Synthesis and characterization of guanine-functionalized mesoporous silica [SBA-16-G]: a metal-free and recyclable heterogeneous solid base catalyst for synthesis of pyran-annulated heterocyclic compounds

Article abstract of DOI:10.1007/s11164-018-3693-5

Abstract: The synthesis of a new solid base catalyst, i.e., guanine-functionalized mesoporous silica [SBA-16-G], is described. The synthesized catalyst has been fully characterized by FTIR, solid state ¹³C NMR, TGA, XRD, BET, FESEM, EDAX, CHNS elemental analysis, CO₂-TPD, and TEM techniques. The surface area and the basicity of the synthesised [SBA-16-G] were found to be 524?m²/g and 3.230?mmol/g, respectively, based on BET and CO₂-TPD analysis. The catalytic activity of the synthesized catalyst has been explored in the synthesis of a series of biologically and pharmaceutically active pyran-annulated heterocyclic compounds from a one-pot three-component reaction of an aromatic aldehyde, malononitrile/ethyl cyanoacetate, and a C–H activated acidic compound, in the presence of a catalytic amount (10?wt%) of [SBA-16-G]. The catalyst is metal-free, easy to synthesize and to isolate from the reaction mixture, and recycled up to four times without significant loss of catalytic activity. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-018-3693-5

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-018-3693-5
Synthesis and characterization of guanine‑functionalized
mesoporous silica [SBA‑16‑G]: a metal‑free and recyclable
heterogeneous solid base catalyst for synthesis
of pyran‑annulated heterocyclic compounds
Radha Gupta1 · Samaresh Layek1 · Devendra Deo Pathak1
Received: 1 October 2018 / Accepted: 28 November 2018
© Springer Nature B.V. 2018
Abstract
The synthesis of a new solid base catalyst, i.e., guanine-functionalized mesoporous
silica [SBA-16-G], is described. The synthesized catalyst has been fully charac-
terized by FTIR, solid state 13C NMR, TGA, XRD, BET, FESEM, EDAX, CHNS
elemental analysis, CO2-TPD, and TEM techniques. The surface area and the basic-
ity of the synthesised [SBA-16-G] were found to be 524 m2/g and 3.230 mmol/g,
respectively, based on BET and CO2-TPD analysis. The catalytic activity of the
synthesized catalyst has been explored in the synthesis of a series of biologically
and pharmaceutically active pyran-annulated heterocyclic compounds from a one-
pot three-component reaction of an aromatic aldehyde, malononitrile/ethyl cyanoac-
etate, and a C–H activated acidic compound, in the presence of a catalytic amount
(10 wt%) of [SBA-16-G]. The catalyst is metal-free, easy to synthesize and to isolate
from the reaction mixture, and recycled up to four times without signifcant loss of
catalytic activity.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-018-3693-5) contains supplementary material, which is available to authorized users.
*
Devendra Deo Pathak
ddpathak@iitism.ac.in
1
Department of Applied Chemistry, Indian Institute of Technology (Indian School of Mines),
Dhanbad, Jharkhand 826004, India
Vol.:(0123456789)
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R. Gupta et al.
Graphical abstract
Keywords Guanine-functionalized SBA-16 · Pyran · Metal-free · Heterogeneous
catalysis · Solid base
Introduction
A chemical reaction can be triggered by an acidic or a basic catalyst in a catalytic
cycle [1]. Over the last few decades, solid bases have been the subject of intense
investigation in the feld of catalysis [2–5]. Pines and Haag [6] reported the use of
sodium alumina as a solid base catalyst for the frst time in 1958, for the isomerisa-
tion of alkenes. Since then, the scope of solid-base catalysts has been extended to a
variety of chemical reactions, such as the oxidation of thiol [7], the synthesis of fne
chemicals [8], degradation reactions [9], biomass conversion [10], multi-component
synthesis [11], and the transesterifcation of trioleins and the production of biofules
[12, 13]. Many solid-base catalysts, such as DABCO [11], K2CO3-loded alumina
[12], metal oxides (MgO, CaO, SrO, BaO, LaO2, ThO2, ZrO2, ZnO, TiO2), zeolites,
supported alkali metal ions, clay minerals, non-oxides [14], CaO/MgO [15], K/BC-
Fe2O3 [16], etc., have been used as heterogeneous catalysts for the synthesis of a
diverse range of value-added chemicals.
