HAp-encapsulated γ-Fe2O3-supported dual acidic heterogeneous catalyst for highly efficient one-pot synthesis of benzoxanthenones and 3-pyranylindoles

Article abstract of DOI:10.1002/aoc.4072

A novel method is reported for the synthesis of benzoxanthenone and 3-pyranylindole derivatives via one-pot three-component reactions using a newly synthesized HAp-encapsulated γ-Fe₂O₃-supported dual acidic heterogeneous catalyst, as a reusable and highly efficient nanocatalyst. In this protocol the use of the nanocatalyst provided a green, useful and rapid method to generate products in short reaction times (4–20?min) and in excellent yields (87–96%). The paramagnetic nature of the catalyst provided a simple, trouble-free and facile approach for the separation of the catalyst by applying an external magnet, and it could be used in eight cycles without significant loss in catalytic efficiency.

Full text of DOI:10.1002/aoc.4072

Received: 16 June 2017
DOI: 10.1002/aoc.4072
Revised: 7 August 2017
Accepted: 8 August 2017
F U L L P A P E R
HAp‐encapsulated γ‐Fe2O3‐supported dual acidic
heterogeneous catalyst for highly efficient one‐pot synthesis
of benzoxanthenones and 3‐pyranylindoles
Leila Kheirkhah | Manouchehr Mamaghani
| Asieh Yahyazadeh | Nosrat Ollah Mahmoodi
Department of Chemistry, Faculty of
A novel method is reported for the synthesis of benzoxanthenone and
3‐pyranylindole derivatives via one‐pot three‐component reactions using a
newly synthesized HAp‐encapsulated γ‐Fe2O3‐supported dual acidic heteroge-
neous catalyst, as a reusable and highly efficient nanocatalyst. In this protocol
the use of the nanocatalyst provided a green, useful and rapid method to gener-
ate products in short reaction times (4–20 min) and in excellent yields (87–96%).
The paramagnetic nature of the catalyst provided a simple, trouble‐free and
facile approach for the separation of the catalyst by applying an external
magnet, and it could be used in eight cycles without significant loss in catalytic
efficiency.
Sciences, University of Guilan, PO Box
41335‐1914, Rasht, Iran
Correspondence
Manouchehr Mamaghani, Department of
Chemistry, Faculty of Sciences, University
of Guilan, PO Box 41335‐1914, Rasht, Iran.
Email: m‐chem41@guilan.ac.ir;
mchem41@gmail.com
KEYWORDS
benzoxanthenone, HAp‐encapsulated, γ‐Fe2O3, nanomagnetic catalyst, 3‐pyranylindole, supported
ionic liquid
1 | INTRODUCTION
fluorescent materials for visualization of biomolecules.[15]
Several procedures for the preparation of benzo[a]xan-
Nanoparticles as heterogeneous catalysts have received
significant attention as efficient catalysts in many organic
reactions[1,2] due to their high surface‐to‐volume ratio,
environmentally benign nature, reusability, simple
work‐up procedures and ease of isolation.[3,4] In particu-
lar, magnetic nanoparticles, have gained an effective role
in organic synthesis[5] and the development of modern
technology such as biomedicine and electronics[6–8] and
have received increasing interest in recent years.[9–11] In
addition, magnetic nanoparticles based on iron oxides
are being used in clinical trials as contrast agents in mag-
netic resonance imaging, and clinical applications in drug
delivery and diagnosis are seriously being considered.
Xanthene derivatives are important for having various
biological and pharmaceutical activities such as antibacte-
rial, antiviral, antimicrobial, antioxidant,[12] anti‐inflam-
matory[13] and anticancer[14] activities. They can also be
used as dyes, in laser technology and as pH‐sensitive
thene‐11‐one derivatives have been reported[16] using var-
ious catalysts such as Zr(HSO4)4,[17] InCl3,[18] TCCA,[19]
NaHSO4⋅SiO2,[20] XSA,[21] HClO4–SiO2,[22] PWA,[23]
nano‐TiO2,[24] Ph3CCl,[25] CeCl3⋅7H2O,[26] HY zeolite,[27]
Sr(OTf)2,[28] RuCl3⋅nH2O and ruthenium anchored on
multi‐walled carbon nanotubes.[29]
However, some of the reported methods suffer from
one or more drawbacks such as use of expensive catalysts
and strong Lewis acids, long reaction times, lower yields,
use of toxic solvents and tedious catalyst separation and
workup procedures.
