β-Cyclodextrin-propyl sulfonic acid: A new and eco-friendly catalyst for one-pot multi-component synthesis of 3,4-dihydropyrimidones via Biginelli reaction

Article abstract of DOI:10.1016/j.tet.2015.05.028

β-Cyclodextrin-propyl sulfonic acid (β-CD-PSA) is reported as a new and eco-friendly catalyst for the synthesis of 3,4-dihydropyrimidinones from one-pot multi-component reaction of aromatic aldehydes, 1,3-dicarbonyl compounds and urea or thiourea under so

Full text of DOI:10.1016/j.tet.2015.05.028

Accepted Manuscript
β-Cyclodextrin-propyl sulfonic acid: a new and eco-friendly catalyst for one-pot multi-
component synthesis of 3, 4-dihydropyrimidones via Biginelli reaction
Kai Gong, Hualan Wang, Shuxin Wang, Xiaoxue Ren
PII:
S0040-4020(15)00686-9
10.1016/j.tet.2015.05.028
TET 26746
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 March 2015
Revised Date: 6 May 2015
Accepted Date: 8 May 2015
Please cite this article as: Gong K, Wang H, Wang S, Ren X, β-Cyclodextrin-propyl sulfonic acid: a new
and eco-friendly catalyst for one-pot multi-component synthesis of 3, 4-dihydropyrimidones via Biginelli
reaction, Tetrahedron (2015), doi: 10.1016/j.tet.2015.05.028.
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ACCEPTED MANUSCRIPT
Graphical Abstract
β-Cyclodextrin-propyl sulfonic acid: a new
and eco-friendly catalyst for one-pot multi-
component synthesis of 3, 4-
Leave this area blank for abstract info.
dihydropyrimidones via Biginelli reaction
*, a
b
a
a
Kai Gong , Hualan Wang , Shuxin Wang and Xiaoxue Ren
a
School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, China
Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Hangzhou
b
Normal University, Hangzhou, 311121, China
R1
R1
3
HO S
O
C
O
O
O
O
H
O
OH
OH
R
2
NH
O
O
NH
2
H
3
N
R
3
R2
H
R : Cl, NO , CH , et al
R : C H O, CH
R : O, S
3
H
2
N
R
3
1
2
3
H C
O
3
2
2
5
3
HO S
3

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
β-Cyclodextrin-propyl sulfonic acid: a new and eco-friendly catalyst for one-pot
multi-component synthesis of 3, 4-dihydropyrimidones via Biginelli reaction
a,
b
a
a
Kai Gong, ∗ Hualan Wang, Shuxin Wang and Xiaoxue Ren
a
School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, China
Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Hangzhou Normal University, Hangzhou, 311121, China
b
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
β-Cyclodextrin-propyl sulfonic acid (β-CD-PSA) is reported as a new and eco-friendly catalyst
for the synthesis of 3, 4-dihydropyrimidinones from one-pot multi-component reaction of
aromatic aldehydes, 1, 3-dicarbonyl compounds and urea or thiourea under solvent-free
conditions. The present methodology offers several advantages, such as shorter reaction time,
high yields, mild reaction conditions and a simple work-up procedure. Furthermore, β-CD-PSA
is inexpensive, biodegradable, and can be reusable. It could be reused six-times without a
significant loss of catalytic activity.
Available online
Keywords:
Multicomponent reactions
One-pot synthesis
2
009 Elsevier Ltd. All rights reserved.
3
, 4-Dihydropyrimidones
Biginelli reaction
7
8
9
10
11
1
. Introduction
SiO -H SO , Fe O -MWCNT, CaF2, TMSCl,
NbCl5,
SBA-15-
mesoporous
2
2
4
3
4
12
13
14
15
Ce(C H SO ) ,
ErCl ,
Gly(NO3),
bentonite/PS-SO H,
IBX,
1
2
25
16
3 3
3
Multi-component reactions (MCRs) have been proven to be
17
18
PrSO H,
Mo/γ-Al O ,
3
2 3
3
remarkably successful in generating molecular complexity in a
single synthetic operation, and shown simple procedures, high
atom-economy and high selectivity due to the formation of
carbon-carbon and carbon-heteroatom bonds in one-pot. Owing
to their bond forming efficient, MCRs are the preferred approach
19
20
21
22
SiO -H PO , PS-PEG-SO H, Amberlyst-70, Carbon-SO H,
2
2
3
3
3
23
24
25
Fe O /PAA-SO H, nano-γ-Fe O -SO H, Fe O @Nb O , and
so on. DHPMs have also been synthesized under microwave
3
4
3
2
3
3
3
4
2
5
19, 26
1
8, 27
and ultrasound irradiations . However, these methodologies
suffer from one or more shortcomings such as unsatisfactory
yields, prolonged reaction times, used of toxic organic solvents,
requirement of excess of reagents or catalysts and harsh reaction
conditions. Therefore, the development of an eco-friendly and
efficient methods using novel catalyst for Biginelli reaction is
still in great demand.
2
in the drug discovery process. The Biginelli reaction is one of
the most important MCRs that offer an efficient route to produce
multi-functionalized 3, 4-dihydropyridin-2(1H)-ones/3, 4-
dihydropyridin-2(1H)-thiones (DHPMs). DHPMs and their
derivatives have been receiving considerable attention because
they exhibit a wide of biological and pharmacological properties,
such as antiviral, antibacterial, antitumor, anticancer,
antihypertensive and most importantly, as calcium channel
modulators. The great potential of DHPMs in pharmaceutical
fields has accordingly triggered growing interest in their
synthetic study.
Cyclodextrins (CDs) are macrocyclic oligosaccharides
possessing hydrophobic cavities that bind substrates selectively
via noncovalent interactions, and this outstanding property
enables them to be used in various applications. Native β-CD
and chemical modification of CDs has been employed as a phase
transfer catalyst in organic synthesis reactions, such as Azide-
3
28
The most simple and straightforward produce, reported by
Biginelli more than 100 years ago, involves the one-pot three-
component condensation of an aldehyde, α, β-ketoester and urea.
Unfortunately, this original protocol suffers from the harsh
conditions, long reaction times and frequently low yields. This
has led to the development of new improved methodologies for
the Biginelli reaction, involving the use of a number of catalysts
29
alkyne cycloaddition reaction, aza-Michael addition, and so on.
Recently, hydrochloric-β-CD, sulfonated β-CD and β-CD
30
31
32
4
have been used as catalyst for the Biginelli reaction. These
methods made some achievements, but there suffer from one or
more shortcomings such as required a co-catalyst, used
hazardous and corrosive regent and prolonged reaction times.
Based on these issues, develop green method exploit new
functionalized CDs is necessary.
5
6
such as ionic liquids or supported ionic liquids, H PMo VO ,
—
4
11
40
——
∗
Corresponding author. Tel.: +86-510-85197769; fax: +86-510-85197769; e-mail: kingong222@163.com

