Biginelli reaction on Fe3O4-MWCNT nanocomposite: Excellent reactivity and facile recyclability of the catalyst combined with ultrasound irradiation

Article abstract of DOI:10.1039/c3ra43014f

A highly efficient and improved synthetic methodology for the preparation of dihydropyrimidinone derivatives using β-dicarbonyl compounds, urea/thiourea and aromatic aldehydes using Fe₃O₄-MWCNT as a nanocatalyst under ultrasound irra

Full text of DOI:10.1039/c3ra43014f

View Article Online
View Journal
RSC Advances
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Z. Zarnegar and J. Safari, RSC Adv.,
2013, DOI: 10.1039/C3RA43014F.
This is an Accepted Manuscript, which has been through the RSC Publishing peer
review process and has been accepted for publication.
Accepted Manuscripts are published online shortly after acceptance, which is prior
to technical editing, formatting and proof reading. This free service from RSC
Publishing allows authors to make their results available to the community, in
citable form, before publication of the edited article. This Accepted Manuscript will
be replaced by the edited and formatted Advance Article as soon as this is available.
To cite this manuscript please use its permanent Digital Object Identifier (DOI®),
which is identical for all formats of publication.
More information about Accepted Manuscripts can be found in the
Information for Authors.
Please note that technical editing may introduce minor changes to the text and/or
graphics contained in the manuscript submitted by the author(s) which may alter
content, and that the standard Terms & Conditions and the ethical guidelines
that apply to the journal are still applicable. In no event shall the RSC be held
responsible for any errors or omissions in these Accepted Manuscript manuscripts or
any consequences arising from the use of any information contained in them.
www.rsc.org/advances
Registered Charity Number 207890

Page 1 of 15
RSC Advances
Dynamic Article Links ►
Journal Name
View Article Online
DOI: 10.1039/C3RA43014F
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
ARTICLE TYPE
Biginelli reaction on Fe3O4ꢀMWCNT nanocomposite: excellent reactivity
and facile recyclability of the catalyst combined with ultrasound
irradiation
Javad Safari,* Zohre Zarnegar
5
Laboratory of Organic Compound Research, Department of Organic Chemistry, College of Chemistry, University of
Kashan, P.O. Box: 87317ꢀ51167, Kashan, I.R., Iran.Corresponding author. Eꢀmail addresses: Safari@kashanu.ac.ir, Tel:
+98 361 591 2320; Fax: +98 361 5912397.
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
10 DOI: 10.1039/b000000x
A highly efficient and improved synthetic methodology for the preparation of Dihydropyrimidinone
derivatives using βꢀdicarbonyl compound, urea/thiourea and aromatic aldehydes using Fe3O4ꢀMWCNT as
a nanocatalyst under ultrasound irradiation is reported. The present method has promising features for the
reaction response such as the shortest reaction time, excellent product yields, simple workꢀup procedure
and operational simplicity. The advantages of this novel protocol as compared to other synthetic methods,
are clean conversion, the amount of catalyst, high catalytic activity and ease of recovery from the reaction
mixture using an external magnet, and several reuse times without significant losses in performance.
15
feature of these nanocatalysts is simple separation of them using
an external magnet without filtration.14ꢀ16
However, these nanoparticles have a great tendency to deform
1. Introduction
Dihydropyrimidinones (DHPMs) and their derivatives, outcomes
20 of the Biginelli reaction, are very important pharmacologically
active molecules and have found applications as calcium channel
blockers, α1aꢀadrenrgic antagonists, antihypertensive agents,
inhibitors of the fatty acid transporter, and mitotic kinesin
and aggregate during the course of chemical reactions and as a
50 result the thermal and chemical stability of these nanostructures
changes. The thermal and chemical stability of these
nanoparticles play pivotal roles in tuning their properties in
advanced applications especially catalytic activity.16,17 Therefore,
a large number of research on stabilizing magnetic nanoparticles
55 have been carried out.18–20 Most importantly in the field of
molecular catalysis, the MNPsꢀsupported catalysts show high
catalytic activity and reusability and high degree of chemical
stability in organic solvents.21–24
Recently, carbon nanotubes (CNTs) have been considered as
60 catalyst supports for catalytic procedures due to their intriguing
nanoscale dimensions, electrical properties, high specific surface
area, uniform nanostructure, thermal and chemical stability.25,26
Immobilization of magnetic nanoparticles using CNTs has drawn
favorable attention because it prevents agglomeration and
65 therefore enhances their performances.27 Also, CNTs can serve
not only as supports but also as components with synergistic and
hybrid properties.28,29
Environmental concerns in chemical research are ever increasing.
