Composite of cross-linked chitosan beads and a cyclodextrin nanosponge: A metal-free catalyst for promoting ultrasonic-assisted chemical transformations in aqueous media

Article abstract of DOI:10.1016/j.jpcs.2021.110157

A novel carbohydrate-based catalytic composite was prepared through covalent decoration of cross-linked chitosan beads with a cyclodextrin nanosponge. In this regard, chitosan beads were fabricated and cross-linked with glutaraldehyde. Subsequently, they

Full text of DOI:10.1016/j.jpcs.2021.110157

Journal of Physics and Chemistry of Solids 156 (2021) 110157
Contents lists available at ScienceDirect
Journal of Physics and Chemistry of Solids
journal homepage: www.elsevier.com/locate/jpcs
Composite of cross-linked chitosan beads and a cyclodextrin nanosponge: A
metal-free catalyst for promoting ultrasonic-assisted chemical
transformations in aqueous media
Samahe Sadjadi*, Fatemeh Koohestani
Gas Conversion Department, Faculty of Petrochemicals, Iran Polymer and Petrochemical Institute, PO Box 14975-112, Tehran, Iran
A R T I C L E I N F O
A B S T R A C T
Keywords:
A novel carbohydrate-based catalytic composite was prepared through covalent decoration of cross-linked chi-
tosan beads with a cyclodextrin nanosponge. In this regard, chitosan beads were fabricated and cross-linked with
glutaraldehyde. Subsequently, they were reacted with an amino-functionalized cyclodextrin nanosponge. The
resultant composite was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning
electron microscopy, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and elemental mapping
analysis. Then the performance of the metal-free catalyst for promoting ultrasonic-assisted synthesis of dihy-
dropyrimidinones and octahydroquinazolinones in aqueous media was appraised. It was found that the com-
posite was highly efficient and recyclable. Moreover, the activity of the composite was superior to that of its
individual components. It is assumed that incorporation of the cyclodextrin nanosponge, which has high capa-
bility for the formation of an inclusion complex in the structure of the composite, allows the catalyst to act as a
molecular nanoreactor and promotes the reactions efficiently in aqueous media.
Chitosan bead
Cyclodextrin nanosponge
Metal-free catalyst
1. Introduction
encapsulation capacities. To solve this issue, recently CD nanosponges
(CDNS) [16,17], which are hyper-cross-linked polymers of CDs, have
Chitosan is one of the most attractive biopolymers, with appealing
features such as availability, biodegradability, biocompatibility,
tunability, and nontoxicity [1–3]. Chitosan has been extensively used to
develop environmentally benign catalysts. Apart from chitosan, chitosan
beads have also been prepared and have found widespread utility in
diverse fields, such as catalysis and sorption [4–8]. The presence of
various –OH and amino functional groups in the structure of chitosan
beads allows functionalization and cross-linking of the beads and tuning
of their stability and physiochemical properties [9].
been considered as alternatives. These polymers, which benefit from the
porosity of both CD and the 3D polymeric network, can host a vast range
of guest molecules with different sizes and polarities. More importantly,
in contrast to CD, CDNS is heterogeneous. This feature is appealing for
the development of catalysts with high recyclability [18,19]. Notably,
applications of CDNS in diverse fields, such as water treatment [20],
removal of hazardous compounds [21], and drug delivery [22,23], have
witnessed growing attention [24,25].
An approach to meet green chemistry principles involves performing
chemical reactions under ultrasonic irradiation [26,27]. Ultrasonic
irradiation used for promoting chemical reactions is mostly in the fre-
quency range from 20 kHz to 2 MHz [28]. Such irradiation generates
microbubbles with high pressure and temperature through a cavitation
phenomenon. This can not only provide better mixing of substrates in
the liquid phase but can also cause physiochemical effects based on the
applied frequency [28].
Cyclodextrins (CDs) have been extensively applied in the field of
catalysis because of their cone-shaped structures and their cavities [10].
