Three-component one-pot synthesis of 4,6-diarylpyrimidin-2(1H)-ones catalyzed by 1-methyl-3-[2-(sulfooxy)ethyl]-1H-imidazol-3-ium chloride

Article abstract of DOI:10.14233/ajchem.2013.14187

An efficient, one-pot, three-component cyclocondensation reaction of aromatic aldehydes, aromatic ketone and urea catalyzed by 1-methyl-3-[2- (sulfooxy)ethyl]-1H-imidazol-3-ium chloride is developed to give 4,6-diarylpyrimidin-2(1H)-ones.

Full text of DOI:10.14233/ajchem.2013.14187

Asian Journal of Chemistry; Vol. 25, No. 11 (2013), 6445-6446
http://dx.doi.org/10.14233/ajchem.2013.14187
NOTE
Three-Component One-Pot Synthesis of 4,6-Diarylpyrimidin-2(1H)-ones
Catalyzed by 1-Methyl-3-[2-(sulfooxy)ethyl]-1H-imidazol-3-ium Chloride
1
2
2
2
2
YU WAN , LIANG-FENG CHEN , HAI-YING WANG , LING-LING ZHAO , SHU-YING HUANG ,
2
2
2
1,2,*
GUI-XIANG LIU , SHU-NING YUE , WEN-LI ZHANG and HUI WU
1Key Laboratory of Biotechnology on Medical Plant of Jiangsu Province, Xuzhou 221116, P.R. China
2School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, P.R. China
*Corresponding author: Fax: +86 516 83500164; Tel: +86 516 83403163; E-mail: wuhui72@yahoo.com.cn
(Received: 8 June 2012;
Accepted: 14 May 2013)
AJC-13489
An efficient, one-pot, three-component cyclocondensation reaction of aromatic aldehydes, aromatic ketone and urea catalyzed by
1-methyl-3-[2-(sulfooxy)ethyl]-1H-imidazol-3-ium chloride is developed to give 4,6-diarylpyrimidin-2(1H)-ones.
Key Words: Synthesis, 4,6-Diarylpyrimidin-2(1H)-ones, 1-Methyl-3-[2-(sulfooxy)ethyl]-1H-imidazol-3-ium chloride.
Pyrimidinones is an important class of heterocycles due
to their relevance to various biological, pharmaceutical and
therapeutic activities1, such as anticancer, anti HIV, antibacterial,
antimalarial, antihypertensive, sedative, anticonvulsant, anti-
thyroid, antihistaminic activities2-4. They are mostly used as
calcium channel blockers5,6, α-antagonista7 and neuropeptide-
antagonists8.
Biginelli9 first reported the one-step synthesis of 3,4-
dihydropyrimidin-2(1H)-one in alcohol using strong mineral
acid. Soon afterwards, various methods were reported con-
cerning the synthesis of pyrimidine derivatives. Few one-pot
syntheses have been published using different catalysts such
as chlorotrimethylsilane10, H3PMo12O4011, H6P2W18O62·18H2O12,
sulfamic acid13, Bi(TFA)3 immobilized in [nbpy]FeCl414, 2,4,6-
trichloro-1,3,5-triazine15, etc.
All melting points are uncorrected and were measured on
1
13
XT5 melting point apparatus. The H and C NMR spectra
were run on a Bruker Advance DMX 400 spectrometer in
CDCl3 using TMS as internal standard. Mass spectra were
obtained on a Bruker MicroTOF-QII instrument. The IR spectra
were obtained in potassium bromide pellets with a Bruker
27FTIR-Tensor using KBr optics.
Synthesis of 4,6-diarylpyrimidin-2(1H)-ones16: The
mixture of aromatic aldehyde (1 mmol), aryl ketone (1 mmol)
urea (4 mmol), ionic liquid (2 mL) and I (0.4 mol %) were
stirred at 90 ºC for the given time. After the completation
(monitored by TLC), the mixture was diluted with water. The
crude solid was filtered and washed with 95 % EtOH and then
recrystallized with 95 % EtOH/DMF (1/4) to provide the pure
product 4 (Scheme-I).
Herein, a novel catalyst synthesized in our lab, 1-methyl-
3-(2-(sulfooxy)ethyl)-1H-imidazol-3-ium chloride (I) was
firstly used to promote the simple preparation of 4,6-diarylethenes
pyrimidin-2(1H)-ones via an efficient one-step three-compo-
nent reaction of aromatic aldehyde, aromatic ketone and urea
in ionic liquid (Scheme-I).
Initially, to optimize the reaction condition, the effects of
solvents, reaction time and temperature on the yield of 4b were
evaluated and the results were summarized in Table-1. It was
found that ionic liquid afforded better yield than other solvents.
[Bpy]BF4 was better than [Bmim]BF4 may be due to its more
suitable polarity and acidity to dissolve the reactants. The
appreciable amount of catalyst was 0.4 mol %. However, the
increasing of catalytic loading could not enhance the yield of
the product (Table-1, entry 7). Subsequently, the best tempe-
rature was investigated. The results in Table-2 indicated the
optimal temperature was 90 ºC.
R1
CHO
COCH3
O
Cat.
N
+
+
[Bpy]BF4, 90oC
H2N
NH2
O
N
H
R2
R1
R2
2
3
4
1
To explore the application of this method, the scope of
the substrates was evaluated with a variety of aromatic
aldehydes and aromatic ketone (Table-3).
Cl
N
N
OSO3H
Cat.= H3C
Scheme-I: Synthesis of 4,6-diarylpyrimidin-2(1H)-ones

