Benzene-1,3,5-tricarboxylic acid-functionalized MCM-41 as a novel and recoverable hybrid catalyst for expeditious and efficient synthesis of 2,3-dihydroquinazolin-4(1H)-ones via one-pot three-component reaction

Article abstract of DOI:10.1007/s11164-020-04179-8

Benzene-1,3,5-tricarboxylic acid-functionalized MCM-41 (MCM-41-Pr-BTA), as a novel hybrid organosilica, was prepared and properly characterized by the Fourier-transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, Brunauer–Emmett–Teller, thermal gravimetric analysis and energy-dispersive X-ray spectroscopy to evaluate the functional groups, crystallinity, surface area, morphology, particle size distribution and loading of functional groups. Interestingly, the 1,3-propylene linker used in this study incorporates appropriate catalytic activity into the MCM-41 framework compared to the more known trialkoxypropyl silanes. This new organosilica can be used as a hybrid nanocatalyst for the expeditious and efficient synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives, as an important pharmaceutical scaffold, in aqueous media via a three-component one-pot condensation of isatoic anhydride and aromatic aldehydes with primary amines or ammonium salts. This method has several advantages such as low catalyst loading, high to excellent yields, short reaction times, working under green conditions and simple workup.

Full text of DOI:10.1007/s11164-020-04179-8

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04179-8
Benzene‑1,3,5‑tricarboxylic acid‑functionalized MCM‑41
as a novel and recoverable hybrid catalyst for expeditious
and eꢀcient synthesis of 2,3‑dihydroquinazolin‑4(1H)‑ones
via one‑pot three‑component reaction
Niusha Nikooei · Mohammad G. Dekamin1 · Ehsan Valiey1
1
Received: 30 March 2020 / Accepted: 11 May 2020
©
Springer Nature B.V. 2020
Abstract
Benzene-1,3,5-tricarboxylic acid-functionalized MCM-41 (MCM-41-Pr-BTA), as
a novel hybrid organosilica, was prepared and properly characterized by the Fou-
rier-transform infrared spectroscopy, ꢀeld emission scanning electron microscopy,
transmission electron microscopy, Brunauer–Emmett–Teller, thermal gravimetric
analysis and energy-dispersive X-ray spectroscopy to evaluate the functional groups,
crystallinity, surface area, morphology, particle size distribution and loading of
functional groups. Interestingly, the 1,3-propylene linker used in this study incor-
porates appropriate catalytic activity into the MCM-41 framework compared to the
more known trialkoxypropyl silanes. This new organosilica can be used as a hybrid
nanocatalyst for the expeditious and eꢁcient synthesis of 2,3-dihydroquinazolin-
4
(1H)-one derivatives, as an important pharmaceutical scaꢂold, in aqueous media
via a three-component one-pot condensation of isatoic anhydride and aromatic alde-
hydes with primary amines or ammonium salts. This method has several advantages
such as low catalyst loading, high to excellent yields, short reaction times, working
under green conditions and simple workup.
Keywords MCM-41 organosilica · Grafting · Mesoporous materials · Hybrid
materials · Acid catalysis · Nanoreactor · Heterogeneous catalysis · Green
chemistry · Quinazoline derivatives · Ring closure
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4
-020-04179-8) contains supplementary material, which is available to authorized users.
*
Mohammad G. Dekamin
mdekamin@iust.ac.ir
1
Pharmaceutical and Heterocyclic Compounds Research Laboratory, Department of Chemistry,
Iran University of Science and Technology, Tehran 16846-13114, Iran
Vol.:(012
1
3456789)
3

