Preparation of a dual-functionalized fumed silica nanoparticle catalysis for synthesis of azaluorenone derivatives

Article abstract of DOI:10.1007/s11164-019-03740-4

Abstract: A dual-functional silica-based catalyst was prepared by treating fumed silica with amino-containing silane then 1,4-butane sultone. The presence of functional groups on the surface of the prepared amino sulfonic acid fumed silica (FSi–PrNH–Bu–SO

Full text of DOI:10.1007/s11164-019-03740-4

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03740-4
Preparation of a dual‑functionalized fumed silica
nanoparticle catalysis for synthesis of azaluorenone
derivatives
Maedeh Bagheri1 · Parisa Gholamzadeh1 · Ghodsi Mohammadi Ziarani1 ·
Alireza Badiei2
Received: 19 September 2018 / Accepted: 12 January 2019
© Springer Nature B.V. 2019
Abstract
A dual-functional silica-based catalyst was prepared by treating fumed silica with
amino-containing silane then 1,4-butane sultone. The presence of functional groups
on the surface of the prepared amino sulfonic acid fumed silica (FSi–PrNH–Bu–
SO3H) was confrmed by Fourier-transform infrared (FT-IR) spectroscopy. Energy-
dispersive X-ray (EDX) elemental analysis showed the presence of S, N, C, O,
and Si on the surface of the catalyst. The size of the agglomerated particles was
observed to lie in the range of 30–50 nm by scanning electron microscopy (SEM).
Finally, thermogravimetric analysis (TGA) revealed that the amount of organic com-
pounds grafted on the surface of FSi–PrNH2 and FSi–PrNH–BuSO3H was 2.59 and
1.12 mmol/g, respectively. After well characterizing the FSi–PrNH–BuSO3H, it
was used to catalyze the reaction of 1,3-indandione, isatin, ethyl acetoacetate, and
ammonium acetate for synthesis of azafuorenone derivatives.
Keywords Fumed silica · Sultone · Azafuorenone · Nanoparticle · Indandione ·
Multicomponent
Introduction
Fumed silica (FSi) is a type of very fne silica consisting of nanosized particles,
produced by pyrolysis of SiCl4 under hydrogen and oxygen atmosphere in a fame
[1]. FSi includes primary particles with size of 10 nm, which are agglomerated
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-03740-4) contains supplementary material, which is available to authorized users.
*
Parisa Gholamzadeh
gholamzadehparisa94@gmail.com; p.gholamzadeh@alzahra.ac.ir
1
2
Department of Chemistry, Alzahra University, Vanak Square, Tehran, Iran
School of Chemistry, College of Science, University of Tehran, Tehran, Iran
Vol.:(0123456789)
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M. Bagheri et al.
together to form aggregates with sizes in the range of 100 nm–5 mm. FSi is
applied in industrial applications as an antifoaming and paper coating agent, for
reinforcement of elastomers, and as an adsorbent [2]. Since silanol groups are
distributed over the surface of FSi, their density is low, hence the FSi surface
is extremely chemically reactive. Silylation of silanol groups is a key reaction
for surface modifcation of FSi [3]. To date, diferent types of modifed FSi have
been used as antibacterial agents [4], rheological additives [5], adhesive agents
[6], etc. However, literature survey reveals no reports on applications of FSi as a
catalyst in organic synthesis.
Azafuorenone is a signifcant framework found in a variety of natural products
such as onychine, dielsinol, and ursuline [7, 8]. So far, natural azafuorenones
have been shown to exhibit antimalarial [9], antifungal [10], and antimicrobial
properties [11]. Diferent procedures for synthesis of azafuorenones have been
described, including oxidative Heck cyclization [12], C–H functionalizations
[13], Diels–Alder cycloaddition [7], and multicomponent reactions (MCRs) [14].
Among existing methods, MCRs are the simplest, being catalyzed by Brønsted
acids and ofering easy procedures and workup [15]. In continuation of our previ-
ous research on the advancement of heterogeneously catalyzed reactions [16–19],
we introduce herein a new FSi-based heterogeneous dual-functionalized catalyst
for synthesis of azafuorenone derivatives via MCR. This is the frst report on the
role of FSi as a catalyst in organic synthesis.
Experimental
IR spectra were recorded from KBr disks using a Bruker Tensor 27 FT-IR instru-
ment. Melting points were measured by capillary tube method using an Electro-
1
thermal 9200 apparatus. H and 13C nuclear magnetic resonance (NMR) spectra
were acquired using a Bruker DPX at 400 and 100 MHz, respectively. Thermo-
gravimetric analysis (TGA) was carried out using a STA503 model (BӒHR Ther-
moanalyse) in the temperature range of 25–1000 °C at ramp rate of 10 °C min−1
under air. The surface morphology of the catalyst was detected by feld-emission
scanning electron microscopy (S-4160; Hitachi, Japan).
