Application of SBA-Pr-NH2 as a nanoporous base silica catalyst in the development of 2,2-Bis(1H-indol-3-yl)acenaphthen-1(2H)-ones syntheses

Article abstract of DOI:10.1007/s13738-015-0639-3

One-pot reaction for the synthesis of symmetrical 2,2-bis(1H-indol-3-yl)-2H-acenaphthen-1-one is reported by condensing acenaphthenequinone and indoles in the presence of catalytic amount of amino-functionalized silica (SBA-Pr-NH₂) under solvent-free conditions at 100°C. (Chemical Equation Presented).

Full text of DOI:10.1007/s13738-015-0639-3

J IRAN CHEM SOC
DOI 10.1007/s13738-015-0639-3
ORIGINAL PAPER
Application of SBA‑Pr‑NH2 as a nanoporous base silica
catalyst in the development of 2,2‑Bis(1H‑indol‑3‑yl)
acenaphthen‑1(2H)‑ones syntheses
G. Mohammadi Ziarani1 · P. Hajiabbasi1 · A. Badiei2
Received: 12 October 2014 / Accepted: 1 April 2015
© Iranian Chemical Society 2015
Abstract One-pot reaction for the synthesis of sym-
metrical 2,2-bis(1H-indol-3-yl)-2H-acenaphthen-1-one is
reported by condensing acenaphthenequinone and indoles
in the presence of catalytic amount of amino-functional-
ized silica (SBA-Pr-NH2) under solvent-free conditions at
100 °C.
Introduction
Mesoporous solids such as amino-functionalized SBA-15
have unique features including high specific surface area,
large pore volume, controllable and narrowly distributed
pore sizes, biocompatibility, and low levels of toxicity [1,
2]. These ordered mesoporous materials have been reported
to have potential applications in several areas such as
adsorption [3], chromatography [4], drug delivery [5], and
catalysis [6].
Graphical Abstract
Indole frameworks have attracted attention of many
chemists due to their pharmacological and biological
activities [7–12]. Moreover, bisindolylalkanes (BIAs)
are an important class of these bioactive compounds
[13–19] whereas benzofuran-bisindole derivatives 1
have anti-hyperlipidemic activities [20]. Bisindole
compound 2 inhibits the growth of both Gram-positive
and Gram-negative bacteria [21], and bisindole deriva-
tives of Catharanthus alkaloids have potential cyto-
toxic properties (Fig. 1) [22]. Also, a number of syn-
thetic methods for preparation of bis(indolyl)alkane
derivatives have been reported in the literature by the
reaction of indole with various aldehydes and ketones
[23–29].
Keywords Multi-component reaction · 2,2-Bis(1H-indol-
3-yl)acenaphthen-1(2H)-ones · SBA-Pr-NH2 · Nanoporous
base silica · Indoles
Due to our interest in developing new synthesis in the
field of nanocatalyst applications, herein we explore the
catalytical activity of amino-functionalized silica (SBA-
Pr-NH2) as an eco-friendly, efficient and reusable cata-
lyst (Fig. 2) to reduce reaction time and temperature in
the synthesis of 2,2-bis(1H-indol-3-yl)-2H-acenaphthen-
1-one derivatives. To date, condensation of acenaph-
thenequinone (3) and indoles (4) was performed under
grinding condition [30] and in the presence of catalytic
amount of ceric ammonium nitrate (CAN) [31] to produce
2,2-bis(1H-indol-3-yl)-2H-acenaphthen-1-ones.
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-015-0639-3) contains supplementary
material, which is available to authorized users.
* G. Mohammadi Ziarani
gmziarani@hotmail.com; gmohammadi@alzahra.ac.ir
1
Department of Chemistry, Alzahra University, Vanak Square,
Tehran, Iran
2
School of Chemistry, College of Science, University
of Tehran, Tehran, Iran
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J IRAN CHEM SOC
utilized under acidic conditions for the synthesis of SBA-
15. Moreover, the post-synthesis grafting method was uti-
lized for surface modifications over the nanoporous silica
with aminopropyl moieties [34].
Experimental
General information
All chemicals were attained commercially and used with-
out further purification. IR spectra were measured from
KBr disk using a FT-IR Bruker Tensor 27 instrument. Melt-
ing points were established using the capillary tube method
General procedure for the preparation of indole
derivatives (4d‑4 g)
1
with an Electrothermal 9200 apparatus. The H and 13C
Indoles (1 mmol), potassium carbonate (1.3 mmol), and
the corresponding alkyl halide (1.1 mmol) were dissolved
in DMF (5 ml) and heated under reflux at 100 °C. Upon
completion of the reaction (monitored by TLC), the crude
product was poured in iced water. The obtained solids
were dissolved in ethyl acetate to give the crystal of pure
products.