Heterocycles containing pyran and indole structural
moieties are another important class of compounds which
possess broad scope of pharmaceutical and biological
activities such as anti‐inflammatory, anticonvulsant, car-
diovascular and antibacterial activities, and also are pres-
ent in various natural products such as alkaloids.[30–32] In
particular, pyranylindoles with both structural units due
Appl Organometal Chem. 2017;e4072.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4072

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KHEIRKHAH ET AL.
to their structural diversity and biological importance
have become attractive targets for synthetic and medicinal
chemists. However, there are only a limited number of
reports of the synthesis and biological evaluation of these
products.[33,34]
Therefore, there is scope for further innovation
towards the development of new eco‐friendly, economical
and greener synthetic protocols that use highly efficient
and reusable catalysts under mild reaction conditions in
the synthesis of xanthene derivatives and pyranylindoles.
In order to advance the development of environmentally
friendly procedures and sustainable methods for the syn-
thesis of these biologically important compounds, we
report here a novel and practical protocol using a three‐
component one‐pot reaction in the presence of a HAp‐
encapsulated γ‐Fe2O3 [Fe2O3@HAp]‐supported dual
acidic nanocatalyst (3; Scheme 1) as a recyclable, hetero-
geneous and highly efficient catalyst.
SCHEME
2
Synthesis of benzoxanthenones and 3‐
pyranylindoles in the presence of [Fe2O3@HAp]‐supported dual
acidic nanocatalyst 3
with 1,4‐butanesultone and further treated with sulfuric
acid to give precursor ionic liquid (IL) 2.[41] In the next
step, [Fe2O3@HAp] nanocrystallites were prepared
according to reported procedures.[3] Finally, a mixture of
[Fe2O3@HAp] and IL 2 was heated in refluxing ethanol
for 24 h to furnish the target supported dual acidic
nanocatalyst 3 as a red powder in 95% yield (Scheme 1).
The catalyst was characterized using various techniques
such as Fourier transform infrared (FT‐IR) spectroscopy,
X‐ray diffraction (XRD), energy‐dispersive X‐ray (EDX)
analysis and thermogravimetric analysis (TGA)
(Figure 1) and scanning electron microscopy (SEM)
(Figure 2).
2 | RESULTS AND DISCUSSION
A great interest has been sparked in the development of
novel catalysts to facilitate various organic transforma-
tions under heterogeneous conditions. In addition, ionic
liquids have also attracted much attention in recent years
in synthetic organic chemistry as green catalysts. Thus,
many efforts have been made by scientists to introduce
new and novel catalysts which would combine the advan-
tages of heterogeneous and ionic liquid catalysis.
In the FT‐IR spectrum (Figure 1a), the hydroxyl band
appeared at 3422 cm−1, the S¼O group band appeared at
1384 cm−1 and the band of surface phosphate groups in
the hydroxyapatite coating overlapped with S‐O
stretching peaks at 566 and 601 cm−1. In XRD analysis
(Figure 1b), the resulting pattern is in agreement with
that of the syn structure of γ‐Fe2O3 (1999JCPDS card no.
39–1346). Diffraction peaks at around 17.4°, 30.4°, 35.3°,
37.5°, 41.6°, 50.7°, 63.3°, 67.6° and 74.6° related to (110),
(211), (220), (221), (311), (400), (422), (511) and (440) thor-
oughly confirm the presence of maghemite in the
In continuation of our research interests in the appli-
cation of heterogeneous and ionic liquid catalysts for
development of useful synthetic methodologies,[35–39] in
the present article we report the synthesis and application
of the novel [Fe2O3@HAp]‐supported dual acidic
nanocatalyst 3 (Scheme 1) in efficient, simple and facile
one‐pot three‐component syntheses of benzo[a]
xanthenone and 3‐pyranylindole derivatives (Scheme 2).
Initially, N‐(3‐propyltriethoxysilane)imidazole (1) was
prepared by the reaction of (3‐chloropropyl)
triethoxysilane and imidazole[40] which was then reacted
SCHEME 1 Synthesis of [Fe2O3@HAp]‐supported dual acidic nanocatalyst 3

KHEIRKHAH ET AL.
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spectrum. SEM analysis (Figure 2a) clearly shows that
the particles of the catalyst are uniformly nanosized (40–
50 nm). For comparison, SEM images of blank support
(γ‐Fe2O3@Hap; Figure 2b) and recycled catalyst
(Figure 2c) after eight runs in the preparation of 5a were
obtained, which show that, after recycling, the mor-
phology of the nanocatalyst has been retained. Thermal
stability of the catalyst up to 380 °C is clearly con-
firmed from TGA and differential thermogravimetric
(DTG) analysis (Figure 1d) and the weight loss in the
temperature range 380–500 °C is mainly due to the
thermal decomposition of the organic layer on the sur-
face of the nanocatalyst.