The less hydrophilic nature of their inner surfaces allows accommoda-
tion of various guest molecules inside, while their more hydrophilic
outer surfaces facilitate transfer of the formed inclusion complexes in
aqueous media [11]. This feature, often called molecular shuttling, is
useful for performing reactions in aqueous media. There are many re-
ports in the literature regarding the role of CD as an inverse phase
transfer catalyst [12–15]. Despite the success of this strategy, the
defined cavity sizes and polarities of CDs have limited their
A well-known procedure for the synthesis of dihydropyrimidinones is
the Biginelli reaction, which is a multicomponent one-pot reaction,
mostly catalyzed by conventional catalysts [29]. More recently, the
* Corresponding author.
E-mail address: s.sadjadi@ippi.ac.ir (S. Sadjadi).
https://doi.org/10.1016/j.jpcs.2021.110157
Received 23 December 2020; Received in revised form 2 May 2021; Accepted 3 May 2021
Available online 8 May 2021
0022-3697/© 2021 Elsevier Ltd. All rights reserved.

S. Sadjadi and F. Koohestani
Journal of Physics and Chemistry of Solids 156 (2021) 110157
development of environmentally benign chemical methods [19,35–37],
here we report a green protocol for the synthesis of dihydropyr-
imidinones and octahydroquinazolinones under ultrasonic irradiation in
aqueous media by using a novel carbohydrate-based catalyst. The
catalyst, bead-CDNS, was fabricated through synthesis of chitosan
beads, followed by their cross-linking with glutaraldehyde (GA) and
covalent conjugation of as-prepared CDNS. It is postulated that in this
composite CDNS acts as a molecular nanoreactor and hosts the sub-
strates in its cavities and transfers them in aqueous media. This allows
the reactions to proceed efficiently in aqueous media.
Fig. 1. Procedure for the preparation of bead–cyclodextrin nanosponge
(CDNS). APTES, (3-aminopropyl)triethoxysilane; β-CD, β-cyclodextrin; CDNS-
N, amino-functionalized cyclodextrin nanosponge; Cs, chitosan; DPC,
diphenyl carbonate; GA, glutaraldehyde.
Biginelli reaction has been used for the synthesis of octahy-
droquinazolinones [30,31]. The importance of these heterocyclic com-
pounds lies in their biological activities, such as antimicrobial,
antibacterial, antifungal, and antiviral activities, which broaden their
use in pharmaceutical applications [32–34].
Fig. 3. Synthesis of octahydroquinazolinones. CDNS, cyclodextrin nanosponge;
As a continuation of our research on catalytic composites for the
US, ultrasound.
Fig. 2. Plausible mechanism for synthesis of bead–cyclodextrin nanosponge (CDNS). CDNS-N, amino-functionalized cyclodextrin nanosponge.
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S. Sadjadi and F. Koohestani
Journal of Physics and Chemistry of Solids 156 (2021) 110157
including X-ray diffraction (XRD), thermogravimetric analysis, differ-
ential scanning calorimetry (DSC), Fourier transform infrared (FTIR)
spectroscopy, scanning electron microscopy, energy-dispersive X-ray
spectroscopy (EDS), and elemental mapping analysis. The XRD pattern
was recorded in the 2θ range from 15◦ to 50◦ with a Siemens D5000
apparatus with a Cu Kα source. Thermogravimetry curves were obtained
with a Mettler Toledo instrument under an N2 atmosphere from 25 ◦C to
800 ◦C with a heating rate of 10 ◦C minꢀ 1. FTIR spectra were obtained in
KBr with a PerkinElmer Spectrum 65 instrument. Scanning electron
microscopy and EDS were performed with a MIRA 3 TESCAN-XMU in-
strument. The Brunauer-Emmet-Teller surface area of the samples was
measured with a Belsorp Mini II apparatus. Degassing was achieved by
heating at 150 ◦C for 2 h.
Fig. 4. General scheme of the Biginelli reaction. CDNS, cyclodextrin nano-
sponge; US, ultrasound.
2.2. Preparation of the catalyst
2.2.1. Synthesis of chitosan beads
Chitosan beads were synthesized according to the literature [38].
