Poly(4-vinylpyridinium) hydrogensulfate catalyzed synthesis of 12-aryl-12H-indeno[1,2-b]naphtho[3,2-e]pyran-5,11,13-triones

Article abstract of DOI:10.1016/j.tetlet.2012.01.092

A simple and facile synthesis of 12-aryl-12H-indeno[1,2-b]naphtho[3,2-e] pyran-5,11,13-trione derivatives was accomplished via the one-pot condensation of 2-hydroxynaphthalene-1,4-dione, aldehydes, and 2H-indene-1,3-dione at 100 °C under solvent-free cond

Full text of DOI:10.1016/j.tetlet.2012.01.092

Tetrahedron Letters 53 (2012) 1637–1640
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Tetrahedron Letters
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Poly(4-vinylpyridinium) hydrogensulfate catalyzed synthesis
of 12-aryl-12H-indeno[1,2-b]naphtho[3,2-e]pyran-5,11,13-triones
⇑
Nader Ghaffari Khaligh
Department of Chemistry, College of Science, University of Guilan, Rasht 41335-19141, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and facile synthesis of 12-aryl-12H-indeno[1,2-b]naphtho[3,2-e]pyran-5,11,13-trione deriva-
tives was accomplished via the one-pot condensation of 2-hydroxynaphthalene-1,4-dione, aldehydes,
and 2H-indene-1,3-dione at 100 °C under solvent-free conditions in the presence of the solid acid
catalyst, poly(4-vinylpyridinium) hydrogensulfate. This method has the advantages of high yields, clean
reactions, simple methodology, and short reaction times. The catalyst could be recycled and reused four
times without significant loss of activity. The structures of the novel compounds were confirmed by IR, 1H
NMR, and elemental analysis.
Received 28 September 2011
Revised 9 January 2012
Accepted 20 January 2012
Available online 28 January 2012
Keywords:
Solid acid
Ó 2012 Elsevier Ltd. All rights reserved.
Indeno[1,2-b]naphtho[3,2-e]pyran-6,11,13-
triones
2-Hydroxynaphthalene-1,4-dione
2H-Indene-1,3-dione
Solvent-free conditions
One-pot condensation
Multicomponent reactions have attracted considerable atten-
tion as they are performed without the need to isolate any inter-
mediates. This reduces time and saves both energy and raw
materials.1 They have merits over two-component reactions
including the simplicity of a one-pot procedure, possible structural
variations, and the easy synthesis of complex molecules.
tional simplicity, environmental compatibility, they are nontoxic,
low cost, and the ease of isolation. As economic and ecologically
benign catalysts, their applications have attracted much attention
in chemistry and industry.20–25 There were more than 100 indus-
trial processes using over 103 solid acids as catalysts as of the
end of the last century.26 Solid acid catalysts offer unique proper-
ties that can influence the catalytic activity. However, they also
have some disadvantages. Some supported catalysts undergo
leaching which leads to a loss of activity.27 Although zeolites dem-
onstrate high activity, their reactions typically give a variety of
undesired by-products due to the high temperatures employed.
Ion exchange resins are limited in application because they are
thermally unstable above 120 °C in the acid form.28
As part of continuing efforts in our laboratory toward the
development of new catalysts and methods in organic synthe-
sis,29–31 we report a simple and efficient method for the preparation
of 12-aryl-12H-indeno[1,2-b]naphtho[2,3-e]pyran-6,11,13-trione
derivatives under solvent-free conditions in the presence of
poly(4-vinylpyridinium) hydrogensulfate [P(4-VPH)HSO4] as an
efficient and versatile catalyst (Scheme 1). To the best of our knowl-
edge, this is the first report on the synthesis of 12-aryl-12H-inde-
no[1,2-b]naphtho[2,3-e]pyran-6,11,13-triones, which may show
pharmaceutical activities.
The synthesis of xanthenes, especially benzoxanthenes, is
important in organic synthesis due to their wide range of biological
and therapeutic properties such as antibacterial,2 antiviral,3 and
anti-inflammatory.4 They are also useful in photodynamic therapy5
and as antagonists of the paralyzing action of zoxazolamine.6 Fur-
thermore, due to their interesting spectroscopic properties, they
are used as dyes,7 in laser technologies,8 and in fluorescent mate-
rials for the visualization of biomolecules.9 Natural compounds
possessing the naphthopyran moiety have been shown to exhibit
antimicrobial,10 antitumor,11 antifungal,12 cytotoxic,13 antioxidant,
and 5-lipoxygenase inhibitory activities.14 A variety of naphthopy-
ran derivatives have been isolated and identified as natural phyto-
chemicals.15 Indenopyrans are ‘privileged medicinal scaffolds’
which are used for the development of pharmaceutical agents with
various applications.16 Compounds with this motif show a wide
spectrum of pharmacological activities including antiulcer,17 anti-
allergenic,18 and antidepressant.19
In recent years, the use of solid acidic catalysts has offered
important advantages in organic synthesis, for example, opera-
To optimize the temperature, the reaction of 2-hydroxynaph-
thalene-1,4-dione (1) (1 mmol), benzaldehyde 2 (1 mmol), and
2H-indene-1,3-dione (3) (1.1 mmol) as a model reaction was
studied under solvent-free conditions using P(4-VPH)HSO4
⇑
Tel.: +98 2166431738; fax: +98 66934046.
E-mail addresses: ngkhaligh@guilan.ac.ir, ngkhaligh@gmail.com
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.01.092

