SiO2-CuCl2: An efficient and recyclable heterogeneous catalyst for one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones

Article abstract of DOI:10.1016/j.molcata.2014.05.022

Silica supported copper(II) chloride is prepared as a green heterogeneous catalyst for the synthesis of biologically and pharmaceutically important 3,4-dihydropyrimidin-2(1H)-ones under microwave and thermal conditions. The catalyst has been characterized

Full text of DOI:10.1016/j.molcata.2014.05.022

Accepted Manuscript
Title: SiO -CuCl : An efficient and recyclable heterogeneous
2
2
catalyst for one-pot synthesis of
,4-dihydropyrimidin-2(1H)-ones
3
Author: Gurpreet Kour Monika Gupta Satya Paul Rajnikant
Vivek. K. Gupta
PII:
S1381-1169(14)00219-2
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2014.05.022
MOLCAA 9122
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
13-3-2014
21-5-2014
22-5-2014
Please cite this article as: G. Kour, M. Gupta, S. Paul, Vk.K. Gupta, SiO -CuCl :
2
2
An efficient and recyclable heterogeneous catalyst for one-pot synthesis of 3,4-
dihydropyrimidin-2(1H)-ones, Journal of Molecular Catalysis A: Chemical (2014),
http://dx.doi.org/10.1016/j.molcata.2014.05.022
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1
SiO -CuCl : An efficient and recyclable heterogeneous
2
2
catalyst for one-pot synthesis of 3,4-dihydropyrimidin-
2(1H)-ones
1
1
1
2
2
Gurpreet Kour , Monika Gupta* , Satya Paul , Rajnikant and Vivek. K. Gupta
1
Department of Chemistry, University of Jammu, Jammu Tawi-180006, India
2
Post-Graduate Department of Physics and Electronics, University of Jammu, Jammu Tawi-
80006, India
1
Abstract
Silica supported copper (II) chloride is prepared as a green heterogeneous catalyst for the
synthesis of biologically and pharmaceutically important 3,4-dihydropyrimidin-2(1H)-ones
under microwave and thermal conditions. The catalyst has been characterized by various
instrumental techniques such as FTIR, SEM, TEM, TGA and AAS. In addition, products are
1
13
characterized by HNMR, IR, CNMR and mass spectral data. The reaction of
m-
nitrobenzaldehyde, ethylacetoacetate and urea produced 5-(Ethoxycarbonyl)-4-(3-
nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2-(1H)-one and its structure has been determined
using X-ray crystallography which also showed the inter-molecular H-bonding packing
arrangement of molecules.
Keywords
Dihydropyrimidinones; diphenic acid; silica; copper (II) chloride; microwave; thermal;
acetonitrile
Email: monika.gupta77@rediffmail.com
*
Corresponding author
Page 1 of 28

2
1
. Introduction
What makes researchers looking into the field of catalysis with continuous discovering every
newer aspect of it is enfolded in its applicability in industry. Catalysis comprises a new way to
meet the demands of energy and sustainability for the synthesis of organic compounds in the
most economical way along with ecological concern [1, 2]. Supporting transition metals onto
the solid supports provide a large surface area for reactants to get adsorbed, come closer and
get able to react faster followed by desorption of reactants leaving the catalyst to be
regenerable. Among transition metals, copper as a choice to explore comes from its mild
nature, easy availability and less toxic nature.
Synthesizing heterocyclic bioactive molecules by replacing the old classical methods with
new eco-friendly techniques like as with heterogeneous catalysts represents one of the most
vibrant research areas in organic chemistry. Dihydropyrimidinones (Bignelli compounds) and
their derivatives belong to an important class of heterocyclic compounds that have attracted
attention due to their interesting pharmacological and biological profiles[3]. Their
applications in the field of drug research have stimulated the development of a wide range of
synthetic methods for their preparation and chemical transformations. Aryl-substituted 3,4-
dihydropyrimidin--2(1H)-one and their derivatives are an important class of substances in
organic and medicinal chemistry. These derivatives have remarkable pharmacological
properties such as calcium channel blockers, α-1a-antagonists, HIV inhibitors of gp-120-CD4,
anti-hypertensive, anti-viral, anti-tumor, anti-bacterial, anti-fungal, anti-cancer, anti-
inflammatory agents[4,5], melanin-concentrating hormone receptor antagonist[6] and
neuropeptide Y (NPY) antagonist[7]. These can be used as therapeutics in cardiovascular
diseases, angina pectoris, or benign prostatic hyperplasia[8]. Moreover, its derivatives are
found in a large family of natural products with broad biological activities. Various marine
Page 2 of 28

