H5PW10V2O40@VOx/SBA-15-NH2 catalyst for the solventless synthesis of 3-substituted indoles

Article abstract of DOI:10.1016/j.tet.2017.08.030

Functionalization of mesoporous SBA-15 frameworks by transition metal oxides offers a flexible route to fabricate new heterogeneous catalysts. Here, an inorganic-organic hybrid nanoporous catalyst H₅PW₁₀V₂O₄₀@VO

Full text of DOI:10.1016/j.tet.2017.08.030

Accepted Manuscript
H PW V O @VO /SBA-15-NH catalyst for the solventless synthesis of 3-
10 2 40
5
x
2
substituted indoles
Narges Mahdizadeh ghohe, Reza Tayebee, Mostafa M. Amini, Amin Osatiashtiani,
Mark A. Isaacs, Adam F. Lee
PII:
S0040-4020(17)30861-X
10.1016/j.tet.2017.08.030
TET 28924
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 26 May 2017
Revised Date: 31 July 2017
Accepted Date: 14 August 2017
Please cite this article as: Mahdizadeh ghohe N, Tayebee R, Amini MM, Osatiashtiani A, Isaacs MA, Lee
AF, H PW V O @VO /SBA-15-NH catalyst for the solventless synthesis of 3-substituted indoles,
5
10 2 40
x
2
Tetrahedron (2017), doi: 10.1016/j.tet.2017.08.030.
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ACCEPTED MANUSCRIPT
H5PW10V2O40@VOx/SBA-15-NH2 catalyst for the solventless synthesis of 3-
substituted indoles
Narges Mahdizadeh ghohea, Reza Tayebee*a, Mostafa M. Aminib, Amin Osatiashtianic, Mark A.
Isaacsc, Adam F. Leec
aDepartment of Chemistry, School of Sciences, Hakim Sabzevari University, Sabzevar 96179-76487, Iran
bDepartment of Chemistry, Shahid Beheshti University, G.C., Tehran 1983963113, Iran
cEuropean Bioenergy Research Institute, Aston University, Birmingham B4 7ET, UK
*Corresponding author: Email: Rtayebee@hsu.ac.ir; Tel: +98-51-44410310
Abstract
Functionalization of mesoporous SBA-15 frameworks by transition metal oxides offers a flexible
route to fabricate new heterogeneous catalysts. Here, an inorganic-organic hybrid nanoporous
catalyst H5PW10V2O40@VOx/SBA-15-NH2, was prepared and utilized as an efficient, eco-
friendly, and recyclable catalyst for the one-pot, multi-component synthesis of 3-substituted
indoles by indole substitution with aldehydes and malononitrile under solvent-free conditions.
Catalysts were prepared by the non-covalent attachment of H5PW10V2O40 to a 3 wt%VOx/SBA-
15 nanoporous support through a 3-(triethoxysilyl)propylamine linker. VOx/SBA-15 was
prepared by a one-pot hydrothermal synthesis from TEOS and vanadium(V) oxytri-tert-butoxide
[VO(O-tBu)3]. The resulting H5PW10V2O40@VOx/SBA-15-NH2 material was characterized by
bulk and surface analysis including N2 porosimetry, FE-SEM, XRD, XPS, FT-IR, TGA-DTA,
UV-Vis and ICP-OES, evidencing retention of the heteropolyacid Keggin structure.
H5PW10V2O40@VOx/SBA-15-NH2 exhibits high activity and excellent yields (70-95 %) of 3-
substituted indoles under mild conditions, with negligible deactivation.
