One-Pot Synthesis of Substituted Piperidinones and 3,4-Dihydropyrimidinones Using a Highly Active and Recyclable Supported Ionic Liquid Phase Organocatalyst

Article abstract of DOI:10.1071/CH15133

1-Ethyl-3-methylimidazolium ethyl sulfate was synthesized and its supported ionic liquid phase form was prepared and used as an organocatalyst for the synthesis of substituted piperidinones and 3,4-dihydropyrimidinones. The ionic liquid was characterized by ¹H NMR, ¹³C NMR, and mass spectrometry. The catalyst is novel, stable, completely heterogeneous, and recyclable for several times and can be easily recovered by filtration. It was characterized with scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, and energy-dispersive X-ray spectroscopy techniques. The workup procedures are very simple, and products were obtained in good-to-excellent yields with reasonable purities without the need for further chromatographic purification.

Full text of DOI:10.1071/CH15133

CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
http://dx.doi.org/10.1071/CH15133
One-Pot Synthesis of Substituted Piperidinones and
3,4-Dihydropyrimidinones Using a Highly Active and
Recyclable Supported Ionic Liquid Phase Organocatalyst
A
A
A B
,
Pankaj Sharma, Manjulla Gupta, Monika Gupta,
A
and Rajive Gupta
A
Department of Chemistry, University of Jammu, Jammu-180006, India.
Corresponding author. Email: monika.gupta77@rediffmail.com
B
1-Ethyl-3-methylimidazolium ethyl sulfate was synthesized and its supported ionic liquid phase form was prepared and
used as an organocatalyst for the synthesis of substituted piperidinones and 3,4-dihydropyrimidinones. The ionic liquid
was characterized by 1H NMR, 13C NMR, and mass spectrometry. The catalyst is novel, stable, completely heterogeneous,
and recyclable for several times and can be easily recovered by filtration. It was characterized with scanning electron
microscopy, transmission electron microscopy, thermogravimetric analysis, and energy-dispersive X-ray spectroscopy
techniques. The workup procedures are very simple, and products were obtained in good-to-excellent yields with
reasonable purities without the need for further chromatographic purification.
Manuscript received: 17 March 2015.
Manuscript accepted: 12 July 2015.
Published online: 11 August 2015.
Introduction
designability, ease of handling, separation, and recycling. Fur-
thermore, based on an economic criterion, it is desirable to
minimize the amount of ionic liquid used in a potential process.
Currently, ionic liquid-based hybrid materials called ‘ionogels’
are also in the ambit of great potential and attractive systems for
synthetic chemistry.[5] Immobilized ionic liquids have been
widely applied as novel solid catalysts e.g. in esterification,
nitration,[6] Baeyer–Villiger reactions,[7] acetal formation,[8]
hydrolysis of cellulose,[9] citral hydrogenation,[10] in the syn-
thesis of many organic compounds,[11] and in the separation of
rare metals.[12]
Diarylpiperidinones and dihydropyrimidinones (DHPMs) are
also important compounds due to their wide range of bioactivities
and their applications in the field of drug research. Compounds
having a piperidinone nucleus have a wide variety of biological
properties such as anti-tumour,[13] anti-cancer,[14] anti-viral,[15]
anti-inflammatory,[16] nutagenic,[17] local anaesthetic,[18] anti-
microbial,[19] and analgesic anti-pyretic properties.[20] The piper-
idinone nucleus is also present as an intermediate in the synthesis
of many physiologically active compounds as reviewed by
Prostakov and Gaivoronkaya.[21] Of the five major bases found
in DNA and RNA, three are pyrimidinone derivatives, which
comprise cytosine, uracil, and thymine. Thus, they have become
very important in the world of synthetic organic chemistry. 3,4-
Dihydropyrimidinones have also been reported to posses diverse
pharmacological properties such as anti-viral, anti-bacterial, and
anti-hypertensive properties, as well as efficacy as calcium
channel modulators and 1a-antagonist.[22] Numerous methods
are available in the literature on the synthesis of DHPMs,[23–25]
which includes certain drawbacks, such as the use of harsh
reaction conditions and expensive and toxic catalysts, and long
reaction times, low yields, and tedious workup procedures.