3
alkaloids containing the dihydropyrimidinone moiety have interesting biological properties,
such as batzelladine alkaloids that are potent HIV gp-120- CD4 inhibitors[9].
Many nucleosides that have 5-substituted pyrimidine moiety have been shown to inhibit the
growth of murine mammary carcinoma virus. Pyrimidine cores with extended π-systems
possess interested fluorescent properties, and similar compounds are useful in the
development of advanced electronic and photonic materials[10,11,12].
In history, the Biginelli reaction represents a classical approach for the preparation of 3,4-
dihydropyrimidin-2(1H)-ones by the one-pot condensation of an aromatic aldehyde, β-
ketoester and urea in the presence of a mineral acid catalyst and alcohol solvent. Various
reagents have been used for the synthesis of dihydropyrimidin-2-(1H)-ones such as
chloroacetic acid[13], InBr
3 3 2
[14]; BF OEt in combination with transition metal salts[15],
amberlyst 15[16], ZnCl [17], SnCl /ChCl[18], SiO -Cl[19] and copper triflates[20]. But the
2
2
2
reported reagents are associated with certain drawbacks such as larger reaction times, tedious
work-up procedures and even handling of catalyst. In order to overcome these drawbacks,
copper(II) chloride in combination with silica has been used as heterogeneous catalyst under
thermal and microwave conditions for one-pot synthesis of Biginelli compounds as shown in
Scheme 1.
Condition A
SiO / CuCl
2
2
Diphenic acid
R
H
O
2
O
O
EtOOC
o
solvent-free, 40 C
NH
RCHO
1
H N
2
NH2
OEt
Condition B
N
O
SiO / CuCl
2
2
H
Microwave, acetonitrile
3
4
a-j
o
8
0 C
Scheme 1
Page 3 of 28

4
2. Experimental
2
.1 Preparation of catalyst- silica supported copper (II) chloride [SiO
2 2
- CuCl ]
In order to support copper(II) chloride onto silica, the silica gel (15 g, K 100) was activated by
adding silica gel (15g, K 100) to a solution of HCl : H
2
O (1:1, 300 mL) in a round-bottom
o
flask (500 mL) and the reaction mixture was stirred at 120 C for 12 h. The activated silica
was filtered at pump, washed with water till washings were neutral and dried in an oven at
o
1
10 C for 5 h. The yield obtained was 13.8g. Then the activated silica (10 g, K 100) was
stirred with anhydrous CuCl (0.2 g) in dry ether (50 ml) at room temperature for 4 h. The
2
catalyst was filtered, washed with water till washings were colourless and dried in an oven at
o
9
0-100 C for 5 h. The yield obtained was 8.6g.
Scheme 1: A schematic approach for the synthesis of silica supported copper(II)chloride
Page 4 of 28

5
2
.2 Characterization of Catalyst
To conform the support of metal onto silica, the catalyst was thoroughly characterized by
various instrumental techniques like FTIR, TGA, SEM, TEM and AAS and the results has
been given as under:
FTIR
-
1
The FTIR spectrum of catalyst showed strong absorption peaks at 473 cm (Si-O-Si bending
-
1
-1
vibration), 805 cm (symmetric stretching) & 1098 cm (anti-symmetric stretching of Si-O),
-
1
-1
1
631 cm (bending vibration of physically adsorbed water and 3433 cm due to Si-OH
-
1
stretching vibration). For SiO -CuCl , an additional peak was observed at 669 cm which
2
2
corresponds to Cu-Cl stretching vibrations (Fig. 1).
TGA
To check the thermal stability of the catalyst (SiO
2
-CuCl
2
), a thermo-gravimetric analysis
o
(
TGA) was done which showed a slight weight loss upto 225 C followed by continuous
o
weight loss upto 718.3 C. The analysis indicated the stability of catalyst up to a range of 0-
o
2
49.1 C and hence is safe to be used in carrying out the reaction under chosen conditions
o
o
(
room temperature, 40 C and 80 C) (Fig. 2).
Scanning Electron Microscope (SEM)
Further to study the microstructure and morphology of the catalyst (SiO -CuCl ), a study of
2
2
Scanning Electron Microscope (SEM) has been performed. The SEM images of the catalyst
showed that the surface of SiO -CuCl was found to be a fine powder with porous structure
and it was observed that copper chloride particles are adsorbed onto the surface of silica (Fig.
).
2
2
3
Page 5 of 28

6
Transmission Electron Microscope (TEM)
A TEM has also been performed to see the morphology of metal particles. The TEM
micrographs indicated that Cu is uniformly distributed onto the surface of silica (Fig. 4). The
mean diameter was found to be 2 nm which confirms the nano-size nature of the catalyst. It
was found that no bulk aggregation of the metal occurred indicating that the Cu was finally
dispersed onto the surface of silica. The TEM micrograph (a) infers formation of nano copper
(
average size 2 nm) and from (b) it is inferred that SiO -CuCl shows the formation of
2 2
molecular sieves which offers entrapment of metal particles inside these sieves of silica and
thus displaying a host-guest relationship.
Atomic Absorption Spectrophotometric Analysis (AAS)
The amount of copper loaded onto the surface of silica was determined by AAS analysis. The
3 2 2
catalyst was stirred in dil. HNO and then subjected to AAS analysis. SiO -CuCl contained
0
.015 g of Cu per gram of catalyst.
2 2
Fig. 1 FTIR of SiO -CuCl
Page 6 of 28

7
2 2
Fig. 2 TGA of SiO -CuCl
(
a)
(b)
2
-CuCl (a) 100, 000 X (b) 600 X
Fig. 3 SEM images of SiO
2
Page 7 of 28