Keywords: Vanadia; SBA-15; heteropolyacid; 3-Substituted indoles; Solventless
1

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1. Introduction
Mesoporous molecular sieves M41S with uniform pore sizes exceeding 20 Å and surface areas
reaching 1000 m2g-1 have proven to be valuable architectures for applications in heterogeneous
catalysis, notably the genesis of solid acids and associated organic transformations.1-4 Among
mesoporous silicas, SBA-15 has attracted considerable attention due to its large and tunable pore
dimensions, thick walls and hence good hydrothermal stability, and flexible adaptation into
hierarchical frameworks.5 Despite the lack of lattice defects, limited redox or basicity/acidity of
pure SBA-15, such physicochemical properties can be readily modified through the introduction
of inorganic and/or organic species either into the silica framework or over its surface to generate
new catalytically active sites.6-12
Various transition metals can be introduced into the siliceous frameworks,1,13 including
vanadium to yield vanadia-functionalized mesoporous MCM-4113 and SBA-1514,15 frameworks
for oxidation and acid catalysis,14,16-18 with high-valent vanadia species increasing SBA-15
acidity.19,20 A high concentration of vanadium, in a range of oxidation states, can be incorporated
into SBA-15 without destroying the mesoporous framework.1 Indeed, vanadium functionalized
mesoporous silicas (e.g. V-SBA-15, V-MCM-41, V-MCM-48, V-MCF) often exhibit uniform
pore sizes and high surface areas, and consequently a high density of accessible (and well-
defined) active VOx centers.9,21-27 Direct incorporation of metal ions within the silica framework
of SBA-15 is challenging and requires strong acidic conditions,9,28,29 and the majority of such
approaches employ post-synthetic grafting of SBA-15 and/or complex experimental conditions;
new approaches to introduce and control the oxidation state of vanadium within mesoporous
SBA-15 are therefore desirable. In this context, vanadium(V) oxytri-tert-butoxide (OV(O-tBu)3)
is known to generate V2O5 clusters under acidic conditions and hence offers a means to attach
isolated, tetrahedral vanadium(V) species to silica surfaces via Si-O-V bonds.9 The loading,
cluster size and oxidation state of various transition metals is known to strongly influence the
activity of doped silica catalysts.30,31 Heteropolyacids (HPAs) are polyoxometalate inorganic
cages which possess tunable (and even superacidic) Brönsted acidity.32 HPAs can be readily
incorporated into mesoporous silicas to promote acid catalyzed transformations such as terpene
isomerization, wherein SBA-15 was recently shown to stabilize highly dispersed
H3PW12O40 clusters improving acid site densities and accessibility,33 and the Biginelli
condensation of substituted aldehydes with ethyl acetoacetate and urea to form 3,4-
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dihydropyrimidin-2-(1H)-ones over piperazine tethered H5PW10V2O40.34 3-Substituted indoles
are important chemical intermediates and pharmaceutical precursors35 and pharmacologically
active analogues of synthetic Ergine, Gramine, and Sumatriptan production, and as aromatase
and integrase inhibitors for breast cancer and HIV-1 therapies, respectively.36 Existing protocols
for the preparation of substituted indoles such as 2-((1H-indol-3-yl)(phenyl)methyl)malononitrile
suffer from disadvantages including long reaction times, high temperatures and the requirement
for stoichiometric catalyst quantities, or deliver unsatisfactory yields or utilize homogeneous
catalysts with associated product separation issues.37-40 New active, low cost catalysts employing
earth abundant elements are thus sought for operation under mild reaction conditions.
Herein, we describe a simple and efficient direct route to introduce vanadium into SBA-
15 by adjusting the pH during a sol-gel synthesis step,9,41,28,42,43 and modifying the resulting
VOx/SBA-15 surface with a 3-(triethoxysilyl)propylamine linker to subsequently non-covalently
bind H5PW10V2O40. The resulting hybrid nanoporous material exhibits Lewis/Brønsted solid acid
character and the associated catalytic activity for the one-pot, multi-component synthesis of 3-
substituted indoles (Scheme 1). Immobilization of the HPA component through electrostatic
interactions suppresses catalyst leaching and hence improves recyclability.
R= halogen, nitro, methoxy; R'= H
Scheme 1. One-pot synthesis of 3-substituted indoles from indole, malononitrile and aldehydes.
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Scheme 2. Preparation of H5PW10V2O40@VOx/SBA-15-NH2.