1638
N. G. Khaligh / Tetrahedron Letters 53 (2012) 1637–1640
R
O
O
O
O
O
P(4-VPH)HSO4
+ R
OH
+
Solvent-free, 100 ºC
O
O
CHO
O
4
1
2
3
Scheme 1. Synthesis of 12-aryl-12H-indeno[1,2-b]naphtho[2,3-e]pyran-5,11,13-triones.
Table 1
(20 mg) at different temperatures. The results are summarized in
Table 1 and show that the reaction at 100 °C gave the highest yield.
To optimize the catalyst loading, the model reaction was inves-
tigated with 10, 20, 30, 40, and 50 mg of P(4-VPH)HSO4 at 100 °C
under solvent-free conditions. The results are summarized in
Table 2. A 20 mg loading of P(4-VPH)HSO4 was found to be suffi-
cient to promote the reaction and increased amounts of the cata-
lyst did not lead to any significant changes in the reaction yield.
Using the optimized reaction conditions, a range of 2-aryl-
12H-indeno[1,2-b]naphtho[3,2-e]pyran-5,11,13-triones were
synthesized via the one-pot condensation of 2-hydroxynaphtha-
lene-1,4-dione, various aldehydes, and 2H-indene-1,3-dione under
solvent-free conditions. The reactions proceeded at 100 °C within
90 min in excellent yields using 20 mg of the solid acid catalyst
P(4-VPH)HSO4 (Table 3). Good yields were obtained using aromatic
aldehydes with electron-donating or electron-withdrawing sub-
stituents. When this reaction was carried out with aliphatic alde-
hydes (entries 11 and 12), TLC and GC–MS analysis of the
reaction mixture showed a combination of starting materials and
numerous products; the yield of the expected product was very
poor (<25%). It should be mentioned that when the reactions were
carried out in the absence of catalyst over a long period of time
(6 h) at 100 °C under solvent-free conditions, the yields of the
products were low (<30%).
The structures of the products were established from their spec-
tral properties (IR, 1H NMR, mass, and elemental analysis). All the
products exhibited a singlet in their 1H NMR spectra at d = 6.02–
6.60 for H-12. A few of the products were partially soluble in
DMSO-d6 and a diagnostic resonance in these cases was seen in
their 13C NMR spectra at d = 40.3–45.4 due to C-12). The reso-
nances of the three non-equivalent carbonyl groups in the 13C
NMR spectra of the products appeared at d = 182.3–182.6, 177.1–
177.4, and 176.9–177.3. The catalyst was isolated by filtration
and could be recycled up to four times without any significant loss
of activity (Table 3, entry 1).
A possible mechanism for this reaction is shown in Scheme 2. A
proton from P(4-VPH)HSO4 is donated to the oxygen atom of the
aldehyde. Next, the carbonyl carbon is attacked by the nucleophilic
2-hydroxynaphthalene-1,4-dione (1) to form intermediate 5. Sub-
sequent Michael addition of 2H-indene-1,3-dione (3) followed by
cyclization provides cyclic hemiketal 6 which on dehydration
afforded the product 4.
In conclusion, a novel and highly efficient method for the syn-
thesis of 12-aryl-12H-indeno[1,2-b]naphtho[3,2-e]pyran-5,11,13-
triones derivatives has been developed. This is the first report of
the synthesis of these compounds via a multicomponent condensa-
tion of 2-hydroxynaphthalene-1,4-dione, various aldehydes, and
2H-indene-1,3-dione in the presence of P(4-VPH)HSO4 as a solid
acid catalyst under solvent-free conditions. The current method
has the advantages of a simple experimental procedure, solvent-
free reaction conditions, utilization of an inexpensive and readily
available catalyst, high to excellent yields of products, and reus-
ability of the catalyst.
Temperature optimization for the synthesis of
12-aryl-12H-indeno[1,2-b]naphtho[3,2-
e]pyran-5,11,13-trionesa
Entry
Temp (°C)
Yieldb (%)
1
2
3
4
5
70
90
100
120
130
54
79
88
87
84
a
Reaction conditions: 2-hydroxynaphtha-
lene-1,4-dione (1) (1 mmol), benzaldehyde 2
(1 mmol), 2H-indene-1,3-dione (3)
(1.1 mmol), P(4-VPH)HSO4 (20 mg), 90 min.
b
Isolated yield after chromatographic
purification.
Table 2
Optimization of the amount of P(4-VPH)HSO4
for the synthesis of 12-aryl-12H-indeno[1,2-
b]naphtho[3,2-e]pyran-5,11,13-trionesa
Entry
Catalyst (mg)
Yieldb (%)
1
2
3
4
5
0
10
20
30
40
0
58
88
90
89
a
Reaction conditions: 2-hydroxynaphtha-
lene-1,4-dione (1) (1 mmol), benzaldehyde 2
(1 mmol), 2H-indene-1,3-dione (3)
(1.1 mmol), 100 °C, 90 min.
b
Isolated yield after chromatographic
purification.
Table 3
Synthesis of 12-aryl-12H-indeno[1,2-b]naphtho[3,2-e]pyran-5,11,13-triones in the
a
presence of P(4-VPH)HSO4
Entry
R
Product
Yieldb (%)
1
2
3
4
5
6
7
8
9
C6H5–
4a
4b
4c
4d
4e
4f
4g
4h
4i
88 (88, 86, 85, 82)c
4-Cl-C6H4–
4-Br-C6H4–
4-F-C6H4–
4-Me-C6H4–
4-MeO-C6H4–
4-NO2-C6H4–
3-NO2-C6H4–
2-Cl-C6H4–
3,4-Cl2-C6H3–
C4H9–
92
91
93
90
84
89
86
90
92
—
10
11
12
4j
4k
4l
C5H11
–
—
a
Reaction conditions: 2-hydroxynaphthalene-1,4-dione (1) (1 mmol), aldehyde 2
(1 mmol), 2H-indene-1,3-dione (3) (1.1 mmol), P(4-VPH)HSO4 (20 mg), 100 °C,
90 min.
b
Isolated yield after chromatographic purification.
Recycled solid acid used.
c