Ionic liquids are considered as alternative ‘green’ solvents
because they offer great potential for the development of clean
catalytic technologies due to their unique properties such as
undetectable vapour pressure and the ability to dissolve many
organic and inorganic substances.[1] They can also be designed
to offer high activity by immobilizing them on the surface of
solid catalysts; heterogenization of catalysts can offer important
advantages in handling and in separation and reuse. The idea of
supported ionic liquid catalysis was developed by Mehnert
et al.[2] in 2002. Supported ionic liquid catalysis has been the
subject of enormous interest in the field of catalysis because of
its potential and wide-range applications in synthetic chemistry.
Homogeneous or liquid-phase catalysts offer several important
advantages e.g. all catalytically active sites are accessible and
uniform. Usually, solvents are indispensable as reaction media
and have even important role in efficient homogeneous cataly-
sis. Over the past years, ionic liquids have been applied as cat-
alysts in different forms, e.g. as supported ionic liquid phase
(SILP) catalyst, solid catalyst with ionic liquid layer (SCILL), or
ionogels. SILP catalysis concept is based on a classical homo-
geneous catalyst that is dissolved in a thin film of ionic liquid,
with the latter being dispersed over the high internal surface area
of a porous support.[3] The SCILL concept is based on coating of
the heterogeneous catalyst material with a thin layer of ionic
liquid to induce specific modifications in the catalytic perfor-
mance. Due to extremely low vapour pressure, the IL film
resides on the catalyst surface. In both concepts, the IL is
immobilized on a porous solid.[4] Modification of supported
catalysts with IL is reported to change both the reactivity and
stability of the catalyst. Immobilized ILs offer combined ben-
efits of ILs and heterogeneous catalysts such as high
Journal compilation Ó CSIRO 2015
www.publish.csiro.au/journals/ajc

B
P. Sharma et al.
Our method involves a metal-free and cost-effective catalyst
that can afford higher yields in shorter reaction times. The
literature survey again reveals that there are a number of
methods for the synthesis of piperidinones,[26–29] but there
is lot of scope to develop more advanced methods. The use of
L-proline, as a homogeneous catalyst, for the synthesis of
piperidinones is well explored in literature.[30,31] Our method
involves the use of L-proline and ionic liquid in heterogeneous
form, resulting in enhanced catalytic activity and recyclability,
thus making the process eco-friendly. Keeping in view the
importance of piperidinones and pyrimidinones and the scope
of SILPC, we wish to report an efficient method for the synthesis
of 1-ethyl-3-methylimidazolium ethyl sulfate [EMIM][EtSO4]
and its supported ionic liquid phase organocatalyst form, silica-
L-proline [EMIM][EtSO4] (SILPOC). The heterogeneous orga-
nocatalyst was used in catalytic amounts in the one-pot synthesis
of piperidinones and 3,4-dihydropyrimidinones.
Based on the literature, the combination of L-proline with
ionic liquids is also known to catalyze organic reactions.[32]
Thus, herein, we tried this combination with silica to explore
the supported ionic liquid catalysis for the synthesis of piper-
idinones and pyrimidinones. In an earlier study, we reported
the use of solid catalyst with ionic liquid layer for the synthesis
of 1,4-dihydropyridines (DHPs).[33]
of reaction, 3.2 mmol of diethylsulfate (0.5 g) was added slowly,
and the reaction was stirred continuously for 10 h, after which
the ice bath was removed and the reaction was stirred further
for 30 h at room temperature. After completion of the reaction
(monitored via thin layer chromatography (TLC)), water
was removed using rotary evaporation, and the ionic liquid
obtained was kept in an oven for 1 h at 1108C to remove the
residual water.
Preparation of SILPOC
SILPOC was prepared by dissolving 5 mmol of L-proline
(0.575g) and 4 mmol (0.944g) of ionic liquid [EMIM][EtSO4] in
5 mL of methanol in a 250-mL round-bottom flask. The solution
was stirred for 10min at room temperature under vacuum con-
ditions. To this reaction mixture, silica (5 g; calcined at 4008C)
was added and stirred at room temperature for 20 h. The solvent
was evaporated under reduced pressure until free-flowing
powder of the catalyst was obtained. The powder was then dried
at 1208C for 4 h (Scheme 2).