General procedure for preparation of aminopropyl‑modifed FSi (FSi–PrNH2)
In a two-necked round-bottomed fask, FSi (10 g) was dried well under reduced
pressure at 100 °C for about 4 h; after cooling to room temperature, it was added
to dry toluene (150 mL). The mixture was heated under refux condition for about
30 min, then 3-(aminopropyl)trimethoxysilane (6 mL) was gradually added to it and
the mixture was refuxed for about 72 h. Finally, toluene was removed under reduced
pressure to obtain the crude functionalized FSi, which was washed well with CH2Cl2
using a Soxhlet apparatus then dried at ambient temperature overnight.
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Preparation of a dual-functionalized fumed silica nanoparticle…
General procedure for preparation of amino sulfonic acid modifed FSi (FSi–
PrNH–BuSO3H)
FSi–PrNH2 (2 g) was poured into a 50-mL Erlenmeyer, and 1,4-butane sultone
(2 mL) and dichloromethane (8 mL) were added to it. The mixture was stirred well
at room temperature overnight; thereafter, it was fltrated and washed well with
dichloromethane, and dried.
General procedure for synthesis of azafuorenone
A mixture of 1,3-indandione (1 mmol, 0.146 g), isatin (1 mmol, 0.147 g), ethyl ace-
toacetate (1 mmol, 0.13 mL), and ammonium acetate (3 mmol, 0.23 g) was treated
in presence of FSi–Pr–NH–Bu–SO3H (0.05 g) for an appropriate time (as mentioned
in Table 3) in refuxing EtOH, yielding azafuorenone in good yield. After comple-
tion of the reaction as monitored by thin-layer chromatography (TLC), the reaction
mixture was diluted with hot EtOH, then the catalyst was removed by simple fltra-
tion. The red product was purifed by recrystallization from EtOH.
Ethyl 2′,5-dioxo-2-phenyl-1,5-dihydrospiro[indeno[1,2-b]pyridine-4,3′-indoline]-
3-carboxylate (5h): Red powder, FT-IR, v=3380 and 3386 (N–H), 3062 (=C–H
1
aromatic), 2994 and 2850 (CH2 and CH3), 1702, 1675 and 1639 (C=O) cm−1. H
NMR, δ=0.5 (t, 3 H, CH3, J=7), 4.35 (q, 2H, CH2), 6.7 (d, 1H, aromatic, J=7.5),
6.8 (t, 1H, aromatic, J=7.5), 7.1 (t, 2H, aromatic, J=7.5), 7.2 (d, 1H, aromatic,
J=7.5), 7.3 (t, 1H, aromatic, J=7.5), 7.39–7.42 (m, 3H, aromatic), 7.48 (m, 3H,
aromatic), 7.73 (d, 1H, aromatic, J=7), 10.3 (s, 1H, NH), 10.6 (s, 1H, NH) ppm.
13C NMR, δ=13.3, 50.2, 59.8, 106.7, 107.9, 109.2, 120.6, 120.9, 121.8, 124.1,
128.5, 128.7, 128.8, 129.5, 130.9, 133.4, 133.5, 136.2, 136.4, 136.5, 142.7, 147.2,
154.6, 165.8, 179.5, 189.8 ppm.
Results and discussion
Preparation and characterization of FSi–PrNH–BuSO3H
Considering the usefulness of the grafting method for surface modifcation, the sur-
face of fumed silica (FSi) was modifed using a silylating agent. As shown in Fig. 1,
silanol groups on the surface of FSi were initially treated with 3-aminopropyltri-
ethoxysilane (APTES) to obtain FSi–PrNH2. The amino groups on the surface of
FSi–PrNH2 were then reacted with 1,4-butane sultone to obtain the target product
FSi–PrNH–BuSO3H, which was subsequently characterized as follows.
TGA–diferential thermal analysis (DTA) curves of both FSi–PrNH2 and
FSi–PrNH–BuSO3H are shown in Fig. 2. The buoyancy efect is the cause of the
mass loss exceeding 100% in Fig. 2a. The weight loss below 100 °C is due to
adsorbed water and solvents. Correspondingly, the weight losses for FSi–PrNH2
and FSi–PrNH–BuSO3H in the temperature range between 100 and 600 °C are 15
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M. Bagheri et al.
