Silica chloride catalysed one-pot synthesis of 13-aryl-indeno[1,2-b] naphtha[1,2-e]pyran-12(13H)-ones under solvent-free conditions

Article abstract of DOI:10.1002/jccs.201000102

A simple and facile synthesis of 13-aryl-indeno[1,2-b]naphtha[1,2-e]pyran- 12(13H)-ones has been accomplished by the one-pot condensation of β-naphthol, aldehydes, and 2H-indene-1,3-dione under solvent-free conditions in the presence of the heterogeneous catalyst silica chloride.

Full text of DOI:10.1002/jccs.201000102

738
Journal of the Chinese Chemical Society, 2010, 57, 738-741
Silica Chloride Catalysed One-pot Synthesis of
13-Aryl-indeno[1,2-b]naphtha[1,2-e]pyran-12(13H)-ones under Solvent-free
Conditions
Li-Qiang Wu* (
Xiao Wang (
), Li-Min Yang (
) and Fu-Lin Yan (
),
)
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China
A simple and facile synthesis of 13-aryl-indeno[1,2-b]naphtha[1,2-e]pyran-12(13H)-ones has been
accomplished by the one-pot condensation of b-naphthol, aldehydes, and 2H-indene-1,3-dione under sol-
vent-free conditions in the presence of the heterogeneous catalyst silica chloride.
Keywords: Indeno[1,2-b]naphtho[1,2-e]pyran-12(13H)-one; Silica chloride; b-Naphthol;
2H-Indene-1,3-dione; Solvent-free.
INTRODUCTION
Natural compounds possessing naphthopyran moiety
Scheme I
have been attracted by their antimicrobial,1 antitumor,2
antifungal,3 cytotoxic,4 antioxidative and 5-lipoxygenase
inhibitory activity.5 A variety of naphthopyran derivatives
have been isolated and identified as natural phytochemi-
cals.6 A plethora of biological activities have also been as-
sociated with a large number of synthetic naphthofuran
analogs.7 Indenopyrans are a ‘privileged medicinal scaf-
folds’ which are used for the development of pharmaceuti-
cal agents of various applications. Compounds with the
motif show a wide range of pharmacological activities such
as antiulcer,8 antiallergenic,9 antidepressant activities.10
Silica chloride (SiO2-Cl), which was easily prepared
from silica gel and thionyl chloride, is a good solid acid in
terms of convenience, cheapness, easy production, and in-
solubility in all organic solvents. Due to its insolubility in
organic solvents, excellent in situ proton generation, and
accepting different nucleophiles, it can be used for differ-
ent purposes in organic chemistry, like SiO2-Cl catalyzed
protection of carbonyl compounds,11a acetylation of alco-
hols,11b synthesis of 2-aminothiazoles,11c SiO2-Cl as a start-
ing material for the preparation of other silica bonded re-
agents.11d In this paper, we report a simple and efficient
synthesis of 13-aryl-indeno[1,2-b]naphtho[1,2-e]pyran-
12(13H)-ones, which may show potential pharmaceutical
activities, under solvent-free conditions in the presence of
SiO2-Cl (see Scheme I).
RESULTS AND DISCUSSION
First, to optimize the amount of catalyst and the reac-
tion temperature, the reaction of b-naphthol (1 mmol),
benzaldehyde (1 mmol) and 2H-indene-1,3-dione (1 mmol)
under thermal solvent-free conditions was selected as a
model. The best result was obtained by carrying out the re-
action using 150 mg/mmol SiO2-Cl at 110 °C under sol-
vent-free conditions.