8
(a) An average size of 2nm
(b) Molecular sieve formation
Fig. 4 TEM micrographs of SiO -CuCl
2
2
2.3 Instrumentation
All melting points were taken on Perfit melting point apparatus and are uncorrected. IR
spectra were recorded using KBr disc on Perkin Elmer FTIR spectrophotometer. The mass
1
spectra were recorded on Esquire 3000 Bruker Daltonics spectrometer (ESI). H NMR spectra
6
were recorded in DMSO-d on Bruker Avance III (400 MHz) spectrometer using TMS as an
internal standard. TGA was recorded on Linseis STA PT-1000 (Germany) Thermal Analyser
o
with heating rate of 10 C/ min. FTIR was recorded on Perkin Elmer-Spectrum RX-IFTIR
o
spectrophotometer. X-ray diffractograms were recorded in 2θ range of 10-80 C on a
Panalytical’s X’Pert Pro X-ray diffraction spectrometer using CuKα radiation.The atomic
absorption spectrometric analysis (AAS) was done on Avanta-M atomic absorption
spectrometric manufactured by GBC scientific agencies. SEM images were recorded on
JEOL JSM-6400 Scanning Electron Microscope. TEM images were recorded on Technai G2
2
0 S Twin (FEI Netherland) Transmission Electron Microscope. Microwave reactions were
carried out in microwave of CEM Discover of MaTHews. NC made in USA with model:
Page 8 of 28

9
Discover System and model no.: 908010 having volts: 180/264 VAC, max. current: 6.3 A,
freq: 50/60 Hz and max. power: 700 w.
2.4 General procedure for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones catalyzed by
SiO / CuCl
2
2
Condition A (under thermal conditions)
All starting materials were purchased from Aldrich and were used without any further
purification. In a typical experiment, a mixture of aldehyde (0.5 mmol), ethyl acetoacetate
(
0.5 mmol), urea (0.5 mmol), diphenic acid (0.02g) were taken in a round-bottom flask (100
o
mL) and SiO / CuCl (0.05g) was added to it and stirred at 40 C in solvent-free conditions
2
2
for appropriate time (Table 3). To this reaction mixture, 25-30 ml of ethylacetate was added
and heated on a water bath. This reaction mixture was filtered while hot under vacuum using a
sintered glass crucible. Washings of hot water were given to remove the water soluble
diphenic acid and impurities. To the resultant, anhydrous sodium sulphate was added and kept
for an overnight. Then, resultant was filtered to remove hydrated sodium sulphate and the
filterate was concentrated to get the crude product. The product thus obtained was purified
through crystallization using ethylacetate. The reaction was monitored through TLC in 15%
1
ethyl acetate and petroleum ether. The structures of the products were confirmed by IR, H
1
3
NMR, C NMR and mass spectral data and comparison with authentic samples available
commercially or prepared according to the literature methods.
o
Condition B (under microwave conditions, temp: 80 C, pressure: 250, power: 200, stirring:
high)
In a microwave tube, aldehyde (0.5 mmol), ethyl acetoacetate (0.5 mmol), urea (0.5 mmol)
o
and SiO
2
/ CuCl
2
(0.05g) were taken and stirred at 80 C in acetonitrile for appropriate time in
a microwave (Table 3). To this reaction mixture, 25-30 ml of ethylacetate was added and
heated on a water bath. This reaction mixture was filtered while hot under vacuum using a
sintered glass crucible. Washings of distilled water were given to remove the water soluble
Page 9 of 28

10
impurities. The resultant was dried over anhydrous sodium sulphate and was filtered to
remove hydrated sodium sulphate. The filterate was concentrated to get the crude product
which was purified by crystallization using ethylacetate. The reaction was monitored through
TLC in 15% ethyl acetate and petroleum ether. The structures of the products were confirmed
1
13
by IR, H NMR, C NMR and mass spectral data and comparison with authentic samples
available commercially or prepared according to the literature methods.
3
. Results and Discussion
3.1 Optimization
To study the catalytic activity of silica supported copper (II) chloride, the synthesis of 3,4-
dihydropyrimidin-2(1H)-ones via one-pot condensation of aldehydes, ethyl acetoacetate and
o
urea was carried out under two set of conditions such as Condition A (Thermal): at 40 C
using 0.02 g of diphenic acid in solvent-free conditions on an oil-bath and Condition B
o
(
Microwave): without diphenic acid in acetonitrile at 80 C. To select the appropriate
2 2
conditions for the catalytic activity of SiO / CuCl , benzaldehyde (0.5 mmol) was selected as
the test substrate and the reaction was carried out in different conditions as shown in Table 1
among which the studied conditions gave the best results. To test the generality of the newly
developed protocol for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones various substituted
aromatic aldehydes, hetero-aromatic aldehydes and aliphatic aldehydes were taken. Aromatic
aldehydes, hetero-aromatic aldehydes gave good to excellent yields (Table 3) but with
aliphatic aldehydes the yields were very low with exception of formaldehyde as substrate
which gave an exceptionally good result. In order to make comparative study, microwave
o
conditions were also tried for the reaction using SiO
2
/ CuCl
2
in acetonitrile at 40 C but the
product formed was impossible to separate from the catalyst so the reaction was carried out in
o
acetonitrile at 80 C in a microwave oven which gave good results in few minutes. For
optimization of reaction conditions under microwave, a test reaction was carried out using
Page 10 of 28