After characterization of the catalyst, one‐pot three‐
component reaction of 2‐naphthol (2; 1 mmol), 4‐
nitrobenzaldehyde (3b; 1 mmol) and dimedone (4;
1 mmol) was used as a model system. The reaction
mixture was heated in the presence of nanocatlyst 3
(0.02 g) in ethanol at 60 °C, which produced the prod-
uct 5a in 4 min and in 96% yield (Scheme 3). To opti-
mize the reaction conditions, the preparation of 5a
was examined in several solvents, namely CH3CN,
1,4‐dioxane, CH2Cl2, water, ethylene glycol and etha-
nol, at various temperatures. The result showed that
ethanol was the most effective solvent giving the prod-
uct at 60 °C in excellent yield (Table 1, entry 3). The
reaction at lower temperatures did not produce the
desired products in reasonable yield (Table 1, entries
1 and 2). We also investigated the amount of catalyst
in the preparation of 5a and the best result was
obtained using 0.02 g of nanocatalyst 3 per mmol of
substrate at 60 °C in ethanol.
To compare the efficiency of nanaocatalyst 3 with
that of various acidic and basic catalysts, the prepara-
tion of 5i was carried out in ethanol (Table 2). It is evi-
dent from the results that the present catalyst is more
efficient, in terms of product yield and reusability of
the catalyst.
Using the optimized conditions, several benzo[a]
xanthenone derivatives were synthesized (Scheme 3).
The results are summarized in Table 3. It is clearly evi-
dent from the results that the reaction with both elec-
tron‐withdrawing and electron‐donating groups leads
to products in short reaction times (4–16 min) and in
excellent yields (87–96%).
FIGURE 1 (a) FT‐IR spectrum, (b) XRD pattern, (c) EDX analysis
and (d) TGA curves
We also examined the reusability of the catalyst.
The nanocatalyst was separated from the reaction mix-
ture simply using an external magnetic field (Figure 3),
washed with hot ethanol, dried under vacuum and
reused for subsequent reactions. After eight successive
runs the activity of the catalyst, within the limits of
experimental errors, remained almost unchanged
(Figure 4).
structure. In addition, characteristic diffraction peaks of
HAp based on the standard XRD pattern of HAp (JCPDS
card no. 24–0033) are readily recognized in the XRD pat-
tern. The EDX spectrum of the nanocatalyst is presented
in Figure 1(c). Signals of atoms such as Fe, Si, S, P and
N related to the catalyst structure are seen in the

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KHEIRKHAH ET AL.
FIGURE 2 SEM images of (a) catalyst 3, (b) blank support and (c) recycled catalyst after eight runs
A plausible mechanism of this multicomponent syn-
thesis involves a Knoevenagel condensation/Michael
addition cascade process. In the synthesis of benzo[a]
xanthenones, the reaction proceeds through the in situ
formation of ortho‐quinonemethide intermediate by the
nucleophilic addition of 2‐naphthol derivative to aldehyde
in the presence of nanocatalyst 3 which is further attacked
by dimedone followed by cyclization and elimination of
water to yield the desired target product 5 (Scheme 4).
Encouraged by these results, we extended the scope of
this protocol to the synthesis of 3‐pyranylindole deriva-
tives (Scheme 5). Thus, the reaction of equimolar
amounts of 3‐cyanoacetylindole (6), arylaldehyde (7) and
malononitrile (8) in the presence of catalyst 3 furnished
the desired 3‐pyranylindole derivatives in excellent yields
(87–93%) and in short reaction times (6–20 min).
To establish the optimum reaction conditions, the
reaction between 3‐cyanoacetyl‐2‐methylindole (1 mmol),
4‐nitrobenzaldehyde (1 mmol) and malononitrile
(1 mmol) was carried out in the presence of nanocatalyst
3 under various conditions. In order to choose suitable
temperature and reaction media, various solvents such
as dichloromethane, tetrahydrofuran (THF), 1,4‐dioxane,
ethanol and water as well as solvent‐free conditions were
used. The best results were obtained in ethanol at 60 °C
using 0.02 g of nanocatalyst 3 per mmol of substrate pro-
ducing the corresponding 3‐pyranylindole (9 h) in 6 min
and in 93% yield (Scheme 5; Table 4, entry 5). Various aryl
aldehydes were reacted using the optimized conditions
providing the desired 3‐pyranylindoles in excellent yields
(87–93%) and in short reaction times (6–20 min)
(Table 5). The recyclability of the catalyst was also inves-
tigated using the preparation of 9 h as a model reaction.
The catalyst was separated using an external magnet as
SCHEME 3 Synthesis of benzo[a]xanthenone derivatives using
nanocatalyst 3
TABLE 1 Effect of solvent on synthesis of benzo[a]xanthenone derivatives (5a) in the presence of nanaocatalyst 3a at various temperatures
Entry
Solvent
Temperature (°C)
Time (min)
Yield (%)b
1
EtOH
25
120
45
2
3
4
5
6
7
8
9
EtOH
40
60
90
4
60
EtOH
96
EtOH
80
4
96
CH3CN
1,4‐Dioxane
CH2Cl2
H2O
60
120
180
60
Trace
Trace
55
100
40
60
90
45
Ethylene glycol
120
120
40
a0.02 g of catalyst/mmol substrate.
bIsolated yield.