Based on the optimized reaction conditions, a range
of 13-aryl-indeno[1,2-b]naphtha[1,2-e]pyran-12(13H)-
ones (4) was synthesized by the reaction of b-naphthol (1, 1
mmol), aldehyde (2, 1 mmol) and 2H-indene-1,3-dione (3,
1 mmol). The reaction proceeded at 110 °C within 2 hour in
excellent yields after the addition of 150 mg/mol SiO2-Cl
(Table 2). The structures of the products were established
from their spectral properties (1H NMR, 13C NMR and ele-
mental analysis). All of the products 4 exhibited a singlet in
1H spectra at d = 5.58-6.05 ppm for H-13 and also a distin-
guishing peak at d = 28.8-35.7 ppm for C-13 in the 13C
NMR spectra. The resonances of carbonyl groups in the 13C
NMR spectrum of 4 appeared at d = 191.6-192.5 ppm. In
* Corresponding author. Tel: +86-373-3029879; Fax: +86-373-3029879; E-mail: wliq870@163.com

Synthesis of Indeno[1,2-b]naphtha[1,2-e]pyran
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 739
Table 1. Optimization one-pot synthesis of 13-aryl-indeno[1,2-
b]naphtha[1,2-e]pyran-12(13H)-onesa
Table 2. Synthesis of 13-aryl-indeno[1,2-b]naphtha [1,2-e]pyran-
12(13H)-ones using SiO2-Cl as catalysta
Entry SiO2-Cl (mg/mmol) Temp. (°C) Time (h) Yield (%)b
Entry
R
Time (h)
Product
Yield (%)b
1
000
050
100
100
100
150
150
150
150
150
200
250
110
110
100
110
120
090
100
110
120
130
110
110
5
3
00
38
62
79
84
72
80
89
88
88
86
89
1
C6H5
1.5
1
4a
4b
4c
4d
4e
4f
89 (81, 75, 71)c
2
2
4-Cl-C6H4
90
80
85
87
89
84
92
91
91
3
3
3
3-NO2-C6H4
2-F-5-CF3-C6H3
4-Me-C6H4
2,4-Cl2-C6H3
2-Cl-C6H4
2
4
2
4
2
5
1.5
2
5
2
6
6
1
7
1.5
1.5
1.5
1.5
1.5
1
7
2
4g
4h
4i
8
8
4-MeO-C6H4
4-F-C6H4
1.5
1
9
9
10
11
12
10
3,4-Cl2-C6H3
1
4j
a Reaction conditions: b-naphthol (1 mmol); arylaldehydes (1
mmol); 2H-indene-1,3-dione (1 mmol); SiO2-Cl (150 mg);
solvent-free; 110 °C.
b Isolated yield after chromatographic purification.
c Yields after three times of catalyst recovery.
a Reaction conditions: b-naphthol (1 mmol); benzaldehyde (1
mmol); 2H-indene-1,3-dione (1 mmol); solvent-free.
b Isolated yield after chromatographic purification.
these experiments the catalyst was isolated by filtration and
could be run up to three recycles without significant loss of
activity (entry 1). When this reaction was carried out with
aliphatic aldehyde such as butanal or pentanal, TLC and 1H
NMR spectra of the reaction mixture showed a combina-
tion of starting materials and numerous products, the yield
of the expected product was very poor.
form an ortho-quinone methide intermediate. Subsequent
Michael addition to the ortho-quinone methide with nu-
cleophile and followed by addition of the phenolic hy-
droxyl moiety to the carbonyl of ketone provides cyclic
hemiketal which on dehydration afforded 4. In 2-naphthol
the electron density at the benzylic C-1 position (which is
in conjugation with the aromatic ring) is higher than that at
the C-3 position. Thus the regioselective formation of the
ortho-quinone methide from this compound involving the
C-1 and C-2 positions is favoured. In simple phenolic com-
pounds and 1-naphthol (which are weaker nucleophiles
compared to 2-naphthol) the electron density at the ortho
position of the hydroxyl group is not sufficient for the reac-
tion of these compounds with the aldehydes leading to the
formation of the corresponding ortho-quinone methides.