11
2
benzaldehyde (0.5 mmol), ethyl acetoacetate (0.5 mmol) and urea (0.5 mmol) using SiO /
o
CuCl
2
(0.05 g) in acetonitrile (2 ml) at 80 C, it was found that reaction under microwave
irradiation produced good results. So a series of reactions have been carried out and found
that good to excellent yields were obtained. Comparative studies between solvent-free
o
o
condition at 40 C using diphenic acid and under microwave condition at 80 C in acetonitrile
without diphenic acid have been carried out as shown in (Table 2) and found that reaction
under microwave irradiation are fast, clean, economic and proceeds with good to excellent
yields. The structure-activity relationship has also been drawn under solvent-free conditions at
o
o
4
0 C and in acetonitrile (microwave) at 80 C and found that in case of aromatic aldehydes
substituted with electron-donating groups gave 85-88% yields while aromatic aldehydes
substituted with electron-withdrawing groups gave 80-95% yields and hetero-aromatic
aldehydes gave 82-92% yields. In case of aliphatic aldehydes, formaldehyde gave an yield of
9
2%, with acetaldehyde and butanal the yields obtained were in traces. Similar methodology
was applied for the synthesis of 3,4-dihydropyrimidin-2(1H)-thiones from aldehyde,
thiourea and ethyl acetoacetate but we found multiple product formation and reaction was not
completed even after prolonged reaction times under the chosen conditions.
In order to study the importance of catalyst in the studied reaction, different control experi-
-
ments was run using m-nitrobenzaldehyde as the substrate. First, the reaction was run using
o
only silica at 40 C thermally (entry 1, Table 2) and the reaction was run for a period of
16hrs. The result obtained were in traces. Second, another experiment with only diphenic acid
o
at 40 C thermally was carried out and it was observed that reaction stops at an intermediate
stage in even after 8hrs of total run (entry 2, Table 2). Third, microwave conditions were
o
shifted to thermal (i.e. 80 C, acetonitrile without diphenic acid, thermally) and an yield of
6
8
0% product was obtained in 4hrs (entry 3, Table 3) in comparison to microwave where it is
8% in 30 mins (entry 4f, Table 3).
Page 11 of 28

12
O
2
O
O
RCHO
1
H N
NH2
2
OEt
3
2 2
SiO -CuCl
SiO / CuCl
2 2
Condition B
Microwave, acetonitrile
Diphenic acid
solvent-free, 40 o
C
Condition A
0 o
8
C
R
H
EtOOC
NH
N
H
O
4
a-j
Scheme 3: SiO
2
-CuCl
2
catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones.
3
.2 Proposed Mechanism
In the proposed mechanism, the initial step involves the formation of imine (A). Cu
coordinate with the nitrogen atom of imine to give an intermediate (B), which activates the
2
+
2
+
C=N bond towards the nucleophilic attack. Further, complexation of β-ketoester with Cu
increases the nucleophilicity of α-carbon of enolate, facilitating the attack on imine carbon
and attack of free amidic group to β-carbonyl carbon results in the formation of six-membered
heterocyclic intermediate (C), which on dehydration gives the desired DHPMs (D) as shown
in Scheme 4.
Role of Diphenic acid
Diphenic acid is a bronsted acid and is a weak acid which shows weak acidic nature in
aqueous solution. Here, in thermal conditions, we assume the acid is needed to provide polar
conditions for reaction to occur and to polarize the carbonyl group of aldehyde to make
nucleophilic-electrophilic attack more fascile. For the purpose of generosity, a control
o
experiment with only diphenic acid, m-nitrobenzaldehyde as substrate moiety at 40 C
thermally was run and it was found that reaction never moved ahead of intermediate stage.
1
o
This intermediate has been trapped and confirmed through H NMR and m.pt of 190 C which
Page 12 of 28

13
doesn’t match to the product and any of reactants used. Also, the diphenic acid can be thought
of acting as co-catalyst but assumption of providing polarity is connected to acetonitrile
providing polar conditions in microwave and no requirement of diphenic acid. So, we propose
diphenic acid to act as a source of providing polar conditions to the reaction occurring
o
thermally at 40 C.
l
a
herm
T
r
e
d
n
U
CN-CH
2
O
C
COOH
In Microwave
H+
+H
OR
O
O
O
OH
O
H
O
H
X
X
X
H
2
N
NH
2
N
NH2
N
NH2
H
SiO
2
A
O
O
O
X
O
Cu2+
C
2
5
H O
NH
O
O
H
O
X
3
H C
O
NH
O
H
3
C
OC
2
H
5
N
NH
2
2
Cu2+
B
O
O
O
SiO
2
X
X
Cu2+
O
O
H
-H O
O
O
O
2
C
2
5
H O
NH
C
2
5
H O
NH
HO
SiO2
3
H C
N
H
O
3
H C
N
O
H
D
C
Scheme 4: Proposed mechanism for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones.
Page 13 of 28

14
Table 1: Effect of different set of conditions for silica supported copper (II) chloride
catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using solvent-free
conditions and microwave irradiation.
a
Entry
Reaction Conditions
Catalyst
Amounts
Yield (%)
1
-
Diphenic acid
-
-
(
Solvent-free)
Catalyst
-
0.05 g
-
b
2
3
4
5
6
7
42
Diphenic acid
(
Solvent-free)
Catalyst
-
b
0.05 g
0.01 g
-
70
Diphenic acid
(
Solvent-free)
b
Catalyst
0.05 g
0.02 g
-
94
Diphenic acid
(
Solvent-free)
c
Catalyst
0.01g
-
50
Diphenic acid
(
(
Acetonitrile)
Catalyst
2 ml
0.02 g
-
c
65
Diphenic
Acetonitrile)
Catalayst
2 ml
0.05 g
-
c
90
Diphenic acid
Acetonitrile)
(
2 ml
Page 14 of 28