On the other hand, greener process involves mainly clean
70 solvents or solveneꢀfree, ultrasound irradiation and microwave
irradiation. Ultrasoundꢀassisted organic synthesis (UAOS) has
increasingly been used in modern synthetic chemistry owing to
its green credentials, because of its advantages including shorter
reaction times, milder reaction conditions, higher yields,
75 improved selectivity and clean reaction in comparison to classical
inhibition.1
Also,
batzelladine
alkaloids
containing
25 dihydropyrimidines core have been found to show potent antiꢀ
HIV activity.2 The most simple and straight forward procedure
for the synthesis of dihydropyrimidinones originally reported by
Biginelli in 1893, involves the acidꢀcatalyzed oneꢀpot
condensation of α,βꢀketo ester with an aldehyde and urea
30 derivatives.3 However, the yields of products were very low (just
20–50%).
This great biological importance of these heterocyclic
compounds has prompted the development of new improved
methodologies for Biginelli reaction, including transition metal
35 Lewis acid catalysis,4 solid phase synthesis,5 ionic liquids,6
activation with certain additives,7 microwaveꢀassisted synthesis
technique,8 ultrasound irradiation,9 solventꢀfree techniques,10
grinding techniques,11 and many new catalysts.12
Recently, have witnessed an exponential growth in the
40 applications of heterogeneous catalysis in organic reactions to
carry out synthetic transformations as a consequence of its
significance in terms of enviroꢀeconomical and practical
aspects.13 Among the heterogeneous catalysts, magnetic
nanoparticles (MNPs) have emerged as
45 heterogeneous nanocatalyst for organic process. An important
a new class of
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

RSC Advances
Page 2 of 15
View Article Online
DOI: 10.1039/C3RA43014F
methods.30ꢀ32 During the ultrasound procedure in organic
synthesis, intense local heating, high pressures, and extremely
sonochemically synthesis of 4a at 40 ◦C. The results are presented
in Table 1. When FeCl3.6H2O and FeCl2ꢁ4H2O was used as a
rapid cooling rates were produced by bubble collapse, based on 60 catalyst, the Biginelli condensation products were obtained in low
acoustic cavitation resulting from the continuous formation,
growth and implosive collapse of the bubbles in a solution.
Chemical reactions could be droved by the transient and localized
hot spots.30ꢀ35
yields. Also in some cases the products could not be isolated and
the catalyst could not be reused for further cycles. When we used
bulk Fe3O4 the yield becomes still lower with no reusability of the
catalyst. However, when the reaction was conducted in the
5
In the context of our ongoing research project on the development 65 presence of nanoꢀFe3O4 catalyst the yield of the condensation
of green methodologies for the synthesis of heterocyclic
product was increased from 30% to 55%. But due to the colloidal
nature of the Fe3O4 nanocatalyst it was reused for only three
cycles. It was noted that when Fe3O4 nanoparticles were
immobilized into MWCNTs (having high surface area) the
10 compounds of biological importance and the use of magnetic
nanocatalysts in organic reactions.36,37 here we would like to
report for the first time, an effective improved synthetic method
for the preparation 3,4ꢀdihydropyrimidinꢀ2ꢀ(1H)ꢀones/thiones via 70 catalytic activity of the nanocatalyst becomes much higher than
the oneꢀpot condensation an aromatic aldehyde, βꢀdicarbonyl
15 compound, urea or thiourea, and Fe3O4ꢀMWCNT as magnetic
nanocatalysts under ultrasound irradiation (Scheme 1).
