Silica-bonded N-propyl sulfamic acid as an efficient recyclable catalyst for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones under heterogeneous conditions

Article abstract of DOI:10.1016/j.cclet.2013.12.022

Silica-bonded N-propyl sulfamic acid (SBNPSA) catalyzed one-pot three component Biginelli condensation of different substituted aromatic aldehydes with ethyl acetoacetate and urea/thoiurea to the respective 3,4- dihydropyrimidin-2-(1H)-ones and thiones in

Full text of DOI:10.1016/j.cclet.2013.12.022

Chinese Chemical Letters 25 (2014) 469–473
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Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Silica-bonded N-propyl sulfamic acid as an efficient recyclable catalyst
for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones under
heterogeneous conditions
*
Srinivasa Rao Jetti , Anjna Bhatewara, Tanuja Kadre, Shubha Jain
Laboratory of Heterocycles, School of Studies in Chemistry & Biochemistry, Vikram University, Ujjain, Madhya Pradesh, 456010, India
A R T I C L E I N F O
A B S T R A C T
Article history:
Silica-bonded N-propyl sulfamic acid (SBNPSA) catalyzed one-pot three component Biginelli
condensation of different substituted aromatic aldehydes with ethyl acetoacetate and urea/thoiurea
to the respective 3,4-dihydropyrimidin-2-(1H)-ones and thiones in environment friendly procedure is
described. The facile reaction conditions, simple isolation and purification procedures of this method
make it a good option for the synthesis of dihydropyrimidinones.
Received 14 October 2013
Received in revised form 24 November 2013
Accepted 5 December 2013
Available online 24 December 2013
ß 2013 Srinivasa Rao Jetti. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Keywords:
Silica-bonded N-propyl sulfamic acid
3,4-Dihydropyrimidin-2-(1H)-ones
Multi component reactions
Heterogeneous catalysis
1. Introduction
InCl3 [12], LaCl3 [13,14], lanthanide triflate [15], H2SO4 [16], ceric
ammonium nitrate (CAN) [17], Mn(OAc)3 [18], ion-exchange resin
Dihydropyrimidinones (DHPMs) and their derivatives have
recently attracted great attention in synthetic organic chemistry
due to their pharmacological and therapeutic properties, such as
antibacterial and antihypertensive activity as well as behaving as
[19],
(BMImBF4) [20], BiCl3 [21], LiClO4 [22], InBr3 [23], FeCl3 [24],
ZrCl4 [25], Cu(OTf)2 [26], Bi(OTf)3 [27], Silica gel-supported
1-n-butyl-3-methyl
imidazolium
tetrafluoroborate
L-
pyrrolidine-2-carboxylic acid-4-hydrogen sulfate [28], SBA-15
sulfonic acid [29], silica sulfuric acid [30], PEG–SO3 [31], p-
dodecylbenzenesulfonic acid (DBSA) [32], etc. have been found to
be effective. Many of these methods involve expensive reagents,
stoichiometric amounts of catalysts, strongly acidic conditions,
long reaction times, unsatisfactory yields and incompatibility with
other functional groups. Therefore, the development of a neutral
alternative would extend the scope of the Biginelli reaction.
The heterogeneous catalysts, useful in making the organic
transformations eco-friendly and economically viable, are now in
high demand in academic laboratories and industries. Several
heterogeneous catalysts are thus finding increasing applications in
the field of catalysis [33]. Solid acid-based catalysts have offered
simpler, more reactive and more benign alternatives than their
homogeneous counterparts [34]. The expensive, organic polymer
chain in traditional polymer supported catalysts has now been
replaced by a silica chain having a covalently anchored organic
spacer to create organic-inorganic hybrid (interphase) catalysts
[35]. In these heterogeneous catalysts, the reactive centers are
highly mobile similar to homogeneous catalysts and at the same
time they can be recovered. Based on these concepts, various types
calcium channel blockers, a-1a-antagonists [1] and neuropeptide
Y (NPY) antagonists [2]. The biological activity of some alkaloids
isolated recently has been attributed to a dihydropyrimidinone
moiety [3]. The first synthesis of these compounds, reported by
Biginelli [4] more than a century ago, makes use of the three
components, one-pot condensation of a
b-ketoester, an aldehyde
and urea under strongly acidic conditions [5]. However, this
method suffers from low yields in the case of substituted aromatic
and aliphatic aldehydes [6]. Owing to the versatile biological
activity of dihydropyrimidinones, development of an alternate
synthetic methodology is of paramount importance.