15
a
Reaction conditions: Aldehyde (0.5 mmol), ethyl acetoacetate (0.5 mmol), urea (0.5 mmol).
b
Isolated yields under thermal condition.
Isolated yields under microwave condition.
c
Table 2:Different control experiments with m-nitobenzaldehyde as substrate
Entry
Control
Experiments
siliica
Time (h)
Results
1
2
16
8
trace
Diphenic acid
Intermediate
stage
3
MW to Thermal
4
60% yield
Table 3: Comparitive studies for the synthesis of 3, 4-Dihydropyrimidin-2-(1H)-ones
o
o
using solvent-free condition at 40 C (thermal) and in acetonitrile at 80 C (microwave)
a
b
o
Entry
R
Thermal
Microwave
M.P./ Lit. M.P. ( C)
c
d
Time Yield(%) Time Yield(%)
(
h)
(min)
4
a
2
94
88
86
15
90
87
80
200-202/ 206-208[16]
214-216/ 215-216[15]
200-202/ 201-202[16]
4
b
2.20
2.45
18
22
4
c
H CO
3
H CO
4
d
3
4.5
84
28
72
232-234/ 233-235[21]
HO
Page 15 of 28

16
NO2
4e
3.5
80
15
82
208-210/ 208-210
[16]
O N
2
4
f
1.20
2
85
95
90
30
40
55
88
82
85
226-229/ 227-229[16]
210-212/ 211-213[16]
230-232/ 230-232[16]
4g
2
O N
H
4
h
2.5
C
C
H
4
i
1.5
92
82
50
45
83
90
198-200/ 200-201[22]
204-206/ 206-208[22]
242/242-244 [ 14]
O
S
4
j
1.45
4k
H
1.30
2.00
92
-
-
-
-
4l
CH
3
trace
4m
n-Bu
6.30
trace
-
-
a
Reaction conditions: Aldehyde (0.5 mmol), ethyl acetoacetate (0.5 mmol), urea (0.5 mmol), SiO
2
/ CuCl
/ CuCl
2
2
o
(
b
0.05g) and diphenic acid (0.02g) at 40 C in solvent-free conditions.
Reaction conditions: Aldehyde (0.5 mmol), ethyl acetoacetate (0.5 mmol), urea (0.5 mmol), SiO
2
o
(
0.05g) in microwave at 80 C in acetonitrile (2 ml) without diphenic acid.
c
Isolated yields refer to the yields obtained by crystallization from ethylacetate : petroleum ether under thermal
condition.
d
Isolated yields refer to the yields obtained by crystallization from ethylacetate : petroleum ether under
microwave condition.
3
.3 Recyclability of SiO / CuCl
2
2
To test the recyclability of SiO
2
2
/ CuCl under thermal and microwave conditions for one-pot
synthesis of 3,4-dihydropyrimidin-2(1H)-ones, a series of five consecutive runs in case of
benzaldehyde (entry 4a, Table 3) were carried out and the results are represented in (Fig. 5).
Page 16 of 28

17
2 2
These results demonstrated that SiO / CuCl was recyclable upto fifth run without any
significant loss of activity and after fifth run little drop in activity of catalyst was observed. To
recycle the catalyst, the used catalyst is given two washings of warm ethylacetate and water
o
each and finally the catalyst is dried under oven at 90- 100 C for 3 hrs.
2 2
Fig. 5 Recyclability of SiO -CuCl in case of benzaldehyde (entry 4a, Table 3) under thermal conditions and
microwave conditions.
4. XRD of 5-(Ethoxycarbonyl)-4-(3-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2-
(1H)-one (4f)
X-ray intensity data of 28767 reflections were collected on X’calibur CCD area-detector
diffractometer using graphite monochromated MoKα radiation (λ = 0.71073 Å). (Table 4)
depicted the unit cell parameters and other crystallographic details. The crystal used for data
collection was of dimensions 0.30 x 0.20 x 0.20 mm. The cell dimensions were determined by
least-squares methods. The data was corrected for Lorentz, polarisation and absorption
factors. The structure was solved by direct methods using SHELXS97[23]. All non-hydrogen
atoms of the molecule were located in the best E-map. During an anisotropic refinement of all
Page 17 of 28

