32
(1H, s, NH), 7.81 (2H, d, J = 8.1, Ar–H), 7.08 (2H, d,
J = 8.5, Ar–H), 6.91 (2H, d, J = 8.1 Hz, Ar–H), 6.40
(2H, d, J = 8.5 Hz, Ar–H), 4.73 (1H, s, CH), 4.14 (1H, q,
J = 7.2 Hz, N–CH2), 3.77–3.71 (1H, q, J = 7.6 Hz, N–
CH2), 2.52 (2H, d, CH2, J = 18.0 Hz), 2.45 (2H, d, CH2,
9,9′-((Butylazanediyl)bis(1,4-phenylene))bis(3,3,6,6-
tetramethyl-10-phenyl-3,4,6,7,9,10-hexahydroac-
ridine-1,8(2H,5H)-dione) (9): Pale yellow solid; mp: 169–
171 °C. IR (KBr, cm−1): 3062, 2960, 1689, 1596, 1571,
1
1494, 1243; H NMR (400 MHz, CDCl3) δ (ppm): 7.61
(2H, d, J = 8.78 Hz, Ar–H), 7.86 (4H, t, J = 7.9 Hz, Ar–H),
7.18 (4H, d, J = 7.74 Hz, Ar–H), 7.13 (4H, t, J = 7.4 Hz,
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J IRAN CHEM SOC
Fig. 1 The X-ray diffrac-
tion pattern of TPA NPs/PAA,
standard pattern of (TPA), and
polymer
Ar–H), 6.68–6.64 (4H, m, Ar–H), 5.31 (2H, s, CH), 3.69
(2H, t, J = 7.7 Hz, N–CH2), 2.38 (8H, s, 4×CH2), 2.05
(8H, s, 4×CH2), 1.32–1.18 (4H, m, 2×CH2), 1.03 (24H,
s, 8×CH3), 0.87 (3H, t, J = 7.7 Hz, CH3), 13C NMR
(100 MHz, CDCl3) δ (ppm): 195.36 (C=O), 160.01 (C=C),
139.14, 139.04, 129.17, 124.29, 122.92, 122.87, 122.80,
122.75 (Ar–C), 110.73 (–C=C), 50.12 (4×CH2), 41.99
(CH2), 41.93 (CH2), 32.25 (4×CH2), 29.55 (4×C(CH3)2),
29.09 (CH2), 28.03 (8×CH3), 27.92 (2×CH), 20.07 (CH2),
13.85 (CH3).
heterogeneous catalyst. Figure 1 shows the XRD patterns
of the pure polymer (a) and prepared catalyst (b). As seen
in Fig. 1, the peak signals at (210), (020), (311), (004),
(214), (215), (430), (512), (043), (434), (051), (516), and
(046) confirmed the formation of the orthorhombic crystal
system, which coincides with the JCPD 038-0178 standard.
The size of TPA NPs/PAA powder was also determined by
X-ray line broad using the Debye–Scherrer formula given
as D = 0.9λ/βcosθ, where D is the average crystalline size,
λ the X-ray wavelength used (1.5406 Å for Cu Kα), β is the
angular line width at half maximum intensity, and θ is the
Bragg’s angle. The average size of tungstophosphoric acid
supported on polyamic acid powder for 2θ = 9.4679° was
estimated around 35 nm.
Results and discussion
Characterization of the catalyst
To investigate the morphology and particle size of tung-
stophosphoric acid supported on polyamic acid, FE-SEM
images of TPA NPs/PAA are presented in Fig. 2. This
result shows that nanoparticles were obtained with an
Nanoparticles of tungstophosphoric acid supported on
polyamic acid (TPA NPs/PAA) were prepared as a new
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J IRAN CHEM SOC
Fig. 2 FE-SEM images of the
catalyst (TPA NPs/PAA)
and confirmed them to be in nanoscale size, where the dark
areas represent the TPA NPs and the gray/white areas the
PAA matrix (Fig. 3). The relatively strong interactions
between the PAA matrix and TPA NPs were responsible for
observing NPs with almost spherical shapes. The NPs size
ranged from 15 to 20 nm, except for a very few agglom-
erates showing a rather spherical shape. The transmission
electron microscopy (TEM) image of the TPA NPs/PAA
was in good agreement with SEM and XRD analysis and
successfully confirmed the supporting of heteropoly acid
nanoparticles on the polymer (Fig. 3).