2
Tetrahedron
In this context, we wish to report
A
a
C
β
C
-cy
E
c
P
lo
T
de
E
xt
D
rin MAPS
NU
A
fr
S
omCR2 mIPol
T
% (Table 1, entry 7-8). Next, the reaction was
functionalized by propyl sulfonic acid (β-CD-PSA), which is
obtained from available and inexpensive staring materials. We
introduce β-CD-PSA successfully as an efficient and eco-friendly
catalyst for the one-pot synthesis of 3, 4-dihydropyrimidinones
under solvent-free conditions with good to excellent yields
carried out in various solvents as well as under solvent-free
conditions. Typically, solvents such as ethanol, H O, CH CN,
2
3
THF, DMF, EtOAc, and ClCH CH Cl were chosen for
2
2
comparison. As a result, the yields were not ideal, only range
from 49% to 84%. For this reaction, it proceeded most readily to
give the highest yield of the product 4a under solvent-free
conditions (Table 1, entry 9-15). Therefore, the optimal
conditions were determined as that the reaction was catalyzed by
(Scheme 1). To the best of our knowledge, this is the first report
on the use of β-CD-PSA in Biginelli reaction.
2
mol% β-CD-PSA under solvent-free conditions at 80 ℃.
R
1
Table 1. Optimization of reaction conditions for the synthesis
of 4a
R
1
a
O
H
O
1
β-CD-PSA
R
2
NH
O
NH
2
H C
N
H
R3
R
2
3
H
O
O
C
1
a
4
H
2
N
R
3
β-CD-PSA
H
3
C
O
O
C
R : Cl, NO , CH , et al
O
NH
1
2
3
2
3
R : C H O, CH
2
2
5
3
NH2
O
H
3
N
O
R : O, S
3
H
H
2
N
O
H
3
O
Scheme 1 One-pot synthesis of 3, 4-dihydropyrimidinones
catalyzed by β-CD-PSA
4a
2a
3a
b
Entry
Solvents
T (℃)
Amount
Time(min)
Yield(%)
2
. Results and discussion
(mol%)
c
1
2
3
4
5
6
7
8
9
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
rt.
80
--
120
120
120
30
20
20
20
20
20
20
30
30
30
30
30
NR
The detailed preparation for β-CD-PSA is shown in Scheme 2.
c
First, commercially available β-CD was reacted with 1, 3-
propane sultone in NaOH solution to afford sulfopropyl ether β-
cyclodextrin (SPE-β-CD), which was further treated with acidic
resin to give β-CD-PSA. β-CD-PSA was identified by FT-IR
--
2
2
2
2
1
3
2
2
2
2
2
2
2
NR
rt.
18
65
91
92
85
93
76
84
58
62
49
70
78
50
1
13
spectroscopy, H NMR, C NMR and elemental analysis. The
80
average degree of substitution for β-CD-PSA was estimated from
1
100
80
H NMR spectroscopy, and it was about 5.04. The loading
amount of propyl sulfonic acid per g catalyst was also determined
by elemental analysis, which is 2.45 mmol/g. The radio of C/S
was also used to calculate the average degree of substitution. It
was 4.99. The results from different methods are in agreement
with each other.
80
H
2
O
80
1
1
1
1
1
1
0
1
2
3
4
5
CH
3
CH
2
OH
Cl
reflux
reflux
reflux
reflux
80
ClCH
2
CH
2
EtOAc
THF
CH
3
CN
DMF
80
a
Reaction condition: benzaldehyde (2 mmol), ethyl acetoacetate (2 mmol)
and urea (2.4 mmol), catalyst: β-CD-PSA, solvent-free or solvent (5 mL).
b
c
Isolated yield. No reaction was observed.
To compare the efficiency of our catalyst with the reported
catalysts for the synthesis of DHPMs, we have tabulated the
results of these catalysts to promote the synthesis of compounds
4a from benzaldehyde, ethyl acetoacetate and urea, in Table 2.
The results showed that β-CD-PSA is a better catalyst with
respect to reaction times and yields of the products.
Scheme 2 synthesis of β-CD-PSA
In order to optimize the conditions, we carried out the reaction
of benzaldehyde (1a), ethyl acetoacetate (2a) and urea (3a) as a
model reaction. The results are summarized in Table 1. Initially,
when the model reaction was carried without any catalysts at
room temperature and 80 ℃, no desirable product was observed
even after prolonging reaction time. It indicated that the catalyst
should be absolutely necessary for this reaction (Table 1, entry 1-
With the optimal conditions, we tended to investigate the
generality and limitation of this method. The reaction of various
aromatic aldehydes, 1, 3-dicarbonyl compounds and urea or
thiourea were explored under the optimal conditions to produce a
series of structurally diverse DHPMs. The results are
summarized in Table 3. Most of the reactions proceeded very
efficiently. Various aromatic aldehydes containing electron-
withdrawing and electron-donating substituents at ortho, meta or
para-positions show equal ease towards the product formation in
high yields ranging from 82% to 93% (Table 3, entry 1-10). We
2
). The same reaction was performed in presence of 2 mol% β-
CD-PSA at room temperature, 50 ℃, 80 ℃ and 100 ℃, the
yields were 18%, 65% 91% and 92%, respectively (Table 1,
entry 3-6). No improvements in the reaction rates and yields were
observed from increasing and decreasing the amount of β-CD-