Fig. 1 Preparation of FSi–PrNH–BuSO3H
Fig. 2 TGA–DTA curves for a FSi–PrNH2 and b FSi–PrNH–BuSO3H
and 21%, respectively. The observed weight loss above 600 °C is due to condensa-
tion of free silanols of FSi structure. Accordingly, the amount of grafted organic
compounds on the surface of FSi–PrNH2 and FSi–PrNH–BuSO3H was calculated to
be 2.59 and 1.12 mmol/g, respectively. The decrease of the organic compound con-
centration on the surface of FSi–PrNH–BuSO3H compared with FSi–PrNH2 may
result from the fact that all amine groups did not completely react with 1,4-butane
sultone, thus both –PrNH–BuSO3H and –PrNH2 groups are present on the surface.
Furthermore, it is possible to leach some grafted PrNH2 groups during the reaction
with 1,4-butane sultone as a result of the mechanical stirring. In the DTA curve of
FSi–PrNH2, three exothermic peaks are observed at around 127, 286, and 320 °C,
corresponding to decomposition of organic groups. The peak at around 655 °C
relates to condensation of free silanols. Same exothermic peaks are detectable for
FSi–PrNH–BuSO3H in addition to the peak at around 550 °C, corresponding to
additional organic groups on the surface in comparison with FSi–PrNH2.
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Preparation of a dual-functionalized fumed silica nanoparticle…
Fig. 3 FT-IR spectra of FSi–PrNH2 and FSi–PrNH–BuSO3H
Fig. 4 SEM image of FSi–PrNH–BuSO3H
Figure 3 depicts the FT-IR spectra of FSi–PrNH2 and FSi–PrNH–BuSO3H. In
general, FSi displays three intense peaks at 800, 960, and 1100 cm−1, related to
symmetric stretching vibration of Si–O, symmetric stretching vibration of Si–OH,
and asymmetric stretching vibration of Si–O–Si, respectively. The presence of
organic moieties is recognized based on the peaks at 2850–2960 cm−1 in both
spectra, which are related to symmetric and asymmetric stretching vibration of
CH and CH2 groups. In the FT-IR spectrum of FSi–PrNH2, the absorbance bands
at 3338 and 1570 cm−1 correspond to stretching and bending vibration of NH2,
respectively. These bands are missing from the spectrum for FSi–PrNH–BuSO3H,
confrming formation of N–C bond in this material.
FESEM of FSi–PrNH–BuSO3H (Fig. 4) revealed agglomerated particles with
size in the range of 30–50 nm. EDX analysis of FSi–PrNH2 proved the presence
of Si, O, C, and N elements, while in EDX analysis of FSi–PrNH–BuSO3H, S
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M. Bagheri et al.
element was also observed (Fig. 5). The high percentage of C atom is due to the
use of carbon-based adhesive to attach the sample to the pin of the instrument.
Catalytic activity of FSi–PrNH–BuSO3H
To identify the best reaction conditions for preparation of azafuorenone deriva-
tives, a model reaction of indandione 1, isatin 3a, ethyl acetoacetate 3, and ammo-
nium acetate 4 was carried out in presence and absence of catalyst. As shown in
Table 1 (entries 1 and 2), running the reaction using FSi–PrNH–BuSO3H under
solvent-free condition did not give good results even when raising the temperature
to 70 °C. Under refuxing in water, the reaction did not progress (entry 3), while in
ethanol (entry 4), it gave the product in high yield within 15 min; hence, this was
selected as the optimized condition. To investigate the efect of catalyst on the pro-
gress of this reaction, it was tested in presence of pure fumed silica (entry 5) and
FSi–PrNH2 (entry 7); considering the increase of the reaction time and decrease of
product yield, it was found that the functional groups on the fumed silica surface
accelerated the reaction rate. Furthermore, product yield of 68% was obtained in
absence of catalyst within 1 h. Therefore, the presence of catalyst is essential for
this reaction. Varying the catalyst amount (Table 2), it was found that increase of
the amount of catalyst to 0.05 g increased the product yield. However, use of 0.06 g
catalyst resulted in a yield drop of about 2% compared with 0.05 g catalyst; this may
Fig. 5 EDX results of a FSi–PrNH2 and b FSi–PrNH–BuSO3H
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Preparation of a dual-functionalized fumed silica nanoparticle…
Table 1 Optimization of reaction conditions for synthesis of azafuorenone 4a
Entry
Catalyst (0.03 g)
Solvent
Condition
Time (min)
Yield (%)
1
2
3
4
5
6
7
FSi–PrNH–BuSO3H
FSi–PrNH–BuSO3H
FSi–PrNH–BuSO3H
FSi–PrNH–BuSO3H
FSi
–
–
r.t.