N. Nikooei et al.
Introduction
Heterogeneous catalysis has fascinated greater attention because of easy separa-
tion and recyclability. The unique properties of heterogeneous catalysts such as
high thermal stability, structural diversity, easy modiꢀcations, strong absorption
and low toxicity have made them attractive in some industrial applications such
as chemical, pharmaceutical, automobile and petrochemical industries [1–6].
One of the best-known support materials having silica structure is mesoporous
MCM-41, which has a hexagonal array of one-dimensional pore structures. This
mesoporous silica can be obtained by a simple procedure and shows outstand-
2
−1
ing structural properties with the high speciꢀc surface area (up to 2000 m g )
and pore diameter in the range 15–100 Å [7–11]. The acidity of MCM-41 is low.
Hence, to overcome this limitation, diꢂerent methods have been improved to
increase their acidity including replacement of Si atoms in the lattice by metal
ions including Al, B, Fe and Zr or anchoring suitable organic functional groups
[
12–16]. The later modiꢀcation of the MCM texture aꢂords mesoporous orga-
nosilicas by post-modiꢀcation and co-condensation methods as well as periodic
mesoporous organosilicas (PMOs) [17–26].
Nowadays, mesoporous organosilicas with unique surface area and porous
structure have been developed as the promising candidates in catalysis of various
kinds of organic transformations and green chemistry. Indeed, these materials can
be prepared with diꢂerent particle sizes and morphologies. On the other hand, the
presence of diꢂerent functional groups on the surface of silica allows these mate-
rials to have diverse tunable physical and chemical properties [27]. Because of
their unique structural properties, mesoporous organosilica materials have many
applications including catalysis [10, 21, 28], drug delivery [29, 30], CO capture
2
or transformation [31–33], environmental cleanup, separation technology, sensing
and optoelectronics [34–36].
Furthermore, one of the environment friendly methods for the synthesis of
organic compounds is the use of one-pot multicomponent reactions (MCRs) [28,
3
7–41]. They can produce the desired products in a single step and also the diver-
sity could be achieved simply by varying the reacting components, which has
advantages such as high atom economy, milder reaction conditions, shorter reac-
tion times, lower energy consumption and cost formation of essential carbon–car-
bon and carbon–heteroatom bonds [13–15, 37, 42–50]. Therefore, MCRs can
be considered as an important tool for synthesis of complex organic compounds
especially for the synthesis of heterocycles demonstrating bioactive scaꢂolds [38,
4
1, 42, 51–58]. Moreover, MCRs that are carried out in water, as a green and
the most abundant solvent, address more environmental concerns [47, 50, 59–62].
Indeed, water oꢂers a unique reactivity and selectivity as well as easy separation
of the products from the reactions mixtures [16, 63].
Quinazolinones and their oxidation products are fused nitrogen-containing hete-
rocycles with unique pharmaceutical and biological activities [64–69]. For example,
2
,3-dihydroquinazolin-4(1H)-one derivatives such as A, B and C are valuable com-
pounds as diuretic, antifungal and thermogenic agents, respectively (Fig. 1) [69–71].
1
3

Benzene‑1,3,5‑tricarboxylic acid‑functionalized MCM‑41…
(
a)
(b)
(c)
Fig. 1 Selected examples illustrating the medicinal importance of quinazolinones
Due to importance of quinazoline derivatives, diꢂerent catalytic systems for
the synthesis of 2,3-dihydro-4(1H)-quinazolinones based on MCR strategy
have been developed. Some recent examples include SrCl [72], Zn(PFO) [73],
2
2
Ga(OTf) [74], I [75], copper-benzenesulfonate [76], aluminum methanesul-
3
2
fonate [77], cation exchange resin [78], p-TSA via ball milling [65], starch sulfate
79], silica sulfuric acid [80], silica-bonded S-sulfonic acid [80], PTSA-formal-
dehyde copolymer [81], β-cyclodextrin-SO H [82], magnetic Fe O nanoparti-
[
3
3
4
cles [62], Al/Al O nanoparticles [80], CuO nanoparticles using sonication [83],
2
2
3
3
nano-ordered In O [84], montmorillonite K-10 [85] and Amberlyst-15 under
microwave irradiation [86]. Some of these procedures show some disadvantages
such as long reaction times, low yields, harsh reaction conditions and the use of
expensive or toxic catalysts. Therefore, to avoid these limitations, the exploration
of an eꢁcient, easily available catalyst with high catalytic activity and short reac-
tion times for the preparation of quinazoline derivatives is still in demand. From
this point of view, benzene-1,3,5-tricarboxylic acid can be used as a bidentate
acidic group for post-modiꢀcation of the MCM-41 surface to carry out various
organic transformations with increased selectivities. We wish herein to disclose
the promising catalytic activity of highly ordered mesoporous MCM-41 func-
tionalized with a grafted benzene-1,3,5-tricarboxylic acid through 1,3-propylene
linker (MCM-41-Pr-BTA, 1) for the one-pot three-component reaction of isatoic
anhydride (2) with diverse amines 3 and aldehydes 4 to aꢂord biologically active
quinazoline derivatives 5 (Scheme 1).
Scheme 1 One-pot three-component reaction of isatoic anhydride (2) with diverse amines 3 and alde-
hydes 4 catalyzed by MCM-41-PR-BTA (1) for synthesis of quinazoline derivatives 5
1
3