3
also found that ethyl acetoacetate and acetyl
used to synthesize DHPMs successfully also with high yields
Table 3, entry 11-16). Thiourea was applied in the reaction
A
ac
C
eto
C
neEPco
T
ul
E
d
D
be MAin
N
ste
U
ad
S
o
C
f
R
ur
I
ea which successfully led to the corresponding
P
T
DHPMs in good to excellent yields (Table 3, entry 17-24).
(
Table 2. Comparison of different catalysts for the synthesis of 4a
Entry
Catalyst
β-CD-PSA
β-CD
Condition
Time
20 min
3 h
Yield(%)
Ref.
a
1
2
3
4
5
6
7
8
9
Solvent-free/80 ℃
Solvent-free/100 ℃
Solvent-free/100 ℃
EtOH/ reflux
91
This work
a
85
32
31
30
24
20
23
18
5b
22
21
19
13
5e
15
9
a
β-CD-SO
β-CD-HCl
nano-γ-Fe -SO
PS-PEG-SO
Fe /PAA-SO
Bentonite/PS-SO
[(CH NC SO H][HSO
Carbon-SO
Amberlyst-70
3
H
2 h
83
a
8 h
92
a
2
O
3
3
H
Solvent-free/60 ℃
Dioxane/80 ℃
3 h
95
a
3
H
10 h
86
a
3
O
4
3
H
Solvent-free/rt.
120 min
30 min
10 min
4 h
90
a
3
H
Solvent-free/120 ℃
89
a
3
)
3
3
H
6
3
4
]
H
CH
H
2
3
2
O/90 ℃
CN/80 ℃
O/90 ℃
94
a
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
3
H
90
c
3 h
81
a
SiO
2
-H
2
PO
3
Solvent-free/60 ℃
Solvent-free/120 ℃
Solvent-free/75 ℃
2.5 h
30 min
45 min
2.5 h
2 h
92
b
ErCl
3
92
a
Mn@PMO-IL
IBX
97
a
H
2
O/60 ℃
90
c
CaF
2
EtOH/ reflux
EtOH/80 ℃
98
a
Ce(C12
H25SO
3
)
3
8 h
93
12
8
c
Fe
3
O
4
-MWCNT
EtOH/ ultrasound Irradiation/50 ℃
20 min
98
a
b
c
Isolated yield. GC/MS data. Not mark.
a
Table 3. Synthesis of DHPMs catalyzed by β-CD-PSA under solvent-free conditions
b
Entry
R
1
R
2
R
3
Product
4a
4b
4c
time
Yield(%)
1
2
3
4
5
6
7
8
9
H
C
C
C
C
C
C
C
C
C
C
2
2
2
2
2
2
2
2
2
2
H
H
H
H
H
H
H
H
H
H
5
5
5
5
5
5
5
5
5
5
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
S
20
20
20
20
20
20
15
25
25
20
30
30
25
30
30
30
30
30
30
25
25
25
30
30
91
90
86
92
84
82
93
80
88
90
88
85
90
86
76
81
86
90
85
91
88
90
83
78
p-Cl
o-Cl
p-NO
2
4d
4e
m-NO
o-NO
p-CH
2
2
4f
3
4g
4h
4i
p-OH
p-OCH
3
1
0
1
p-N(CH
3
)
4j
1
H
CH
CH
CH
CH
CH
CH
3
4k
4l
1
1
1
1
1
1
1
1
2
2
2
2
2
2
3
4
5
6
7
8
9
0
1
2
3
4
p-Cl
3
3
3
3
3
p-NO
p-CH
p-OH
2
4m
4n
4o
4p
4q
4r
3
p-OCH
3
H
C
C
C
C
C
C
C
C
2
2
2
2
2
2
2
2
H
H
H
H
H
H
H
H
5
O
O
O
O
O
O
O
O
p-Cl
o-Cl
5
5
5
5
5
5
5
S
S
4s
p-NO
2
S
4t
m-NO
2
S
4u
4v
4w
4x
p-CH
p-OCH
p-OH
3
S
3
S
S
a
Reaction condition: aromatic aldehydes (2 mmol), 1, 3-dicarbonyl compounds (2 mmol), urea or thiourea (2.4 mmol), β-CD-PSA (0.02 mmol), 80 ℃.
Isolated yield.
b