In recent years, several synthetic procedures for the preparation
of DHPMs have been reported including classical conditions with
microwave irradiation [7] and by using Lewis acids, as well as
protic acids and silica supported solid acids as promoters. Such
promoters as conc. HCl [8], BF3ÁOEt2 [9], PPE [10], KSF clay [11],
*
Corresponding author.
E-mail address: srinujetti479@gmail.com (S.R. Jetti).
1001-8417/$ – see front matter ß 2013 Srinivasa Rao Jetti. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.12.022

470
S.R. Jetti et al. / Chinese Chemical Letters 25 (2014) 469–473
on Merck 60 F-254 silicagel gel plates. Products obtained are all
known compounds and were identified by comparing their
physical and spectral data with those reported in the literature.
2.2. Catalyst preparation
To a mixture of 3-aminopropylsilica 1 (5 g) in chloroform
(20 mL), chlorosulfonic acid (1 g, 0.6 mL) was added dropwise at
0 8C over 2 h. After addition was complete, the mixture was stirred
for 2 h until HCl gas evolution stopped. Then, the mixture was
filtered and washed with ethanol (30 mL) and dried at room
temperature to obtain silica-bonded N-propyl sulfamic acid (2) as a
cream colored powder (5.13 g). The nitrogen content of 3-
aminopropylsilica (1) and sulfur content of silica-bonded N-propyl
sulfamic acid (2) determined by conventional elemental analysis
were 5.13% and 9.29%, respectively.
Scheme 1. Preparation of silica-bonded N-propyl sulfamic acid (2).
of functionalized, sulfonic acid silica, as Bronsted acid sites, have
been considered in selectively catalyzing chemical transforma-
tions can be created [35,36].
2.3. General procedure for the synthesis of 3,4-dihydropyrimidin-
The utility of heterogeneous catalysts can be improved by using
high surface area materials, since the transport of the reactants to
the active site on the particle surface can be enhanced by this
method. Mesoporous silicas functionalized with sulfonic acid
groups have been obtained by the condensation of alkoxy silanes
and 3-mercapto propyl trimethoxy silanes, which are further
oxidized to obtain their corresponding propyl sulfonic acid groups
[37]. Shi et al. [38] had recently reported on a sulfonic acid-
functionalized polypropylene fiber catalyst which was prepared by
a simple process from inexpensive, readily available polypropylene
fiber and the performance of the catalyst was tested in the
successful completion of the Biginelli reaction. Excellent results, in
terms of chemical yields, catalyst levels, work-up procedures and
catalytic recyclability, are reported on the metal-free catalyzed,
one-pot synthesis of a number of substituted 3,4-dihydropyrimi-
din-2-(1H)-ones/-thiones (DHPMs).
2(1H)-ones and -thiones 4(a–n) using SBNPSA as catalyst
To a mixture of ethyl acetoacetate 1 (2.5 mmol), aromatic
aldehyde 2 (2.5 mmol) and urea or thiourea 3 (2.5 mmol) in a
round bottomed flask (100 mL), ethanol (15 mL) was added
(Scheme 2). The reaction mixture was stirred at r.t. for 5 min
and then catalyst 2 (0.2 g, 2.4 mol% of SO3H) was added and the
stirring was continued at 80 8C for an appropriate time. After
completion of the reaction (monitored by TLC), the reaction
mixture was filtered off. The product was obtained after removal of
the solvent under reduced pressure followed by treatment with
water and finally crystallization from EtOH. The residue was
washed with warm ethanol, dried at 100 8C for 2 h and re-used for
eight times without loss of significant activity.
5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimi-
din-2(1H)-one (4a): 1H NMR (DMSO-d6):
d 1.09 (t, 3H, J = 7.1 Hz,
In this report, we describe a one-pot method for the Biginelli
reaction using silica-bonded N-propyl sulfamic acid (SBNPSA) as a
recyclable, heterogeneous, solid acid catalyst. The reaction
involves the synthesis of a variety of 3,4-dihydropyrimidin-
OCH2CH3), 2.25 (s, 3H, CH3), 3.97 (q, 2H, J = 7.1 Hz, OCH2), 5.05
(d, 1H, J = 2.15 Hz, –CH), 7.28 (m, 5H, Ar–H), 7.75 (s, 1H, NH), 9.20
(s, 1H, NH); 13C NMR (DMSO-d6):
d 14.11, 17.94, 54.91, 60.05,
100.95, 112.85, 113.05, 125.15, 125.81, 129.05, 131.20, 150.16,
155.47, 163.81; IR (KBr, cmÀ1): nmax 3240, 1722, 1638; ESI-MS
261 (M + H); HRMS calcd. for C14H16N2O3: 260.1161, found:
260.1163.