As a useful technique, FT-IR can be used for the study of
surface interactions between HPA and organic compounds.
Figure 4 shows the FT-IR spectra of pure PAA, TPA, and
TPA/PAA. The FT-IR spectrum of the 30 % w/w of TPA
on PAA shows four bands in the range 1065 to 634 cm−1
related to Keggin bands of heteropoly acid in TPA/PAA
Fig. 3 Transmission electron microscopy (TEM) image of TPA/PAA
(Fig. 4c). However, small shifts of νW = Od (980 cm−1
)
average diameter of 40 nm as confirmed by XRD analy-
sis. The transmission electron microscopy (TEM) image of
TPA NPs/PAA demonstrated a homogeneous nanostructure
and νW–Oc–W (634 cm−1) vibrations were registered indi-
cating interactions of the support with the most external
atoms Od and Oc of the Keggin anion.
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Energy-dispersive X-ray spectroscopy (EDAX) showed
the presence of C, N, O, P, and W in tungstophosphoric
acid nanoparticles supported on polyamic acid (Fig. 5).
The elemental distribution mapping of this analysis shows
signals of carbon:nitrogen:oxygen:phosphorous:tungsten in
the ratio of 31.7:4.9:16.6:0.7:46.0 wt%, respectively. This
confirms the successful incorporation of the expected ele-
ments in the material network.
The percentage of tungsten (W) in the catalyst was
also determined by ICP-OES analysis which showed
33.6 %w/w of tungsten.
Since the catalyst at different temperatures to be used
should also be investigated thermal resistance. For this
purpose, the thermogravimetric analyzer (TGA) was used.
We observed that the TPA/PAA (Fig. 6) and polyamic acid
[32] remained unchanged until 300 °C, but around 40 %
decomposed at higher temperatures up to 600 °C. The mass
remaining above 600 °C is attributed to the weight percent-
age of polymer left undecomposed under nitrogen atmos-
phere [32]. From these data, it is clear that no change in
the thermal stability of the polymer occurred on support-
ing tungstophosphoric acid on polyamic acid [32]. The
TG diagram also shows that the supported PAA is decom-
posed slower than free PAA [32], so that its main decom-
position initiates at higher temperature (about 50 °C).
This means that TPA enhances the thermal stability of the
supported PAA. Moreover, some activation parameters
of decomposition thermal steps were evaluated based on
the Coats–Redfern model [33] and the results have been
compiled in Table 1. Relatively high values of activation
energy of decomposition steps confirm the stability of the
catalyst. The positive values of enthalpy change and Gibbs
free energy indicate the endothermic character of the pro-
cesses. The negative values of entropy change suggest the
Fig. 4 FT-IR spectra of TPA (a), PAA (b), and TPA/PAA (c)
Fig. 5 Energy-dispersive
spectroscopy (EDAX) pattern of
TPA/PAA
Element
Carbon
Series
K-series
K-series
K-series
K-series
L-series
Sum:
[wt. %]
31.7417026
4.89175618
16.6157551
0.74346449
46.0073217
100
[Norm. at. %]
61.39100601
8.113022304
24.12515192
0.557596412
5.813223355
100
Nitrogen
Oxygen
Phosphorus
Tungsten
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Fig. 6 Thermal gravimetric
analysis curves of TPA/PAA
Table 1 Thermal analysis data including temperature range, differential thermogravimetry (DTG) peak, mass loss, and thermokinetic param-
eters of the thermal decomposition process
Compound Temp. range (°C) Mass loss (%) Peak temp. (°C) E* (kJ/mol) A* (1/S)
∆S* (kJ/mol) ∆H* (kJ/mol) ∆G* (kJ/mol)
TPA/PAA
160–240
240–346
346–500
8.71
12.5
37
198.21
277.42
405.56
99.3736
37.4135
76.1098
2.03 × 108 −8.97 × 101 95.4548
1.38 × 102
1.64 × 102
1.98 × 102
4.30
−2.38 × 102 32.8360
2.31 × 103 −1.87 × 102 70.4670
abnormal nature of the decomposition process of the cur-
rent catalyst.