N. Nikooei et al.
Results and discussion
Characterization of the MCM‑41‑Pr‑BTA catalyst (1)
The prepared MCM-41-Pr-BTA nanocatalyst (1) was characterized by FT-IR
Fig. 2). The FT-IR spectra of MCM-41 (b) and MCM-41-Pr-BTA (c) show the
(
−
1
−1
−1
absorption bands around 806 cm , 960 cm and 1074 cm with a shoulder
−1
at∼1070 cm which are ascribed to the symmetric stretching of Si–O–Si, Si–OH
and the asymmetric stretching of Si–O–Si, respectively. On the other hand, the sig-
nal at 1600 is for water absorbed by the surface of MCM-41 (b). Furthermore, the
−
1
catalyst showed an adsorption band at 1390–1400 cm which is assigned to C=C
of the BTA (a, c). Also, the spectrum of the BTA-functionalized MCM-41 (1) shows
−1
a broadband at 3600–2400 cm for hydroxyls groups of BTA as well as MCM-41.
−1
The sharp band at 1715 cm was attributed to the carbonyl groups of BTA. By
comparing spectra of MCM-41, BTA and MCM-41-Pr-BTA (1), it can be concluded
that BTA has been successfully grafted on the surface of MCM-41.
Also, the crystallinity and orderliness of the MCM-41-Pr-BTA (1) were deter-
mined by XRD patterns. The low- and wide-angle XRD patterns for the MCM-41-
Pr-BTA are shown in Fig. 3. The peaks located at 2θ=2.5°, 3.5°, 3.8°, 4.5°, 5.7°,
6
.3° and 6.6° are typical for the amorphous silica of mesoporous MCM-41, which
indicates a hexagonally packed mesoporous structure [87]. Indeed, the peak at 2.5°
is the characteristic peak for MCM-41. On the other hand, the wide-angle XRD of
MCM-41 usually shows a broad peak in 2θ=20°-30°. These patterns of the catalyst
demonstrate ꢀve characteristic peaks at 2θ=11°, 13°, 24°, 27° and 30°, respectively.
The reference codes for MCM-41 and 1,3,5-benzenetricarboxylic acid are 00-049-
1
712 and 00-045-1880, respectively, which are attributed to the presence of these
moieties in the structure of MCM-41-Pr-BTA.
FE-SEM analysis was used to determine the surface morphology and particle
size distribution for the nanocatalyst (1). Figure 4 shows the obtained images for the
Fig. 2 FT-IR spectra of the
commercial BTA (a), MCM-41
(
b), MCM-41-Pr-BTA (1, c)
1
3

Benzene‑1,3,5‑tricarboxylic acid‑functionalized MCM‑41…
Fig. 3 XRD pattern of the catalyst 1 a low angle, b wide angle
1
3