< Scheme 1>
that of the corresponding nanoꢀFe3O4 catalyst. Moreover, in this
case the magnetic nanocatalyst can be recycled 15 times and
magnetic separation was easily achieved by using a simple bar
magnet. The difference in the catalytic activity between the
75 simple and supported catalytic systems might be explained on the
basis of the highly dispersed Fe3O4 on MWCNT. Interestingly,
when the reaction was carried out in the presence of (0.03 g)
Fe3O4ꢀMWCNTs, it led to the desired product in 75% yield
(Table 1, Entry 5).
2. Results and discussion
20 The first step entails the synthesis of highly stable Fe3O4ꢀ
MWCNT. The preparation procedure of Fe3O4ꢀMWCNTs is
illustrated in scheme 2.38 As it shows, acidꢀtreated MWCNTs are
functionalized with negative carboxylic groups which have
affinity with positive ferrous and ferric ions. After the addition of
25 NH3 aqueous solution, Fe3O4 nanoparticles will be formed on the
surface of MWCNTs.
80
<Table 1>
The results indicated that the solvents had a significant effect on
the Biginelli product yield. The use of dichloromethane as solvent
gave poor yields (Table 2, Entry 1). Solvents like CH3CN DMF,
and toluene gave moderate yields (Table 2, Entries 2, 3 and 4).
85 The best conversion was observed when the reaction was
performed in EtOH (Table 2, Entry 9). Based on these results,
EtOH was then selected as the solvent for the Biginelli
condensation. The effect of reaction temperature on the model
reaction in the presence of Fe3O4ꢀMWCNTs under ultrasound
90 irradiation was also observed. As shown in Table 2, when the
<Scheme 2>
The XRD patterns of oxidized MWCNTs and Fe3O4ꢀMWCNT
nanocomposites are shown in Fig.1. The diffraction of the Fe3O4
30 nanoparticles observed in nanocomposite including the peaks at
2θ=26.30°, 30.54°, 35.92°, 43.62°, 54.02°, 57.54° and 63.16°in
Fig. 1 (a). These data are in good agreement with that of Fe3O4
particles (JCPDS card No. 88ꢀ0315) reported before. The broad
peak located at approximately 2θ = 26.2° is characteristic of a
35 MWCNTs in Fig. 2 (b) (JCPDS card No. 75ꢀ1621).38
<Fig. 1>
Typical TEM micrographs for the oxidized MWCNTs and SEM
of Fe3O4ꢀMWCNT are shown in Fig. 2. The MWCNTs with
tubular structure have the diameters of 20–40 nm and lengths of
40 several microns (Fig. 3 (a)). The Fe3O4 nanoparticles are
deposited onto the surface of MWCNTs under ultrasonication
process (Fig. 3 (b) and (c)).
◦
temperature was 50 C, the yield of 4a was 98%. Consequently,
the reaction temperature played an efficient role in this reaction.
<Table 2>
To test the generality of this Biginelli reaction, various aldehydes
95 were used. As shown in Tables 3, a series of aromatic aldehydes
were successfully employed to prepare the corresponding 3,4ꢀ
dihydropyrimidinꢀ2ꢀ(1H)ꢀones/thiones in excellent yields. Most
importantly, aromatic aldehydes carrying either electronꢀdonating
or electronꢀwithdrawing substituents all reacted very well, giving
100 excellent yields.
<Table 3>
<Fig. 2>
The possible reaction pathway for the Biginelli condensation
mediated by Fe3O4ꢀMWCNTs is outlined in scheme 3. The
electrophilicity of the carbonyl carbon atom of both aldehyde and
105 active methylene compound (here ethyl acetoacetate) increases
through coordinate bonds owing to Fe3O4 empty orbital. Then the
aromatic aldehyde and ethyl acetoacetate undergo aldol type
condensation to offer the corresponding aldolꢀtype product.