2. Results and discussion
2.1. Structure of functionalized SBA-15
Elemental analysis by ICP-OES demonstrated the actual V loading of the VOX/SBA-15 and
VOX/SBA-15-NH2 materials as 3.7 and 3 wt%, respectively. Textural properties of the
functionalized mesoporous SBA-15 silicas were characterized by porosimetry and the resulting
adsorption-desorption isotherms shown in Figure 1 and corresponding surface areas and pore
volumes summarized in Table 1. All materials exhibited type IV isotherms characteristic of a
conventional SBA-1533 with type H3 hysteresis loops (indicative of slit-shaped pores),44 with
dimensions for the as-prepared VOx/SBA-15 similar to those reported for SBA-15, indicating
that V incorporation into the sol-gel step had minimal impact on the mesopore structure. The
small micropore contribution is often observed in the cooperative self-assembly route employed
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in this work, in contrast to true liquid crystal templating routes which offer reduced
microporosity.45 Amine-grafting, and subsequent HPA incorporation, significantly lowered the
surface area and total pore volume relative to VOx/SBA-15, and eliminated microporosity, yet
had negligible impact on the mean mesopore diameter. These changes indicate that both post-
functionalization steps induced substantial pore blockage.
600
VOx/SBA-15
VOx/SBA-15-NH2
500
H5PW10V2O40@VOx/SBA-15-NH2
400
300
200
100
0
0
0.2
0.4
0.6
0.8
1
Relative pressure / p/p0
Figure 1. N2 adsorption-desorption isotherms for functionalized SBA-15.
Table 1. Textural properties of functionalized SBA-15
Sample
BET surface area / BJH pore diameter / Total pore volume / Micropore volume /
m2.g-1
Nm
cm3.g-1
cm3.g-1
VOX/SBA-15
VOX/SBA-15-NH2
H5PW10V2O40@VOX/SBA-15-
NH2
695
3.9
0.81
0.015
128
99
3.9
3.8
0.28
0.21
-
-
Crystallinity was subsequently probed by low (Figure S1) and wide angle (Figure 2)
XRD. All three samples exhibited a broad feature between 2θ = 18° and 30° characteristic of the
amorphous silica framework. In addition, the parent VOx/SBA-15 exhibited sharp, but weak,
reflections indicative of V2O5 (JCPDS card: 41-1426) with d values of 5.75, 4.39, 4.10, 3.41,
2.88, 2.77, 2.61, 2.19, 1.99, 1.92 and 1.78 Å, indicating the presence of a crystalline VOx phase
on the SBA-15 with 60 nm crystallite size according to Scherrer analysis of the peak width,
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which must co-exist as a discrete phase, and not within the SBA-15 pore network. However, the
low intensity of these V2O5 reflections relative to the background indicates that only a small
proportion of the 3.7 wt% vanadium incorporated is present in these large crystallites, with the
remainder presumably present in smaller particles or clusters (< 2 nm and hence below the
instrumental sensitivity limit) dispersed throughout the SBA-15 pore network as depicted in
Scheme 2. These reflections were lost following amine functionalization and anchoring of HPA,
indicating disruption of the V2O5 crystallites, while the absence of H5PW10V2O40 reflections
suggests that the HPA was highly dispersed throughout the 3%VOx/SBA-15-NH2 material, as
observed for low loadings (<9 wt% W) of H3PW12O40 over unmodified SBA-1533 and
H15P5W30O110 (~5 wt%) on the inner surface of modified MCM-41.46 The low angle XRD
pattern of HPA@VOx/SBA-15-NH2 shows an intense peak at 2θ = 0.6° evidencing retention of
the mesoporous silica framework following functionalization by the amine linker and
H5PW10V2O40. However, higher order reflections expected for the p6mm hexagonal close-packed
SBA-15 network11,33 were absent, suggesting poor long-range ordering of mesopores, and indeed
ordered mesopore arrays could not be imaged by HR-TEM. The absence of higher order
reflections and poor long-range ordering probably reflects the in situ synthesis of VOx/SBA-15
in this work; ordered mesopore arrays are only reported for vanadium oxide on SBA-15 prepared
by post-synthetic hydrothermal functionalization of the silica support.47 XPS revealed V 2p3/2
binding energies around 515.4 eV for all three materials, consistent with high valent (IV or V)
vanadium48 and the V2O5 phase observed by XRD.