Briefly, chitosan (2 g) was dissolved in acetic acid solution (100 mL, 2%)
and kept under stirring for 3 h to obtain a homogeneous solution. Af-
terwards, the chitosan solution was transferred to a burette and gradu-
ally dropped into NaOH aqueous solution (0.5 M) to form small chitosan
beads. The beads were kept overnight in the basic solution and subse-
quently rinsed with distilled water.
2.2.2. Cross-linking of beads with GA: synthesis of bead-GA
Wet beads were cross-linked. For this purpose, the beads were sus-
pended in GA solution in EtOH (5 wt%) and the solution was stirred at
70 ◦C for 12 h. Finally, the cross-linked beads were collected, washed
with EtOH, and dried at room temperature overnight.
Fig. 5. Fourier transform infrared spectra of beads, bead–glutaraldehyde (GA),
and bead–cyclodextrin nanosponge (CDNS).
2.2.3. Synthesis of amino-functionalized CDNS
To synthesize amino-functionalized CDNS (CDNS-N), CDNS was first
prepared according to our previous procedure [39]. Typically, β-CD (1
mmol) was gradually poured into molten diphenyl carbonate. After-
wards, the white solid generated was vigorously mixed at 120 ◦C for 12
h. Finally, the reaction vessel was cooled to room temperature and CDNS
was crushed to a fine powder. For purification, CDNS was first rinsed
with acetone and distilled water several times and then purified via
Soxhlet extraction with EtOH. To ensure removal of phenol, CDNS was
also treated with NaOH solution. As phenol forms phenoxide ion, which
is soluble in aqueous media, the remaining phenol was separated.
Finally, the resultant CDNS was dried overnight at ambient temperature.
In the next step, CDNS was amino-functionalized. For this purpose,
CDNS (1.5 g) was suspended in EtOH (60 mL) and the mixture was
stirred for 10 min Then, a solution of APTES (1 mL) in EtOH (10 mL) was
gently added to the above-mentioned suspension and the mixture was
refluxed overnight under an inert atmosphere. Finally, the product,
CDNS-N, was filtered, washed several times with EtOH, and dried.
Fig. 6. Thermogravimetry curves of beads and bead–cyclodextrin nano-
2.2.4. Synthesis of bead-CDNS
sponge (CDNS).
Typically, the as-prepared bead-GA (0.5 g) was added to a mixture of
EtOH (40 mL) and distilled water (20 mL). The resulting suspension was
stirred for 10 min, and then CDNS-N (0.3 g) and K2CO3 (0.1 g) as a base
were added to the above-mentioned reaction mixture. The mixture ob-
tained was mechanically stirred continuously under reflux overnight. On
completion of the reaction, the obtained bead-CDNS was separated,
rinsed with EtOH, and dried at ambient temperature. The schematic
synthetic route for bead-CDNS is illustrated in Fig. 1.
2. Experimental section
2.1. Materials and instrumentation
Chitosan (Mr = 50,000–190,000, deacetylation degree 75% or
greater, viscosity 20 cP for 1 wt%, in 1% acetic acid), GA, β-CD, diphenyl
carbonate, (3-aminopropyl)triethoxysilane (APTES), benzaldehyde,
dimedone, urea, ethyl acetoacetate, acetic acid, K2CO3, NaOH, MeOH,
and EtOH were used for the synthesis of the catalyst and examination of
its catalytic activity. All the above-mentioned chemicals and reagents
were purchased from Sigma-Aldrich Chemical Company and were used
without further purification.
The reaction mechanisms for the formation of bead-GA and bead-
CDNS are presented in Fig. 2. As shown, formation of bead-GA is ach-
ieved through nucleophilic substitution. In more detail, the ion pair of
the amino group of chitosan attacks the carbonyl functionality of GA.
This reaction is followed by dehydration and formation of an imine
bond. In the next step, the amino group of CDNS-N reacted with the free
carbonyl groups of bead-GA to conjugate the two components through
The structure of bead-CDNS was confirmed by various techniques,
3

S. Sadjadi and F. Koohestani
Journal of Physics and Chemistry of Solids 156 (2021) 110157
Fig. 7. (A) Scanning electron microscopy images of a bead, bead–glutaraldehyde (GA), and bead–cyclodextrin nanosponge (CDNS). (B) Elemental mapping and
energy-dispersive X-ray spectroscopy analyses of bead-CDNS.
an imine bond.