4
Tetrahedron
ACCEPTED MANUSCRIPT
To increase the catalyst worth, its recyclability was tested upon
the synthesis of compound 4a. After completion of the reaction,
water was added and the reaction mixture was filtered. The
solution of β-CD-PSA was dried under vacuum for recycling
catalyst in next run. The procedure was repeated and the results
indicated that the catalyst could be recycled six-times with only a
slight loss of catalytic activity (Fig. 1).
R
1
R
1
R1
NH2
H
2
N
R
3
ΟΗ
H
+
3
H
NH
H
NH
H
OH
-
2
H O
H
2
N
R
3
H
2
N
R
3
H+
I
II
O
OH
C
R
1
R
2
R2
1
H
3
C
O
H
3
O
H
O
2
III
R
1
R
R
1
1
O
O
O
-H
2
O
H
R
2
NH
R
2
NH
R
NH
2
H
3
C
R
3
O
2
H N
H
3
C
N
H
R
3
H
C
N
H
R
3
3
OH
4
IV
Fig. 1 Reusability of β-CD-PSA for the synthesis of 4a
Scheme 3 Plausible mechanism for the synthesis of DHPMs
catalyzed by β-CD-PSA
The recovered catalyst after six runs had no obvious change in
structure, referring to FT-IR spectrum in comparison with fresh
catalyst (Fig. 2). Furthermore, the loading amount of propyl
sulfonic acid after using six-times was determined by elemental
analysis, and which was 2.38 mmol/g. These results indicate that
the catalyst was very stable and could endure this reaction’s
conditions.
3
. Conclusion
In summary, we have developed a facile, efficient and eco-
friendly procedure for the one-pot synthesis of 3, 4-
dihydropyrimidinones from a multi-component reaction of
aromatic aldehydes, 1, 3-dicarbonyl compounds and urea or
thiourea using β-CD-BSA as a powerful catalyst under solvent-
free conditions. β-CD-BSA is easily prepared from commercially
available starting materials. The notable advantages of this
method are high catalytic activity, short reaction time, excellent
yields, reusability of catalyst, simple work-up and mild reaction
conditions. Thus, this procedure is a better and more practical
alternative for green chemistry.
Fresh
Reused
4
. Experimental section
.1 General
Melting points were determined on an X6-data microscopic
4
melting points apparatus and were uncorrected. FT-IR spectra
were recorded on a BRUKER VECTER 22 (KBr). NMR spectra
were obtained from solution D O or DMSO-d with TMS as
3
500
3000
2500
2000
1500
1000
-
1
Wavenumber (cm )
2
6
internal standard using a BRUKER AVANCE III (400 MHz)
spectrometer. Elemental analysis was performed on an Elementar
VARIOEL III spectrometer.
Fig. 2 FT-IR spectrum comparison of the fresh catalyst and the
catalyst used after six-times
Although we have not established the mechanism of reaction
experimentally, a possible explanation is proposed in Scheme 3,
on the basis of the literature and substrate trends. The β-CD-PSA
as a BrØnsted acid participate in the reaction which activate the
aldehyde 1 followed by nucleophilic addition of urea or thiourea
4
.2 Synthesis of β-CD-PSA
First, β-CD (1 g) was dissolved in NaOH solution (5M, 10
mL) in a 50 mL round bottom flask at 75 ℃. To the solution, 1,
3-propane sultone (1.1 g) was added dropwise. Then the mixture
was stirred for 4 h. The reaction solution was cooled to room
temperature, which was adjusted to neutral using HCl solution (3
M). The mixture was dropped in ethanol to afford sulfopropyl
ether β-cyclodextrin (SPE-β-CD).
3
forming the N-acylimine intermediate I. Then the iminium
intermediate II generated, which is the key rate-determining step,
acts as an electrophile for the nucleophilic addition of the enol
form of the β-keto ester III. The ketone carbonyl of the resulting
open-chain of the resulting open-chain ureide adduct IV
undergoes intramolecular cyclocondensation with the urea NH2
followed by dehydration to give the cyclized product 4.
Second, the acidic resin was activated in a saturated aqueous
solution of NaCl for 1 day, followed by the treatment of 2.5 wt %
NaOH aqueous solution for 80 min, and then washed with
distilled water until pH 7.0, and finally it was treated with 5.0
wt % HCl aqueous solution for 12 h. Afterwards, the resin was
transferred to a column and washed with deionized water until
the eluent reached pH 7.0.