In summary, an efficient methodoly for the synthesis
of 13-aryl-indeno[1,2-b]naphtha[1,2-e]pyran-12(13H)-
This synthetic strategy enhanced the utilization effi-
ciency of the modified silica chloride, decreases the pro-
duction of chemical waste without using highly toxic re-
agent for the synthesis of 13-aryl-indeno[1,2-b]naphtha-
[1,2-e]pyran-12(13H)-ones. The Si-Cl bond is labile and
can give rise to Lewis acid centers on silica (see Scheme
II). The Cl is easily displaced selectively by the oxygen
atom of an aldehydes by a nucleophilic substitution reac-
tion generating a cationic centre on the carbonyl carbon
which is easily attacked by the nucleophilic 2-napthol to
Scheme II

740 J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010
Wu et al.
ones has been developed. To our best knowledge, this is the
first report for the synthesis of these compounts by multi-
component condensation of b-naphthol, arylaldehydes,
and 2H-indene-1,3-dione in the presence of SiO2-Cl as a
catalyst under solvent-free conditions. The simple experi-
mental procedure, solvent-free reaction conditions, utiliza-
tion of an inexpensive and readily available catalyst, short
period of conversion and excellent yields are the advan-
tages of the present method.
Anal. calcd for C26H16O2: C, 86.65; H, 4.47. found: C,
86.73; H, 4.38.
13-(4-Chlorophenyl)-indeno[1,2-b]naphtho[1,2-e]pyran-
12(13H)-one (4b)
1
Yellow solid, mp 225-226 °C. H NMR (400 MHz,
CDCl3) d: 7.88-7.84 (m, 2H), 7.75 (t, J = 9.2 Hz, 1H), 7.51
(d, J = 8.8 Hz, 1H), 7.45-7.25 (m, 8H), 7.18 (d, J = 8.4 Hz,
2H), 5.63 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3) d:
192.3, 167.3, 149.0, 142.1, 136.7, 132.3, 132.2, 131.9,
131.6, 130.2, 129.9, 129.5, 128.7, 128.6, 127.3, 125.4,
124.2, 121.7, 118.4, 117.7, 116.0, 110.4, 35.1 ppm. Anal.
calcd for C26H15ClO2: C, 79.09; H, 3.83. found: C, 79.29;
H, 3.75.
EXPERIMENTAL
NMR spectra were determined on Bruker AV-400 in-
strument at room temperature using TMS as internal stan-
dard, coupling constants (J) were measured in Hz; Elemen-
tal analysis were performed by a Vario-III elemental ana-
lyzer; Melting points were determined on a XT-4 binocular
microscope and were uncorrected. Commercially available
reagents were used throughout without further purification
unless otherwise stated.
13-(3-Nitrophenyl)-indeno[1,2-b]naphtho[1,2-e]pyran-
12(13H)-one (4c)
1
Yellow solid, mp 240-241 °C. H NMR (400 MHz,
CDCl3) d: 8.07 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.93 (d, J =
8.8 Hz, 1H), 7.89-7.87 (m, 1H), 7.79 (d, J = 7.6 Hz, 1H),
7.68 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 9.2 Hz, 1H), 7.47-7.41
(m, 6H), 7.35-7.31 (m, 1H), 5.77 (s, 1H) ppm. 13C NMR
(100 MHz, CDCl3) d: 192.1, 167.7, 149.2, 148.5, 145.7,
136.5, 134.4, 132.5, 132.1, 132.0, 131.3, 130.5, 130.4,
129.4, 128.8, 127.5, 125.5, 125.5, 123.9, 123.0, 121.9,
118.7, 117.9, 115.0, 109.5, 35.6 ppm. Anal. calcd for
C26H15NO4: C, 77.03; H, 3.73; N, 3.46. found: C, 76.85; H,
3.70; N, 3.58.
Preparation of SiO2-Cl
To an oven-dried (120 °C, vacuum) sample of silica
gel (10 g) in a round bottomed flask (250 mL) equipped
with a condenser and a drying tube, was added thionyl
chloride (40 mL) and the mixture was refluxed for 48 h.
The unreacted thionyl chloride was distilled off. The result-
ing white-grayish powder was flame-dried and stored in a
tightly capped bottle.