2.4. General procedure for the synthesis of dihydropyrimidinone
derivatives
2.3. General procedure for the synthesis of octahydroquinazolinone
derivatives
All reagents—that is, aldehydes (1 mmol), ethyl acetoacetate (1
mmol), urea (1.5 mmol), and bead-CDNS (30 mg)—were mixed in H2O
(10 mL) and sonicated for 15 min (ultrasonic power of 120 W); see
Fig. 4. The reaction progress was continuously monitored by thin-layer
chromatography. After completion of the reaction, bead-CDNS was
rinsed with distilled water and reused for the next reaction run after
being dried at 60 ◦C. The organic product was obtained after evapora-
tion of the solvent and was purified by column chromatography (ethyl
acetate/hexane mixture).
Aldehydes (1 mmol), dimedone (1 mmol), urea (1 mmol), and the
bead-CDNS catalyst (30 mg) were mixed in EtOH (15 mL). The reaction
mixture was then subjected to ultrasonic irradiation with a power 120 W
for 10 min (Fig. 3). After completion of the organic transformation,
monitored by thin-layer chromatography, bead-CDNS was filtered,
washed with MeOH, and dried at 60 ◦C for further use. To obtain the
organic product, the solvent was evaporated and the product was pu-
rified by column chromatography.
3. Result and discussion
The FTIR spectra of the beads, bead-GA, and bead-CDNS are
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S. Sadjadi and F. Koohestani
Journal of Physics and Chemistry of Solids 156 (2021) 110157
Fig. 7. (continued).
conjugation of CDNS. The characteristic bands of CDNS overlapped with
those of bead-GA.
The thermograms related to beads and bead-CDNS are shown and
compared in Fig. 6. According to the thermogravimetry curve of the
beads, degradation of the beads occurred at 260 ◦C. In the case of bead-
CDNS, the thermogravimetry curve was different. In this case, apart
from loss of water (120 ◦C) and degradation of beads (260 ◦C), an
additional weight loss at 460 ◦C can be discerned. This weight loss is
ascribed to the degradation of CDNS and GA.
The morphologies of the beads, bead-GA, and bead-CDNS are pre-
sented and compared in Fig. 7A. As depicted, all samples exhibited
spherical morphology. However, the surface features of the samples are
distinguished. In more detail, the bead surface is smooth with no sig-
nificant porosity, while bead-GA and bead-CDNS possess rough surfaces.
The results of EDS and elemental mapping analyses for bead-CDNS is
illustrated in Fig. 7B. As depicted, the catalyst possesses C, N, O, and Si
atoms. C, N, and O atoms are representative of chitosan. On the other
hand, C and O atoms are indicative of GA and CDNS. The presence of Si
proves the conjugation of APTES. As shown in the elemental mapping
analysis, the dispersion of Si atoms is approximately uniform, implying
that CDNS had been uniformly functionalized with APTES.
Fig. 8. X-ray diffraction pattern of bead–cyclodextrin nanosponge.
compared in Fig. 5. According to the literature [40], the characteristic
bands of the beads can be seen at 3420 cmꢀ 1 (–OH and –NH), 2924 cmꢀ 1
(–C–H), 1045 cmꢀ 1 (stretching of C–O), and 1637 cmꢀ 1 (N–H bending
vibration and stretching for primary amine). In the FTIR spectrum of
bead-GA, the characteristic absorption bands of the beads can be
observed. The distinguishing band in this spectrum is the broad band in
the range from 1569 cmꢀ 1 to 1700 cmꢀ 1. This band is assigned to the
The crystalline nature of bead-CDNS was appraised via powder XRD
(Fig. 8). The characteristic peak at 2θ = 20◦–25◦ is related to the
amorphous structure of bead-CDNS. Both beads and CDNS as carbohy-
drates exhibit a characteristic peak at 2θ = 20◦–25◦ [41].