24
13
120
15
35
1 h
30
43
51
–
85
72
68
75
70 °C
Refux
Refux
Refux
Refux
Refux
H2O
EtOH
EtOH
EtOH
EtOH
–
FSi–PrNH2
1,3-Indandione (1 mmol), isatin (1 mmol), ethyl acetoacetate (1 mmol), ammonium acetate (3 mmol),
catalyst (0.03 g), and solvent (3 mL)
Table 2 Optimization of
Entry Amount of Amount of catalytic Time (min) Yield (%)
catalyst amount for synthesis of
catalyst (g) sites used (mol%)
azafuorenone 4a
1
2
3
4
0.03
0.04
0.05
0.06
3.36
4.48
5.6
15
10
7
85
90
93
91
6.7
7
Scheme 1 Synthesis of azafuorenone derivatives
be explained by higher adsorption of organic compounds on the greater amount of
silica surface. Therefore, the optimized amount of FSi–PrNH–BuSO3H for this reac-
tion was established as 0.05 g.
The generality of this reaction was studied by applying diferent isatin 2a–g and
β-ketoester compounds 3a, b (Scheme 1). As shown by the results in Table 3, isatin
2a gave the best results regarding the reaction time, while electron-withdrawing sub-
stituents on the phenylene ring of isatin led to decreased product yield (5b–g) and
increased reaction time. In addition, replacing ethyl acetoacetate 3a by ethyl benzoy-
lacetate 3b (entries 8 and 9) resulted in a signifcant drop of the product yield (5h).
The role of FSi–PrNH–BuSO3H as catalyst in the synthesis of azafuorenone
derivatives is shown by the plausible mechanism in Scheme 2. Initially, indandione
1 is converted to its enolic form 1′. Then, the latter condenses with the carbonyl
group of isatin 2′ which was previously activated by the catalyst, thus intermediate
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M. Bagheri et al.
Table 3 Synthesis of azafuorenone derivatives in presence of FSi–PrNH–BuSO3H
Entry
No.
R1
X
R2
R3
Time (min)
Yield (%)
M.p. (°C)
Reference
m.p. (°C)
[20]
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
H
H
H
H
H
H
Bn
H
H
Et
Et
Et
Et
Et
Et
Et
Et
Me
Me
Me
Me
Me
Me
Me
Ph
7
11
15
15
14
12
16
40
93
91
90
84
72
76
68
76
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
New
Cl
Br
NO2
I
F
H
5g
5h
H
Scheme 2 Plausible mechanism for synthesis of azafuorenone derivatives in presence of FSi–PrNH–
BuSO3H
7 is formed after a dehydration process. Simultaneously, β-ketoester 3 reacts with
ammonium acetate 4 to obtain intermediate 8, which is then added to the condensed
compound 7 by Michael addition. Finally, the azafuorenone 5 is produced by intra-
molecular cyclization of 9 and a subsequent dehydration process. The catalyst plays
an important role in both protonation and deprotonation steps due to the presence of
both acidic and basic functions on its surface.
Three methodologies have been reported for synthesis of azafuorenone deriva-
tives (Table 4, entries 1–3). Bazgir and coworkers employed pyridine and toluene
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Preparation of a dual-functionalized fumed silica nanoparticle…
Table 4 Comparison of methods applied for synthesis of azafuorenone derivatives
Entry
Catalyst
Solvent
Condition
Time (h)
Yield (%)
Ref.
1
2
3
4
Pyridine
–
Activated alumina
FSi–PrNH–BuSO3H
Toluene
EtOH:H2O (9:1)
–
Refux
r.t.
100 °C
24
6
4
75–92
70–86
60–90
68–93
[20]
[21]
[22]
This work
EtOH
Refux
7–40 min
as catalyst and solvent, respectively, in this reaction (entry 1); Mukhopadhyay and
coworkers tried this synthesis in a mixture of ethanol and water with no catalyst;
while in other work, activated alumina catalyzed this reaction under neat condition.
Use of unsafe solvent, harsh conditions, and long reaction time are drawbacks of
the mentioned methods. In this report, the catalyst is safe, the solvent and reaction
condition are green, and the reaction time is very short compared with the others. It
can thus be concluded that this new catalyst is efcient in terms of reaction time and
product yield, ofering green conditions that are safe for the environment.
Conclusions
The surface of FSi was modifed with dual functions of acid (SO3H) and base (NH),
then characterized by FT-IR spectroscopy, TGA–DTA, SEM, and EDX spectros-
copy. All analyses confrmed efective grafting of organic groups on the silica sur-
face. The resulting FSi–PrNH–BuSO3H catalyzed synthesis of azafuorenone deriv-
atives in refuxing EtOH. In terms of high product yield, chemoselectivity, and short
reaction time, it can be claimed that FSi–PrNH–BuSO3H is an efcient heterogene-
ous catalyst for organic reactions. Investigation of the special properties of the pre-
pared azafuorenone is in progress.
Acknowledgements We gratefully acknowledge the fnancial support from the Research Council of
Alzahra University and the University of Tehran.
Compliance with ethical standards
Confict of interest There are no conficts of interest to declare.
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