Mesoporous silicas (MSs) were discovered in 1969 [17, 18]. MSs have a large
surface area, high pore volume, and uniform pore radius. As a consequence, these
materials have been used in drug delivery [19], sorption [20], energy storage [21],
catalysis [22], etc. MSs are thermally robust and ideally suitable for functionaliza-
tion with suitable organic scafolds to yield functionalized MSs. The functionalized
MSs have opened up new vistas of research in catalysis, sensors, energy, and bio-
medical felds [23–31]. Presently, there is a renaissance of interest in the synthesis
1 3

Synthesis and characterization of guanine-functionalized…
and applications of functionalized or grafted MSs [32–36]. Aspartic acid, polyethyl-
enimine, and β-cyclodextrin-functionalized MSs have recently been reported [37].
Pyran-annulated coumarins are an integral part of several pharmaceuticals and
are abundant in nature [38]. These coumarin scafolds display a variety of biologi-
cal activities [39]. Furthermore, these compounds exhibit a wide spectrum of prop-
erties, such as diuretic, analgesic, myorelaxant [40], anticoagulant [41], anticancer
[42], antifungal [43], antibacterial [44], antirheumatic [44], antiHIV [45] and antitu-
mor [46]. A few biologically active pyran-annulated heterocycles and their proper-
ties are shown in Fig. 1. Apart from these applications, these compounds are also
useful in the treatment of neurodegenerative ailments, i.e., Alzheimer’s disease,
amyotrophic parallel sclerosis, and Huntington’s and Parkinson’s diseases [46–50].
Other miscellaneous applications of these compounds include beauty care products
and pigments [51], photoactive materials, etc [52].
A literature survey reveals that several acid/base catalysts, such as DMAP
[53], urea [54], DBU [55], TBBDA and PBBS [56], (NH4)2HPO4 [57], heterop-
oly acids [58], basic ionic liquid [59], nano-ZnO [60], C19H42BrN [61], magnetic
nanocatalyst [62], hydroxyapatite [63], per-6-amino-β-cyclodextrin [64], nano-
Al2O3 [65], γ-Fe2O3@Cu3Al-LDH-TUD [66]. etc., have been used for the synthe-
sis of pyran-annulated coumarin derivatives. All these methods sufer from one
of a number of drawbacks, such as high temperature, use of hazardous solvents
and metals, tedious work-up, recyclability of catalysts and low yield of products.
In order to circumvent these inherent problems, currently there is much emphasis
on the design and development of green, sustainable, and metal-free catalysts for
organic synthesis [67–70]. In continuation of the earlier work [37, 71] and our
Fig. 1 Some representative examples of active pharmacology synthetic pyran-annulated heterocyclic
compounds
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R. Gupta et al.
current interest on metal-free catalysis, we report the synthesis of a new solid
base, i.e. guanine-functionalized SBA-16 (Scheme 1) and its application as a het-
erogeneous catalyst for the synthesis of pyran-annulated heterocyclic compounds
(Scheme 2).
Experimental
Materials and reagents
Tetraethoxysilane (TEOS, ≥ 99%), 3-(triethoxysilyl)-propionitrile (≥ 98%),
and pluronic F127 (EO106PO70EO106) were purchased from Sigma Aldrich.