5
Lastly, the sodium salt of SPE-β-CD (0.5 g
A
) w
C
as
C
d
E
iss
P
o
T
lve
E
d
D
in MA
R
N
efe
U
re
S
nc
C
es
R
anIP
d notes
T
water (100 mL), and the solution was allowed to flow through the
acidic resin column at a speed of 20 drops per minute. The acidic
eluent was collected and then freeze-dried for 12 h to obtain β-
CD-PSA product.
1. (a) Zhu, J.; Bienaymé, H. Multicomponent Reactions, Wiley-
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FT-IR (KBr, cm-1): 3354, 2930, 2365, 1653, 1361, 1153,
1
1
030, 791, 700. H NMR (400 MHz, D O): δ 5.01-5.11 (m, C -
2
1
H), 3.49-3.8 (m, -OCH CH CH SO H and CH), 2.95 (s, -OCH
2
2
2
3
2
13
CH CH SO H), 1.98 (s, -OCH CH CH SO H). C NMR (101
2
2
3
2
2
2
3
MHz, D O): δ 80.92, 72.72, 72.00, 71.68, 69.48, 60.18, 47.91,
2
3
4
7.68, 24.50, 24.28. Anal. Found: C 33.52, S 7.834, H 6.67.
4
.3 General procedure for the synthesis of 3, 4-
1
043-1062. (c) Lal, J.; Gupta, S. K.; Thavaselvam, D.; Agarwal,
dihydropyrimidinones
D. D. Bioorg. Med. Chem. Lett, 2012, 22, 2872-2876. (d) Fátima,
Â.; Braga, T. C.; Neto, L. S.; Terra, B. S.; Oliveira, B.G.F.; Silva,
D. L.; Modolo, L. V. J. Adv. Res., 2015, doi:10.1016/j.jare.2014.
A mixture of aldehyde 1 (2 mmol), 1, 3-dicarbonyl
compounds (ethyl acetoacetate or acetylacetone, 2 mmol), urea or
thiourea (2.4 mmol), and β-CD-PSA (0.02 mmol) was stirred at
00 ℃ for the appropriate time (monitored by TLC). Then, water
5 mL) was added and the reaction mixture filtered. The solution
of β-CD-PSA was dried under vacuum for recycling catalyst in
next run. Pure 3, 4-dihydropyrimidinones were afforded by
evaporation of the solvent followed by recrystallization from
ethanol. All were characterized by spectral data and comparison
of their physical data with the literature.
1
0.006.
4
5
.
.
(a) Biginelli, P. Gazz. Chim. Ital., 1893, 23, 360-416. (b) Li, N.;
Chen, X. H.; Song, J.; Luo, S. W.; Fan, W.; Gong, L. Z. J. Am.
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K.; Awasthi, C. Tetrahedron, 2008, 64, 1420-1429. (d) Alvim, H.
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Abdelnur, P. V.; Silva, W. A.; Neto, B. A. D. ACS Catal., 2013, 3,
1
(
1
420-1430. (e) Elhamifar, D.; Nasr-Esfahani, M.; Karimi, B.;
1
13
The spectral (FT-IR, H NMR, C NMR) and analytical data
for some selected 1-amidoalkyl-2-naphthols are presented below:
Moshkelgosha, R.; Shábani, A. ChemCatChem, 2014, 6, 2593-
2599. (f) Elhamifar D.; Shábani, A. Chem. Eur. J., 2014, 20,
3
212-3217.
Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-
6. (a) Rafiee, E.; Shahbazi, F. J. Mol. Catal. A: Chem., 2006, 250,
57-61. (b) Maradur, S. P.; Gokavi, G. S.; Catal. Commun., 2007, 8,
5
-carboxylate (Table 3, entry 1): white crystals, mp.: 201-202 ℃.
-1
2
79-284.
7. Nandi, G. C.; Samai, S.; Singh, M. S. J. Org. Chem., 2010, 75,
785-7795.
Safari, J.; Zarnegar, Z. RSC Adv., 2013, 3, 17962-17967.
FT-IR (KBr, cm ): 3246, 3119, 2978, 1726, 1649, 1466, 1292,
1
1
1
3
2
223, 1094, 783, 700. H NMR (400 MHz, DMSO-d ) δ 9.21 (s,
6
7
H, NH), 7.75 (s, 1H, NH), 7.32 (m, 2H, ArH), 7.24 (m, ArH,
8
.
H), 5.14 (d, J= 3.2 Hz, 1H, CH), 3.98 (q, J = 7.1 Hz, 2H, CH ),
9. Chitra, S.; Pandiarajan, K. Tetrahedron Lett., 2009, 50, 2222-
2
13
.24 (s, 3H, CH ), 1.09 (t, J = 7.1 Hz, 3H, CH ). C NMR (101