Characterization of the Catalyst
The surface morphology of the catalyst was studied using
scanning electron microscopy (SEM). The SEM images of the
surface of the catalyst are presented in Fig. 1. The SEM image
showed that the catalyst have porous irregular shaped particles.
The transmission electron microscopy (TEM) (Fig. 2)
images of the catalyst provide direct observation of the
morphology and distribution of L-proline and ionic liquid
on the surface of silica and indicate the fine structure of the
catalyst with no bulk aggregation of ionic liquid or L-proline.
It is further inferred that some molecules are arranged in a way
to form blobs.
The stability of the catalyst was determined by thermogravi-
metric analysis (TGA). The TG curve shows an initial weight
loss at 31.98C,which may be attributed to the loss of physically
adsorbed gases and residual solvent on the surface of the
catalyst. The small weight loss near 1008C can be attributed to
the loss of water trapped into the surface of the catalyst. The
subsequent weight loss above 2508C can be attributed to the loss
of L-proline and the weight loss above 5008C may be due to the
thermal degradation of the ionic liquid. Hence, from the TG
curve (Fig. 3), we may conclude that the catalyst is stable and it
Results and Discussion
Synthesis of [EMIM][EtSO4]
[EMIM][EtSO4] was prepared by first transferring 10 mmol of
1-methylimidazole (0.82 g) and 20 mL of water to a 100-mL
round-bottom flask placed in an ice bath. The resulting mixture
was allowed to stir (Scheme 1). Then, 3.6 mmol of diethylsulfate
(0.54 g) was added dropwise to control the vigorous nature of the
reaction. After 10 h, 3.2 mmol of diethylsulfate (0.5 g) was
slowly added under continuous stirring in an ice bath. After 20 h
C2H5
O
S
O
S
N
N
ϩ
Water, stirring
Ϫ
O
ϩ
C2H5O
OC2H5
OC2H5
N
N
O
O
CH3
CH3
Scheme 1. Preparation of 1-ethyl-3-methylimidazolium ethyl sulfate.
L-Proline
[EMIM][EtSO4]
L-
Proline
Ionic
liquid
phase
Silica
Silica
(Support material)
Ionic
liquid
Scheme 2. Illustration of the synthesis of supported ionic liquid phase organocatalyst.

Supported Ionic Liquid-Catalyzed Synthesis of Heterocycles
C
Fig. 1. SEM images of the supported ionic liquid phase organocatalyst.
3.74 nm
50 nm
Fig. 2. TEM images of the supported ionic liquid phase organocatalyst.
100 nm
is safe to conduct the synthesis of pyrimidinones and piperidi-
nones at 608C. The energy-dispersive X-ray spectroscopy
(EDX) pattern of the catalyst showed the presence of all the
important elements i.e. C, N, O, Si, and S of the supported ionic
liquid phase catalyst (Fig. 4).
other solvents, such as acetonitrile, toluene, and water, were
also tried. Unfortunately, the results obtained were not satis-
factory as presented in Table 1.
Optimization of Reaction Conditions for the Synthesis of 3,4-
Dihydropyrimidinones
Optimization of Reaction Conditions for the Synthesis of
Piperidinones
For the optimization of temperature for the synthesis of
3,4-dihydropyrimidinones, we tried the reaction among ethy-
lacetoacetate, 4-methoxybenzaldehyde and urea at different
temperatures (r.t., 408C, 608C, 808C) under solvent-free condi-
tions, and results are presented in Table 1. It was observed that at
room temperature and at 408C, products were formed in lower
yields. At 608C, the reaction yielded excellent amounts of pro-
ducts, whereas at 808C, there was no significant increase in the
yield of the product. Hence, a temperature of 608C was found
to be the optimum reaction temperature for the synthesis of
3,4-dihydropyrimidinones. Furthermore, we explored the effect
of solvent on the synthesis of 3,4-dihydropyrimidinones, and
results are presented in Table 1. As observed, the solvent-free
conditions gave the best results.