Moreover, electron deficient sites present at the surface of the
110 Fe3O4 nanoparticle grafted MWCNTs could coordinate with the
Nꢀdonor sites of urea and activate it for the 1,4ꢀaddition reaction
of urea. This leads to the aldol type intermediate (A) to generate
ureides (B) that ultimately cyclize to Biginelli products (C) with
the elimination of a water molecule.42 Here the role of the
115 magnetic nanoparticles is firstly easy magnetic recovery and
Typical magnetization curve as a function of applied field at
45 room temperature (300 K) are shown in Fig. 3. The Fe3O4ꢀ
MWCNT nanocomposites have a saturated magnetization of Ms
31.2 emu/g. Also, there is no pronounced hysteresis loop, which
indicates that both the retentivity and the coercivity of the
composites are zero.38
50
<Fig. 3>
To investigate the catalytic activity of Fe3O4ꢀMWCNTs
composites, we carried out the Biginelli reaction between
benzaldehyde, ethyl acetoacetate, and urea as the model under
various conditions and ultrasound irradiation. When the molar
55 ratio is 1:1:1.5, the reaction gave the best results. A wide variety
of iron catalysts including FeCl3.6H2O FeCl2ꢁ4H2O, bulk Fe3O4,
nanoꢀFe3O4, MWCNT and Fe3O4ꢀMWCNTs were employed for
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 15
RSC Advances
View Article Online
DOI: 10.1039/C3RA43014F
separation. Further, the surface Feꢀsites in the Fe3O4 grafted
3.2. Catalyst preparation
nanocatalyst could stabilize the urea molecules by adsorbing at its
surface, which facilitates the reaction, and the high surface area
of the supporting mesoporous host is necessary for the high turnꢀ
over frequency of the reaction.42
Fe3O4ꢀMWCNT were prepared using chemical coprecipitation
described in the literature.38 The MWCNTs were treated by
60 adding 30 mL of sulfuric and nitric acid mixture (3:1 in volume)
in an ultrasonic bath at 60 °C for 5 h. The mixture was diluted by
distillated water and it was filtrated. The acidꢀtreated MWCNTs
was washed by distillated water and dried by vacuum oven. Next,
48 mg acidꢀtreated MWCNTs were dispersed in 30 mL of
65 distilled water by sonication for 30 min. Then 40.5 mg of FeCl3ꢀ
6H2O and 60 mg of FeCl2ꢀ4H2O were added g for 30 min under
Ar atmosphere. 4 ml of concentrated NH3ꢀH2O diluted with 20
mL of distilled water was added into the mixture and then the
5
<Scheme 3>
Magnetic separation is a more attractive and simple technique
than the filtration or centrifugation techniques as it prevents the
loss of the nanocatalyst and increases the reusability of the
10 nanocatalyst. The recycling performance of the Fe3O4ꢀMWCNTs
in the model reaction was also inverstigated. Surprisingly, this
catalyst demonstrated excellent recoverability and reusability.
After completion of the reaction, the isolated Fe3O4ꢀMWCNTs
was washed with ethyl acetate, oven dried and then directly used
15 for the next cycle reaction without further purification. The
recycled catalyst could be reused 15 times without any significant
loss of its activity under ultrasonication (Fig. 4).
°
solution was heated to 60 C for 2 h. The reaction mixture was
70 then centrifuged, washed with distilled water and dried at 50 °C.
3.3. General procedure for Fe3O4ꢀMWCNTs mediated
synthesis of dihydropyrimidinones /thiones via Biginelli
condensation under ultrasound irradiation
< Fig. 4>
3. Experimental
In a twoꢀnecked flask, a solution of benzaldehyde (1 mmol, 106
75 mg), ethyl acetoacetate (1 mmol, 132 mg) and urea (1.5 mmol, 90
20 3.1. Chemicals and apparatus
mg) in 5 ml of absolute ethanol, the Fe3O4ꢀMWCNTs
nanocatalyst (30 mg) was sonicated at 50 °C, for appropriate
times (monitored by TLC). After completed reaction magnetic
catalyst was separated by an external magnet. The reaction
80 mixture was evaporated to remove solvent The residue was
stirred in water (3×15 mL) and then filtered. The solid was
washed with hexane (3×15 mL) and reꢀcrystallized from ethanol
to give the pure product.