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Figure 2. Wide angle XRD patterns of functionalized SBA-15.
Thermogravimetric (TGA-DTA) profiles of the H5PW10V2O40@VOX/SBA-15-NH2
performed under air in Figure 3 reveal a weak endotherm and concomitant small weight loss
associated with the desorption of physisorbed water between 50-150 °C. A second, larger weight
loss and coincident broad exotherm around 285 ºC is most reasonably associated with
combustion of the tethered amine, and equates to an amine loading of 2.4 mmol.g-1. A second
weak exothermic peak (relative to the sloping baseline) was observed spanning 425-525 °C,
coincident with a small mass loss observed in the TGA profile of the parent H5PW10V2O40
(Figure S2), and hence is attributed to thermal decomposition of the heteropolyacid. The
absence of a second mass loss in Figure 3 associated with the heteropolyacid decomposition in
the functionalized silica is not surprising given that this process only accounts for a 2 % mass
loss in the parent H5PW10V2O40 (which itself only comprises 35 wt% of the composite, see
below).
Figure 3. TGA-DTA profiles for H5PW10V2O40@VOX/SBA-15-NH2
Electronic properties of the H5PW10V2O40@VOx/SBA-15-NH2 sample were explored by
UV-Vis spectroscopy during the HPA immobilization step (Figure 4): VOx/SBA-15-NH2 (1.0 g)
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was suspended in a 60 mL H5PW10V2O40 methanolic solution at an initial HPA concentration of
18000 ppm under reflux. UV-Vis spectra of the pure HPA exhibit two ligand→metal charge-
transfer bands originating from different oxygen species. The strong band around 210 nm is
assigned to Od→W charge-transfer from the terminal oxygens, while that at 265 nm is assigned
to O→V charge-transfer from the bridging oxygen atoms.49 Periodic analysis of aliquots
withdrawn from the above solution revealed a systematic decrease in the 265 nm band
characteristic of the parent H5PW10V2O40, with quantification against calibration curves
evidencing a final HPA loading of 0.14 mmol g−1 (~37 wt%) in excellent agreement with ICP-
OES (35.1 wt%).
Figure 4. Evolution of UV-Vis spectra during H5PW10V2O40 addition to VOx/SBA-15-NH2.
The surface morphology of the H5PW10V2O40@VOx/SBA-15-NH2 material was further
investigated by FE-SEM (Figure 5a,b), which visualized irregular, micron-scale aggregates
comprised of approximately 25 nm spherical nanoparticles possessing a narrow size distribution.
Functionalization by 3-(triethoxysilyl)propylamine and subsequent HPA immobilization had
minimal impact on the parent VOX/SBA-15 morphology. Moreover, to establish the chemical
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composition of the nanohybrid catalyst, HPA@VOx/SBA-15-NH2, energy dispersive X-ray
(EDX) analysis was also compiled (Figure 5c). The EDX analysis showed the presence of
tungsten in addition to vanadium and silicon in the nanocatalyst framework, indicating that
vanadium and silicotungstic acid were successfully grafted onto SBA-15 mesoporous silica in
accordance with ICP.
Figure 5. (a-b) FESEM micrograph and (c) corresponding EDX spectrum of
H5PW10V2O40@VOx/SBA-15-NH2.
Surface properties of the mesoporous silicas were probed by FT-IR between 400-1400
cm-1 (Figure 6), to confirm the successful incorporation of NH2 and HPA functionalities. The
parent VOx/SBA-15 exhibited a strong band around 1080 and a weak feature at 806 cm-1
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attributed to the asymmetric and symmetric Si–O–Si stretching vibrations respectively,50 while a
weak shoulder ~960 cm-1 has been previously associated with vibrations of [SiO4] units bound to
vanadium (Si–O–V) in vanadium modified MCM-4151. A broad band centered around 3500 cm-1
due to surface Si–OH and V–OH groups was also observed.52 Evidence for successful amine
functionalization was indicated by the appearance of additional C-H and N-H stretches around
2929 and 1652 cm-1 respectively in the VOx/SBA-15-NH2 sample. Subsequent HPA
functionalization conferred additional fingerprint bands at 1084, 940, 890, and 796 cm−1
characteristic of the primary Keggin unit (Figure S3):53,54 the 1084 cm−1 band is attributed to
symmetric stretching of PO4 tetrahedra; that at 940 cm−1 to W-Od stretches of the terminal
oxygens; the 890 cm−1 band to W-Ob-W stretches associated with corner bridged oxygens; and
the band at 796 cm−1 to W–Oc-W vibrations associated with side bridged oxygens.55-57 Note that
identification of HPA vibrations is hindered by overlap of the W-O-W and P-O bands with
contributions from Si-O-Si stretches in the underlying VOx/SBA-15 support.