1-hydroxy-benzotriazole hydrate (HOBt, ≥ 98%), 4-hydroxycoumarin, and
1-(3-dimethyl amino propyl)-3-ethyl carbodiimide hydrochloride (EDC-HCl,
≥ 98%), were procured from Avra Chemicals. Guanine (≥ 98%) was purchased
from Alfa Aesar. Toluene (~ 98%), hydrochloric acid (HCl ~ 37%), petroleum
Scheme 1 Proposed scheme for the synthesis of [SBA-16-G]
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Synthesis and characterization of guanine-functionalized…
Scheme 2 Proposed reaction scheme for the synthesis of pyran-annulated heterocyclic compounds
ether (≥ 98%), ethylacetate (≥ 98%), thin-layer chromatographic (TLC) plates,
dichloromethane (DCM), and sulfuric acid (~ 98%) were procured from Merck
India. All those chemicals were used without further purifcation.
Synthesis of [SBA‑16‑G]
SBA-16 was synthesized using the well-known reported procedure [72]. An
amount of 0.0248 mol (4.0 g) of pluronic F127 was dissolved in 30.0 mL of water
and 120.0 mL of 2 M HCl solution and stirred at 35 °C. Then, 10.6 mL of TEOS
was added into that solution and stirred at the same temperature for 20 h. The
mixture was aged at 80 °C for 2 days without stirring. The solid product was
recovered, washed, and air-dried at 130 °C for 6 h. Calcination was carried out
at 500 °C for 8 h to remove the surfactant at a heating rate of 5 °C/min for 3 h.
Before functionalization, the formed material was refuxed in concentrated HCl
for 12 h to activate the surface silanol (Si–OH) groups [37, 71]. Thereafter, the
material was made acid-free by washing with distilled water three times and dried
under vacuum at 100 °C for 24 h.
The SBA-16-CN was prepared following the reported procedure [37, 71]. Ini-
tially, 3-(triethoxysilyl)-propionitrile (0.1 mol) and 3 g of activated SBA-16 in
dry toluene (50 mL) were mixed and stirred in a round-bottom fask at 110 °C for
18 h, resulting in cyano-functionalized SBA-16. It was repeatedly treated with
dry toluene and dried at 125 °C under reduced pressure. Then, SBA-16-CN was
refuxed with 50 mL of ~ 50% H2SO4 at 120 °C for 18 h and aforded SBA-16-
COOH [37, 71]. Then, the as-synthesized SBA-16-COOH was washed exten-
sively with distilled water to make it free from acid and dried at 110 °C under
reduced pressure. Finally, [SBA-16-G] was synthesized when 0.3 mol of EDC-
HCl and 0.3 mol HOBt were mixed in 3.0 g of SBA-16-COOH in 25 mL of dry
DCM at room temperature (RT) followed by the treatment with 0.3 mol of gua-
nine in 25 mL of dry DCM at RT.
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R. Gupta et al.
General procedure for catalytic experiment
Well-dispersed 10 wt% [SBA-16-G] in 4 mL ethanol, prepared by sonication for
10 min, was added to the combined mixture of 4-chlorobenzaldehyde (1 mmol)
and malononitrile (1 mmol). The resultant reaction mixture was stirred at RT for
20 min and the reaction was monitored using TLC. Thereafter, 4-hydroxycou-
marin (1 mmol) was added to the reaction mixture and heated at refux for 4.5 h.
After completion of the reaction, the reaction mixture was cooled to room tem-
perature. After this, the reaction mixture was fltered. The residue was washed
with hot ethanol and the catalyst was separated and the pure product was found
by the evaporation of the ethanol. The as-synthesized product was analyzed by
FTIR, 1H NMR, and 13C NMR and the data are given in the supplementary infor-
mation (SI).