Chemical reagents in high purity were purchased from Merck and
Aldrich and were used without further purification. MWNTs
were purchased from Nanotech Port Co. (Taiwan). These
MWNTs were produced via the chemical vapor deposition (CVD,
25 or sometimes called catalytic pyrolysis) method. The outer
diameter of CNT was between 20–40 nm. Melting points were
determined in open capillaries using an Electrothermal Mk3
1
apparatus and are uncorrected. H NMR and 13C NMR spectra
4. Conclusions
were recorded with a Bruker DRXꢀ400 spectrometer at 400 and
30 100 MHz respectively. FTꢀIR spectra were obtained with
potassium bromide pellets in the range 400ꢀ4000 cm–1 with a
Perkin–Elmer 550 spectrometer. The element analyses (C, H, N)
were obtained from a Carlo ERBA Model EA 1108 analyzer
carried out on Perkin–Elmer 240c analyzer. Nanostructures were
35 characterized using a Holland Philips Xpert Xꢀray powder
diffraction (XRD) diffractometer (CuK, radiation, λ= 0.154056
nm), at a scanning speed of 2°/min from 10° to 100° (2θ).
Transmission electron microscopy (TEM) images were obtained
on a Philips EM208 transmission electron microscope with an
40 accelerating voltage of 100 kV. Scanning electron microscope
(SEM) was performed on a FEI Quanta 200 SEM operated at a 20
kV accelerating voltage. The samples for SEM were prepared by
spreading a small drop containing nanoparticles onto a silicon
wafer and being dried almost completely in air at room
45 temperature for 2 h, and then were transferred onto SEM
conductive tapes. The transferred sample was coated with a thin
layer of gold before measurement. Purity of the compounds
synthesized was monitored by TLC, visualizing with ultraviolet
light. Sonication was performed in Shanghai BransonꢀBUG40ꢀ06
50 ultrasonic cleaner (with a frequency of 35 kHz and a nominal
power 200 W). A circulating water bath (DC2006, Shanghai
Hengping Apparatus Factory) with an accuracy of 0.1 K was
adopted to keep the reaction temperature at a constant. The
known products were characterized by 1H and 13C NMR, IR data
55 and melting point respectively and compared with the reported
values. All yields refer to isolated products after purification.
85 We have developed Fe3O4ꢀMWCNT nanocomposits as a robust,
and magnetically recoverable heterogeneous catalyst for the oneꢀ
pot Biginelli condensation for the synthesis of 3,4ꢀ
dihydropyrimidinꢀ2ꢀ(1H)ꢀones/thiones
under
ultrasound
irradiation. The magnetic nature of this heterogeneous
90 nanocatalyst allows for its easy separation from the reaction
mixture by using a simple bar magnet. This method offers several
advantages including green procedure, short reaction time,
excellent yields, and simple workꢀup, ease of separation, as well
as the ability to tolerate a wide variety of substitutions in the
95 reagents.
Acknowledgments
We gratefully acknowledge the financial support from the
Research Council of the University of Kashan for supporting this
work by Grant NO. (256722/III).
100 References
1. (a) K. S. Atwal, G. C. Rovnyak, B. C. O’Reilly, J. Schwartz, J.
Org. Chem., 1989, 54, 5898; (b) C. O. Kappe, W. M. F.
Fabian, M. A. Semones, Tetrahedron., 1997, 53, 2803; (c) C.
Blackburn, B. Guan, J. Brown, C. Cullis, S. M. Condon, T. J.
105
Jenkins, S. Peluso, Y. Ye, R. E. Gimeno, S. Punreddy, Y.
Sun, H. Wu, B. Hubbard, V. Kaushik, P. Tummino, P.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

RSC Advances
Page 4 of 15
View Article Online
DOI: 10.1039/C3RA43014F
Sanchetti, D. Yu Sun, T. Daniels, E. Tozzo, S. K. Balanic, P.
Raman, Bioorg. Med. Chem. Lett., 2006, 16, 3504.
2. A. D. Patil, N. V. Kumar, W. C. Kokke, M. F. Bean, A. J.
Freyer, C. DeBrosse, S. Mai, A. Truneh, D. J. Faulkner, J.
Org. Chem., 1995, 60, 1182.