Figure 6. FT-IR spectra of functionalized SBA-15.
2.2 Catalytic synthesis of 3-substituted indoles
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2-((1H-indol-3-yl)(phenyl)methyl)malononitrile synthesis from benzaldehyde, indole, and
malononitrile was first investigated over H5PW10V2O40@VOx/SBA-15-NH2 in the absence of
solvent at 50 °C. Only 10 % of the 3-substituted indole product was formed in the absence of a
catalyst, even after the extended reaction time of 90 min (Table 2). In contrast, almost
stoichiometric yields of 2-((1H-indol-3-yl)(phenyl)methyl)malononitrile were observed in the
presence of 30 mg H5PW10V2O40@VOX/SBA-15-NH2 after only 20 min reaction (Figure S4),
although additional catalyst had minimal impact with a plateau attained at 95 % yield for ≥30
mg. The effect of reaction temperature on the condensation of benzaldehyde, indole, and
malononitrile was also studied (Figure S5), revealing a maximum around 50 ºC, with a decrease
at higher temperature associated with formation of the undesired by-product
bis(indolyl)methane.39,40 The catalytic activity of the components constructing
H5PW10V2O40@VOX/SBA-15-NH2, including H5PW10V2O40, VOX/SBA-15-NH2 and VOX/SBA-
15,
were
independently
tested
in
the
preparation
of
2-((1H-indol-3-
yl)(phenyl)methyl)malononitrile under the standard reaction conditions (Table 2). Immobilizing
the heteropolyacid onto the modified material, VOX/SBA-15-NH2 increased the dispersion of the
catalytically active Brønsted acid sites throughout the silica pore network, and hence increased
activity. Hot filtration tests evidenced negligible leaching of any catalytically active components.
In these tests, a reaction was carried out at 50 ºC for 10 min in the presence of the
H5PW10V2O40@VOX/SBA-15-NH2 catalyst, at which point the product yield reached 45 %.
Ethanol was then added to the reaction mixture, and the catalyst removed immediately by
filtration; the remaining filtrate was monitored for an additional 30 min at reaction temperature,
however no further increase in product yield was observed, confirming the heterogeneous nature
of the catalysis. The reproducibility and recyclability of H5PW10V2O40@VOX/SBA-15-NH2 for
2-((1H-indol-3-yl)(phenyl)methyl)malononitrile production was also assessed. A triplicate
reaction evidenced product yields were reproducible within ±2 % error. Catalyst re-use was
assessed by filtering the H5PW10V2O40@VOX/SBA-15-NH2 catalyst after one reaction, washing
it repeatedly with ethanol to remove residual organic species and subsequent drying at 90 ºC for
4 h, and then adding to a fresh solution of the reaction mixture. Excellent catalyst stability was
also observed from recycle experiments in which a smaller mass of catalyst was employed, and
then spent catalyst recovered by filtration, washed with ethanol and dried at 110 °C for 2 h, and
subsequently added to a fresh reaction mixture of the benzaldehyde, indole, and malononitrile.
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Production of 2-((1H-indol-3-yl)(phenyl)methyl)malononitrile decreased by only 10 % over 8
consecutive re-uses (Figure S6). The FT-IR spectrum of the spent H5PW10V2O40@VOX/SBA-
15-NH2 catalyst after 8 re-uses was identical to that of the as-prepared material, confirming
preservation of the parent Keggin structure (Figure S7) and its immobilization over the amine-
functionalized VOx/SBA-15 support.