Characterizations
Fourier-transform infrared (FTIR) spectroscopic analyses were carried out on a
FTIR spectrometer (Perkin Elmer, Spectrum 2000) using KBr pellet method. Ther-
mogravimetric analysis (TGA; NETZSCH STA-449f3, Jupiter) was executed on a
thermal analyser in the temperature range 25–900 °C at a heating rate of 5 °C/min
in N2 fow. X-ray difraction (XRD) patterns were determined using a Thermal ARL
X-ray difractometer (CuKα radiation). The BET surface area measurements were
carried out at 77 K with a Nova 3200e (Quantachrome, USA). Field emission scan-
ning electron microscopic (FESEM) analyses with energy-dispersive X-ray analysis
(EDAX; Supra 55, Zeiss, Germany), CHNS elemental analysis, CO2-temperature
programmed desorption (CO2-TPD) were analyzed by BEL’s new fully-automated
catalyst analyzer and transmission electron microscopic (TEM) analyses (JEM-2100;
JEOL, Japan) were performed to obtain clear evidence about the pre- and post-mate-
rial surface properties of SBA-16 and [SBA-16-G]. The solid-state 13C spectra were
analyzed using a JEOL ECA400 MHz instrument operated with 4 mm CD/MAS at
RT. For catalytic reactions, the reaction product was collected and analyzed using
FTIR, 1H NMR and a 13C NMR spectrometer operating at 400 MHz and 500 MHz,
using DMSO-d6, CDCl3 as the solvent and tetramethylsilane as an internal standard.
δ values are reported in parts per million (ppm) and coupling constants (J) in Hertz
(Hz). The melting point was recorded on a Buchi melting point apparatus.
Results and discussion
Synthesis and characterizations of pre‑ and post‑functionalized materials
The starting material, SBA-16, was synthesized by the reported method [73]. The
synthesis of guanine-functionalized [SBA-16-G] is outlined in Scheme 1. The syn-
thesized material was used in the heterogeneous catalytic reaction.
1 3

Synthesis and characterization of guanine-functionalized…
Fig. 2 a FTIR spectra of SBA-16, SBA-16-CN, SBA-16-COOH, and [SBA-16-G]; b TGA plots of SBA-
16 and [SBA-16-G]; c XRD spectra; and d surface area measurements of SBA-16 and [SBA-16-G]
The FTIR spectrum of SBA-16 (Fig. 2a) shows a broad –OH stretching
band at 3476 cm−1. The symmetric and asymmetric Si–O–Si stretching vibra-
tional modes were observed at 806 cm−1 and 1080 cm−1, respectively [37]. A
band at 1640 cm−1 was assigned to the bending mode of Si–OH [37]. SBA-
16-CN showed a new peak at 2256 cm−1 which is due to the attachment of the
–CN group in the product. The product SBA-16-COOH showed a broad band
of ν-OH at 3432 cm−1, –CH2 symmetric and asymmetric stretching bands near
2847 cm−1 and 2956 cm−1, and a band at 1063 cm−1 due to the asymmetric
Si–O–Si stretching mode. The –OH bending of the Si–OH group is shifted from
1640 to 1632 cm−1, a scissoring vibrational mode of the –CH2 group appeared
at 1418 cm−1 and a symmetric Si–O–Si stretching band at 802 cm−1. A typical
band of the –C=O stretching vibration of the carboxylic acid group appears at
1721 cm−1. This suggests the successful formation of carboxylic acid moieties
on the material. On the other hand, for [SBA-16-G], the Si–OH band was shifted
from 3432 to 3367 cm−1, –CH2 symmetric and asymmetric stretching bands
shifted to 2709 cm−1 and 2936 cm−1 respectively, asymmetric Si–O–Si stretch-
ing band shifted to 1055 cm−1, scissoring vibrational mode of the –CH2 group
1 3

R. Gupta et al.
shifted to 1399 cm−1, symmetric Si–O–Si stretching band shifted to 796 cm−1,
and –C=O stretching vibration of the carboxylic acid group shifted to 1700 cm−1.
Moreover, a N–H bending vibration appears at 702 cm−1 and the bands appearing
at 1598 cm−1 and 1472 cm−1 confrm the presence of C=N and C–N stretching
bands in [SBA-16-G] [74].
The TGA of both SBA-16 and [SBA-16-G] are shown in Fig. 2b. Initially, the
weight loss (~ 5%) up to 150 °C is ascribed to the removal of surface-adsorbed
water molecules from both materials [74]. A signifcant weight loss (~ 25%) was
observed in the temperature range between 275 and 575 °C for [SBA-16-G],
owing to the decomposition of the guanine moiety present in the material.