3. P. Biginelli, Gazz. Chim. Ital., 1893, 23, 360.
4. (a) D. S. Bose, L. Fatima, H. B. Mereyala, J Org Chem., 2003,
68, 587; (b) M. Adib, K. Ghanbary, M. Mostofi, M. R.
Ganjal, Molecules., 2006, 11, 649; (c) M. A. Chari, K.
Syamasundar, J Mol Catal A., 2004, 221, 137.
5. D. Dallinger, N. Yu Gorobets, C. O. Kappe, Org Lett. 2003, 5,
1205.
6. (a) E. H. Hu, D. R. Sidler, U. H. Dolling, J Org Chem., 1998,
63, 3454; (b) A. Dondoni, A. Massi, Tetrahedron Lett., 2001,
42, 7975; (c) J. Peng, Y. Deng, Tetrahedron Lett., 2001, 42,
5917.
25. C. Y. Lu, M. Y. T. Wey, Fuel., 2007, 86, 1153.
60 26. M. Trépanier, A. Tavasoli, K. Dalai, N, Abatzoglou, Fuel
Process Technol., 2009, 90, 367.
27. J. Deng, X. Wen, Q. Wang, Mater Res Bull., 2012, 47, 3369.
28. D. Eder, Chem. Rev., 2010, 110, 1348.
29. H. S. Shin, Y. S. Jang, Y. Lee, Y. Jung, S. B. Kim, H. C.
Choi, Adv. Mater., 2007, 19, 2873.
30. J. Safari, S.H. Banitaba, S. D. Khalili, Ultrason. Sonochem.,
2013, 20, 401.
31. J. Safari, S. H. Banitaba, Sh. Dehghan Khalili, Ultrason
Sonochem., 2012, 19, 1061.
70 32. (a) A. Ziarati, J. SafaeiꢀGhomi, S. Rohani. Ultrason
Sonochem., 2013, 20, 1069; R. Katoh, Y. Tasaka, E.
Sekreta, M. Yumura, F. Ikazaki, Y. Kakudate, S. Fujiwara,
Ultrason Sonochem., 1999, 6, 185.
5
10
15
20
65
33. B. Datta, M. A. Pasha, Ultrason Sonochem., 2013, 20, 303.
7. (a) J. S. Yadav, B. V. Subba Reddy, K. Bhaskar Reddy, K. S. 75 35. F. Mohandes, M. SalavatiꢀNiasari, Ultrason Sonochem.,
Raj, A. R. Prasad, J Chem Soc Perkin Trans., 2001, 1, 1939;
(b) I. Saxena, D. C. Borah, J. C. Sarma, Tetrahedron Lett.,
2005, 46, 1159; (c) J. C. Bussolari, P. A. McDonnell, J Org
Chem., 2000, 65, 6777.
2013, 20, 354.
36. J. Safari, Z. Zarnegar, C. R, Chimie., DOI:
10.1016/j.crci.2013.01.019.
37. J. Safari, Z. Zarnegar, Ultrason. Sonochem., 2013, 20, 74.
8. (a) C. O. Kappe, D. Kumar, R. S. Varma, Synthesis., 1999, 80 38. L. Konga, X. Lub, W. Zhang, J Solid State Chem., 2008, 181,
1799; (b) E. H. Hu, D. R. Sidler, U. H. Dolling, J Org Chem.,
1998, 63, 3454.
25 9. (a) J. T. Li, J.F. Han, J. H. Yang, T. S. Li, Ultrason Sonochem.,
2003, 10, 119; (b) H. R. Memarian, M. Soleymani, Ultrason
Sonochem., 2011, 18, 745.
10. D. Alessandro, M. Alessandro, Tetrahedron Lett., 2001, 42,
7975.
30 11. B. C. Ranu, A. Hajra, S. S. Dey, Org Process Res Develop.,
2002, 6, 817.
628.
39. R. J. Kalbasi, A. M. Massah, R. D. Daneshvarnejad, Appl clay
sci., 2012, 55, 1.