Table 2. Effect of catalyst mass on 2-((1H-indol-3-yl)(phenyl)methyl)malononitrile synthesis
Sample
Mass Reaction time Product yield
/ mg
/ min
90
20
20
20
20
20
20
/ %
10
48
55
67
87
90
95
95
95
0
H5PW10V2O40
VOx/SBA-15
VOx/SBA-15-NH2
8.1
17.8
22
H5PW10V2O40@VOX/SBA-15-NH2 10
H5PW10V2O40@VOX/SBA-15-NH2 20
H5PW10V2O40@VOX/SBA-15-NH2 30
H5PW10V2O40@VOX/SBA-15-NH2 40
H5PW10V2O40@VOX/SBA-15-NH2 50
20
20
Reaction conditions: Benzaldehyde (1.0 mmol), indole (1.0 mmol), malononitrile (1.0 mmol) and the
nanocatalyst were mixed to form a uniform liquid mixture which was stirred at 50 °C for the appropriate
time. The progress of the reaction was monitored by TLC. Work-up was carried out as described in the
experimental section.
The catalytic performance of H5PW10V2O40@VOx/SBA-15-NH2 was benchmarked
against literature metal oxides previously reported for similar condensations (Table 3), from
which it is evident that only TiO2 modified clinoptilotite offers a comparable yield to that of our
supported HPA system.
Table 3. Catalyst performance in 2-((1H-indol-3-yl)(phenyl)methyl)malononitrile synthesis.
Yield
Catalyst
/ %
H5PW10V2O40@10%VOx/SBA-15-NH2
95
55
80
50
87
65
70
74
SBA-15
V/SBA-15
MCM-41
TiO2-clinoptilotite
Clinoptilotite
ReO
ZnO
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TiO2
70
68
CeO2
0.3 mmol of each catalyst was utilized in all cases. 0.03 g of the nanohybrid catalyst was used. All of
them was conducted at 20 min. ReO refers to a rare earth oxide mixture including La2O3 and Ce2O3.
Yield% refers to the isolated yield.
An E-factor analysis employing the method proposed by Sheldon58,59 highlights the
excellent atom efficiency of the condensation reaction. For 1 mmol benzaldehyde, 1 mmol indole
and 1 mmol malononitrile reacting over H5PW10V2O40@VOx/SBA-15-NH2 under solvent-free
conditions the E-factor is calculated below at 0.13. This compares very favorably with
alternative literature systems for the same reaction (Table S1), which vary between 0.13 and 150
and require extended reaction times spanning 2 to 48 h (versus 20 min in this work):
E-factor = [(0.106 g benzaldehyde + 0.117 g indole + 0.066 g malononitrile) − 0.256 g
product]/0.256 g product] = 0.13
The efficacy of H5PW10V2O40@VOx/SBA-15-NH2 for the generic synthesis of 3-
substituted indoles from diverse aromatic aldehydes possessing electron withdrawing or donating
substituents was also studied.38,39 Table 4 demonstrates that high yields were obtained for most
of the aromatic aldehydes, with electron-withdrawing groups affording slightly enhanced yields
of 78-95 % (entries 1-7) relative to electron-donating groups (73-76 %, entries 8-9).
Table 4. Synthesis of 3-substituted indoles over H5PW10V2O40@10%VOX/SBA-15-NH2
R= electron-withdrawing (donating) group
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Reaction time Product yield Melting point
Entry
Aldehyde
Product
/ min
/ %
/ °C
20
95
79-80
1
35
85
113-115
2
15
95
173-175
3
30
89
135-137
4
20
91
160-162
5
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30
78
179-180
6
30
40
35
82
122-124
7
76
160-162
8
73
113-115
9
Reaction conditions are provided in Table 1.