2224.
3
3
1
1
0. Wan, J. P.; Pan, Y. J. Chem. Commun., 2009, 19, 2768-2770.
1. Cai, Y. F.; Yang, H. M.; Li, L.; Jiang, K. Z.; Lai, G. Q.; Jiang, J.
X.; Xu, L. W. Eur. J. Org. Chem., 2010, 26, 4986-4990.
MHz, DMSO-d ) δ 165.81, 152.61, 148.85, 145.33, 128.87,
6
1
27.75, 126.72, 99.70, 59.67, 54.42, 18.26, 14.55.
1
1
2. Qiu, Y.; Sun, H.; Ma, Z.; Xia, W. J. Mol. Catal. A: Chem., 2014,
5
-Acetyl-6-methyl-4-p-tolyl-3,4-dihydropyrimidin-2(1H)-one
3
92, 76-82.
(
Table 3, entry 14): white crystals, mp.: 168-170 ℃. FT-IR (KBr,
3. Oliverio, M.; Costanzo, P.; Nardi, M.; Rivalta, I.; Procopio, A.
-1
cm ): 3289, 1699, 1616, 1512, 1466, 1423, 1389, 1364, 1327,
ACS Sustainable Chem. Eng., 2014, 2, 1228-1233.
1
1
(
(
265, 1236, 1184, 1140, 1105, 999, 964, 793, 733, 685. H NMR
400 MHz, DMSO-d ) δ 9.17 (s, 1H, NH), 7.79 (s, 1H, NH), 7.12
s, 4H, ArH), 5.21 (d, J= 3.0 Hz, CH, 1H), 2.26 (m, 6H, Ar-CH
and CH CO), 2.08 (s, 3H, CH ). C NMR (101 MHz, DMSO-d6)
δ 194.79, 152.60, 148.43, 141.78, 136.97, 129.52, 126.83, 110.00,
4.01, 30.71, 21.12, 19.35.
14. Sharma, N.; Sharma, U. K.; Kumar, R.; Sinha, A. K. RSC Adv.,
2012, 2, 10648-10651.
1
6
5. Takale, S.; Parab, S.; Phatangare, K.; Pisal, R.; Chaskar, A. Catal.
Sci. Technol., 2011, 1, 1128-1132.
6. Karimi, B.; Mobaraki, A.; Mirzaei, H. M.; Zareyee, D.; Vali, H.
ChemCatChem., 2014, 6, 212-219.
3
13
3
3
1
5
17. Kouachi, K.; Lafaye, G.; Pronier, S.; Bennini, L.; Menad, S. J.
Mol. Catal. A: Chem., 2014, 395, 210-216.
1
Ethyl-4-(4-chlorophenyl)-6-methyl-2-thioxo-1,2,3,4-tetra-
hydropyrimidine-5-carboxylate (Table 3, entry 18): Light yellow
solid, mp.: 193-194 ℃. FT-IR (KBr, cm ): 3423, 3327, 2361,
672, 1574, 1458, 1327, 1283, 1198, 1119, 748, 669. H NMR
400 MHz, DMSO-d ) δ 10.41 (s, 1H, NH), 9.69 (s, 1H, NH),
.43 (d, J= 8.4 Hz, ArH, 2H), 7.22 (d, J = 8.4 Hz, 2H, ArH), 5.16
d, J= 3.4 Hz, 1H, CH), 4.00 (q, J= 6.9 Hz, CH , 2H), 2.29 (s, 3H,
8. Kalbasi, R. J.; Massah, A. R.; Daneshvarnejad, B. Appl. Clay Sci.,
2012, 55, 1-9.
-
1
19. Pramanik, M.; Bhaumik, A. ACS Appl. Mater. Interfaces, 2014, 6,
33−941.
0. Quan, Z. J.; Da, Y. X.; Zhang, Z.; Wang, X. C. Catal. Commun.,
009, 10, 1146-1148.
1
9
1
(
7
(
2
2
6
2
1. Chandak, H. S.; Lad, N. P.; Upare, P. P. Catal. Lett., 2009, 131,
2
469-473.
13
CH ), 1.09 (t, J= 7.1 Hz, 3H, CH ). C NMR (101 MHz, DMSO-
22. Konkala, K.; Sabbavarapu, N. M.; Katla, R.; Durga, N. Y. V.;
Reddy, V. K.; Devi, B. L. A. P.; Prasad, R. B. N. Tetrahedron
Lett., 2012, 53, 1968-1973.
2
2
3
3
d6) δ 174.69, 165.46, 145.87, 142.85, 132.73, 129.08, 128.79,
00.73, 100.00, 60.14, 53.90, 17.66, 14.48.
1
3. Zamani, F.; Izadi, E. Catal. Commun., 2013, 42, 104-108.
4. Kolvari, E.; Koukabi, N.; Armandpour, O. Tetrahedron, 2014, 70,
1383-1386.
Acknowledgments
2
2
5. Lima, C. G. S.; Silva, S.; Gonçalves, R. H.; Leite, E. R.; Schwab,
R. S.; Corrêa, A. G.; Paixão, M. W. ChemCatChem., 2014, 6,
We gratefully acknowledge the financial support from the
National Natural Science Foundation of China (NO. 51303069),
the Fundamental Research Funds for the Central Universities
3
455-3463.
6. Harikrishnan, P. S.; Rajesh, S. M.; Perumal, S.; Almansour, A. I.
Tetrahedron Lett., 2013, 54, 1076-1079.
(JUSRP11236).
27. Memarian, H. R.; Soleymani, M. Ultrason. Sonochem., 2011, 18,
45-752.
7