For the optimization of temperature for the synthesis of
2,6-diarylpiperidinoes, we tried the reaction among ethyl-
methylketone, 4-methoxybenzaldehyde, and ammonia at
different temperatures (room temperature (r.t.), 408C, 608C,
808C) under solvent-free conditions. It was found that at room
temperature and at 408C, traces of products were formed
(monitored by TLC). At 608C, the reaction yielded excellent
amounts of the products (Table 1), whereas at 808C, the pro-
ducts obtained were not very pure, likely due to multiple
product formation (monitored by TLC). Hence, a temperature
of 608C was found to be the optimum reaction temperature for
the synthesis of 2,6-diarylpiperidinones. Furthermore, some

D
P. Sharma et al.
15
10
Ϫ0.5
Ϫ1.0
Ϫ1.5
Ϫ2.0
Ϫ2.5
Ϫ3.0
Ϫ3.5
Ϫ4.0
31.9ЊC Ϫ0.687 %
dMass-rel [S1.]
330.2ЊC Ϫ1.312 %
391.4ЊC Ϫ1.904 %
5
0
467.7ЊC Ϫ3.004 %
Ϫ5
Ϫ10
Ϫ15
588.1ЊC Ϫ3.612 %
Heat flow (smoothed) [S1.]
100
100
200
200
300
400
400
500
600
Temperature [ЊC]
300
500
600
Temperature (smoothened) [ЊC]
Fig. 3. TG graph (blue curve) and differential thermal analysis curve (black curve) of the supported ionic liquid phase
organocatalyst.
Acquire EDX
2500
C
N
O
2000
1500
1000
500
Si
S
10
20
30
40
Energy [keV]
Fig. 4. EDX spectrum of the supported ionic liquid phase organocatalyst.
In order to determine the role of supported ionic liquid phase
heterogeneous catalyst was selected for the synthesis of
2,6-diarylpiperidinones and 3,4-dihydropyrimidinones.
organocatalyst, as the heterogeneous catalyst, the reactions with
test substrates for the synthesis of 2,6-diarylpiperidinones and
3,4-dihydropyrimidinones were carried out in the presence of
activated silica, silica-L-proline, homogeneous L-proline-IL,
and absence of catalyst. The results are summarized in Table 2.
Under homogeneous conditions, using ionic liquid and
L-proline only, the reactions did not yield satisfactory results
for further investigation. Moreover, to make the process cost
effective and heterogeneous, the loading of ionic liquid with
L-proline on the surface of silica makes the system attractive,
selective, and effective, thereby giving higher yields and afford-
ing simple workup procedures. Moreover, the catalyst can be
easily recovered and recycled for several runs, thus making
the process more efficient and cost effective. Thus, the
To make the developed protocol general, the synthesis of
these heterocyclic compounds was extended using different
aromatic aldehydes, possessing both electron-withdrawing and
electron-donating groups, a,b-unsaturated aldehydes, and het-
erocyclic aldehydes. It was found that aromatic aldehydes that
possess electron-withdrawing groups are more efficient for the
synthesis of their corresponding products. In contrast, aliphatic
aldehydes did not afford a satisfactory product yield.
Recyclability
The recyclability and deactivation of a catalyst is more impor-
tant when dealing with heterogeneous catalysts. To test these

Supported Ionic Liquid-Catalyzed Synthesis of Heterocycles
E
Table 1. Comparison of solvents and temperature in the synthesis of heterocycles
Entry
Solvent
Conditions
PiperidinoneA
Time [min]
3,4-DihydropyrimidinoneB
Time [min]
YieldC [%]
YieldC [%]
1
2
3
4
5
6
7
8
9
No solvent
No solvent
No solvent
No solvent
Acetonitrile
Ethanol
r.t.
60
60
60
60
60
60
60
60
60
Trace
40
20
20
20
20
20
20
20
20
20
40
60
97
97
60
70
40
50
60
408C
608C
808C
608C
608C
608C
608C
608C
95
95
50
60
Toluene
50
Water
45
DMF
55
AReaction conditions: ethyl methyl ketone (1 mmol), 4-methoxybenzaldehyde (2 mmol), ammonia (1 mmol), and catalyst (0.1 g).