N. Nikooei et al.
Fig. 4 FE-SEM images of the
a MCM-41 b, c MCM-41-Pr-
BTA 1
1
3

Benzene‑1,3,5‑tricarboxylic acid‑functionalized MCM‑41…
MCM-41 before and after grafting of BTA molecules with no signiꢀcant agglom-
eration on the surface of the catalyst 1. By comparing of FE-SEM images, it can be
realized that the surface morphology of the MCM-41-Pr-BTA (1) is mainly spheri-
cal and diꢂerent from that of the pure MCM-41. Furthermore, it can be concluded
that 1,3,5-benzenetricarboxylic acid molecules have been successfully grafted onto
the surface of MCM-41.
Moreover, the EDX analysis was used to ꢀnd the percentage of elements which
are present in the structure of both MCM-41 and MCM-41-Pr-BTA (1). Figure 5a
reveals the existence of only Si and O atoms for MCM-41. On the other hand, the
appearance of the C peak proves that both BTA and 1,3-propylene linker have been
successfully grafted on the surface of the MCM-41(Fig. 5b). Indeed, the weight per-
centage of the elements of Si and O was found to be 32.40 and 67.60, respectively.
However, the weight percentage of these elements in the structure of MCM-41-Pr-
BTA was 18.14 and 54.11, respectively; meanwhile, the percentage of C was found
to be 27.75.
The thermogravimetric analysis (TGA) was used to show the percentage of chem-
isorbed organic layers onto the surface of mesoporous MCM-41. The TGA curve of
MCM-41-Pr-BTA (1) shows three-step mass losses (Fig. 6). The ꢀrst step shows the
small amount of weight loss about 5% below 200 °C which is due to the desorption
of physically adsorbed water and organic solvents. The second one occurred between
3
00 and 400 °C, which was assigned to the decomposition of covalently bonded
organics (4% weight loss). The third step of mass loss was about 2% between 400
and 500 °C which may be attributed to the thermal dehydration of silanol groups to
the siloxane ones [33].
On the other hand, the speciꢀc surface area of the MCM-41-Pr-BTA mesoporous
catalyst (1) was measured by Brunauer, Emmett and Teller (BET) method. The
N sorption isotherms of MCM-41-Pr-BTA are illustrated in Fig. 7. Based on the
2
IUPAC classiꢀcation, the catalyst 1 exhibits a type IV isotherm with H hysteresis
2
loop which is characteristic of the typical of mesoporous materials. The analysis for
the ꢀnal catalyst 1 and its precursor materials are reported in Table 1. The observed
decrease in the BET surface area, pore volume and pore size could be attributed
to the covalent bonding of organic BTA and 1,3-propylene linker on the surface of
MCM-41 channels.
Investigation of the catalytic activity of mesoporous MCM‑41‑Pr‑BTA
for three‑component 2,3‑dihydroquinazolin‑4(1H)‑one derivatives
After the characterization of the catalyst 1, the three-component reaction of isatoic
anhydride (2) with ammonium acetate (3a) and 4-cholorobenzaldehyde (4a) was
chosen as the model reaction. Then, the eꢂect of diꢂerent temperatures and solvents
was systemically studied on the progress of model reaction with various loadings of
MCM-41-Pr-BTA (1) as the catalyst. The results are summarized in Table 2. The
amount of the catalyst 1 played an important role in the model reaction. Indeed,
the reaction in the absence of the MCM-41-Pr-BTA aꢂords a poor yield of the
desired 2-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one (5a) after 24 h under
1
3

N. Nikooei et al.
Fig. 5 Energy-dispersive X-ray (EDX) spectroscopy pattern of a MCM-41, b catalyst (1)
reꢃux conditions (entry 1, Table 2). As can be seen in Table 2, adding 0.01 g of the
mesoporous hybrid catalyst 1 did signiꢀcantly improve the yield of the desired prod-
uct 5a (entries 2–4). The highest yield of the desired product 5a was obtained by
0
.01 g catalyst in H O under reꢃux conditions (entry 4, Table 2). On the other hand,
2
the eꢂect of sonication was also studied under the same conditions (entries 4, 5).
In our hands, classical heating aꢂorded better yield than ultrasonic conditions. The
same result was obtained in water at room temperature (entry 6, Table 2). Moreo-
ver, the eꢂect of other solvents including MeOH, MeCN, CH Cl , THF and toluene
2
2
was also studied on the progress of the model reaction under same catalyst loading
(
entries 7–11). Consequently, among all the solvents screened water was selected as
1
3