N. G. Khaligh / Tetrahedron Letters 53 (2012) 1637–1640
1639
H+
from P(4-VPH)HSO4
O
O
R
H
R
O
O
O
R
H+ from P(4-VPH)HSO4
2
HO
HO
H2O
O
OH
HO
O
O
1
5
O
H
3
-
H2O
O
R
O
R
O
O
R
O
O
O
O
O
-H2O
O
O
HO
HO
O
4
6
Scheme 2. A plausible mechanism.
7.16–7.54 (m, 6H, ArH), 7.64–7.92 (m, 4H, ArH), 7.99 (d,
J = 8.4 Hz, 1H, ArH), 8.12 (d, J = 7.6 Hz, 1H, ArH), 8.17 (d,
J = 7.6 Hz, 1H, ArH) ppm; MS (m/z, %) 390 (M, 57), 313 (100). Anal.
Calcd for C26H14O4: C, 79.99; H, 3.61. Found: C, 79.64; H, 3.66.
Preparation of P(4-VPH)HSO4 solid acid
H2SO4 (1.5 ml, 16.5 mmol, 96% standard solution) was added to
a suspension of powdered poly(4-vinylpyridine) (5.0 g) in dry EtOH
(25 mL). The mixture was stirred at room temperature for 8 h then
EtOH was removed under reduced pressure to give the P(4-
VPH)HSO4 catalyst. Excess sulfuric acid was removed from the cat-
alyst by washing with deionized water until the sulfate anions
were absent from the eluent (checked by reaction with BaCl2).
The resulting solid was dried under vacuum at 65 °C for 48 h to af-
ford P(4-VPH)HSO4 (6.16 g) as a pale-yellow powder.29
12-(4-Nitrophenyl)-12H-indeno[1,2-b]naphtho[3,2-e]pyran-
5,11,13-trione(4g)
Yellow powder, mp >330 °C; IR (KBr)
m = 3076, 1664, 1636,
1590 cmÀ1 1H NMR (300 MHz, DMSO-d6) d = 6.06 (s, 1H, CH),
;
7.46–7.68 (m, 6H, ArH), 7.79–7.96 (m, 4H, ArH), 8.06 (d,
J = 8.8 Hz, 1H, ArH), 8.12 (d, J = 7.6 Hz, 1H, ArH) ppm; MS (m/z,%):
435 (35), 313 (75). Anal. Calcd for C26H13NO6: C, 71.72; H, 3.01.
Found: C, 71.68; H, 2.96.
Typical procedure for the preparation of 12-aryl-12H-
indeno[1,2-b]naphtho[3,2-e]pyran-5,11,13-triones 4
Acknowledgment
To a mixture of 2-hydroxynaphthalene-1,4-dione (1) (1 mmol),
aldehyde 2 (1 mmol), and 2H-indene-1,3-dione (3) (1.1 mmol),
P(4-VPH)HSO4 (20 mg) was added. The mixture was stirred (using
a high power ball-mill mixer) at 100 °C for 90 min (Table 3). After
completion of the reaction (TLC), CH2Cl2 (20 mL) was added, and
P(4-VPH)HSO4 was removed by filtration. The solid acid catalyst
was dried at 50 °C under vacuum and then reused. The solvent
was evaporated and the crude product was purified by silica gel
column chromatography. Due to the very low solubility of the
products we are unable to report the 13C NMR data for these
products.
The author is thankful to the Guilan University Research Coun-
cil for partial support of this work.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2012.01.092.
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