6
Tetrahedron
ACCEPTED MANUSCRIPT
2
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1
2
4
Rao, K. R. Tetrahedron Lett., 2006, 47, 2125-2127. (c) Kiasat, A.
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Nezhad, A.; Panahi, F. ACS Sustainable Chem. Eng., 2014, 2,
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Tetrahedron, 2013, 69, 8245-8249.
1
3
3
3
2
Supplementary Material
Supplementary related to this article can be found at…

ACCEPTED MANUSCRIPT
Supporting Information
β-Cyclodextrin-propyl sulfonic acid: a new and eco-friendly catalyst for one-pot
multi-component synthesis of 3, 4-dihydropyrimidones via Biginelli reaction
,
a
b
a
a
Kai Gong* , Hualan Wang , Shuxin Wang and Xiaoxue Ren
a
School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, China
b
Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of
Education, Hangzhou Normal University, Hangzhou, 311121, China
Table of Contents
Spectral data of β-CD-PSA and selected compounds ............................................ S1-S2
1
13
Copies of FT-IR, H and C NMR spectra of β-CD-PSA .................................... S3-S4
1
13
Copies of FT-IR, H and C NMR spectra of selected Compounds................... S4-S8
*
Corresponding author. Tel.: +86-510-85197769; fax: +86-510-85197769;
E-mail: kingong222@163.com.