Next, Brunauer-Emmet-Teller analysis of chitosan beads, bead-GA,
and bead-CDNS was conducted. It was found that the specific surface
area of chitosan beads was 26.5 m2 gꢀ 1. The value for the cross-linked
beads, bead-GA, was similar (24.6 m2 gꢀ 1). These results are in good
accordance with the literature [42]. On introduction of CDNS and for-
–
–
–C N functionality and confirms the successful cross-linking with GA.
The FTIR spectrum of bead-CDNS is very similar to that of bead-GA, and
all of the aforementioned characteristic bands are present in the FTIR
spectrum of the catalyst. This indicated that bead-GA did not collapse on
mation of bead-CDNS, the specific surface area decreased to 11 m2 gꢀ 1
.
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S. Sadjadi and F. Koohestani
Journal of Physics and Chemistry of Solids 156 (2021) 110157
Fig. 9. Synthesis of octahydroquinazolinones and dihydropyrimidinones using bead–cyclodextrin nanosponge (CDNS) as a catalyst. The reaction conditions were as
follows: substrate (1 mmol), dimedone (1 mmol), ethyl acetoacetate (1 mmol), and urea (1 and 1.5 mmol) in EtOH and H2O as a solvent under ultrasonic irradi-
ation (US).
3.1. Catalyst activity
encaging various reagents and bringing them together in aqueous
media. Because of the presences of the cavities of CD monomers and the
polymeric network, CDNS has more potential than bare CD and allows
encapsulation of guest molecules with a vast range of polarity and size.
Apart from the use of a metal-free catalyst and aqueous media, ultra-
sonic irradiation was applied to promote the reactions. Ultrasonic irra-
diation can not only facilitate and accelerate the reaction through the
In this research, the development of an environmentally benign
protocol for chemical synthesis was the aim. In this regard, the features
of chitosan and CD were combined to design and fabricate an efficient
metal-free catalyst that can promote the reaction in aqueous media.
More precisely, CDNS was applied as a molecular nanoreactor for
6

S. Sadjadi and F. Koohestani
Journal of Physics and Chemistry of Solids 156 (2021) 110157
cavity effect but also provides a clean procedure for performing chem-
ical transformations.
To commence the catalytic activity tests, ultrasonic-assisted syn-
theses of octahydroquinazolinones and dihydropyrimidinones (products
6 and 4) in aqueous media were selected as model multicomponent re-
actions. In the first step, the optimum catalyst dosage was found by our
examining the yields of the two model reactions (reaction of benzalde-
hyde, urea, dimedone, and ethyl acetoacetate) in the presence of
different loadings of bead-CDNS. The results indicated that for both
reactions the optimum catalyst amount was 30 mg per mole of the
substrates, and excellent reaction yields (98% and 100% for products 4
and 6, Fig. 9, entry 1 in the table) were achieved for both desired
products. Next, to elucidate the efficiency of ultrasonic irradiation, the
model reactions were performed under conventional stirring and reflux
conditions with the optimum amount of the catalyst and solvents. The
results implied that in both reflux and stirring conditions, the reaction
times were prolonged to 90 min. These results affirmed that ultrasonic
irradiation can efficiently accelerate the reactions.
Fig. 10. Differential scanning calorimetry thermograms of bead–cyclodextrin
nanosponge (CDNS) and the inclusion complex of bead-CDNS with benzalde-
hyde and dimedone.
3.2. Comparison of the activity of CDNS, bead-GA, and bead-CDNS
The hypothesis behind this research was that conjugation of CDNS to
bead-GA should improve the activity of bead-GA. To validate this
assumption and study whether the activity of bead-CDNS is truly supe-
rior to that of its individual components, the activities of bead-GA,
CDNS, and bead-CDNS for the synthesis of the model dihydropyr-
imidinone under optimum reaction conditions were compared. The
comparative study established that the activities of CDNS and bead-GA
were significantly lower than the activity of bead-CDNS (CDNS led to
50% of the corresponding product, while bead-GA furnished 40% yield).