13-(2-Fluoro-5-(trifluoromethyl)phenyl)-indeno[1,2-b]-
Typical Procedure: Preparation of 13-aryl-indeno[1,2-
b]naphtha[1,2-e]pyran-12(13H)-one
naphtho[1,2-e]pyran-12(13H)-one (4d)
1
Yellow solid, mp 216-217 °C. H NMR (400 MHz,
To a mixture of b-naphthol (1 mmol), aldehyde (1
mmol), 2H-indene-1,3-dione, and SiO2-Cl (150 mg) was
added. The mixture was stirred at 110 °C for an appropriate
time (see Table 1). After completion of the reaction (TLC),
CH2Cl2 (20 mL) was added, and the solid catalyst was re-
moved by filtration. The solvent was evaporated and the
crude product were puried by silica gel column chromatog-
raphy using CH2Cl2 as eluent.
CDCl3) d: 7.91-7.81 (m, 3H), 7.54-7.32 (m, 9H), 7.17 (t, J
= 8.8 Hz, 1H), 5.92 (s, 1H) ppm. 13C NMR (100 MHz,
CDCl3) d: 191.7, 168.1, 149.0, 136.6, 132.4, 132.1, 131.9,
131.8, 131.4, 130.5, 130.2, 128.7, 127.6, 127.3, 126.1,
125.5, 124.8, 123.1, 122.1, 121.8, 118.7, 117.8, 116.5,
116.2, 115.2, 109.1, 28.8 ppm. Anal. calcd for C27H14F4O2:
C, 72.65; H, 3.16. found: C, 72.48; H, 3.12.
13-(4-Methylphenyl)-indeno[1,2-b]naphtho[1,2-e]pyran-
12(13H)-one (4e)
13-Phenyl-indeno[1,2-b]naphtho[1,2-e]pyran-12(13H)-
1
Yellow solid, mp 192-193 °C. H NMR (400 MHz,
one (4a)
1
Yellow solid, mp 202-203 °C. H NMR (400 MHz,
CDCl3) d: 7.88-7.82 (m, 3H), 7.50 (d, J = 9.2 Hz, 1H),
7.43-7.28 (m, 6H), 7.21 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 8.0
Hz, 2H), 5.61 (s, 1H), 2.24 (s, 3H) ppm. 13C NMR (100
MHz, CDCl3) d: 192.4, 167.2, 149.0, 140.8, 136.9, 136.1,
132.4, 132.2, 131.9, 130.0, 129.5, 129.2, 128.4, 128.0,
127.1, 125.2, 124.4, 121.6, 118.2, 117.7, 116.8, 111.2,
35.3, 21.0 ppm. Anal. calcd for C27H18O2: C, 86.61; H,
CDCl3) d: 7.89-7.82 (m, 3H), 7.51 (d, J = 8.8 Hz, 1H),
7.43-7.29 (m, 8H), 7.23 (t, J = 7.6 Hz, 2H), 7.12 (t, J = 7.4
Hz, 1H), 5.64 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3) d:
192.3, 167.3, 149.0, 143.7, 136.9, 132.4, 132.2, 131.9,
131.8, 130.1, 129.6, 128.5, 128.4, 128.1, 127.1, 126.6,
125.2, 124.4, 121.6, 118.3, 117.1, 116.6, 111.0, 35.7 ppm.

Synthesis of Indeno[1,2-b]naphtha[1,2-e]pyran
J. Chin. Chem. Soc., Vol. 57, No. 4A, 2010 741
4.85. found: C, 86.49; H, 7.92.
NMR (100 MHz, CDCl3) d: 192.1, 167.5, 149.1, 143.8,
136.6, 132.6, 132.4, 132.2, 131.9, 131.5, 130.7, 130.4,
130.2, 130.0, 128.7, 127.6, 127.5, 125.5, 124.0, 121.8,
118.5, 117.8, 115.3, 35.0 ppm. Anal. calcd for C26H14Cl2O2:
C, 72.74; H, 3.29. found: C, 72.60; H, 3.40.