ACCEPTED MANUSCRIPT
Spectral data of β-CD-PSA and selected compounds
Spectral data of β-CD-PSA
1
FT-IR (KBr, cm-1): 3354, 2930, 2365, 1653, 1361, 1153, 1030, 791, 700. H NMR
(
400 MHz, D O): δ 5.01-5.11 (m, C -H), 3.49-3.8 (m, -OCH CH CH SO H and CH),
2
1
2
2
2
3
1
3
2
.95 (s, -OCH CH CH SO H), 1.98 (s, -OCH CH CH SO H). C NMR (101 MHz,
2
2
2
3
2
2
2
3
D O): δ 80.92, 72.72, 72.00, 71.68, 69.48, 60.18, 47.91, 47.68, 24.50, 24.28.
2
Spectral data of selected compounds
Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate:
O
O
NH
N
O
H
-1
white crystals, mp.: 201-202 ℃. FT-IR (KBr, cm ): 3246, 3119, 2978, 1726, 1649,
1
1
7
3
466, 1292, 1223, 1094, 783, 700. H NMR (400 MHz, DMSO-d ) δ 9.21 (s, 1H, NH),
6
.75 (s, 1H, NH), 7.32 (m, 2H, ArH), 7.24 (m, ArH, 3H), 5.14 (d, J= 3.2 Hz, 1H, CH),
1
3
.98 (q, J = 7.1 Hz, 2H, CH ), 2.24 (s, 3H, CH ), 1.09 (t, J = 7.1 Hz, 3H, CH ). C
2
3
3
NMR (101 MHz, DMSO-d ) δ 165.81, 152.61, 148.85, 145.33, 128.87, 127.75,
6
1
26.72, 99.70, 59.67, 54.42, 18.26, 14.55.
Ethyl-4-(4-chlorophenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxyl
ate:
Cl
O
O
NH
N
S
H
S1

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-1
white crystals, mp.: 168-170 ℃. FT-IR (KBr, cm ): 3289, 1699, 1616, 1512, 1466,
1
1
423, 1389, 1364, 1327, 1265, 1236, 1184, 1140, 1105, 999, 964, 793, 733, 685. H
NMR (400 MHz, DMSO-d ) δ 9.17 (s, 1H, NH), 7.79 (s, 1H, NH), 7.12 (s, 4H, ArH),
6
5
.21 (d, J= 3.0 Hz, CH, 1H), 2.26 (m, 6H, Ar-CH and CH CO), 2.08 (s, 3H, CH ).
3 3 3
1
3
C NMR (101 MHz, DMSO-d ) δ 194.79, 152.60, 148.43, 141.78, 136.97, 129.52,
6
1
26.83, 110.00, 54.01, 30.71, 21.12, 19.35.
5
-Acetyl-6-methyl-4-p-tolyl-3,4-dihydropyrimidin-2(1H)-one:
O
NH
N
O
H
-1
Light yellow solid, mp.: 193-194 ℃. FT-IR (KBr, cm ): 3423, 3327, 2361, 1672,
1
1
1
2
574, 1458, 1327, 1283, 1198, 1119, 748, 669. H NMR (400 MHz, DMSO-d ) δ
6
0.41 (s, 1H, NH), 9.69 (s, 1H, NH), 7.43 (d, J= 8.4 Hz, ArH, 2H), 7.22 (d, J = 8.4 Hz,
H, ArH), 5.16 (d, J= 3.4 Hz, 1H, CH), 4.00 (q, J= 6.9 Hz, CH , 2H), 2.29 (s, 3H,
2
13
CH ), 1.09 (t, J= 7.1 Hz, 3H, CH ). C NMR (101 MHz, DMSO-d ) δ 174.69, 165.46,
3
3
6
1
45.87, 142.85, 132.73, 129.08, 128.79, 100.73, 100.00, 60.14, 53.90, 17.66, 14.48.
S2

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13
Copies of FT-IR, H and C NMR spectra of selected Compounds
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Fig. S1 FT-IR spectrum of β-CD-BSA in KBr
1
Fig. S2 H NMR spectrum of β-CD-BSA in D O
2
S3

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Fig. S3 C NMR spectrum of β-CD-BSA in D O
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Fig. S4 FT-IR spectrum of compound 4a
S4

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Fig. S5 H NMR spectrum of compound 4a
1
3
Fig. S6 C NMR spectrum of compound 4a
S5

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Fig. S7 FT-IR spectrum of compound 4n
1
Fig. S8 H NMR spectrum of compound 4n
S6

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Fig. S9 C NMR spectrum of compound 4n
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Fig. S10 FT-IR spectrum of compound 4r
S7

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Fig. S11 H NMR spectrum of compound 4r
1
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Fig. S9 C NMR spectrum of compound 4r
S8