BReaction conditions: 4-methoxybenzaldehyde (2 mmol), ethyl acetoacetate (2 mmol), urea (2 mmol), and catalyst (0.1 g).
CIsolated yields.
Table 2. Comparison of catalyst activity for the synthesis of piperidinonesA and 3,4-dihydropyrimidinonesB at 608C
under solvent-free conditions
Catalyst (0.1 g for entries 2 and 5, 0.01 g L-proline and 0.1 g activated silica for entry 3, 0.01 g L-proline and 0.2 g [EMIM]
[EtSO4] for entry 4)
Entry
Catalyst
PiperidinoneA
3,4-DihydropyrimidinoneB
Time [min]
YieldC [%]
Time [min]
YieldC [%]
1
2
3
4
5
No catalyst
60
60
60
60
60
No reaction
20
No reaction
Trace
40
Activated silica
Silica-L-proline
L-Proline-[EMIM][EtSO4]
SILPOC
No reaction
20
20
20
20
30
40
95
55
97
AReaction conditions: ethyl methyl ketone (1 mmol), 4-methoxybenzaldehyde (2 mmol), and ammonia (1 mmol).
BReaction conditions: 4-methoxybenzaldehyde (2 mmol), ethyl acetoacetate (2 mmol), and urea (2 mmol).
CIsolated yields.
100
properties, a series of seven consecutive runs for the synthesis of
Pyrimidinone
Piperidinone
2,6-diarylpiperinones and 3,4-dihydropyrimidinones was car-
ried out using 4-methoxybenzaldehyde as the test substrate in
the synthesis of both heterocycles and each time the amount of
substrate used was proportional to the amount of catalyst
recovered. The results of the recyclability studies are shown in
Fig. 5. As observed, the catalyst is highly active and recyclable
up to seventh run with small loss of activity. The small loss in
activity after every use may be due to the deactivation of the
some active sites.
95
90
85
80
75
70
65
60
1
2
3
4
5
6
7
Proposed Mechanism for the Synthesis of Piperidinones
Number of runs
In the proposed mechanism (Scheme 3), besides providing
larger surface area and active sites for catalysis, SILPOC played
an important role in the synthesis of 2,6-diarylpiperidinoes as
this catalytic system involves more efficient use of ionic liquid,
L-proline, and catalyst. In the first step, aldehyde was activated
by catalyst for nucleophilic attack, leading to the formation of a,
b-unsaturated ketones A. The second step involves nuclephilic
attack of ammonia on the electrophilic centre of the second
aldehyde activated by the catalyst, thereby resulting in the
formation compound B. Then, the catalyst activated compounds
A and B for cyclization to give the final product as shown in
Scheme 3.
Fig. 5. Recyclability graph of the supported ionic liquid phase
organocatalyst.
Proposed Mechanism for the Synthesis of
3,4-Dihydropyrimidinones
The supported ionic liquid phase organocatalyst, as a hetero-
geneous catalyst, provided active sites and larger surface area
for the reaction to proceed. Moreover, the ionic liquid phase
provided polarity for the reaction to proceed. In the proposed

F
P. Sharma et al.
[EMIM][EtSO4]
[EMIM][EtSO4]
Ionic
Ionic
liquid
phase
60 o
C
liquid
phase
60 o
C
L-Proline
Silica
L-Proline
Silica
O
O
H
C
H
O
STEP 1
H3C
H3C
CH3
Ϫ
Ar
H
[EMIM][EtSO4]
Ionic
liquid
phase
60 o
C
O
L
-Proline
Silica
STEP 2
Ar
H
O
H
H2C
Ar
NH3
NH
ϪH2O
C
Ar
B
H
A
Ϫ
O
O
H2C
H2C
Ar
C
CH
Ar CH
NH
Ar
N
H
Ar
H
Ϫ
O
Ionic
liquid
phase
60 o
C
ϩ
[EMIM][EtSO4
]
N
H
Ar
Ar
L-Proline
Silica
Product
Scheme 3. Proposed mechanism for the synthesis of piperidinones.