NMR (100 and 500 MHz) was performed on a Bruker DPX
using TMS as an internal standard. Gas chromatography–
mass spectrometry (GC–MS) analysis was recorded on an
Agilent 6890-5973 GC/MS detector.
SBA‑15 nanoporous silica synthesis
and functionalization
General procedure for the preparation of compound
(5a‑5i)
As previously reported [32, 33], pluronic P123 nonionic
surfactant as a structure-directing agent and TEOS were
The SBA-Pr-NH2 (0.02 g) was activated in vacuum at
100 °C and then after cooling to room temperature,
acenaphthenequinone 3 (1 mmol) and indoles 4 (2 mmol)
were added to it. The mixture was stirred under solvent-
free condition at 100 °C for an appropriate time to pro-
duce
2,2-bis(1H-indol-3-yl)-2H-acenaphthen-1-one
derivatives 5a-5i. The completion of reaction was indi-
cated by TLC, the resulting solid product was dissolved
in hot ethyl acetate, filtered for removing the unsolvable
catalyst and then the filtrate was cooled to give the pure
yellow product. The spectroscopic and analytical data
for compounds are offered in the following part. Finally,
the recovered catalyst could then be reused after washing
sequentially with diluted aqueous Et3N solution, water,
and acetone.
Fig. 1 Representative examples of bisindolylalkanes compounds
Fig. 2 Amino-functionalized
silica (SBA-Pr-NH2) as catalyst
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J IRAN CHEM SOC
Scheme 1 Synthesis of
2,2-bis(1H-indol-3-yl)
acenaphthen-1(2H)-one deriva-
tives (5a‑5i) in the presence of
SBA-Pr-NH2
2,2‑Bis(1‑hexyl‑1H‑indol‑3‑yl)acenaphthylen‑1(2H)‑one (5e)
mp: 255–257 °C. IR [KBr, νmax (cm−1)]: 3061, 2923,
2654, 1720 (C=O), 1597, 1275, 1013, 891, 777. H NMR
30.3, 30.5, 42.4, 60.5 (C-Spiro), 110.2, 110.2, 112.6, 125.7,
126.8, 129.0, 129.2, 129.4, 129.6, 129.8, 129.8, 130.1,
130.7, 131.2, 133.4, 135.6, 136.1, 139.1, 139.5, 182.3
(C=O). EI-MS: 622 (M+), 396 (10), 207 (12), 182 (100),
154 (C11H6O•, 100), 126 (C10H•6, 100), 74 (22), 50 (10).
1
(500 MHz, DMSO-d6): δ 1.01 (m, 6H, CH3), 2.07–2.19 (m,
12H, CH2), 2.50–2.60 (m, 4H, CH2), 3.34 (m, 4H, CH2),
6.78 (d, J = 7.6, 2H, Ar–H), 6.88 (t, J = 7.1, 3H, Ar–H),
6.98 (d, J = 6.9, 4H, Ar–H), 7.13 (td, 3H, Ar–H), 7.22
(m, 2H, Ar–H), 7.30 (s, 2H, Ar–H). 13C NMR (100 MHz,
CDCl3): δ 20.2, 23.6, 27.1, 29.0, 30.5, 40.2, 60.3 (C-Spiro),
112.0, 112.6, 112.7, 125.7, 126.5, 129.2, 129.5, 129.5,
129.6, 129.8, 130.0, 130.2, 131.1, 133.4, 135.5, 135.9,
140.0, 139.5, 139.7, 189.7 (C=O). EI-MS: 566 (M+), 442
(6), 332 (28), 299 (65), 282 (64), 270 (60), 254 (98), 182
(89), 154 (C11H6O•, 100), 126 (C10H•6, 90), 63 (24), 50 (15).
2,2‑Bis(5‑methyl‑1H‑indol‑3‑yl)
acenaphthylen‑1(2H)‑one (5 h)
mp: 261–263 °C. IR [KBr, νmax (cm−1)]: 3424 (NH), 3059,
1
1720 (C=O), 1596, 1275, 1210, 1057, 892, 831, 777. H
NMR (300 MHz, CDCl3): δ 1.61 (s, 6H, CH3), 7.85 (t,
J = 7.6, 6H, Ar–H), 8.12 (d, J = 7.0, 5H, Ar–H), 8.29 (d,
J = 8.3, 5H, Ar–H, NH). 13C NMR (100 MHz, CDCl3):
δ 25.7, 63.2 (C-Spiro), 111.1, 112.3, 112.5, 125.1, 126.7,
128.6, 128.9, 129.2, 129.4, 129.7, 130.2, 130.4, 130.5,
131.6, 133.3, 135.7, 136.1, 139.5, 184.2 (C=O). EI-MS:
426 (M+), 296 (18), 207 (22), 182 (100), 154 (C11H6O•,
100), 126 (C10H•6, 100), 98 (19), 63 (33), 50 (10).