KHEIRKHAH ET AL.
5 of 11
TABLE 2 Comparison of catalysts in the synthesis of 5i
Entry
Ar
Catalysta
Time (min)
Yield (%)b
1
3‐BrC6H5
Nanocatalyst 3
6
93 (this work)
90 (this work)
90[42]
2
3
4
5
6
7
8
3‐BrC6H5
3‐BrC6H5
3‐BrC6H5
3‐BrC6H5
3‐BrC6H5
3‐BrC6H5
3‐BrC6H5
Il 2
60
30
30
9
Fe3O4/CS‐ag NPs
Orange peel
[pyridine–SO3H]cl
p‐TSA
90[43]
90[44]
91[45]
120
60
60
Imidazole
Trace (this work)
Trace (this work)
Product 1
aAmount of catalyst used for entries: 1 (0.02 g), 2 (10%), 3 (0.015 g), 4 (0.05 g), 5 (3 mol%), 6 (10 mol%), 7 (10 mol%), 8 (10 mol%).
bIsolated yield.
TABLE 3 Synthesis of benzo[a]xanthenone derivatives (5a–x) under optimized conditions
Entry
Ar
Product
5a
Time (min)
Yield (%)
M.p. (°C)
1
4‐O2NC6H4
4
96
173–176 (175–178)[44]
177–179 (179–180)[46]
184–186 (185–187)[44]
174–176 (176–178)[46]
179–181 (180–182)[46]
149–151 (150–151)[46]
202–204 (204–205)[46]
2
2‐ClC6H4
5b
5c
8
11
16
6
90
90
87
92
93
88
93
93
94
95
90
91
92
93
90
90
90
88
90
91
92
93
3
4‐BrC6H4
4
4‐CH3C6H4
4‐ClC6H4
5d
5e
5
6
C6H5
5f
11
11
6
7
4‐CH3OC6H4
3‐O2NC6H4
3‐BrC6H4
5 g
5 h
5i
[44]
8
166–169 (168–170)
9
6
160–163 (161–164)[44]
[46]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4‐FC6H4
5j
7
183–185 (185–186)
2,4‐Cl2C6H3
5‐CH3thienyl
4‐HOC6H4
2‐CH3OC6H4
2‐(2‐nitrophenyl)acryl
3‐ClC6H4
5 k
5 l
5 m
5n
5o
5p
5q
5r
5
180–181 (181–182)[44]
11
6
229–231
222–224 (223–225)[46]
166–167 (167–168)[46]
175–177
16
6
11
11
16
16
16
11
6
173–176 (175–178)[44]
238–241 (240–241)[44]
131–133 (135–137)[46]
159–161 (160–163)[44]
177–179 (178–180)[44]
169–171 (170–172)[44]
220–221 (220–222)[46]
181–183 (183–184)[46]
3‐OHC6H4
2‐HOC6H4
2‐CH3C6H4
3‐CH3C6H4
2‐BrC6H4
5 s
5 t
5u
5w
5x
2‐O2NC6H4
2‐Thienyl
10
in the previous protocol and used in the next run, which
after eight consecutive runs did not show almost any
decrease in the catalytic activity within the limits of exper-
imental errors (Figure 5).
In the synthesis of 3‐pyranylindoles the reaction pro-
ceeds through the in situ formation of intermediate (i)
by the nucleophilic addition of 3‐cyanoacetylindole to
aldehyde in the presence of catalyst 3. Intermediate (i)

6 of 11
KHEIRKHAH ET AL.
undergoes Michael addition with the tautomer of
malononitrile to give (ii). Compound (ii) enolizes to
afford intermediate (iii) which gives (iv) by nucleophilic
addition of hydroxyl group to the cyano group. Finally
(iv) rearranges via hydrogen transfer to yield 3‐
pyranylindole derivatives 9a–k (Scheme 6).
The reaction profile of the present protocol is very
clean and no side‐products are formed.
The structures of all the newly synthesized products
1
were confirmed using spectroscopic (IR, H NMR, 13C
NMR) and elemental analyses. For the known derivatives,
their spectroscopic data and melting points were com-
pared with those of literature reports.