Benzene‑1,3,5‑tricarboxylic acid‑functionalized MCM‑41…
Fig. 6 TGA of the MCM-41-Pr-BTA (1)
Fig. 7 Adsorption/desorption isotherms of the MCM-41-Pr-BTA (1)
the optimal solvent in next experiments. The eꢂect of lower catalyst loadings than
0
.01 g was further studied (entries 13–15). Moderate yields of the desired product
5
a were obtained in all studied cases.
1
3

N. Nikooei et al.
Table 1 Textural parameters of the MCM-41 and MCM-41-Pr-BTA (1) samples
3
Samples
BET surface area
Total pore vol. (cm /g)
Pore size (nm)
2
(
m /g)
(p/p =0.98)
0
MCM-41 [16]
MCM-41-Pr-BTA (1)
926
435
1.09
0.36
4.07
3.37
Table 2 Optimization of the three-component reaction of isatoic anhydride (2) with ammonium acetate
a
(
3a) and 4-cholorobenzaldehyde (4a) under various conditions.
b
Entry
Catalyst load- Solvent
ing (g)
Temperature (°C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
–
EtOH
EtOH
Reꢃux
Reꢃux
Reꢃux
Reꢃux
Ultrasonic
r.t.
Reꢃux
Reꢃux
Reꢃux
Reꢃux
Reꢃux
100
24 h
55
35
15
60
75
30
45
40
Trace
82
78
92
40
53
75
55
45
52
35
71
79
60
55
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.007
0.005
0.003
H O/EtOH (1:1)
2
H O
2
H O
2
H O
2
MeOH
MeCN
Toluene
CH Cl
1
1
1
1
1
1
a
0
1
2
3
4
5
30
2
2
THF
–
100
135
25
40
50
H O
Reꢃux
Reꢃux
Reꢃux
2
H O
2
H O
2
Reaction conditions: isatoic anhydride (2, 1 mmol), ammonium acetate (3a,1.2 mmol),4-chlorobenzal-
b
dehyde (4a, 1 mmol), MCM-41-Pr-BTA (1) and solvent (2 mL). Isolated yields
The optimized conditions were developed to other aromatic aldehydes 4a–j or
amine sources 3a–c, in the next step of study. The obtained results are summarized
in Tables 3 and 4, respectively. Indeed, all the studied aldehydes or amine sources
were involved in the optimized conditions to aꢂord a wide range of pharmaceuti-
cally active products 5–7 in high to excellent yields. From data provided in Tables 3
and 4 condensation of ammonium acetate (3a) or aniline derivatives 3b-c with aro-
matic aldehydes 4, it can be concluded that aldehydes having electron-withdrawing
1
3