Figure 2c shows XRD spectra of both the pre- and post-functionalized materi-
als. The SBA-16 shows the characteristic peaks at 2θ values 0.618°, 1.289°, and
1.778° corresponding to the 110, 200, and 211 planes, respectively, consistent
with the reported data [73]. In the guanine-functionalized SBA-16, the intensities
of all three peaks were slightly diminished and shifted towards lower 2θ values,
presumably due to functionalization with the guanine.
The BET surface area measurements data for SBA-16 and [SBA-16-G] are
summarized in Table 1 and the hysteresis loops shown in Fig. 2d. Table 1 indicates
that SBA-16 has a large surface area (781 m2/g), pore diameter (11.9 nm cm3/g)
and pore volume (0.86 cm3/g) [75]. However, after guanine-functionalization, the
surface area, pore diameter and pore volume (524 m2/g, 9.2 nm, and 0.77 cm3/g,
respectively) were decreased. This occurs because the guanine moieties occupy
space in the pores of SBA-16.
Both the FESEM and TEM images for SBA-16 and [SBA-16-G] are depicted
in Fig. 3. Figure 3a reveals that SBA-16 is a well-developed, spherical, and
crystalline material. The FESEM image of [SBA-16-G] shows an agglomerated
morphology (Fig. 3b). The TEM image of SBA-16 indicates a sheet-like surface
morphology and ordered lattice arrays of the virgin material (Fig. 3c) [75]. How-
ever, after guanine functionalization, no signifcant changes were observed in the
ordered lattice arrays (Fig. 3d). Therefore, it is inferred from the TEM image that
the ordered structure was retained and the guanine functionalities were deposited
in the pores of SBA-16.
The guanine-functionalization onto SBA-16 was confrmed by the solid-state
13C NMR (Fig. 4). This shows strong peaks at δ 8.1, 14.6, 28.3, and 43.9 cor-
responding to the presence of aliphatic carbons of the chain attached to the silica
in [SBA-16-G] [37]. The peaks at δ 178.2, and δ 108.8 are assigned to the –C=O
of the amide linkage and the C–N bond, respectively. Moreover, strong signals at
around δ 158.6 and δ 160.5 may be attributed to diferent carbons of the guanine
Table 1 BET surface area,
Entry Materials
BET surface Average pore Total pore
average pore diameter, and total
pore volume of SBA-16 and
[SBA-16-G]
area (m2/g)
diameter (nm) volume
(cm3/g)
1.
2.
SBA-16
[SBA-16-G] 524
781
11.9
9.2
0.86
0.77
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Synthesis and characterization of guanine-functionalized…
Fig. 3 FESEM of SBA-16 (a) and [SBA-16-G] (b); TEM of SBA-16 (c) and [SBA-16-G] (d)
Fig. 4 Solid-state 13C NMR spectrum of [SBA-16-G]
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R. Gupta et al.
moiety. A signal at δ 144 is assigned to the residual benzene which was used as a
solvent during the synthesis of [SBA-16-G].
The basicity of the SBA-16 and [SBA-16-G] were measured using the CO2-TPD
technique. The CO2-TPD profle of SBA-16 showed three peaks, at 148 °C, 308 °C,
and 695 °C, as denoted by α, β and γ, respectively (Fig. 5) [76]. The temperature
and area of the CO2 desorption peaks can be used to access the apparent strength
and quantity of the basic property of the materials. Therefore, three peaks in the
CO2-TPD of SBA-16 were attributed to weak, moderate and strong basic sites,
respectively. However, CO2-TPD of [SBA-16-G] showed four intense peaks, at
197 °C, 407 °C, 498 °C and 715 °C, as denoted by α′, β′, δ′ and γ′, respectively.
Moreover, a comparison of CO2-TPD studies of SBA-16 and [SBA-16-G] showed
that the [SBA-16-G] exhibited an additional strong and new peak δ′ at 498 °C and
the shifting of the remaining peaks at 197 °C (α′), 407 °C (β′) and 715 °C (γ′), which
indicated that, after guanine functionalization, the basicity has been substantially
increased, from 0.458 to 3.230 mmol/g.