FIGURE 3 Separation of catalyst from reaction mixture using an
external magnet
3 | CONCLUSIONS
In summary, we have reported the synthesis of
tetrahydrobenzo[a]xanthene‐11‐ones and 3‐pyranylindole
derivatives using [Fe2O3@HAp]‐supported dual acidic
nanocatalyst as a new, heterogeneous and reusable cata-
lyst in green media. This protocol involves mild reaction
conditions, excellent yields and short reaction times. A
green and cost‐effective catalyst, an easy work‐up proce-
dure and avoiding the use of large volumes of hazardous
organic solvents make it a useful alternative to previ-
ously applied procedures. Also, the magnetic nature of
the nanoparticles allows for easy recovery using an exter-
nal magnetic field and subsequent recycling of the
catalyst.
FIGURE 4 Reusability of catalyst 3 in synthesis of benzo[a]
xanthenone 5a
SCHEME 4 Plausible reaction
mechanism for synthesis of benzo[a]
xanthenone derivatives using nanocatalyst
3

KHEIRKHAH ET AL.
7 of 11
SCHEME 5 Synthesis of
3‐pyranylindole derivatives using
nanocatalyst 3
TABLE 4 Effect of solvent on synthesis of 3‐pyranylindole deriv-
atives (9 h) in the presence of nanaocatalyst 3a at various
temperatures
Temperature
(°C)
Time
(min)
Entry
Solvent
Yield (%)b
1
THF
65
100
25
120
120
30
30
6
45
2
3
4
5
6
7
8
9
1,4‐Dioxane
EtOH
93
50
61
93
91
35
25
70
EtOH
45
EtOH
60
EtOH
80
6
CH2Cl2
H2O
40
60
90
85
100
60
FIGURE 5 Reusability of nanocatalyst 3 in synthesis of 3‐
pyranylindole 9 h
Solvent‐free
a0.02 g of catalyst/mmol substrate.
bIsolated yield.
spectra were recorded with a 400 MHz Bruker DRX‐400
in DMSO‐d6 using tetramethylsilane as an internal stan-
dard. Elemental analyses were performed with a Carlo‐
Erba EA1110CNNO‐S analyser and agreed (within 0.30)
with the calculated values. XRD was carried out with a
Philips X‐Pert MPD diffractometer using a Co tube. SEM
images were obtained with a Philips XL30 electron micro-
scope. All chemicals were purchased from Merck and
4 | EXPERIMENTAL
4.1 | General
Melting points were measured with an Electrothermal
9100 apparatus. IR spectra were obtained with on a
1
Shimadzo IR‐470 spectrometer. H NMR and 13C NMR
TABLE 5 Synthesis of 3‐pyranylindole derivatives (9a–k)
Entry
Ar
R
Product
9a
Time (min)
Yield (%)a
M.p. (°C)
1
4‐ClC6H4
H
11
90
258–261
260–262[34]
214–216[34]
224–226[34]
256–258[34]
242–244[34]
226–228[34]
(this work)
(this work)
(this work)
(this work)
(this work)
2
2‐ClC6H4
C6H5
H
9b
9c
9d
9e
9f
16
18
10
10
20
13
6
88
91
89
93
87
90
93
88
90
91
211–213
221–223
253–256
241–243
224–227
239–241
290–291
217–219
256–258
261–263
3
H
4
4‐FC6H4
H
5
3‐O2NC6H4
2‐Thienyl
3‐BrC6H4
4‐O2NC6H4
3‐HOC6H4
4‐BrC6H4
3‐O2NC6H4
H
6
H
7
CH3
CH3
CH3
CH3
CH3
9 g
9 h
9i
8
9
17
12
11
10
11
9j
9 k
aIsolated yield.

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KHEIRKHAH ET AL.
SCHEME 6 Plausible reaction mechanism for synthesis of 3‐pyranylindole derivatives using catalyst 3
used without further purification. All solvents used were
dried and distilled according to standard procedures.
completion of the reaction, which was monitored by
TLC, the reaction mixture was diluted with hot ethanol
and the catalyst was easily separated from the reaction
mixture using an external magnet. The catalyst was
washed with ethanol and dried for reuse in the next run.
The combined organic solution was concentrated and
the solid product obtained was collected by filtration
and washed with ethanol to afford the desired pure prod-
uct (5a–x).
4.2 | Grafting of 3‐sulfobutyl‐1‐(3‐
propyltriethoxysilane)imidazolium
hydrogen sulfate on [Fe2O3@HAp] (3)
N‐(3‐Propyltriethoxysilane)imidazole (1), 3‐sulfobutyl‐1‐
(3‐propyltriethoxysilane)imidazolium hydrogen sulfate
(IL 2) and [Fe2O3@HAp] were synthesized according to
procedures reported in the literature.[34,35] To a solution
of IL 2 (1.0 g) in absolute ethanol (30 ml), [Fe2O3@HAp]
(2.0 g) was added. The mixture was refluxed overnight
under an argon atmosphere. The solvent was removed
using a rotatory evaporator. The resulting magnetic nano-
particles were separated using an external magnet device
(Figure 2) and washed twice with diethyl ether (100 ml)
then dried under vacuum at room temperature to afford
the supported dual acidic nanocatalyst 3 as a red powder
in 95% yield.