2(1H)-ones by the reaction of b-ketoester with urea (or thiourea)
and various aromatic aldehydes in ethanol at reflux temperatures.
The preparation procedure for catalyst 2 is outlined in Scheme 1
with slight modification than the previously reported method [35].
5-(Ethoxycarbonyl)-4-(4-nitrophenyl)-6-methyl-3,4-dihydro-
pyrimidin-2(1H)-one (4b): 1H NMR (DMSO-d6):
d 1.11 (t, 3H, J =
2. Experimental
7.04 Hz, OCH2CH3), 2.32 (s, 3H, CH3), 4.03 (q, 2H, J = 7.12 Hz,
OCH2CH3), 5.78 (d, 1H, J = 2.28 Hz, –CH), 7.51 (d, 2H, J = 9.18 Hz,
Ar–H), 7.69 (s, 1H, NH), 8.16 (d, 2H, J = 9.16 Hz, Ar–H), 9.05
2.1. Materials and methods
(s, 1H, NH); 13C NMR (DMSO-d6):
d 14.22, 18.71, 55.81, 60.15,
Reagents and solvents were of analytical grade or were purified
by standard procedures prior to use. The 1H NMR spectra were
recorded on Varian FT-200 MHz (Gemini) in DMSO-d6. Chemicals
101.60, 118.15, 130.37, 138.34, 152.26, 153.41, 159.15, 165.85; IR
(KBr, cmÀ1): nmax 3235, 1740, 1631; ESI-MS 306 (M + H); HRMS
calcd. for C14H15N3O5: 305.1012, found: 305.1010.
shifts are reported in parts per million (
d) relative to tetra-
5-(Ethoxycarbonyl)-4-(3-chlorophenyl)-6-methyl-3,4-dihydro-
methylsilane ( 0.0) as an internal standard. Mass spectra were
d
pyrimidin-2(1H)-one (4c): 1H NMR (DMSO-d6):
d 1.10 (t, 3H, J =
7.14 Hz, OCH2CH3), 2.28 (s, 3H, CH3), 3.88 (q, 2H, J = 7.16 Hz,
OCH2CH3), 5.65 (d, 1H, J = 2.28 Hz, –CH), 7.25–7.41 (m, 4H,
recorded under electron impact at 70 eV on Finnigan Mat 1020B
mass spectrometer. Melting points were recorded on Buchi 535
and are uncorrected. Thin-layer chromatography was performed
Scheme 2. SBNPSA catalyzed synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones.

S.R. Jetti et al. / Chinese Chemical Letters 25 (2014) 469–473
471
Ar–H), 7.61 (s, 1H, NH), 9.11 (s, 1H, NH); 13C NMR (DMSO-d6):
14.17, 18.60, 55.70, 60.20, 101.52, 126.312, 127.92, 128.42, 130.29,
135.51, 142.21, 153.23, 159.32, 165.75; IR (KBr, cmÀ1):
max 3234,
1724, 1631; ESI-MS 295 (M + H); HRMS calcd. for C14H15ClN2O3:
294.0771, found: 294.0772.
d
nmax 3240, 1720, 1640, 1595, 1530; ESI-MS 277 (M+H); HRMS
calcd. for C14H16N2O2S: 276.0932 found: 276.0932.
5-(Ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihy-
dropyrimidin-2(1H)-thione (4k): 1H NMR (DMSO-d6):
d 1.17 (t,
3H, J = 7.11 Hz, OCH2CH3), 2.37 (s, 3H, CH3), 4.12 (s, 3H, –OCH3),
4.15 (q, 2H, J = 7.10 Hz, OCH2CH3), 5.44 (d, 1H, J = 2.15 Hz, –CH),
7.11 (d, 2H, J = 8.15 Hz, Ar–H), 7.37 (d, 2H, J = 8.11 Hz, Ar–H), 7.84
n
5-(Ethoxycarbonyl)-4-(4-chlorophenyl)-6-methyl-3,4-dihy-
dropyrimidin-2(1H)-one (4d): 1H NMR (DMSO-d6):
d 1.12 (t, 3H,
J = 7.14 Hz, OCH2CH3), 2.30 (s, 3H, CH3), 3.91 (q, 2H, J = 7.16 Hz,
OCH2CH3), 5.70 (d, 1H, J = 2.28, –CH), 7.21 (d, 2H, J = 9.18, Ar–H),
(s, 1H, NH), 9.43 (s, 1H, NH); 13C NMR (DMSO-d6):
d
14.32, 18.05,
55.24, 55.49, 60.45, 101.84, 114.32, 127.74, 137.25, 147.15, 159.45,
165.62, 182.48; IR (KBr, cmÀ1):
max 3240, 1725, 1635, 1574, 1540;
7.69 (s, 1H, NH), 7.94 (d, 2H, J = 9.18, Ar–H), 9.16 (s, 1H, NH); 13
C
n
NMR (DMSO-d6)
d
: 14.18, 18.62, 55.72, 60.21, 101.55, 118.17,
ESI-MS 307 (M+H); HRMS calcd. for C15H18N2O3S: 306.1038,
found: 306.1040.