Catalytic studies
The catalytic activity of the synthesized [SBA-16-G] was investigated for the syn-
thesis of the pyran-annulated heterocyclic compound, as shown in Scheme 2.
In order to optimize the reaction conditions, diferent screening parameters, such
as catalyst loading, solvent and time were carried out and their results are shown in
Table 2. The reaction of 4-chlorobenzaldehyde (1 mmol), malononitrile (1 mmol)
and 4-hydroxycoumarin (1 mmol) in ethanol (4 mL) was chosen as a model reac-
tion. In the absence of the catalyst, at RT, no desired product was found after 18 h
(Table 2, entry 1). Similarly, in the absence of the catalyst even at 80 °C, no product
was formed (Table 2, entry 2). However, in the presence of 2 wt% of [SBA-16-G]
Fig. 5 CO2-TPD profle for SBA-16 (a) and [SBA-16-G] (b)
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Synthesis and characterization of guanine-functionalized…
Table 2 Optimization of reaction conditions for the synthesis of pyran-annulated heterocyclic compound
from 4-chlorobenzaldehyde, malononitrile, and 4-hydroxycoumarin
Entry
Catalyst (wt%)
Solvent
Time (h)
Temp. (°C)
Yield (%)a
1
2
3
4
–
–
2
5
EtOH
EtOH
EtOH
EtOH
18
18
10
7
RT
80
80
n.r.
Trace
65
80
88
5
10
EtOH
5
80
92
6
7
8
9
10
11
12
10
10
10
10
10
10
CH3CN
H2O
Benzene
EtOH:H2O (1:1)
Ethylacetate
THF
19
15
9.5
10
16
18
5
80
40
35
51
72
n.r.
27
75
100
100
80
80
80
10 (Guanine)
EtOH
80
Reaction conditions: aldehyde 1 (1 mmol), ethyl cynoacetate/malononitrile 2 (1 mmol) and dimedone 3b
(1 mmol)
aIsolated pure yield; n.r. no reaction
in ethanol (4 mL) at refuxing condition, the desired product was formed in 65%
yield (Table 2, entry 3). In the presence of 5 wt% of [SBA-16-G] in ethanol (4 mL)
at 80 °C, the product was formed at 88% in yield (Table 2, entry 4). In the presence
of 10 wt% of [SBA-16-G] in ethanol (4 mL) at refuxing condition, 92% yield of
product was obtained within 5 h (Table 2, entry 5). Thereafter, in order to optimize
the efect of the solvent, the reaction was performed in various solvents, such as
ethanol, CH3CN, C6H6, H2O, ethanol:H2O, ethylacetate, THF, etc. (Table 2, entries
6–11). When the reaction was carried out in benzene or ethanol:H2O, only 51%
and 72%, respectively, of the desired product were formed (Table 2, entries 8, 9).
However, in pure ethanol, the product yield increased to 46% and 25%, respectively
(Table 2, entries 8, 9). In the presence of CH3CN and H2O, the desired products
were obtained at only 40% and 35%, respectively (Table 2, entries 6, 7). In the pres-
ence of ethylacetate, no product was found after 16 h, while in THF, only 27% of the
desired yield was formed after 18 h (Table 2, entries 10, 11). Finally, in the presence
of just guanine as the catalyst, in ethanol (4 mL) at 80 °C, 75% of thedesired yield
was found (Table 2, entry 12).
After the optimization conditions, to check the scope and generality of
the present catalyst, a series of reactions were carried out using diferent
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R. Gupta et al.