Benzene‑1,3,5‑tricarboxylic acid‑functionalized MCM‑41…
substituents produced corresponding quinazoline derivatives 5–7 in shorter reaction
times or higher yields than aldehydes bearing electron-donating ones.
According to the obtained results, a plausible mechanism can be proposed for
the synthesis of 2,3-dihydroquinazolin-4(1H)-ones 5–7 from condensation of isatoic
anhydride (2) with diꢂerent amine sources 3a–c and aldehydes 4 in the presence
of MCM-41-Pr-BTA mesoporous hybrid catalyst 1 (Scheme 2). First, the isatoic
anhydride (2) is activated by MCM-41-Pr-BTA (1) for nucleophilic addition of the
amine sources 3a–c to aꢂord intermediate (III) through intermediates (I) and (II)
with CO elimination. Then, the N-nucleophilic amine attack of anthranilamide (III)
2
on the activated carbonyl functional group of aldehydes 4 produces iminium inter-
mediate (V) with losing of H O. Subsequently, intramolecular nucleophilic attack of
2
the amide nitrogen to the activated imine moiety produces heteroannulated products
5
–7.
One of the advantages of heterogeneous catalysts is their easy separation from the
reaction mixture and subsequent reusing in catalytic systems. Therefore, the reus-
ability can be very important in industry. In this part of our study, the reusability of
MCM-41-Pr-BTA (1) was investigated in the model reaction for further runs. After
completion of the reaction indicated in Table 3, the nanocatalyst was removed by
ꢀ
ltration from the reaction mixture and washed with EtOH, EtOAC and n-hexane,
respectively. Then, it was dried in an oven at 70 °C for 1 h. The recycled catalyst
1
was used again in the model reaction. To our delight, the reaction yield did not
change signiꢀcantly after ꢀve consecutive runs and a little loss of catalytic activity
of these new heterogeneous catalyst was observed (Fig. 8).
Finally, the eꢁciency of nanomaterial 1 was compared with some diꢂerent
reported catalytic systems for the synthesis of 2-(4-chlorophenyl)-2,3-dihydro-
quinazolin-4(1H)-one (5a) and the results are listed in Table 5. As data provided in
Table 5 demonstrate, the hybrid organocatalyst 1 gives better yield in shorter reac-
tion times than the compered catalysts. Interestingly, the 1,3-propylene linker used
in this study incorporates appropriate catalytic activity into the MCM-41 framework
compared to the more known trialkoxypropyl silanes.
Conclusions
In summary, we have employed an eꢂective and practical procedure for the synthe-
sis of 2,3-dihydroquinazolin-4(1H)-ones derivatives via the one-pot three-compo-
nent condensation of isatoic anhydride, aromatic aldehyde and amine using catalytic
amount of MCM-41-Pr-BTA under reꢃux conditions. The hybrid organosilica nano-
catalyst is highly eꢁcient, easily prepared from commercially available precursors
and non-toxic. The other attractive features of this new methodology are low loading
transition metal-free catalyst, high to excellent yields, facile workup environmen-
tally friendly procedure, mild conditions and short reaction times.
1
3

N. Nikooei et al.
Table 3 MCM-41-Pr-BTA (1)-catalyzed synthesis of 2,3-dihydroquinazolin-4(1H)-ones 5 under opti-
mized conditionsa
b
Entry Aldehyde 4 Product
Time (min) Yield (%) Mp (°C) found Mp (°C) reported
1
15
25
20
92
88
86
200–210
189–193
232–235
198–200 [78]
192–193 [88]
233–234 [89]
2
3
4
5
15
18
90
93
197–200
352–350
199–200 [74]
351–352 [74]
6
7
15
20
85
84
210–214
215–220
213–214 [74]
216–217 [74]
8
20
94
200–204
202–204 [78]
1
3