18
the non-hydrogen atoms, atoms C19 and C20 were found to be thermally disordered and their
occupancies were refined to two equally occupied orientations here labeled (C19A and C19B)
and (C20A and C20B), respectively [occupancies 0.60 (1) and 0.40 (1)]. All the hydrogen
atoms (except N1 and N3 H atoms) were geometrically fixed and allowed to ride on the
corresponding non-hydrogen atoms with C-H= 0.93-0.98 Å, with Uiso(H) = 1.2Ueq(C), except
for the methyl groups where Uiso(H) = 1.5Ueq(C). Full-matrix least-squares refinement was
carried out using SHELXL97. The geometry of the molecule was calculated using the
PLATON[24] and PARST[25] softwares. Atomic scattering factors were taken from
International Tables for X-ray Crystallography (1992, Vol. C, Tables 4.2.6.8 and 6.1.1.4).
The crystallographic data are summarized in (Table 4). CCDC- 940361 has been given to the
compound (4f). Fig. 4 shows the ORTEP diagram of (4f)[26] and it comprises of a
pyrimidine ring and a phenyl ring (Fig. 4). Bond lengths and angles of the (4f) are within
o
normal ranges[27]. The dihedral angle between the pyrimidine and phenyl ring is 82.42 (6) .
Packing view of the molecules in the unit cell viewed down the (a and b) axis is shown in
(
Fig. 5). In the crystal, molecules are stabilized and held together by strong N-H…O and C-
H…O intermolecular interactions (Table 5).
Table 4: Crystal and experimental data of 5-(Ethoxycarbonyl)-4-(3-nitrophenyl)-
6
-methyl-3, 4-dihydropyrimidin-2(1H)-one (4f)
__________________________________________________________________
CCDC No
940361
Crystal description
Crystal colour
Block-shaped
white
Crystal size
0.3 x 0.2 x 0.2 mm
C H N O
Empirical formula
1
4
15
3
5
Formula weight
305.29
Mo Kα, 0.71073 Å
Radiation, Wavelength
Page 18 of 28

19
Unit cell dimensions
a =8.6831(3), b =11.8302(3), c = 13.7550(4) Å,
β= 93.399(3) º
Monoclinic
P 21/n
Crystal system
Space group
Unit cell volume
1410.47(7)
4
No. of molecules per unit cell, Z
Temperature
293(2)
-
1
Absorption coefficient
F(000)
0.111 mm
640
Scan mode
ω scan
θ range for entire data collection
Range of indices
3.43 <θ<26.00 º
h= -10 to 10, k= -14 to 14, l= -16 to 16
28767 / 2764
Reflections collected / unique
Reflections observed (I > 2σ(I))
1786
R
int
0.0751
R
sigma
0.0465
Structure determination
Refinement
Direct methods
2
Full-matrix least-squares on F
No. of parameters refined
215
Final R
0.0535
2
wR(F )
0.1203
2
2
2
Weight
1/[σ (F )+( 0.0499 P) + 0.4217 P]
o
2
2
where P=[F +2F ] / 3
o
c
Goodness-of-fit
1.055
0.001 (for tors H16A)
(
Δ/ σ )max
-
3
Final residual electron density
Measurement
- 0.277 <Δρ < 0.234 Å
X’calibur system – Oxford diffraction make,
U.K.
Software for structure solution
Software for refinement
SHELXS97 (Sheldrick, 2008)
SHELXL97 (Sheldrick, 2008)
Software for molecular plotting
Software for geometrical calculation
ORTEP-3 (Farrugia, 2012) PLATON (Spek, 2009)
PLATON (Spek, 2009) PARST (Nardelli, 1995)
________________________________________________________________________
Page 19 of 28

20
Table 5: Hydrogen–bonding geometry (e.s.d.`s in parentheses)
_______________________________________________________________________
_
o
D–H…A
D–H(Å)
H…A(Å)
D…A(Å)
D–H…A( )
________________________________________________________________________
i
N1-H1…O2
0.93(2)
0.96
1.88(2)
2.58
2.811(3)
3.428(3)
3.051(3)
174(2)
148
i
C16-H16B…O2
ii
N3-H3…O17
0.86(3)
2.25(2)
155(2)
Symmetry: (i) -x,-y+1,-z+2 (ii) -x+1/2,+y-1/2,-z+1/2+1
__________________________________________________________________________
_
Fig. 6 ORTEP diagram representation of 5-(Ethoxycarbonyl)-4-(3-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-
(1H)-one (4f)
2
Page 20 of 28

21
(
a)
Fig. 7 The packing arrangement of molecules (a) viewed down the a-axis
b) viewed down the b-axis
(b)
(
5
. Conclusion
In conclusion, we have developed methodologies for one-pot synthesis of 3,4-
dihydropyrimidin-2(1H)-ones using silica supported copper (II) chloride as solid
heterogeneous catalyst under thermal and microwave conditions. The benefits of the new
protocol include greener reaction conditions such as less toxicity of metal, economical nature
of copper, easy work-up of reaction, less reaction times with greater yields and tolerance for
various functional groups. Moreover, recyclability of catalyst using solvent-free conditions
and in acetonitrile makes process economic and cost-effective that lies in the area of “Green
Chemistry”.
6
(
. Spectral Data of 3,4-dihydropyrimidin-2(1H)-ones
4a-j )
5
-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (4a)
Page 21 of 28