40. A. Kuraitheerthakumaran, S. Pazhamalai, M. Gopalakrishnan,
Arab J Chem., 2011, Doi:10.1016/j.arabjc.2011.06.005
41. J. Azizian, A. A. Mohammadi, A. R. Karimi, M. R.
Mohammadizadeh, Appl Catal A: Gen., 2006, 300, 85.
42. J. Mondal, T. Sen, A, Bhaumik, Dalton Trans., 2012, 41,
6173.
85
90
12. (a) M. Kidwai, S. Bala, A. D. Mishra, Ind. J. Chem. B., 2004,
43, 2485; (b) J. Mondal, T. Sen, A. Bhaumik, Dalton Trans.,
2012, 41, 6173; (c) F. Xu, D. Huang X. Lin, Y. Wang, Org.
35
Biomol. Chem., 2012, 10, 4467; (d) A. Pourjavadi, S. H.
Hosseini, R. Soleyman, J. Mol. Catal. A. Chem., 2012, 365,
55; (e) S. Saha, J. N. Moorthy, J. Org. Chem., 2011, 76, 396.
13. (a) A. Corma, Chem Rev., 1997, 97, 2373; (b) J.H. Clark, D.J.
Macquarrie, Chem Soc Rev., 1996, 303.
40 14. K. K. Senapati, C. Borgohain, P. Phukan, J. Mol. Catal. A.
Chem., 2011, 339, 24.
15. C. W. Lim, I. S. Lee, Nano Today., 2010, 5, 412.
16. D. K. Yi, S. S. Lee, J. Y. Ying, Chem. Mater., 2006, 18, 2459.
17. A. H. Lu, W. C. Li, N. Matoussevitch, et al. Chem.Commun.,
45 2005, 1, 98.
18. D. Tasis, N. Tagmatarchis, A. Bianco, M. Prato, Chem. Rev.,
2006, 106, 1105.
19. Z. M. Liu, B. X. Han, Adv. Mater., 2009, 21, 825.
20. C. Q. Li, N. J. Sun, J. F. Ni, J et al. J. Solid State Chem.,
50 2008, 181, 2620.
21. K. K. Senapati, S. Roy, C. Borgohain, P. Phukan, J. Mol.
Catal. A: Chem., 2012, 352, 128.
22. D. Lee, J. Lee, H. Lee, S. Jin, T. Hyeon, B.M. Kim, Adv.
Synth. Catal., 2006, 348, 41.
55 23. R. AbuꢀRezig, H. Alper, D. Wang, M.L. Post, J. Am. Chem.
Soc. 2006, 128, 5279.
24. E. Karaoğlu, A. Baykal, H. Erdemi, L. Alpsoy, H. Sözeri, J.
Alloys Compd. 2011, 509, 9218.
4
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 5 of 15
RSC Advances
View Article Online
DOI: 10.1039/C3RA43014F
Table 1. Screening of iron catalysts for the formation of 4a.a
Entry
1
Catalyst (g)
Time (min)
Yield (%)
FeCl3.6H2O (0.03)
45
35
2
3
4
5
6
7
8
9
10
FeCl2ꢁ4H2O (0.03)
bulk Fe3O4 (0.03)
nanoꢀFe3O4 (0.03)
MWCNTs
Fe3O4ꢀMWCNTs (0.03)
Fe3O4ꢀMWCNTs (0.02)
Fe3O4ꢀMWCNTs (0.025)
Fe3O4ꢀMWCNTs (0.035)
None
45
40
35
40
35
35
35
35
120
25
40
50
35
75
50
62
75
ꢀ
a Under ultrasonic waves at 40 ◦C in EtOH.
5

RSC Advances
Page 6 of 15
View Article Online
DOI: 10.1039/C3RA43014F
Table 2. The effect of solvent and temperature on the synthesis of 4a.
Entry
Solvent
CH2Cl2
CH3CN
DMF
PhMe
THF
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
T/◦C
40
40
40
40
40
40
30
45
50
55
60
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
50
35
35
35
40
35
40
20
20
20
20
25
65
67
70
45
75
58
85
98
98
97
10
11
6
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 7 of 15
RSC Advances
View Article Online
DOI: 10.1039/C3RA43014F
Table 3. Synthesis of dihydropyrimidinones (thiones) catalyzed with Fe3O4ꢀMWCNTs in EtOH under ultrasound irradiation at
50 ◦C.