Table 3 Aromatic aldehydes, malononitrile and 4-hydroxycoumarin used for the synthesis of di
hydropyrano[3,2-c]chromene derivatives catalyzed by [SBA-16-G]
Entry
1
Aromatic
aldehydes
Product
Time
(h)
Yield
(%)a
Mp. °C
5
3.5
9
92
91
92
92
267–269
[264 –266]53
4aa
4ab
2
3
4
253–255
[254–256]54
257–259
[258–260]53
4ac
1
230–232
[234]54
4ad
4ae
5
6
91
259–261
[261–262]54
6
7
1.5
5
88
90
252–254
[254–256]54
4af
139–141
[142–144]53
4ag
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Synthesis and characterization of guanine-functionalized…
Table 3 (continued)
8
3
91
196–198
[194–195]53
4ah
9
4
4.5
2
79
83
87
186–188
[187–189]53
4ai
10
238–240
[242–245]53
4aj
11
237–239
[241–244]48
4ak
12
4.5
3
70
89
214–216
[209–212]53
4al
13
199–201
[205]60
4am
Reaction conditions: aldehyde 1 (1 mmol), ethyl cynoacetate/malononitrile 2 (1 mmol) and 4-hydroxy-
coumarin 3a (1 mmol) and 10 wt% [SBA-16-G] used as catalyst in 4 mL ethanol at room temperature
followed by refuxing condition
aIsolated yield
substituted aldehydes, malononitrile/ethyl cyanoacetate, and 4-hydroxycoumarin/
dimedone/4-hydroxyindole under optimizations condition,s and their results were
summarized in Tables 3 and 4. The reactions of malononitrile with benzaldehyde
and 4-hydroxycoumarin were executed under the same reaction conditions to get
the desired product 4ab in 90% yield. The reactions of the aldehydes with elec-
tron-donating groups such as, –CH3, –OCH3 etc. (Table 2, entries 4ac, 4ad) as
well as electron-withdrawing groups, i.e. –Cl, –F, –NO2 (Table 3, entries 4aa,
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R. Gupta et al.
Table 4 Aromatic aldehydes, ethyl cynoacetate, and diketones used for the synthesis of chromene deriva-
tives catalyzed by [SBA-16-G]
Entry
1
Dimedone
Product
Time (h) Yield (%)a
Mp. °C
2.5
92
214–2 16
[212–2 14]54
4ba
2
3
2.5
4
91
90
202–204
[205–2 06]54
4bb
142–144
[139–1 42]53
4bc
4bd
4be
4bf
4bg
4
5
6
7
3
91
86
90
90
145–1 47
[144–1 46] 53
1.5
159–1 61
[154–1 56]53
1
169–1 71
141–1 43
3.5
Reaction conditions: aldehyde 1 (1 mmol), ethyl cynoacetate/malononitrile 2 (1 mmol) and dimedone
3b (1 mmol) and 10 wt% [SBA-16-G] used as catalyst in 4 mL ethanol at room temperature followed by
refuxing condition
aIsolated yield
4ae, 4af) also gave the desired products in very good yield under optimization
conditions. Similarly, the reactions of ethyl cyanoacetate with aromatic aldehydes
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Synthesis and characterization of guanine-functionalized…
Scheme 3 Three-component reaction of malononitrile, 4-chlorobenzaldehyde and 4-hydroxyindole
Table 5 A comparative study of catalysts for synthesis of pyran-annulated heterocycles from the reaction
of 4-chlorobenzeldehyde, malononitrile, and 4-hydroxycoumarine
Entry Catalyst
Solvent/conditions Time
Yield (%) References
93 [54]
1
2
Urea (10 mol %)
EtOH:H2O
EtOH:H2O
7 h
3.25 h and 3 h 89 and 90 [56]
TBBDA and PBBS
(18 mol% and 0.1 g)
3
4
5
6
Nano Al2O3
γ-Fe2O3@Cu3Al-LDH-TUD Solvent-free
SBA-16
[SBA-16-G]
EtOH
5 h
80
90
08
92
[65]
[66]
This work
This work
18 min
24 h
5 h
EtOH
EtOH
and 4-hydroxycoumarine were also carried out under the same reaction condi-
tions and the products were obtained in high yield (Table 3, entries 4ag–4al).