A plausible reaction mechanism for the reaction of benzaldehyde, indole, and malononitrile is
shown in Scheme 3, beginning with a Knoevenagel condensation to form (I) via nucleophilic
addition of malononitrile to the carbonyl group of the aldehyde. The indole may subsequently
react with (I) through a Michael addition to afford the desired 2-((1H-indol-3-
yl)(phenyl)methyl)malononitrile product. We propose that the heteropolyacid protonates the
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carbonyl of the aromatic aldehyde thereby increasing its Lewis acidity: electron-donating
substituents deactivate the aldehyde to nucleophilic attack by the malononitrile, while in contrast
electron- withdrawing groups activate the aldehyde carbonyl.60,39
Scheme 3. Plausible mechanism for the synthesis of 3-substituted indoles.
3. Conclusions
A bifunctional, mesoporous solid acid catalyst was synthesized incorporating both vanadate and
heteropolyacid functions, the latter immobilized via a 3-(triethoxysilyl)propylamine linker. The
structure of the resulting catalyst was fully characterized by bulk and surface analytical
techniques, which confirmed preservation of the H5PW10V2O40 following its immobilization. The
resulting H5PW10V2O40@VOx/SBA-15-NH2 catalyst offers an atom efficient route to the one-pot
preparation of 3-substituted indoles through the condensation of indole, malononitrile, and
aromatic aldehydes under solvent-free and mild reaction conditions. A 95 % yield of 2-((1H-
indol-3-yl)(phenyl)methyl)malononitrile was obtained from benzaldehyde in only 20 min at 50
16

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°C, with the catalyst recyclable with negligible deactivation over
8
re-uses.
H5PW10V2O40@VOx/SBA-15-NH2 is a versatile catalyst delivering yields of 3-substituted
indoles between 70-95 % for a range of aromatic aldehydes possessing electron-withdrawing or -
donating substituents, the former proving more reactive possibly due to activation of the
carbonyl towards Knoevenagel condensation with malononitrile. The low E-factor and high
activity of H5PW10V2O40@VOx/SBA-15-NH2 unlocks a new and attractive approach to the
synthesis of biologically active 2-((1H-indol-3-yl)(phenyl)methyl)malononitrile and its
analogues.
4. Experimental
4.1 General information
Starting materials and solvents for catalyst synthesis were from commercial sources and utilized
as obtained, with the exception of VO(O-tBu)3 which was prepared according to the literature.61
4.2 Characterization
Morphologies of the prepared materials were observed with a Mira 3-XMU Field emission
scanning electron microscope (FE-SEM). Crystallinity was evaluated by powder X-ray
diffraction (XRD) on a PW1800-PHILIPS diffractometer with Cu Kα radiation (λ = 1.5418 Ǻ) at
40 kV and 30 mA. Fourier transform infrared (FT-IR) spectra were recorded on an 8700
Shimadzu Fourier Transform spectrophotometer between 400 to 4000 cm−1 employing samples
diluted in KBr pellets. Thermogravimetric and differential thermal analysis (TGA-DTA) was
performed on a Bahr STA-503 instrument in air at a heating rate of 10 °C/min−1. Ultraviolet-
visible (UV-Vis) spectra were obtained on a Shimadzu Model UV-2550 spectrophotometer.
Melting points were recorded on a Bamstead electrothermal type 9200 melting point apparatus.
13
1H- and C-NMR spectra were recorded on a Bruker AVANCE 300 MHz spectrometer using
TMS as an internal reference. Elemental analysis was performed with a Thermo Finnigan Flash-
1112EA microanalyzer and a Varian Vista-PRO ICP-OES. Porosimetry measurements were
conducted by N2 physisorption on a Quantachrome Nova 4200e porosimeter with data analysis
employing Novawin v11.0 software: samples were degassed at 120 °C for 4 h prior to analysis
by nitrogen adsorption at -196 °C, with BET surface areas calculated over the range P/P0 = 0.05-
0.35 where a linear relationship was maintained, while pore size distributions were calculated
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using the BJH model from the desorption isotherm. XPS analysis was performed on a Kratos
Axis HSi photoelectron spectrometer equipped with a charge neutralizer and magnetic focusing
lenses, employing monochromatic Al Kα radiation (1486.6 eV) with energy referencing to the C
1s peak at 284.8 eV.