mechanism (Scheme 4), the initial step involves the formation of
imine 1. The catalyst coordinated with the nitrogen atom of
imine to give an intermediate 2, which activates the C¼N bond
towards nucleophilic attack. Furthermore, complexation of
b-ketoester with the catalyst increases the nucleophilicity of
a-carbon of enolate, thus facilitating the attack on imine carbon
and attack of free amidic group to b-carbonyl carbon, thereby
resulting in the formation of six-membered heterocyclic inter-
mediate 3, which upon dehydration gives the desired DHPMs D
as shown in Scheme 4.
and ecologically clean procedure will make the present method a
useful and attractive strategy for the synthesis of these biolog-
ically important heterocycles.
Experimental
Materials and Instrumentation
Silica gel was purchased from ACROS Organics, and diethyl-
sulfate and 1-methylimidazole were purchased from Sigma-
Aldrich; these chemicals were used without further purification.
The infrared (IR) spectra of the catalyst and synthesized com-
pounds were recorded in the range of 4000–300 cmꢀ1 on a
Shimadzu Prestige-21 spectrophotometer. TGA of the catalyst
was conducted on a Linesis thermal analyzer, using a heating
rate of 108C minꢀ1. The SEM images were recorded on a JEOL
scanning electron microscope and the TEM images were
recorded on a TECHNAI G2 20 S-TWIN microscope (FEI,
The Netherlands). 1H NMR and 13C NMR analyses of the
compounds were performed on a Bruker Avance III (400 MHz)
spectrometer. Mass spectra of the products were obtained on a
Bruker Daltonics Esquire 3000 spectrometer.
Conclusion
In conclusion, we prepared 1-ethyl-3-methylimidazolium ethyl
sulfate and used this IL for the synthesis of supported ionic
liquid phase organocatalyst. By using this catalyst, we have
developed a clean methodology for the synthesis of substituted
piperidinones and 3,4-dihydropyrimidinones using silica
immobilized with L-proline in [EMIM][EtSO4] as a re-useable,
non-toxic, and cost-effective organocatalyst. Moreover, the low
temperature, mild reaction conditions, ease of workup, com-
patibility with various functional groups, high yield of products,

Supported Ionic Liquid-Catalyzed Synthesis of Heterocycles
G
O
O
OH
O
1
H
X
X
ϩ
H2N
NH2
N
H
NH2
Ionic
liquid
phase
o
60
C
[EMIM][EtSO ]
4
L-Proline
Ionic
liquid
Silica
60 o
C
phase
X
[EMIM][EtSO ]
4
L-Proline
Silica
O
NH
C2H5O
H
O
OH
O
X
O
H3C
O
N
NH2
H3C
OC2H5
2
NH2
Ionic
liquid
60 o
C
phase
[EMIM][EtSO ]
4
L
-Proline
Silica
X
X
3
O
O
H
ϪH2O
C2H5O
NH
NH
C2H5O
HO
N
H
N
H
H3C
O
H3C
O
Ionic
liquid
phase
4
60 o
C
ϩ
Ionic
liquid
phase
[EMIM][EtSO ]
60 oC
4
L-Proline
Silica
[EMIM][EtSO ]
4
L-Proline
Silica
Scheme 4. Proposed mechanism for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones.
using a vacuum pump. The filtrate was treated with water,
and the organic layer was separated, concentrated, and
kept at room temperature till a solid product was formed,
which was finally crystallized from ethanol to obtain the
pure product.
O
O
R
SILPOC
R
R1CHO
2
Stirring at 60ЊC,
60–90 min
ϩ
N
H
R1
R1
NH3
1a–1n
General Procedure for the Synthesis of 3,4-
Dihydropyrimidinones
Scheme 5. General procedure for the synthesis of piperidinones.
First, 2 mmol of aldehyde, 2 mmol of ethyl acetoacetate, and
2 mmol of urea were stirred for 5 min at 608C, and then the
catalyst (0.1 g) was added, and stirring was continued at 608C
using a magnetic stirrer (Scheme 6) for an appropriate time
(Table 4). After completion of the reaction (monitored by
TLC), the product was extracted with ethylacetate and filtered
off using a vacuum pump. The product was obtained after
removal of the solvent under reduced pressure and finally
crystallized from ethanol.