22
-
1
IR (KBr, ʋmax in cm ): 3243, 1726, 1649.
1
H-NMR (DMSO-d
CH
.19 (bs, 1H, -NH).
6
): δ 1.07 (t, 3H, J= 7.2Hz, -OCH
2 3 3
CH ), 2.25 (s, 3H, -CH ), 3.95 (q, 2H,
J= 7.2Hz, -OCH
2
3
), 5.14 (d, 1H, J= 3.2Hz, -CH), 7.23 (m, 5H, Ar-H), 7.74 (bs, 1H, -NH),
9
1
3
C-NMR (DMSO-d
6
): δ 14.52, 18.22, 54.42, 59.68, 99.77, 126.70, 127.75, 128.86, 145.28,
148.79, 152.62, 165.82.
MS (ESI): 261 (M+1).
-(Ethoxycarbonyl)-6-methyl-4-(4-methylphenyl)-3,4-dihydropyrimidin-2(1H)-one (4b)
5
-
1
IR (KBr, ʋmax in cm ): 3158, 1715, 1632.
1
H-NMR (DMSO-d
), 3.96 (q, 2H, J= 7.1Hz, -OCH
.82 (bs, 1H, -NH), 9.18 (bs, 1H, -NH).
6
): δ 1.08 (t, 3H, J= 7.1Hz, -OCH
2 3 3
CH ), 2.18 (s, 3H, -CH ), 2.76 (s, 3H, -
CH
3
2
CH ), 5.09 (d, 1H, J= 2.7Hz, -CH), 7.18 (s, 4H, Ar-H),
3
7
1
3
C-NMR (DMSO-d
6
): δ 14.51, 18.26, 34.26, 53.65, 60.61, 101.02, 123.26, 125.65, 134.78,
148.39, 151.92, 156.42, 165.56.
MS (ESI): 275 (M+1).
-(Ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4c)
5
-
1
IR (KBr, ʋmax in cm ): 3243, 1725, 1651.
1
H-NMR (DMSO-d
), 3.97 (q, 2H, J= 7.2Hz, -OCH
.4Hz, Ar-H), 7.13 (d, 2H, J= 8.4Hz, Ar-H), 7.67 (bs, 1H, -NH), 9.15 (bs, 1H, -NH).
6
): δ 1.08 (t, 3H, J= 7.2Hz, -OCH
2 3 3
CH ), 2.24 (s, 3H, -CH ), 3.37 (s, 3H, -
OCH
3
2
CH ), 5.08 (d, 1H, J= 3.2Hz, -CH), 6.86 (d, 2H, J=
3
8
1
3
C-NMR (DMSO-d
6
): δ 14.57, 18.21, 53.79, 55.52, 59.61, 100.04, 114.17, 127.85, 137.51,
148.46, 152.61, 158.91, 165.84.
MS (ESI): 291 (M+1).
-(Ethoxycarbonyl)-4-(4-hydroxy-3-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (4d)
5
Page 22 of 28

23
-
1
IR (KBr, ʋmax in cm ): 3374, 3239, 1721, 1655.
1
H-NMR (DMSO-d
), 3.82 (q, 2H, 6.9Hz, -OCH
m, 3H, Ar-H), 7.94 (bs, 1H, -NH), 9.31 (bs, 1H, -NH).
6
): δ 1.09 (t, 3H, J= 7.2Hz, -OCH
2 3 3
CH ), 2.12 (s, 3H, -CH ), 3.42 (s, 3H, -
OCH
3
2
CH ), 5.41 (d, 1H, J= 2.8HZ, -CH), 5.68 (s, 1H, -OH) 7.62
3
(
1
3
C-NMR (DMSO-d
39.18, 142.67, 146.24, 151.55, 158.69, 167.42.
MS (ESI): 307 (M+1).
-(Ethoxycarbonyl)-4-(2-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4e)
6
): δ 14.54, 18.21, 50.18, 56.41, 59.64, 101.02, 112.32, 117.72, 121.24,
1
5
-
1
IR (KBr, ʋmax in cm ): 3237, 1730, 1618.
1
H-NMR (DMSO-d
CH
.36 (bs, 1H, -NH).
6
): δ 1.07 (t, 3H, J= 7.2Hz, -OCH
2 3 3
CH ), 2.26 (s, 3H, -CH ), 3.96 (q, 2H,
J= 6.8Hz, -OCH
2
3
), 5.27 (d, 1H, J= 3.2Hz, -CH), 7.40 (m, 4H, Ar-H), 7.90 (bs, 1H, -NH),
9
1
3
C-NMR (DMSO-d
6
): δ 14.52, 18.33, 54.08, 60.03, 98.66, 124.32, 128.08, 128.13, 133.53,
138.08, 149.05, 150.17, 152.74, 165.16.
MS (ESI): 306 (M+1).
-(Ethoxycarbonyl)-4-(3-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4f)
5
-
1
IR (KBr, ʋmax in cm ): 3229, 1724, 1630.
1
H-NMR (DMSO-d
CH
.36 (bs, 1H, -NH).
6
): δ 1.08 (t, 3H, J= 7.2Hz, -OCH
2 3 3
CH ), 2.28 (s, 3H, -CH ), 3.96 (q, 2H,
J= 7.0Hz, -OCH
2
3
), 5.30 (d, 1H, J= 3.2Hz, -CH), 7.64 (m, 4H, Ar-H), 8.13 (bs, 1H, -NH),
9
1
3
C-NMR (DMSO-d
6
): δ 14.47, 18.31, 54.00, 59.88, 98.81, 121.46, 122.84, 130.71, 133.46,
147.44, 148.20, 149.89, 152.25, 165.54.
MS (ESI): 306 (M+1).
-(Ethoxycarbonyl)-4-(4-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4g)
5
-
1
IR (KBr, ʋmax in cm ): 3235, 1740, 1631.
Page 23 of 28