Under the optimized conditions, the reaction of ethyl cyanoacetate with hetero-
cyclic aldehyde, i.e., thiophene-2-carbaldehyde and 4-hydroxycoumarin, was also
carried out to give the product in 89% yield (Table 3, entry 4am). Isolated prod-
ucts were fully characterized by standard spectroscopic methods and their data
and spectras are given in the SI (Figs. S2–S26).
The present study was also successful when the reactions of substituted aromatic
aldehyde, malononitrile and dimedone were carried out under similar reaction condi-
tions and aforded the corresponding three-component condensation products in very
good yields (Table 4, entries 4ba, 4bb). The reactions of dimedone with substitute
aromatic aldehydes and ethyl cyanoacetate were also analyzed and the desired prod-
uct were found in good yield under optimized reaction conditions (Table 4, entries
4bc–4bg). It is important to describe that in all cases, aromatic aldehydes substituted
with either electron-withdrawing groups or electron-donating groups underwent the
reaction very smoothly and gave the desired products in good to excellent yields under
the optimized conditions (Table 4). We have also carried out the reaction of malon-
onitrile, 4-chlorobenzaldehyde and 4-hydroxyindole under optimized conditions and
it aforded 76% in yield (Scheme 3). Isolated products were fully characterized by
1
FTIR, H NMR and 13C NMR spectroscopic methods and their data and spectra are
given in SI (Fig. S27–S41). Furthermore, Table 5 also indicates the comparison of the
activity of the diferent reported catalysts [54, 56, 65, 66], with that of the synthesized
[SBA-16-G] catalyst. We observed that the current [SBA-16-G] catalyst gives the best
1 3

R. Gupta et al.
Fig. 6 Plausible mechanism for the synthesis of pyran-annulated heterocyclic compounds
catalytic activities in respect of yields, catalyst loading, reaction times, etc., for the syn-
thesis of pyran-annulated heterocyclic compounds.
Regeneration of [SBA‑16‑G] catalyst
The catalyst can be regenerated in the dichloromethane solution and dried at 100 °C
in a vacuum oven after completion of the reaction. It has been observed that [SBA-
16-G] can be reused and is recyclable up to four consecutive cycles without afect-
ing the catalytic efciency of [SBA-16-G] (SI, Fig. S42). Besides this, FESEM
and EDAX analyses (SI, Fig. S43) were carried out to check the changes made in
the surface morphology and elemental composition of the spent catalyst. It was
observed that the surface morphology and the elemental composition (C, O, Si, and
N) of the spent catalyst remained unperturbed.
Plausible mechanism pathway
Based on previous reports [50] and our observations, a plausible mechanism for
the synthesis of pyran-annulated via a three-component condensation reaction with
[SBA-16-G] is outlined in Fig. 6. The synthetic pathway involves (1) depronation
of malononitrile/ethylcyanoacetate, (2) Knoevenagel condensation of the aromatic
aldehyde with the deprotonated product, (3) Michael addition of intermediate [A]
with a C–H activated acidic compound to give product [B], (4) intermediate [B]
1 3

Synthesis and characterization of guanine-functionalized…
undergoing intermolecular cyclization to [C], and (5) tautomerization of intermedi-
ate [C] to aford the fnal pyran-annulated product [D].
Conclusion
In summary, a new solid base, [SBA-16-G], has been synthesized for the frst
time and fully characterized by FTIR, TGA, XRD, BET, FESEM, EDAX, TEM,
CO2-TPD, and solid-state 13C NMR. The [SBA-16-G] showed prominent catalytic
activity toward the synthesis of a number of pyran-annulated heterocyclic com-
pounds. The attractive features of this protocol are mild reaction conditions, high
yield of products, simple operation, no chromatography, recyclability up to four
times, and environmental acceptability of the catalyst due to metal-free catalysis.
Acknowledgements RG and SL acknowledge the Director, IIT (ISM), Dhanbad, for awarding research
fellowships. The authors would like to thank CRF at IIT (ISM), Dhanbad, for the FESEM images. We are
grateful to Vijay Gupta, SRF, Department of Chemistry, IISER Mohali, Punjab, India, for recording the
1H and 13C NMR data.
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