130.32, 142.29, 152.31, 153.39, 159.17, 165.83; IR (KBr, cmÀ1):
nmax 3225, 1720, 1615; ESI-MS 295 (M+H); HRMS calcd. for
5-(Ethoxycarbonyl)-4-(3-nitrophenyl)-6-methyl-3,4-dihydro-
pyrimidin-2(1H)-thione (4l): 1H NMR (DMSO-d6):
d 1.15 (t, 3H,
C
14H15ClN2O3: 294.0771, found:294.0773.
5-(Ethoxycarbonyl)-4-(3-bromophenyl)-6-methyl-3, 4-dihy-
J = 7.14 Hz, OCH2CH3), 2.27 (s, 3H, CH3), 4.02 (q, 2H, J = 7.11 Hz,
OCH2CH3), 5.81 (d, 1H, J = 2.06 Hz, –CH), 7.23–7.37 (m, 4H, Ar–H),
dropyrimidin-2(1H)-one (4e): 1H NMR (DMSO-d6):
d 1.02 (t, 3H,
J = 7.05 Hz, OCH2CH3), 2.30 (s, 3H, CH3), 3.75 (q, 2H, J = 7.05 Hz,
OCH2CH3), 5.41 (d, 1H, J = 2.25 Hz, –CH), 7.05–7.34 (m, 4H, Ar–H),
7.78 (s, 1H, NH), 9.34 (s, 1H, NH); 13C NMR (DMSO-d6):
d 14.14,
18.60, 55.64, 60.21, 101.34, 126.25, 128.02, 129.32, 130.75,
135.65, 144.34, 160.40, 165.64, 182.65; IR (KBr, cmÀ1): nmax
3245, 1725, 1632, 1575, 1545; ESI-MS 322 (M+H); HRMS calcd. for
7.51 (s, 1H, NH), 9.05 (s, 1H, NH); 13C NMR (DMSO-d6):
d 14.16,
18.59, 55.74, 60.18, 101.57, 126.35, 127.82, 128.48, 130.32, 135.59,
143.94, 153.21, 159.30, 165.74; IR (KBr, cmÀ1): nmax 3212, 1731,
1620; ESI-MS 339 (M+H); HRMS calcd. for C14H15BrN2O3:
338.0266, found: 338.0268.
5-(Ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihy-
dropyrimidin-2(1H)-one (4f): 1H NMR (DMSO-d6)
d: 1.15 (t, 3H,
C
14H15N3O4S: 321.0783, found: 321.0781.
3. Results and discussion
In the FT-IR spectrum of catalyst (2), the major peaks for silica
(SiO2) are broad non-symmetric Si–O–Si stretching from
1300 cmÀ1 to 1010.6 cmÀ1 and symmetric Si–O–Si stretching near
880–852.5 cmÀ1. For sulfuric acid functional group, the FT-IR
absorption range of the O–S–O asymmetric and symmetric
stretching modes lie in 1170 and 1060 cmÀ1, respectively. FT-IR
spectrum shows the overlap asymmetric and symmetric stretching
bands of SO2 with Si–O–Si stretching bands in the silica
functionalized alkyl-sulfuric acid. The spectrum also shows a
J = 7.12 Hz, OCH2CH3), 2.33 (s, 3H, CH3), 3.78 (s, 3H, –OCH3), 4.06
(q, 2H, J = 7.12 Hz, OCH2CH3), 5.34 (d, 1H, J = 2.28 –CH), 6.82 (d, 2H,
J = 8.60, Ar–H), 7.22 (d, 2H, J = 8.60, Ar–H), 7.76 (s, 1H, NH), 9.26 (s,
1H, NH); 13C NMR (DMSO-d6)
d:14.32, 18.80, 55.23, 55.40, 60.17,
101.68, 114.06, 127.97, 136.22, 146.16, 153.59, 159.30, 165.87; IR
(KBr, cmÀ1): nmax 3232, 1720, 1638; ESI-MS 291 (M+H); HRMS
calcd. for C15H18N2O4: 290.1267, found: 290.1265.