13-(2,4-Dichlorophenyl)-indeno[1,2-b]naphtho[1,2-e]-
pyran-12(13H)-one (4f)
1
Yellow solid, mp 252-253 °C. H NMR (400 MHz,
CDCl3) d: 7.89-7.81 (m, 3H), 7.51-7.41 (m, 7H), 7.35-7.31
(m, 1H), 7.02-6.97 (m, 2H), 6.01 (s, 1H) ppm. 13C NMR
(100 MHz, CDCl3) d: 191.6, 167.5, 148.8, 140.1, 136.7,
133.5, 132.9, 132.3, 132.2, 131.9, 131.7, 131.6, 130.4,
130.0,129.4, 128.6, 127.8, 127.5, 125.5, 123.8, 121.7,
118.5, 117.7, 116.5, 110.0, 32.4 ppm. Anal. calcd for
C26H14Cl2O2: C, 72.74; H, 3.29. found: C, 72.85; H, 3.18.
13-(2-Chlorophenyl)-indeno[1,2-b]naphtho[1,2-e]py-
ran-12(13H)-ones (4g)
ACKNOWLEDGEMENT
We are pleased to acknowledge the financial support
from Xinxiang Medical University.
Received December 5, 2009.
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1
Yellow solid, mp 240-241 °C. H NMR (400 MHz,
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CDCl3) d: 7.91-7.81 (m, 3H), 7.51-7.30 (m, 8H), 7.06-7.02
(m, 3H), 6.05 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3) d:
191.7, 167.4, 148.8, 136.8, 132.8, 132.3, 132.2, 131.9,
131.8, 130.8, 130.2, 129.8, 129.7, 128.5, 127.9, 127.4,
127.3, 125.3, 124.1, 121.6, 118.3, 117.7, 117.1, 32.7 ppm.
Anal. calcd for C26H15ClO2: C, 79.09; H, 3.83. found: C,
79.25; H, 3.92.
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13-(4-Methoxylphenyl)-indeno[1,2-b]naphtho[1,2-e]py-
ran-12(13H)-one (4h)
1
Yellow solid, mp 225-226 °C. H NMR (400 MHz,
CDCl3) d: 7.87-7.82 (m, 3H), 7.49 (d, J = 9.2 Hz, 1H),
7.43-7.27 (m, 6H), 7.23 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.8
Hz, 2H), 5.58 (s, 1H), 3.71 (s, 3H) ppm. 13C NMR (100
MHz, CDCl3) d: 192.5, 167.0, 158.1, 148.9, 136.9, 136.1,
132.4, 132.2, 131.9, 131.8, 130.0, 129.5, 129.1, 128.4,
127.1, 125.2, 124.4, 121.6, 118.2, 117.7, 116.8, 113.9,
111.2, 55.1, 34.8 ppm. Anal. calcd for C27H18O3: C, 83.06;
H, 4.65. found: C, 82.96; H, 4.75.
13-(4-Fluorophenyl)-indeno[1,2-b]naphtho[1,2-e]pyran-
12(13H)-one (4i)
1
Yellow solid, mp 208-209 °C. H NMR (400 MHz,
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CDCl3) d: 7.90-7.76 (m, 3H), 7.50 (d, J = 8.8 Hz, 1H),
7.43-7.28 (m, 8H), 6.91 (t, J = 8.6 Hz, 2H), 5.63 (s, 1H)
ppm. 13C NMR (100 MHz, CDCl3) d: 192.3, 167.2, 149.0,
139.4, 136.8, 132.3, 131.9, 131.7, 130.2, 129.8, 129.7,
129.6, 128.5, 127.2, 125.3, 124.3, 121.7, 118.3, 117.7,
116.3, 115.5, 115.3, 35.0 ppm. Anal. calcd for C26H15FO2:
C, 82.53; H, 4.00. found: C, 82.44; H, 4.17.
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13-(3,4-Dichlorophenyl)-indeno[1,2-b]naphtho[1,2-e]-
pyran-12(13H)-one (4j)
1
Yellow solid, mp 245-246 °C. H NMR (400 MHz,
CDCl3) d: 7.93-7.86 (m, 2H), 7.73-7.71 (m, 1H), 7.52 (d, J
= 9.2 Hz, 1H), 7.48-7.22 (m, 9H), 5.61 (s, 1H) ppm. 13C