4.4 | Selected spectral data of 12‐aryl‐
8,9,10,12‐tetrahydrobenzo[a]‐xanthen‐11‐
one derivatives (Table 3)
9,10‐Dihydro‐9,9‐dimethyl‐12‐((5‐methylthiophen‐2‐yl)
methyl)‐8H–benzo[α]xanthen‐11(12H)‐one (5 l). Creamy
solid; m.p. 229–231 °C. IR (KBr, ν, cm−1): 2959, 1651
1
(CO), 1222, 1173. H NMR (400 MHz, CDCl3, δ, ppm):
8.11 (d, 1H, J = 8.4 Hz, Ar‐H), 7.96 (d, 1H, J = 7.2 Hz, Ar‐
H), 7.95 (d, 1H, J = 9.2 Hz, Ar‐H), 7.58 (dt, 1H, J = 6.8,
1.4 Hz, Ar‐H), 7.50 (dt, 1H, J = 8.0, 1.2 Hz, Ar‐H),7.44 (d,
1H, J = 9.2 Hz Ar‐H), 6.62 (d, 1H, J = 3.6 Hz, Ar‐H), 6.46
(m, 1H, Ar‐H), 5.84 (s, 1H), 2.70, 2.68 (d, 2H, J = 17.4 Hz,
CH2), 2.39, 2.24 (d, 2H, J = 15.8 Hz, CH2), 2.24 (s, 3H),
1.1 (s, 3H, CH3), 1.02 (s, 3H, CH3). 13C NMR (100 MHz,
CDCl3, δ, ppm): 196.4, 164.8, 147.5, 146.5, 138.2, 131.5,
131.1, 129.7, 129.1, 127.8, 125.6, 125.1, 124.9, 123.6, 117.6,
117.3, 113.2, 50.6, 40.6, 32.4, 31.2, 29.3, 26.9, 15.3. Anal.
4.3 | General procedure for synthesis of
12‐aryl‐8,9,10,12‐tetrahydrobenzo[a]‐
xanthen‐11‐one derivatives
To a mixture of aldehyde (1 mmol), 2‐naphthol (1 mmol)
and dimedone (1 mmol) was added dual acidic
nanaocatalyst 3 (0.02 g) and the reaction mixture was
stirred mechanically in ethanol (1 ml) at 60 °C. After

KHEIRKHAH ET AL.
9 of 11
Calcd for C24H22O2S (374.5) (%): C, 76.97; H, 5.92. Found
(%): C, 76.81; H, 5.74.
61.27; H, 3.51; N, 12.99. Found (%): C, 61.10; H, 3.38;
N, 12.82.
9,9‐Dimethyl‐12‐(1‐(2‐nitrophenyl)vinyl)‐9,10‐
dihydro‐8H‐benzo[a]xanthen‐11(12H)‐one (5o). Creamy
solid; m.p. 175–177 °C. IR (KBr, ν, cm−1): 2941, 1649
2‐Amino‐6‐(2‐methyl‐1H‐indol‐3‐yl)‐4‐(4‐nitrophe-
nyl)‐4H–pyran‐3,5‐dicarbonitrile (9 h). Yellow solid; m.p.
290–291 °C. IR (KBr, ν, cm−1): 3486, 3303 (N―H
1
1
(CO), 1515, 1376, 1226. H NMR (400 MHz, CDCl3, δ,
stretch), 2200 (CN stretch). H NMR (400 MHz, CDCl3,
ppm): 8.14 (d, 1H, J = 8.4 Hz, Ar‐H), 7.96 (t, 2H,
J = 9.4 Hz, Ar‐H), 7.86 (d, 1H, J = 8.0 Hz, Ar‐H), 7.63 (t,
1H, J = 7.4 Hz, Ar‐H), 7.58 (m, 2H, Ar‐H), 7.52 (t, 1H,
J = 7.2 Hz, Ar‐H), 7.45–7.41 (m, 2H, Ar‐H), 6.55 (s, 1H,
CH2¼), 6.54 (s, 1H, CH2¼) 5.25 (s, 1H), 2.7, 2.6 (d, 2H,
J = 17.4 Hz, CH2), 2.4, 2.3 (d, 2H, J = 16.0 Hz, CH2), 1.12
(s, 6H, CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 196.6,
165.5, 147.9, 147.8, 137.0, 133.8, 131.6, 131.4, 131.3, 129.7,
129.0, 128.9, 128.5, 127.8, 125.6, 125.4, 124.6, 123.9, 117.6,
115.9, 111.1, 50.7, 40.8, 32.4, 31.6, 29.3, 27.2. Anal. Calcd
for C27H23NO4 (425.48) (%): C, 76.22; H, 5.45; N, 3.29.