2,2‑Bis(1‑heptyl‑1H‑indol‑3‑yl)
acenaphthylen‑1(2H)‑one (5f)
mp: 255–257 °C. IR [KBr, νmax (cm−1)]: 3059, 2923, 1719
1
(C=O), 1598, 1306, 1013, 891, 831. H NMR (500 MHz,
2,2‑Bis(5‑chloro‑1H‑indol‑3‑yl)
acenaphthylen‑1(2H)‑one (5i)
DMSO-d6): δ 2.50 (m, J = 1.7, 6H, CH3), 2.98 (m, 16H,
CH2), 3.34 (m, 4H, CH2), 3.51 (m, 4H, CH2), 7.91–7.94
(m, 4H, Ar–H), 8.08 (d, J = 7.1, 6H, Ar–H), 8.44 (d,
J = 8.3, 4H, Ar–H), 8.53–8.57 (m, 2H, Ar–H). 13C NMR
(100 MHz, CDCl3): δ 20.4, 23.6, 27.4, 28.8, 30.2, 30.3,
42.2, 59.5 (C-Spiro), 112.2, 112.6, 112.8, 125.4, 126.4,
129.4, 129.6, 129.6, 129.7, 129.8, 129.9, 130.6, 131.1,
133.4, 135.6, 136.0, 139.0, 139.3, 139.5, 180.5 (C=O).
EI-MS: 594 (M+), 332 (12), 254 (10), 182 (68), 154
(C11H6O•, 100), 126 (C10H•6, 100), 74 (22), 50 (20).
mp: 263–265 °C. IR [KBr, νmax (cm−1)]: 3421 (NH), 3059,
1
1719 (C=O), 1596, 1275, 1012, 892, 830, 777. H NMR
Table 1 The optimization of reaction condition in the synthesis of
2,2-bis(1H-indol-3-yl)acenaphthen-1(2H)-ones
Entry Conditions Temperature Catalyst
Time (min) Yield
1
2
3
4
5
6
7
8
9
Neat
r. t.
SBA-Pr-NH2 40
Trace
45 %
71 %
82 %
71 %
65 %
50 %
55 %
58 %
Neat
40 °C
80 °C
100 °C
120 °C
100 °C
100 °C
100 °C
100 °C
SBA-Pr-NH2 30
SBA-Pr-NH2 20
SBA‑Pr‑NH2 10
SBA-Pr-NH2 10
2,2‑Bis(1‑octyl‑1H‑indol‑3‑yl)acenaphthylen‑1(2H)‑one
(5 g)
Neat
Neat
Neat
mp: 258–260 °C. IR [KBr, νmax (cm−1)]: 3059, 2923, 1719
Neat
–
55
1
(C=O), 1595, 1274, 1011, 890, 830. H NMR (500 MHz,
CH3CN
H2O
SBA-Pr-NH2 40
SBA-Pr-NH2 60
SBA-Pr-NH2 40
CDCl3): δ 2.08 (m, 6H, CH3), 2.42 (m, 20H, CH2), 3.18 (m,
4H, CH2), 3.45 (m, 4H, CH2), 7.86–7.89 (m, 6H, Ar–H),
8.14 (d, J = 6.8, 5H, Ar–H), 8.30 (d, J = 8.3, 5H, Ar–H).