4.3 Preparation of VOx/SBA-15
Vanadium modified SBA-15 was prepared using tetraethylorthosilicate (TEOS, Sigma Aldrich
99 %) as a silica source and Pluronic P123 (Mav= 5,800, Sigma Aldrich) as a structure directing
agent, and vanadium(V) oxytri-tert-butoxide as the vanadium precursor. Incorporation of
vanadium alkoxide in the siliceous framework was achieved in-situ. In a typical synthesis, P123
(3.0 g) was dissolved in deionized water (69 mL) to obtain a transparent solution; separately
TEOS (6.9 g) was added to deionized water (20 mL), and the resultant mixture added dropwise
to the surfactant solution and aged at 40 °C for 10 min. The desired quantity of vanadium
alkoxide (3 and 6 mmol) was then introduced to the aged mixture to obtain a nominal V:Si molar
ratio of 10. An appropriate amount of 0.30 M aqueous HCl was then added to adjust the pH to 3.
Finally, the resulting blend was stirred for 2 h at 40 °C and then transferred to a Teflon lined
autoclave and heated to 100 °C for 48 h. The resultant precipitate was filtered, washed with
deionized water until a neutral filtrate was obtained, and dried at room temperature overnight.
The organic surfactant was removed by calcination in static air at 540 °C (ramp rate 3 °C/min)
for 6 h to yield the mesoporous VOx/SBA-15 (I).
4.4 Surface modification of VOx/SBA-15 by 3-(triethoxysilyl)propylamine and H5PW10V2O40
Amine functionalized VOx/SBA-15 (II) was prepared by dispersing the parent VOx/SBA-15 (1.0
g) in toluene (30-40 mL) by 30 min ultrasonication. Subsequently, 3-(triethoxysilyl)propylamine
(1.40 mL) was added to the suspension and refluxed for 24 h. The resulting VOx/SBA-15-NH2
was separated by filtration, washed with acetone, and dried at room temperature. H5PW10V2O40
was prepared according to the earlier reports62 and immobilized on VOx/SBA-15-NH2 by the
addition of HPA (0.4 g) to the mesoporous silica (0.8 g) in methanol (50 mL) and subjected to 5
h reflux. The final material was filtered and washed with methanol repeatedly (until the filtrate
became clear) and finally dried at room temperature. The overall catalyst synthesis is depicted in
Scheme 2.
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4.5 Catalytic synthesis of 2-((1H-indol-3-yl)(aryl)methyl)malononitriles
H5PW10V2O40@VOx/SBA-15-NH2 (30 mg) was added to a mixture of aldehyde (1.0 mmol),
indole (1.0 mmol) and malononitrile (1.0 mmol) and heated to 50 °C. Aldehyde (liquid and/or
solid), indole (solid, m.p. 52–53 °C) and malononitrile (freshly crystallized) and the catalyst
formed a dense liquid with a total volume of ∼0.3 mL. The progress of reactions was monitored
by TLC (n-hexane:ethylacetate, 3:2 molar ratio), and on their completion, hot ethanol (3 mL)
was added to the reaction mixture and stirred for 10 min. The heterogeneous catalyst was then
quickly filtered and the filtrate cooled to 5 °C to precipitate the product which was then purified
by filtration of any unreacted (soluble) reactants. Products were characterized by comparison of
their physical data with those of known 2-((1H-indol-3-yl)(aryl)methyl)malononitriles.59,63,37-40,64
Acknowledgements
We thank the Research Councils of Hakim Sabzevari and Shahid Beheshti Universities for
partial financial support.
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Graphical Abstract
H5PW10V2O40@VOx/SBA-15-NH2 was prepared, characterized, and introduced as an effective
catalyst for the one-pot synthesis of 3-substituted indoles. The catalyst could be easily separated
without noticeable reduction in activity.
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-
An inorganic-organic nanoporous material H5PW10V2O40@VOx/SBA-15-NH2 is
synthesised
-
-
An efficient and environmentally benign route to 3-substituted indoles is shown
H5PW10V2O40@VOx/SBA-15-NH2 offers wide scope for a variety of aldehyde substrates