5-(Ethoxycarbonyl)-4-(2,4-dichlorophenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (4 g): 1H NMR (DMSO-d6):
d 1.18
broad OH stretching absorption around 3600–2520 cmÀ1
.
(t, 3H, J = 7.23 Hz, OCH2CH3), 2.64 (s, 3H, CH3), 4.07 (q, 2H,
J = 7.24 Hz, OCH2CH3), 5.92 (d, 1H, J = 2.30 Hz, –CH), 7.21–7.51 (m,
The BET surface area and total pore volume of Silica-bonded N-
propylsulfamic acid (2) were found to be 2.91 m2 gÀ1 and
0.456 cm3 gÀ1, respectively.
In order to optimize the reaction conditions, the synthesis of
compound 4f was used as a model reaction. Therefore, a mixture of
3H, Ar–H), 7.69 (s, 1H, NH), 9.16 (s, 1H, NH); 13C NMR (DMSO-d6):
d
14.20, 18.60, 55.75, 60.24, 101.56, 127.82, 128.91, 129.52, 131.29,
142.52, 143.25, 153.23, 159.32, 165.75; IR (KBr, cmÀ1):
max 3255,
n
1731, 1651; ESI-MS 329 (M+H); HRMS calcd. for C14H14Cl2N2O3:
328.0381, found: 328.0379.
ethyl
acetoacetate
(2.5 mmol),
4-methoxybenzaldehyde
(2.5 mmol), and urea (2.5 mmol) with different amounts of
SBNPSA (Table 1) was selected. The efficiency of the reaction is
mainly affected by the amount of the catalyst. No product could be
detected in the absence of this catalyst even after 12 h (entry 1),
while good results were obtained in the presence of SBNPSA. The
optimal amount of the catalyst was 0.2 g (entry 5), whereas a
higher amount of the catalyst did not increase the yield noticeably
(entry 6).
5-(Ethoxycarbonyl)-4-(3-nitrophenyl)-6-methyl-3,4-dihydro-
pyrimidin-2(1H)-one (4 h): 1H NMR (DMSO-d6):
d 1.12 (t,
3H, J = 7.10 Hz, OCH2CH3), 2.25 (s, 3H, CH3), 3.65 (q, 2H,
J = 7.14 Hz, OCH2CH3), 5.71 (d, 1H, J = 2.20 Hz, –CH), 7.21–7.54
(m, 4H, Ar–H), 7.74 (s, 1H, NH), 9.26 (s, 1H, NH); 13C NMR (DMSO-
d6):
d 14.16, 18.59, 55.74, 60.18, 101.57, 126.25, 127.45, 128.74,
130.56, 135.46, 144.81, 153.64, 159.45, 165.30; IR (KBr, cmÀ1):
nmax 3229, 1724, 1630; ESI-MS 306 (M+H); HRMS calcd. for
14H15N3O5: 305.1012, found: 305.1013.
As can be seen from (Table 2) compared to the classical Biginelli
method, one additional important feature of the present protocol is
the ability to tolerate variations in all three components
C
5-(Ethoxycarbonyl)-4-(4-flurophenyl)-6-methyl-3,4-dihydro-
pyrimidin-2(1H)-one (4i): 1H NMR (DMSO-d6):
d 1.15 (t, 3H,
J = 7.16 Hz, OCH2CH3), 2.41 (s, 3H, CH3), 4.12 (q, 2H, J = 7.17 Hz,
OCH2CH3), 5.88 (d, 1H, J = 2.25 Hz, –CH), 7.69 (s, 1H, NH), 7.81
(d, 2H, J = 8.5 Hz, Ar–H), 7.94 (d, 2H, J = 9.18 Hz, Ar–H), 9.16 (s, 1H,
Table 1
Influence of the amount of SBNPSA on the synthesis of 4f at reflux temperature.a
NH); 13C NMR (DMSO-d6):
d
14.18, 18.62, 55.72, 60.21, 101.55,
121.19, 132.42, 144.20, 153.39, 157.25, 159.17, 165.83; IR (KBr,
cmÀ1):
max 3250, 1741, 1654; ESIMS 279 (M+H); HRMS calcd. for
14H15FN2O3: 278.1067, found: 278.1069.