Based on the functional groups in the polymer structure
(NH, C=O) and TPA (OH, P=O), it seems that hydrogen
bonding and some other polar forces are the most interac-
tive between PAA and TPA [34].
selected solvents, such as water, ethanol, chloroform, ace-
tonitrile, methanol, toluene, ethanol–water, and a solvent-
free system, the best result was obtained after 40 min in
ethanol–water (v/v = 1) as a solvent under reflux condi-
tions in excellent yield (Table 2, entry 8).
For investigation of the effect of various amounts of
TPA loading on PAA in the synthesis of 1,8-dioxo-decahy-
droacridines, different weight percents of heteropoly acid
were used. Table 2 and Fig. 7a show the differences in the
catalytic activity among 10–40 wt% catalysts loading of
TPA on PAA. Increment in the loading of the supported
tungstophosphoric acid from 10 to 30 wt% causes the
acceleration of the reaction rate. Also, no increment in the
catalytic activity was observed by increasing the amount of
acid on PAA from 30 to 40 wt%. Since 30 wt% of TPA was
the best catalyst loading, it was used to study the effect of
various parameters on yields. For polyamic acid alone, no
noticeable catalytic activity was observed (Table 2, entry
14).
Effect of solvent and catalyst concentration on the
synthesis of 1,8‑dioxo‑decahydroacridines
To evaluate the catalytic activity of TPA NPs/PAA, the
reaction of 5,5-dimethyl-1,3-cyclohexanedione (dimedone)
(1), benzaldehyde (2a), and ammonium acetate was carried
out as a model reaction. Various reaction parameters such
as solvent, catalyst loading, and the molar ratio of reactants
were optimized.
For comparison of the results in a solvent and solvent-
free conditions, the condensation of ammonium acetate
(1 mmol), benzaldehyde (1 mmol), and dimedone (2 mmol)
was studied in the presence of TPA NPs/PAA (0.04 g of
30 % w/w tungstophosphoric acid supported on poly-
mer) as a model reaction. As shown in Table 2, among the
The catalyst concentration was also investigated in the
range of 0.01–0.05 g from 30 wt% of the catalyst. The
yields of the corresponding 1,8-dioxo-decahydroacridines
1 3

J IRAN CHEM SOC
Table 2 Optimization of the
Entry
(Wt%) Catalyst (g)
Temp. (°C)
Solventc
Time (Min)
Yieldb (%)
model reactiona
1
(30 %) TPA/PAA (0.04)
(30 %) TPA/PAA (0.04)
(30 %) TPA/PAA (0.04)
(30 %) TPA/PAA (0.04)
(30 %) TPA/PAA (0.04)
(30 %) TPA/PAA (0.04)
(30 %) TPA/PAA (0.04)
(30 %) TPA/PAA (0.04)
(30 %) TPA/PAA (0.03)
(30 %) TPA/PAA (0.05)
(20 %) TPA/PAA (0.04)
(40 %) TPA/PAA (0.04)
TPA (0.012)
100
–
60
60
60
60
60
60
60
40
40
40
40
45
40
60
60
70
2
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
H2O
85
3
C2H5OH
85
4
CH3CN
75
5
CH3OH
80
6
CHCl3
50
7
Toluene
75
8
C2H5OH/H2O
C2H5OH/H2O
C2H5OH/H2O
C2H5OH/H2O
C2H5OH/H2O
C2H5OH/H2O
C2H5OH/H2O
C2H5OH/H2O
92
9
85
10
11
12
13
14
15
92
70
90
70
PAA
Trace
Trace
–
a
Reaction condition: dimedone (2 mmol), benzaldehyde (1 mmol), and ammonium acetate (1 mmol)
b
c
Isolated yields
2 mL of solvent(s) (v/v = 1)
(Fig. 7b). Therefore, in further reactions 0.0092 mmol of
H+ (equal to 0.32 mol% of TPA) was used for 30 wt% of
tungstophosphoric acid (Table 2, entry 8).