13C NMR (100 MHz, CDCl3): δ 21.4, 23.5, 27.4, 28.5,
MeOH
Bold values indicate the best condition
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J IRAN CHEM SOC
Table 2 Synthesis of
2,2-bis(1H-indol-3-yl)
acenaphthen-1(2H)-one
derivatives
Entry
R1
R2
R3
Product
Time (min)
Yield (%)
Mp (°C)
Mp [Lit]
1
2
3
4
5
6
7
8
9
H
H
Me
H
H
H
H
H
H
H
H
5a
5b
5c
5d
5e
5f
10
10
10
20
30
40
20
10
10
82
78
69
70
65
63
60
88
72
286–289
290–292
>300
289–290 [30]
292–293 [30]
>300 [31]
>300 [30]
New
H
H
H
OMe
H
Me-
n-Hexyl
n-heptyl
n-octyl
H
>300
H
255–257
255–257
258–260
261–263
263–265
H
New
H
5g
5h
5i
New
Me-
Cl
New
H
New
(300 MHz, CDCl3): δ 7.85–7.90 (m, 6H, Ar–H), 8.13 (d,
J = 7.1, 5H, Ar–H), 8.29 (d, J = 8.4, 5H, Ar–H, NH). 13C
NMR (100 MHz, CDCl3): δ 63.3 (C-Spiro), 111.2, 112.4,
112.7, 125.2, 126.5, 128.4, 128.7, 129.2, 129.3, 129.7,
130.2, 130.4, 130.5, 131.6, 133.1, 135.6, 136.1, 139.2,
182.5 (C = O). EI-MS: 467 (M+), 182 (29), 154 (C11H6O•,
100), 126 (C10H•6, 42), 98 (4), 74 (6), 63 (5), 50 (4).
The reaction was probably preceded as shown in
Scheme 2. Acenaphthenequinone 3 may be subject to addi-
tional nucleophilic attack by indoles which is converted
to 2-hydroxy(2-indo-3-lyl)acenaphthylen-1(2H)-one (7).
This intermediate (7) then undergoes a nucleophilic sub-
stitution reaction via another molecule of indole to prepare
2,2-bis(1H-indol-3-yl)-2H-acenaphthen-1-ones by elimina-
tion of water. Thus, 2-hydroxy(2-indo-3-lyl)acenaphthylen-
1(2H)-one 7 may be formed in situ as a key intermediate
using catalytic amount of SBA-Pr-NH2.
Results and discussion
The synthesis of the N-alkylated indoles was performed
by reaction of the indole with different alkyl halides in
DMF in the presence of K2CO3 (Scheme 3) [37].
In the continuation of our interest in the synthesis of vari-
ous compounds of biological importance [35, 36] using
amino-functionalized silica (SBA-Pr-NH2) as a heteroge-
neous nanocatalyst, herein we report the synthesis of some
90
80
70
60
50
40
30
20
10
0
2,2-bis(1H-indol-3-yl)-2H-acenaphthen-1-one
deriva-
tives under mild reaction condition. Thus, the reaction of
acenaphthenequinone (3) and indoles (4) in the presence
of catalyst at 100 °C has been shown to give the desired
products in good yields (Scheme 1). The reaction was opti-
mized using different reaction conditions for obtaining the
best yield of compound 5a. The results are summarized
in Table 1. It was observed that solvent‑free condition in
the presence of 0.02 g catalyst at 100 °C provides the best
result in terms of yield and time (entry 1). The product was
obtained in a moderate yield (50–58 %) using other sol-
vents such as MeCN, H2O, and MeOH (entries 3–5). Then,
to investigate the scope of the reaction further, a series of
differently substituted 2,2-bis(1H-indol-3-yl)-2H-acenaph-
then-1-ones were successfully prepared and the results
were illustrated in Table 2. Corresponding products were
synthesized successfully in good yields (60–88 %) under
solvent‑free condition in the presence of SBA-Pr-NH2.
Finally, the reusability of the catalyst was investigated
for the synthesis of the model compound 5a. The filtered
catalyst was washed sequentially with diluted aqueous Et3N
solution, water, and acetone to reuse without any noticeable
loss in activity. As illustrated in Fig. 3, the process of recy-
cling was fulfilled four times that were established to be 82,
78, 73, and 65 %, respectively.
1
2
3
4
Cycle
Fig. 3 Reusability of catalyst in the synthesis of compound 5a
Scheme 3 Synthesis of N-alkylated indoles
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J IRAN CHEM SOC
Scheme 2 Proposed mechanism for the formation of compound (5a-5i)
Acknowledgments We gratefully acknowledge the financial sup-
port from the Research Council of Alzahra University and the Univer-
sity of Tehran.
Catalyst
As a part of our current studies on the development of new
routes in using nanoporous silica in the multi-component
reactions [35, 36], here we reported an efficient synthetic
route of 2,2-bis(1H-indol-3-yl)-2H-acenaphthen-1-ones
in the presence of catalytic amount of SBA-Pr-NH2. The
catalyst surface was analyzed by different methods such as
N2 adsorption–desorption isotherms, textural properties of
NH2-SBA-15, XRD pattern, FT-IR spectra, TGA analysis
and TEM image of SBA-Pr-NH2 were discussed in our pre-
vious report and demonstrated that the organic groups (pro-
pyl amine) were immobilized into the pores [38].
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