24
1
H-NMR (DMSO-d
6
): δ 1.07 (t, 3H, J= 7.2Hz, -OCH
), 5.27 (d, 1H, J= 2.28Hz, -CH), 7.49 (d, 2H, J= 9.18Hz, Ar-H), 7.90 (bs,
H, -NH), 8.21 (d, 2H, J= 9.16Hz, Ar-H), 9.37 (bs, 1H, -NH).
2 3 3
CH ), 2.08 (s, 3H, -CH ), 3.97 (q, 2H,
2 3
J= 7.2Hz, -OCH CH
1
1
3
C-NMR (DMSO-d
6
): δ 14.49, 18.32, 31.15, 54.11, 59.91, 98.64, 124.31, 128.13, 147.16,
149.86, 152.23, 165.54.
MS (ESI): 306 (M+1).
-(Ethoxycarbonyl)-6-methyl-4-styryl-3,4-dihydropyrimidin-2(1H)-one (4h)
5
-
1
IR (KBr, ʋmax in cm ): 3242, 1702, 1652.
1
H-NMR (DMSO-d
6
): δ 1.18 (t, 3H, J= 7.2Hz, -OCH
2 3 3
CH ), 2.08 (s, 3H, -CH ), 4.09 (q, 4H,
J= 7.2Hz, -OCH CH
2
3
), 4.73 (d, 1H, J= 2.8Hz, -CH), 6.16 (dd,1H, J= 16Hz, 6.4Hz, -CH=C–
H), 6.33 (d,1H, J= 15.6Hz, H-C=CH) 7.23 (m, 5H, Ar-H), 7.55 (bs, 1H, -NH), 9.14 (bs, 1H, -
NH).
1
3
C-NMR (DMSO-d
30.40, 136.69, 149.00, 153.08, 165.69.
MS (ESI): 287 (M+1).
-(Ethoxycarbonyl)-4-(2-furfuryl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4i)
6
): δ 14.71, 18.21, 52.33, 59.71, 98.27, 126.79, 128.06, 128.59, 129.15,
1
5
-
1
IR (KBr, ʋmax in cm ): 3225, 1695, 1640.
1
H-NMR (DMSO-d
6
2 3 3
): δ 1.12 (t, 3H, J= 7.1Hz, -OCH CH ), 2.26 (s, 3H, -CH ) 4.01 (q, 2H,
J=7.1Hz, -OCH
H, -NH).
2
CH ), 5.19 (s, 1H, -CH), 6.08 (m, 3H, Ar-CH), 7.75 (bs, 1H, -NH), 9.24 (bs,
3
1
1
3
C-NMR (DMSO-d
6
): δ 14.18, 18.25, 48.93, 59.76, 100.12, 121.14, 126.04, 131.18, 149.23,
152.16, 155.94, 165.62.
MS (ESI): 251 (M+1).
-(Ethoxycarbonyl)-6-methyl-4-(2-thienyl)-3,4-dihydropyrimidin-2(1H)-one (4j)
5
-
1
IR (KBr, ʋmax in cm ): 3215, 1734, 1668.
Page 24 of 28

25
1
H-NMR (DMSO-d
6
): δ 1.15 (t, 3H, J= 7.2Hz, -OCH
2 3 3
CH ), 2.22 (s, 3H, -CH ), 4.05 (q, 2H,
J= 7.2Hz, -OCH
H, -NH).
2
CH
3
) 5.41 (1H, s, -CH), 6.89 (m, 3H, Ar-CH), 7.91 (bs, 1H, -NH), 9.31 (bs,
1
1
3
C-NMR (DMSO-d
6
): δ 14.61, 18.13, 49.79, 59.85, 100.27, 123.99, 125.10, 127.15, 149.11,
149.21, 152.72, 165.51.
MS (ESI): 267 (M+1).
5
-(Ethoxycarbonyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4k)
1
H-NMR (DMSO-d
6 2 3 3
): δ 1.16 (t, 3H, J= 7.2Hz, -OCH CH ), 2.14 (s, 3H, -CH ), 3.88 (1H, s, -
CH), 4.02 (q, 2H, J= 7.2Hz, -OCH CH ), 7.02 (bs, 1H, -NH), 8.86 (bs, 1H, -NH).
2
3
1
3
C-NMR (DMSO-d
6
): δ 14.73, 17.89, 59.60, 94.83, 149.20, 153.22, 165.83.
Acknowledgements
We are thankful to Department of Chemistry, University of Jammu, for providing us the
1
13
necessary facilities for H NMR, C NMR and TGA and also we are thankful to Department
of Physics, University of Jammu for providing us the XRD data of crystal obtained; IIIM,
Jammu for providing necessary FTIR and Mass spectral studies and IIT, Bombay for SEM;
SAIF, Chandigarh for TEM and IIT, Roorke for AAS.
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28
Highlights:
ꢀ
ꢀ
2 2
We have prepared a novel recyclable heterogeneous catalyst: SiO -CuCl .
The catalyst has been fully characterized by FTIR, SEM, TEM, TGA AND AAS
studies.
ꢀ
ꢀ
ꢀ
3,4-dihydropyrimidinones have been synthesized under thermal and microwave
condition.
1
13
Products of the reaction have been characterized using HNMR, CNMR, mass and
IR.
X-ray : 5-(Ethoxycarbonyl)-4-(3-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-
one.
Page 28 of 28