This result clearly shoes the benefit of conjugation of the two compo-
nents. According to the literature [43], the catalytic activity of bead-GA
can be ascribed to the functional groups (i.e., amino and –OH groups) of
chitosan. The catalytic activity of CDNS also can be attributed to the
–OH groups of CD monomers. Moreover, CDNS is capable of accom-
modating organic substrates in its pores and transferring them in
aqueous media. This is referred as the formation of an inclusion complex
[18,39]. This capability facilitated the reactions in water and increased
the yield of the reaction. Although the as-prepared CDNS is a solid and
acts as a heterogeneous catalyst, it is very fine and needs to be separated
from the reaction mixture via centrifugation. In the case of bead-CDNS,
in which CDNS is hybridized with bead-GA, the recovery of the catalyst
improved significantly and bead-CDNS can be separated simply via
conventional filtration. On the other hand, bead-CDNS benefits from the
presence of functional groups of both CDNS and bead-GA as well as the
capacity of CDNS as a molecular shuttle. Hence, it showed higher cat-
alytic activity.
Fig. 11. The proposed reaction mechanism for the synthesis of
dihydropyrimidinones.
To confirm the formation of the inclusion complex between bead-
CDNS and the substrates (benzaldehyde, dimedone and urea), DSC
analysis of bead-CDNS, benzaldehyde, dimedone and urea for the for-
mation of the model octahydroquinazolinones was performed. Bead-
CDNS was treated with the substrate for a short reaction time and
then recovered and subjected to DSC analysis. As can be observed in
Fig. 10, the DSC thermogram of bead-CDNS exhibited an endothermic
peak at about 250 ◦C and two exothermic peaks at approximately 642 ◦C
and 743 ◦C.
In the case of the bead-CDNS recovered from the model reaction of
synthesis of octahydroquinazolinones, an additional endothermic peak
at 338 ◦C was detected. Considering the DSC thermograms of the sub-
strates (Fig. S1) and the DSC thermogram of the bead-CDNS recovered
from the model reaction of synthesis of octahydroquinazolinones, the
new endothermic peak can be assigned to urea, while no characteristic
peaks of benzaldehyde and dimedone were observed. The absence of the
peaks of benzaldehyde and dimedone indicates that they had been
encapsulated in the composite, while the peak of urea shows that this
small hydrophilic substrate was located on the composite.
Fig. 12. The proposed reaction mechanism for the synthesis of
octahydroquinazolinones.
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S. Sadjadi and F. Koohestani
Journal of Physics and Chemistry of Solids 156 (2021) 110157
Table 1
The yields of the model dihydropyrimidinone by use of different catalysts under ultrasonic irradiation.
Catalyst
Catalyst amount
Temperature (◦C)
Solvent
Time (min)
Yield (%)
Reference
Polyindole
1.5 wt%
30 mg
–
SF
25
20
15
50
25
40
15
97
98
97
97
90
97
100
[44]
Fe3O4-MWCNT composites
NDL
50
EtOH
EtOH/H2O
EtOH
EtOH
EtOH
H2O
[45]
5 wt%
45–50
50
[46]
Nano-La2O3
SBA-15-SO3H
NH2SO3H
8 mol%
10 mol%
1.5 mmol
30 mg
[47]
25
[48]
25–30
25
[49]
Bead-CDNS
This work
CDNS, cyclodextrin nanosponge; MWCNT, multiwalled carbon nanotube; NDL, natural dolomitic limestone; SF, solvent-free.
The catalytic activity of SBA-15-SO3H is slightly lower than that of
bead-CDNS. On the other hand, synthesis of SBA-15 requires multistep
and precise procedures. The activity of natural dolomitic limestone,
which is a natural heterogeneous catalyst, is comparable to that of bead-
CDNS. In this case, the reaction temperature was slightly higher and the
reaction time was slightly longer than for bead-CDNS. Similarly, nano-
La2O3 acted under a relatively high reaction temperature to furnish a
high yield of the product in a longer reaction time compared with bead-
CDNS. Polyindole also showed high catalytic activity. However, the
biocompatible nature of bead-CDNS compared with polymeric catalysts
is a merit of bead-CDNS. In summary, this comparative study indicates
that bead-CDNS is an efficient catalyst that can promote the model re-
action under mild reaction conditions and its activity is comparable with
that of other reported catalysts.