Found (%): C, 76.11; H, 5.24; N, 3.17.
δ, ppm): 11.84 (br. s, 1H, NH), 8.34 (d, 2H, J = 8.6 Hz,
Ar‐H), 7.72 (d, 2H, J = 8.6 Hz, Ar‐H), 7.49 (d, 1H,
J = 8.0 Hz, Ar‐H), 7.42–7.39 (m, 3H, NH2, Ar‐H), 7.17
(td, 1H, J = 7.4, 1.0 Hz, Ar‐H), 7.12 (td, 1H, J = 7.2,
1.0 Hz, Ar‐H), 4.78 (s, 1H, C―H), 2.44 (s, 3H, CH3).
13C NMR (100 MHz, CDCl3, δ, ppm): 159.6, 156.7,
150.9, 147.6, 139.9, 135.4, 129.6, 126.3, 124.8, 122.3,
120.8, 119.7, 119.5, 118.0, 111.8, 103.4, 89.3, 55.1, 39.3,
14.0. Anal. Calcd for C22H15N5O3 (397.39) (%): C,
66.49; H, 3.80; N, 17.62. Found (%): C, 66.35; H, 3.60;
N, 17.43.
2‐Amino‐4‐(3‐hydroxyphenyl)‐6‐(2‐methyl‐1H‐indol‐
3‐yl)‐4H–pyran‐3,5‐dicarbonitrile (9i). White solid; m.p.
217–219 °C. IR (KBr, ν, cm−1): 3449, 3336 (N―H stretch),
1
4.5 | General procedure for synthesis of 3‐
pyranylindole derivatives
2211 (CN stretch). H NMR (400 MHz, CDCl3, δ, ppm):
11.78 (br. s, 1H, NH), 9.58 (br. s, 1H, OH), 7.46 (d, 1H,
J = 7.6 Hz, Ar‐H), 7.39 (d, 1H, J = 8.0 Hz, Ar‐H), 7.24 (t,
1H, J = 7.6 Hz, Ar‐H), 7.21 (br.s, 2H, NH2), 7.16 (td, 1H,
J = 7.2, 1.2 Hz, Ar‐H), 7.11 (td, 1H, J = 7.4, 1.2 Hz, Ar‐
H), 6.81–6.73 (m, 3H, Ar‐H), 4.36 (s, 1H, C―H), 2.43 (s,
3H, CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 159.4,
158.3, 155.9, 145.1, 139.4, 135.4, 130.4, 126.4, 122.3,
120.7, 119.8, 119.6, 118.6, 118.3, 115.3, 114.6, 111.7,
103.6, 90.9, 56.3, 39.3, 13.85. Anal. Calcd for C22H16N4O2
(368.39) (%): C, 71.73; H, 4.38; N, 15.21. Found (%): C,
71.58; H, 4.25; N, 15.33.
To a mixture of 3‐cyanoacetylindole or 2‐methyl‐3‐
cyanoacetylindole (1 mmol), arylaldehyde (1 mmol) and
malononitrile (1 mmol) was added dual acidic
nanocatalyst 3 (0.02 g) and the reaction mixture was
stirred mechanically in ethanol (1 ml) at 60 °C. After com-
pletion of the reaction, which was monitored by TLC, the
reaction mixture was diluted with hot ethanol and the cat-
alyst was easily separated from the reaction mixture using
an external magnet. The catalyst was washed with etha-
nol and dried for reuse in the next run. The combined
organic solution was concentrated and the solid product
obtained was collected by filtration and washed with eth-
anol to furnish the desired pure product (9a–k).
2‐Amino‐4‐(4‐bromophenyl)‐6‐(2‐methyl‐1H‐indol‐3‐
yl)‐4H–pyran‐3,5‐dicarbonitrile (9j). White solid; m.p.
256–258 °C. IR (KBr, ν, cm−1): 3482, 3328 (N―H stretch),
1
2197 (CN stretch). H NMR (400 MHz, CDCl3, δ, ppm):
11.80 (br. s, 1H, NH), 7.67 (d, 2H, J = 8.4 Hz, Ar‐H),
7.47 (d, 1H, J = 7.6 Hz, Ar‐H), 7.39 (d, 1H, J = 7.6 Hz,
Ar‐H), 7.38 (d, 2H, J = 8.4 Hz, Ar‐H), 7.30 (br. s, 2H,
NH2), 7.16 (td, 1H, J = 7.5, 1.2 Hz, Ar‐H), 7.11 (td, 1H,
J = 7.5, 1.2 Hz, Ar‐H), 4.55 (s, 1H, C―H), 2.43 (s, 3H,
CH3). 13C NMR (100 MHz, CDCl3, δ, ppm): 159.5,
156.2, 143.1, 139.6, 135.5, 132.4, 130.4, 126.4, 122.3,
121.5, 120.8, 119.74, 119.70, 118.2, 111.8, 103.6, 90.2,
55.7, 39.3, 14.0. Anal. Calcd for C22H15BrN4O (431.28)
(%): C, 61.27; H, 3.51; N, 12.99. Found (%): C, 61.15; H,
3.32; N, 12.87.