5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimi-
din-2(1H)-thione (4j): 1H NMR (DMSO-d6):
1.11 (t, 3H,
Entry
Catalyst
Amount of catalyst (g)
Time (h)
Yield (%)b
n
1
2
3
4
5
6
None
–
12
10
8
<10
57
C
SBNPSA
SBNPSA
SBNPSA
SBNPSA
SBNPSA
0.050
0.1
71
0.150
0.2
6
83
d
4
94
J = 7.21 Hz, OCH2CH3), 2.29 (s, 3H, CH3), 4.12 (q, 2H,
J = 7.24 Hz, OCH2), 5.16 (d, 1H, J = 2.05 Hz, –CH), 7.51 (m, 5H,
0.250
4
95
a
The reaction conditions: ethyl acetoacetate 1 (2.5 mmol), 4-methoxybenzal-
dehyde 2 (2.5 mmol) and urea 3 (2.5 mmol) in ethanol (15 mL) under reflux
temperature.
Ar–H), 7.81 (s, 1H, NH), 9.41 (s, 1H, NH); 13C NMR (DMSO-d6):
d
14.23, 17.91, 54.85, 60.15, 100.90, 112.84, 115.12, 125.15,
126.85, 129.64, 131.45, 150.27, 162.63, 180.25; IR (KBr, cmÀ1):
b
Isolated yields.

472
S.R. Jetti et al. / Chinese Chemical Letters 25 (2014) 469–473
Table 2
SBNPSA catalyzed synthesis of 3,4-dihydropyrimidin-2-(1H)-ones and thiones.
Entry
Ar
X
Producta
Yield (%)b
M.p (8C)
Found
Reportedc
1
2
C6H5
O
O
O
O
O
O
O
O
O
S
4a
4b
4c
4d
4e
4f
95
92
90
91
92
94
91
93
93
95
94
91
201–03
209–10
192–93
214–15
185–17
200–201
248–50
227–28
183–85
209–10
151–52
205–07
202–03
208–10
191–93
215–16
184–16
199–201
249–51
227–29
185–86
208–10
150–52
206–08
4-NO2-C6H4
3-Cl-C6H4
4-Cl-C6H4
3-Br-C6H4
4-OCH3-C6H4
2,4-Cl-C6H3
3-NO2-C6H4
4-F-C6H4
3
4
5
6
7
4g
4h
4i
8
9
10
11
12
C6H5
4j
4-OCH3-C6H4
3-NO2-C6H4
S
4k
4l
S
a
All the products known, characterized by spectral analysis and by comparison
of their physical properties with those of the authentic compounds.
b
Isolated yields.
c
Melting points of compounds are consistent with reported values [10,26,27,39].
Fig. 1. Recycling of SBNPSA for model reaction.
Table 3
Acknowledgments
Comparison our results with results obtained by other groups.
Catalyst
Conditions
Yield (%)
70–88
Time (h)
48
Reference
[12]
The authors are thankful to Madhya Pradesh Council of Science
& Technology (MPCOST, Bhopal) for their financial support.
Authors are also thankful to Deputy Director and Head, SAIF,
Central Drug Research Institute (CDRI), Lucknow, for providing
elemental analysis and spectral data and the Department of
Chemistry, Vikram University, Ujjain, for extending laboratory
facilities and IR data.
Montmorillonit
KSF
Solvent-free/130 8C
Yb(III)-resin
Ceric ammonium
nitrate
Solvent-free/120 8C
Sonication/MeOH
63–80
84–92
48
[20]
[18]
5–7
ZrCl4
Reflux EtOH
Reflux EtOH/N2
Reflux EtOH
83–94
82–95
90–95
5–6
[26]
In(OTf)3
4–13.5
3–4
[40]
SBNPSA
This work
References
simultaneously. Most importantly, many of the pharmacological
relevant substitution patterns on the aromatic ring could be
introduced without any reduction in efficiency. Aromatic alde-
hydes carrying either electron-donating or electron-withdrawing
substituents afforded high yields of products in high purity.
Thiourea has been used with similar success to provide the
corresponding dihydropyrimidin-2(1H)-thiones (4j–4l), which are
also of much interest with regard to biological activity. Thus,
variation in all three components has been accomplished
conveniently.
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this new procedure.

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