3.6. Catalyst recyclability
Following examination of the activity of bead-CDNS, its recyclability
for both model reactions was studied. Bead-CDNS could be easily
separated from the reaction media by simple filtration and reused for the
next run of the model chemical processes after washing with EtOH. The
recycling test (Fig. 13) showed that bead-CDNS could be used as a
catalyst for five successive runs for both reactions. The comparison of
the yields of the reactions indicated that after each run the reaction
yields decreased slightly. This is attributed to the possibility of coverage
of the surface and pores of bead-CDNS with the organic substrates and
products. This can prevent the substrates reaching the active sites of the
catalyst and consequently leads to the decrease of the efficiency of bead-
CDNS.
Fig. 13. Recyclability of bead–cyclodextrin nanosponge for the synthesis of (A)
model dihydropyrimidinone and (B) model octahydroquinazolinone in water
under ultrasonic irradiation.
3.3. Reliability of the protocol developed
In the next step, it was appraised whether this protocol can be
generalized to other aldehydes. In this respect, aldehydes with different
electronic features were used as reagents. The results (Fig. 9) indicate
that various substrates can undergo the reaction to give high reaction
yields for products 4 and 6.
3.4. Reaction mechanism
4. Conclusion
The reaction mechanisms for the synthesis of dihydropyrimidinones
and octahydroquinazolinones are depicted in Figs. 11 and 12. In the first
step of both reactions, the carbonyl group of the aldehydes is activated
by the catalyst. Subsequently, the amine group of urea attacks the
activated carbonyl. This reaction is followed by dehydration and for-
mation of an intermediate that will tolerate the reaction with the enol
form of ethyl acetoacetate or dimedone to form a cyclic intermediate.
The final product is achieved through dehydration.
Bead-CDNS was prepared through covalent attachment of CDNS to
bead-GA. The resultant composite was then characterized and used as a
metal-free catalyst for promotion of the Biginelli reaction for the syn-
thesis of dihydropyrimidinone and octahydroquinazolinone derivatives
under ultrasonic irradiation in aqueous media. Study of the catalytic
performance of the catalyst revealed that it could catalyze both reactions
effectively to furnish the desired products in high yields in a short re-
action time. The activity of the catalyst developed was superior or
comparable to that of some previously reported catalysts. Moreover, the
catalyst could be readily separated from the reaction mixture and reused
for five runs. The comparative study of the activity of CDNS, bead-GA,
and bead-CDNS indicated the superior performance of the latter,
proving that conjugation of bead-GA to CDNS is beneficial for the
catalysis. The role of CDNS in catalysis is attributed to its capability as a
molecular shuttle. Use of biocompatible carbohydrates, performing the
reactions in aqueous media, high recyclability of the catalyst, and use of
ultrasonic irradiation render the present protocol an environmentally
benign method.
3.5. Comparative study
Motivated by the high activity of bead-CDNS under ultrasonic irra-
diation, we compared the performance of the catalyst for the synthesis of
the model dihydropyrimidinone with the performance of some previ-
ously reported ultrasonic-assisted protocols (Table 1). As presented in
Table 1, various methods using different catalysts have been reported.
Compared with homogeneous catalysts, such as NH2SO3H, bead-CDNS,
which is a heterogeneous catalyst, benefits from facile recovery and
recyclability. On the other hand, the required reaction time for
NH2SO3H is relatively long. Fe3O4–multiwalled carbon nanotube com-
posites exhibited high activity. However, multiwalled carbon nanotubes
are costly and the reaction temperature is higher than for bead-CDNS.
Author statement
Samahe Sadjadi: Design of the catalyst, supervision, financial
8

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Acknowledgments
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The authors appreciate the partial support of the Iran Polymer and
Petrochemical Institute. Samahe Sadjadi thanks the Iran National Sci-
ence Foundation for grant no. 99011126.
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Appendix A. Supplementary data
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