Hence, performing the reaction in refluxing ethanol–
water and in the presence of 0.04 g of 30 wt% of catalyst
was determined as the optimal condition. Using the opti-
mized reaction conditions, the scope and limitations of this
protocol were evaluated using a variety of aromatic alde-
hydes (Table 3).
Surprisingly, it was observed that both mono- and bis-
1,8-dioxo-decahydroacridines can be selectively obtained
by this catalytic system. As shown in Table 3, mono- and
bis-1,8-dioxo-decahydroacridines were produced from
dialdehydes 5 (as bulky molecules) in 70–80 % yields with
appropriate reaction times (50–60 min). The preparation
of mono-dioxo-decahydroacridines from dialdehydes is of
great interest, because the remaining formyl group can be
converted to other useful functional groups.
A substituted amine with three different ligands is chi-
ral, but racemization via pyramidal N-inversion is often too
fast for separation of enantiomers at room temperature. In
general, the barrier energy of nitrogen inversion decreases
as the bulkiness of the substituents increases because of
destabilizing steric repulsion in the pyramidal ground state.
Inversion at the sp3-hybridized nitrogen occurs via a planar
transition state. An increase in the p-character of the nitro-
gen bonds, therefore, prevents N-inversion [43].
Due to these scientific principles, the optical rotations of
6 and 8 as bulky chiral amines were investigated and the
change in the orientation of monochromatic plane-polar-
ized light (+109.2° and +71.5° specific rotations using
Fig. 7 Catalytic activities of nanoparticles H3PW12O40/polyamic acid
in the synthesis of 3a: a conversions and yields against different load-
ing of catalyst on the polymer, b conversions and yields for different
amounts of 30 wt% of the catalyst
were increased with increasing catalyst concentration
from 0.0072 to 0.0096 mmol of H+ (0.03–0.04 g, Fig. 7b).
Further addition of catalyst had no noticeable effect on
the yield, because there exist an excess of catalyst sites
over what is actually required by the reactant molecules
1 3

J IRAN CHEM SOC
Table 3 Synthesis of
1,8-dioxo-decahydroacridines
Entry Ar
Amine
Product Time (min) Yield (%)b Mp (°C)c Ref.
and bis (1,8-dioxo-
decahydroacridine) catalyzed by
nanoparticles TPA/PAAa
1
C6H5
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
Aniline
3a
3b
3c
3d
3e
3f
40
30
28
45
33
35
50
38
30
25
45
30
35
48
53
92
95
96
85
90
92
80
90
97
95
88
90
95
82
70
290–291
307–308
284–286
278–280
298–300
308–310
276–278
253–255
298–300
288–290
260–262
244–246
254–256
219–221
161–163
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[13]
[16]
[16]
[13]
[16]
[13]
–
2
3-NO2C6H4
4-NO2C6H4
4-CH3C6H4
4-ClC6H4
3
4
5
6
4-BrC6H4
7
4-CH3OC6H4
C6H5
3g
4a
4b
4c
4d
4e
4f
8
9
3-NO2C6H4
4-NO2C6H4
4-CH3C6H4
4-ClC6H4
Aniline
10
11
12
13
14
15
Aniline
Aniline
Aniline
4-BrC6H4
Aniline
4-CH3OC6H4
Aniline
4 g
6
NH4OAc
16
Aniline
8
55
75
106–109
–
17
18
NH4OAcd
Anilined
7
9
60
50
73
80
231–233
169–171
–
–
a
Reaction conditions: dimedone (2 mmol), aldehyde (1 mmol), amine (1 mmol), catalyst (0.04 g), solvent
(2 mL)
b
c
d
Melting points are uncorrected
Isolated yield
Dimedone (4 mmol), amine (2 mmol, ammonium acetate for 7 and aniline for 9), and catalyst (0.08 g)
6 and 8 solutions with 0.021 and 0.033 g/mL concentra-
tion in CHCl3 as a solvent, respectively) was surprisingly
observed. According to the observed optical rotation for
the polymer ([α]2D0 = +38.4°, c = 0.005 g/mL in DMF),
it seems that this chirality characteristic of the polymer is
the main factor for these asymmetric syntheses of the chiral
amines.