General Procedure for the Synthesis of Piperidinones
To a mixture of 2 mmol of aldehyde, 1 mmol of ketone, and
1 mmol of ammonia in a round-bottom flask, the catalyst (0.1 g)
was added. The reaction mixture was stirred at 608C using a
magnetic stirrer (Scheme 5) for an appropriate time (Table 3).
After completion of the reaction (monitored by TLC),
the product was extracted with ethylacetate and filtered

H
P. Sharma et al.
Table 3. One-pot synthesis of piperidinones at 608C under solvent-free conditionsA using SILPOC
Entry
Product
R
R1
Time [min]
YieldB [%]
mp/lit. mp [8C]
1
1a
1b
1c
1d
1e
1f
CH3
C6H5
90
60
80
80
90
70
70
60
90
60
70
90
90
90
90
95
85
88
80
90
85
92
92
89
87
Trace
–
86–89/87[34]
136–138/138[35]
93–94/93[35]
124–126/126[31]
128–130/132[31]
126–128/128[31]
110–113/113[35]
87–88/88[35]
129–130/128[31]
75–77/78[36]
42–45/40[37]
–
2
CH3
4-OCH3C6H4
2-OCH3C6H4
4-CH3C6H4
2-ClC6H4
4-ClC6H4
C6H5
3
CH3
4
CH3
5
CH3
6
CH3
7
1g
1h
1i
COOC2H5
COOC2H5
COOC2H5
CH3
8
4-OCH3C6H4
4-ClC6H4
3-NO2C6H4
2-Furyl
9
10
11
12
13
14
1j
1l
CH3
1n
1o
1p
CH3
H
CH3
CH3
–
COOC2H5
H
–
–
AReaction conditions: aldehyde (2 mmol), ketone (1 mmol), ammonia (1 mmol), and catalyst (0.1 g) stirred at 608C under solvent-free conditions.
BIsolated yields.
R
O
R
O
O
H
NH
SILPOC
O
1
H2N
H2N
O
ϩ
O
Stirring at 60ЊC,
20–120 min
N
H
O
O
2
4a–4n
3
Scheme 6. General procedure for the synthesis of 3,4-dihydropyrimidinones.
Table 4. One-pot synthesis of 3,4-dihydropyrimidinones at 608C under solvent-free conditionsA using SILPOC
Entry
Product
R
Time [min]
YieldB [%]
mp/lit. mp [8C]
1
4a
4b
4c
4d
4e
4f
C6H5
4-MeOC6H4
4-OH-3-MeOC6H3
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
4-CH3C6H4
2-Thienyl
2-Furyl
30
20
90
97
205–206/206–208[38]
200–202/201–202[38]
232–234/232–234[39]
209–210/ 208–210[38]
226–227/227–229[38]
210–211/211–213[38]
214–215/215–216[40]
206–207/206–208[41]
198–200/200–201[41]
230–232/230–232[38]
213–215/216–217[42]
239/242–244[40]
2
3
25
85
4
30
90
5
20
90
6
30
95
7
4g
4h
4i
40
85
8
25
96
9
20
92
10
11
12
13
14
4j
CH¼CH–C6H5
4-ClC6H4
H
60
80
4k
4l
40
97
90
88
4m
4n
CH3
120
120
Trace
Trace
–
n-Bu
–
AReaction conditions: aldehyde (2 mmol), ethyl acetoacetate (2 mmol), urea (2 mmol), and catalyst (0.1 g) stirred at 608C under solvent-free conditions.
BIsolated yields.
Supplementary Material
of Chemistry, University of Jammu, for use of spectral facilities and
TGA analysis.
NMR and mass spectra of the ionic liquid and products are
available on the Journal’s website.
References
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Acknowledgements
We thank the Director, Indian Institute of Integrative Medicines, Jammu,
for use of spectral facilities; Head of Central Research facility section,
Indian Institute of Technology, Ropar, for SEM services, and Indian
Institute of Technology, Roorkee, for TEM services; and the Department
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