4.6 | Selected spectral data of 3‐
pyranylindole derivatives (Table 5)
2‐Amino‐4‐(3‐bromophenyl)‐6‐(2‐methyl‐1H‐indol‐3‐yl)‐
4H–pyran‐3,5‐dicarbonitrile (9 g). White solid; m.p. 239–
241 °C. IR (KBr, ν, cm−1): 3472, 3321 (N―H stretch),
1
2192 (CN stretch). H NMR (400 MHz, CDCl3, δ, ppm):
11.82 (br. s, 1H, NH), 7.60 (d, 1H, J = 1.2 Hz, Ar‐H),
7.59–7.57 (m, 1H, Ar‐H), 7.49–7.44 (m, 3H, Ar‐H), 7.39
(d, 1H, J = 7.6 Hz, Ar‐H), 7.32 (br. s, 2H, NH2), 7.17 (t,
1H, J = 7.0 Hz, Ar‐H), 7.12 (t, 1H, J = 7.2 Hz, Ar‐H),
4.58 (s, 1H, C―H), 2.44 (s, 3H, CH3). 13C NMR
(100 MHz, CDCl3, δ, ppm): 159.5, 156.4, 146.3, 139.7,
135.4, 131.8, 131.2, 130.8, 127.3, 126.3, 122.6, 122.3,
120.8, 119.7, 119.6, 118.1, 111.8, 103.5, 90.0, 55.6, 39.3,
13.9. Anal. Calcd for C22H15BrN4O (431.28) (%): C,
2‐Amino‐6‐(2‐methyl‐1H‐indol‐3‐yl)‐4‐(3‐nitrophe-
nyl)‐4H–pyran‐3,5‐dicarbonitrile (9 k). Yellow solid; m.p.
261–263 °C. IR (KBr, ν, cm−1): 3406, 3305 (N―H stretch),
1
2199 (CN stretch). H NMR (400 MHz, CDCl3, δ, ppm):
11.84 (br. s, 1H, NH), 8.27–8.24 (m, 2H, Ar‐H), 7.94 (d,
1H, J = 8.0 Hz, Ar‐H), 7.80 (t, 1H, J = 7.8 Hz, Ar‐H),

10 of 11
KHEIRKHAH ET AL.
[17] N. Foroughifar, A. Mobinikhaledi, H. Moghanian, Int. J. Green
Nanotechnol. Phys. Chem. 2009, 1, 57.
7.50 (d, 1H, J = 7.6 Hz, Ar‐H), 7.41(br. s, 2H, NH2), 7.40
(d, 1H, J = 7.6 Hz, Ar‐H), 7.17 (td, 1H, J = 7.5, 1.4 Hz,
Ar‐H), 7.12 (td, 1H, J = 7.5, 1.0 Hz, Ar‐H), 4.84 (s, 1H,
C―H), 2.46 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3, δ,
ppm): 159.7, 156.8, 148.6, 145.8, 139.9, 135.5, 135.0,
131.3, 126.4, 123.4, 122.6, 122.4, 120.8, 119.7, 119.6,
118.1, 111.8, 103.5, 89.5, 55.3, 39.3, 14.0. Anal. Calcd for
C22H15N5O3 (397.39) (%): C, 66.49; H, 3.80; N, 17.62.
Found (%): C, 66.31; H, 3.65; N, 17.55.
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Habibabadi, Iran J. Chem. 2009, 2, 118.
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ACKNOWLEDGEMENT
[23] H. J. Wang, X. Q. Ren, Y. Y. Zhang, Z. H. Zhang, J. Braz. Chem.
Soc. 2009, 28, 1939.
The authors are grateful to the Research Council of Uni-
versity of Guilan for financial support of this research
work.
[24] A. Khazaei, A. R. Moosavi‐Zare, Z. Mohammadi, A. Zare, V.
Khakyzadeh, G. Darvishi, RSC Adv. 2013, 3, 1323.
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ORCID
[26] M. Kidwai, A. Jahan, N. K. Mishra, C. R. Chim. 2012, 15, 324.
Manouchehr Mamaghani
2054-8685
http://orcid.org/0000-0002-
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