Benzene‑1,3,5‑tricarboxylic acid‑functionalized MCM‑41…
Table 3 (continued)
b
Entry Aldehyde 4 Product
Time (min) Yield (%) Mp (°C) found Mp (°C) reported
9
27
86
165–167
165–167 [79]
1
0
20
87
218–220
218–220 [90]
a
Reaction conditions: isatoic anhydride (2, 1 mmol), ammonium acetate (3a,1.2 mmol), 4-chlorobenzal-
b
dehyde (4a, 1 mmol), MCM-41-Pr-BTA (1) in H O (2 mL) under reꢃux conditions. Isolated yields
2
Experimental section
Reagents and apparatus
All chemicals and reagents were purchased from Merck and Aldrich and used
without further puriꢀcation, except for aniline and benzaldehyde, for which fresh
distilled samples were used. FT-IR spectra were recorded as KBr pellets on a Shi-
madzu FT-IR-8400S spectrometer. All diꢂuse reꢃectance spectra were recorded at
1
room temperature against KBr and were plotted in terms of absorbance. HNMR
(
500 MHz) spectra were obtained using a Bruker DRX-500 Avance spectrometer.
1
All HNMR spectra were run in CDCl solution, relative to TMS (0.00 ppm), at
3
ambient temperature. Melting points were determined using an Electrothermal 9100
apparatus and uncorrected. MCM-41 and MCM-41-Pr-Br materials were prepared
according to our previously reported procedure and characterized by FT-IR spec-
1
troscopy [16]. All products were characterized by spectroscopic methods (IR and
HNMR spectra) and melting points.
Preparation of the MCM‑41‑Pr‑BTA
The mesoporous silica (MCM-41, 0.2 g) was suspended in toluene (20 ml), and 1 g
1
.3-dibromopropane was added to the obtained mixture at room temperature and
stirred for 24 h. After that, the obtained white solids were ꢀltered and washed with
toluene (2.5 ml) and EtOH (2.5 ml), respectively, and dried in an oven to aꢂord
MCM-41-Pr-Br. After that, 0.1 g MCM-41-Pr-Br and 0.01 g KI were suspended in
DMSO (30 ml) and stirred for 10 h at room temperature. Then, 1,3,5-benzenetricar-
boxylic acid (BTA, 0.1 g) and K CO (0.055 g) were added to the obtained mixture
2
3
and stirred for 1 h. Finally, the obtained white solids of the catalyst 1 were ꢀltered,
washed with H O (2.5 ml) and EtOH (2.5 ml) and dried in an oven.
2
1
3

N. Nikooei et al.
Table 4 MCM-41-Pr-BTA (1) catalyzed reaction between isatoic anhydride (2), aniline (3b) or p-tolui-
dine (3c) and aromatic aldehydes (4a–h) under optimized conditionsa
Entry Aldehyde
Product
Time (min) Yield (%) Mp (°C) found Mp (°C)
[lit.]
reported
1
25
90
213–215
214–217 [61]
2
3
35
30
86
80
200–204
214–216
204–205 [73]
215–216 [62]
4
28
87
232–236
235–238 [91]
5
6
30
35
81
79
194–196
185–188
194–196 [73]
186–188 [92]
7
40
86
200–215
212–214 [72]
1
3

Benzene‑1,3,5‑tricarboxylic acid‑functionalized MCM‑41…
Table 4 (continued)
Entry Aldehyde
Product
Time (min) Yield (%) Mp (°C) found Mp (°C)
[lit.]
reported
8
25
85
200–215
214–215 [74]
9
20
25
23
30
87
83
86
81
250–252
240–245
240–245
195–200
250–252 [74]
243–246 [74]
241–243 [62]
197–198 [62]
10
11
12
a
Reaction conditions: Isatoic anhydride (2, 1 mmol), ammonium acetate (3a,1.2 mmol), 4-chlorobenzal-
b
dehyde (4a, 1 mmol), MCM-41-Pr-BTA (1) in H O (2 mL) under reꢃux conditions. Isolated yields
2
Typical procedure for the one‑pot synthesis of 2,3‑dihydroquinazolin‑4(1H)‑ones
MCM-41-Pr-BTA (0.01 g) was added to a mixture of isatoic anhydride (2, 1.0 mmol,
0
1
.163 g), primary amine or ammonium acetate (3, 1.2 mmol) and aryl aldehydes (4,
.0 mmol) in 2 ml of distilled water, and the obtained mixture was stirred under
reꢃux conditions for the appropriate times indicated in Table 2. The reaction pro-
gress was monitored by TLC (eluent: n-hexane/EtOAC, 3:1). After completion of
the reaction, the solvent was evaporated; then, hot EtOH was added to the mixture
and the catalyst was separated by ꢀltration. n-Hexane was then added to the ꢀltrate
dropwise and allowed to cool over time to give pure crystals of the desired 2,3-dihy-
droquinazolin-4(1H)-one derivatives.
Selected Spectral Data
2
2
‑(2‑Chlorophenyl)‑3‑phenyl‑2,3‑dihydroquinazolin‑4(1H)‑one (6 g) White solid, Mp:
1
00–215 °C. HNMR (500 MHz, DMSO-d6): δ (ppm) 6.6 (d, J=6.2 Hz,1H), 6.7
1
3