The dialdehyde 5 was synthesized using the Vilsmeier
reaction according to the literature (Scheme 4) [44]. 1-Bro-
mobutane was reacted with diphenylamine in the presence
of sodium hydroxide in DMSO to give N-butyl-N-pheny-
laniline. Under a nitrogen atmosphere, POCl3 was added to
DMF, then the amine was added to this solution, and the
resulting mixture was stirred. After cooling and basifying
with sodium hydroxide solution, the resulting mixture was
extracted and purified by column chromatography to give
4,4′-(butylazanediyl) dibenzaldehyde (5).
100
80
60
40
20
0
Fresh
1
2
3
4
5
Run
Fig. 8 Recyclability of TPA NPs/PAA in the synthesis of 1,8-dioxo-
decahydroacridines
It is noteworthy that the catalyst was recovered simply by
filtration without any acidic or basic workup even after its
five uses. After completion of the reaction of benzaldehyde,
amine, and dimedone, the catalyst was recovered from the
reaction mixture and the recovered catalyst was washed
with ethanol and dried. By ICP-OES analysis, it was
Recovery and reusability of the catalyst
From the industrial viewpoint, the recovery and reusability
of the catalyst are important for the large-scale operation.
1 3

J IRAN CHEM SOC
Fig. 9 FT-IR spectra of a fresh
TPA/PAA and b reused catalyst
Scheme 5 The proposed
mechanism for the TPA/PAA
promoted the synthesis of
1,8-dioxo-decahydroacridine
showed that the amount of tungsten present in the filtrate
was very low (3.5 × 10−4 %w/w of supported heteropoly
acid).
those obtained for the fresh catalyst, which confirmed that
the structure of the catalyst remained unchanged after recy-
cling (Fig. 9).
The recovered catalyst was added to fresh substrates
under the same experimental conditions for five runs with-
out a noticeable decrease in the product yield and its cata-
lytic activity (Fig. 8). The IR peaks appeared at the cata-
lyst spectrum after the reaction was well in agreement with
As TPA/PAA is not soluble in ethanol and water, no cat-
alyst leaching, as well as no contribution of homogeneous
catalysis in the course of the reaction, was expected. To rule
out the contribution of homogeneous catalysis, the standard
leaching experiment was conducted. A model reaction was
1 3

J IRAN CHEM SOC
Table 4 Comparison of the
efficiency of various catalysts
in the synthesis of 1,8-dioxo-
decahydroacridine
Entry Catalyst
Conditions
Time (min)
Yield (%)
Ref.
1
2
3
4
5
6
7
Ceric ammonium nitrate
PEG-400/50 °C
EtOH/H2O/reflux
EtOH/reflux
210–240
180–420
60–100
240–480
240–420
150–210
25–60
93–98
Trace-83
82–91
90–98
78–89
70–90
70–96
[13]
[18]
[19]
[27–31]
[45]
[46]
–
FSG-Hf(NPf2)4
TiO2 NPs
Triethylbenzylammonium chloride
[Hmim]TFA
H2O/reflux
Solvent free/80 °C
EtOH/reflux
HY-Zeolite
TPA NPs/PAA
EtOH/H2O/reflux
Acknowledgments We are grateful to the Yasouj University for
financial assistance.
preceded for 5 min in the presence of the catalyst and then
the catalyst was removed by filtration. The reaction was
allowed to proceed without a catalyst. There was no change
in the progress of the reaction even after 6 h, indicating that
no leaching had occurred and therefore, no homogeneous
catalyst was involved.
The proposed mechanism in which TPA/PAA has cata-
lyzed this transformation is shown in Scheme 5. The reac-
tion proceeds via one-pot Knoevenagel condensation,
Michael addition, enamine formation, and cyclodehydra-
tion. The acid catalyst changes the aldehyde into conveni-
ent electrophile via activation of the carbonyl group and
then one molecule of dimedone condenses with the alde-
hyde to produce an intermediate (I). Then the second mol-
ecule of dimedone reacts with this intermediate to give
intermediate II. Nucleophilic attack of the amine group
to the carbonyl group is followed by cyclization lead-
ing to the formation of intermediate III. Finally, by the
removal of one water molecule, acridine derivatives will
be obtained.
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