M.p (◦C)
Ref.
Entry
Ar
X
R1 Product
Time (min)
Yield (%)
Foun
Reporte
1
2
3
4
5
6
7
8
Ph
3ꢀClꢀC6H4
O
O
O
O
S
S
O
S
OEt
4a
4b
4c
4d
4e
4f
4g
4h
4i
20
25
20
20
20
30
20
25
25
25
98
98
97
96
93
90
96
94
90
88
205ꢀ206
195ꢀ196
222ꢀ224
215ꢀ217
205ꢀ206
151ꢀ152
213ꢀ214
220ꢀ221
169ꢀ170
210ꢀ212
204ꢀ206
39
40
40
41
39
39
39
39
39
39
OEt
OEt
OEt
OEt
OEt
Me
Me
Me
Me
194ꢀ196
222ꢀ224
216ꢀ218
206ꢀ207
150ꢀ152
212ꢀ215
220ꢀ222
168ꢀ170
210ꢀ212
3ꢀNO2ꢀC6H4
2ꢀTiophen
Ph
4ꢀOMeꢀC6H4
Ph
Ph
9
10
4ꢀOMeꢀC6H4
3ꢀNO2ꢀC6H4
S
S
4j
7

RSC Advances
Page 8 of 15
View Article Online
DOI: 10.1039/C3RA43014F
O
Ar
X
O
O
O
1
Fe3O4ꢀMWCNT
+
+
NH
R
H2N
NH2
R
Ar
H
)))), EtOH, 50°C
N
H
X
2
3
4
Ar= Aryle, Hetero aryle; X= O, S; R = Me, OEt
Scheme 1. Synthesis of dihydropyrimidinones under ultrasound irradiatin.
8
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 9 of 15
RSC Advances
View Article Online
DOI: 10.1039/C3RA43014F
Scheme 2. Simplified schematic representation of the preparation of Fe3O4ꢀMWCNTs.38
9

RSC Advances
Page 10 of 15
View Article Online
DOI: 10.1039/C3RA43014F
Scheme 3. Catalytic cycle for the Biginelli condensation reaction.
10 | Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 11 of 15
RSC Advances
View Article Online
DOI: 10.1039/C3RA43014F
(b)
(a)
Fig. 1. XRD scattering patterns of: (a) functionalized CNTs; (b) Fe3O4ꢀMWCNTs composites.
11

RSC Advances
Page 12 of 15
View Article Online
DOI: 10.1039/C3RA43014F
(a)
(b)
(c)
Fig. 2. Images of the samples (a) TEM of the pristine MWCNTs, (b) and (c) SEM of Fe3O4ꢀMWCNTs.
12 | Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 13 of 15
RSC Advances
View Article Online
DOI: 10.1039/C3RA43014F
40
30
20
10
0
-10
-20
-30
-40
-10000 -8000 -6000 -4000 -2000
0
2000 4000 6000 8000 10000
Applied Field(Oe)
Fig. 3. Magnetization curve for the Fe3O4ꢀMWCNTs at room temperature.
13

RSC Advances
Page 14 of 15
View Article Online
DOI: 10.1039/C3RA43014F
100
98
96
94
92
90
88
86
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Run
Fig. 4. Reusability and recycling of nanocatalyst for synthesis of 4a under ultrasound irradiation.
14 | Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 15 of 15
RSC Advances
View Article Online
DOI: 10.1039/C3RA43014F
Graphical Abstract
Biginelli reaction on Fe3O4-MWCNT nanocomposite: excellent reactivity and facile
recyclability of the catalyst combined with ultrasound irradiation
Javad Safari, Zohre Zarnegar
O
Ar
X
O
O
O
1
Fe3O4-CNT
+
+
NH
R
H2N
NH2
R
Ar
H
)))), EtOH, 50°C
N
H
X
2
3
4
Ar= Aryle, Hetero aryle; X= O, S; R = Me, OEt