N. Nikooei et al.
Scheme 2 Proposed mechanism of synthesis of 2,3-dihydroquinazolin-4(1H)-ones of MCM-41-Pr-BTA
mesoporous hybrid catalyst 1
Fig. 8 Reusability of the nanocatalyst 1 in ꢀve consecutive runs for the synthesis of 5a
1
3

Benzene‑1,3,5‑tricarboxylic acid‑functionalized MCM‑41…
Table 5 Comparative synthesis of compound 5a using the reported heterogeneous catalysts versus the
present method
Entry Catalyst
Product Catalyst load- Conditions
ing
Time (min) Yield (%) References
1
2
Nano-ZnO
4a
20 mol%
20 mol%
Solvent free
Solvent free
180
300
80
80
[83]
[83]
Silica sulfuric 4a
acid
3
Oxalic acid
4a
20 mol%
EtOH/
40
90
[93]
H O1:1(v/v)
2
4
5
6
7
β-Cyclodextrin 4a
0.2 mol%
0.03 g
0.01 g
Reꢃux H O
Reꢃux EtOH
180
45
120
15
84
80
67
92
[74]
[94]
This work
This work
2
Al-SBA-15
MCM-41
MCM-41-PR- 4a
4a
4a
Reꢃux H O
2
0.01 g
Reꢃux H O
2
BTA
8
BTA
4a
0.01 g
Reꢃux H O
45
60
This work
2
(
q, 2H), 7.2 (m, 3H), 7.3 (m, 5H), 7.4 (m, 1H), 7.5 (d, J=8.7 Hz, 1H), 7.6 (m, 1H),
−1
7
.7 (d, J=7.9 Hz,1H); IR (KBr) max (cm ): 3292, 3028, 1631, 1487.
2
2
6
8
‑(2‑Chlorophenyl)‑2,3‑dihydroquinazolin‑4(1H)‑one (5 h) White solid, Mp: 200–
1
04 °C. HNMR (500 MHz, DMSO-d6): δ(ppm) 6.1 (s, 1H), 6.7 (t, 1H, J=6.7 Hz),
.8 (d, 1H, J=7.6 Hz), 7.02 (s, 1H), 7.2 (m, 4H), 7.4(m, 3H), 7.6 (d, 2H, J=4.3 Hz),
−1
.2 (s, 1H); IR (KBr) max (cm ): 3303, 3174, 3033, 1654, 1483, 1481.
2
1
7
7
‑(4‑Methylphenyl)‑2,3‑dihydroquinazolin‑4(1H)‑one (5c) White solid, Mp: 189–
1
93 °C. HNMR (500 MHz, DMSO-d6): δ(ppm) 8.2 (s, 1H),7.6 (d, J=8.3 Hz, 1H),
.3 (d, 2H, J=7.9 Hz), 7.2 (doublet of triplet, 1H, J=8.1),7.1 (d, J=7.7 Hz, 2H),
.0 (s, 1H), 6.7 (d, 1H, J=7.9 Hz), 6.6 (m, 1H), 5.7 (s, 1H), 2.3 (s, 3H); IR (KBr)
−1
max (cm ): 3290, 3164, 3024, 2929, 2821, 1500, 1250.
Acknowledgements The ꢀnancial support from The Research Council of Iran University of Science and
Technology (IUST), Tehran, Iran (Grant No: 160/18517), is highly appreciated. The partial ꢀnancial sup-
port of The Iran Nanotechnology Initiative Council (INIC) is gratefully acknowledged.
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