6446 Wan et al.
Asian J. Chem.
O
H
TABLE-1
SYNTHESIS OF 4b UNDER DIFFERENT CONDITIONSa
H
H
OH
O
OH
Ar'
O
OH O
+
H2N
..
NH2
Ar
Ar'
Ar
Ar'
Ar
H
Catalyst
(mol %)
Time
(h)
Isolated
yield (%)
3
1
2
Entry
Solvent
-H2O
O
O
1
2
CH3COCH3
EtOH
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.6
0.5
0.3
0.2
0.1
12
12
12
12
12
6
Nrb
NPc
Nrb
NPc
Nrb
79
O
..
NH2
OH
-H2O
HN
H2N
NH2
O
HN
Ar
N
3
DMF
Ar
Ar
Ar'
4
CH3CN
Ar'
4
Ar'
c
5
THF
Scheme-II
6
[Bmim]BF4
[Bpy]BF4
[Bpy]BF4
[Bpy]BF4
[Bpy]BF4
[Bpy]BF4
[Bpy]BF4
7
6
88
In summary, we report here a high yield one-pot synthesis
8
6
87
of 4,6-diarylpyrimidin-2(1H)-ones, from readily available
aromatic aldehydes, aromatic ketones and urea catalyzed by
1-methyl-3-[2-(sulfooxy)ethyl]-1H-imidazol-3-ium chloride.
This new protocol provides an environmentally benign route
along with the associated advantages of simplicity of operation
and higher atomic efficiency.
9
6
88
10
11
12
6
74
6
62
6
53
aReaction condition: 3,4-dimethoxybenzaldehyde (1 mmol), 4-
nitroacetophenone (1 mmol), and urea (4 mol) in 2 mL of different
b
solvents at 90 ºC using 0.4 mol % 0.4 mol % of I as catalyst. No
reaction. cNo desired products.
ACKNOWLEDGEMENTS
TABLE-2
SYNTHESIS OF 4b AT DIFFERENT TEMPERATUREa
The authors are grateful to the foundation of the Priority
Academic Program Development of Jiangsu Higher Educa-
tion Institutions, Qing Lan Project in Jiangsu Province (No.
08QL001T), Key Basic Research Project in Jiangsu University
(No. 10KJA430050), the Post-Graduate Innovation Project in
Jiangsu Province (No. CXZZ12_0979) and the Natural Science
Foundation of Jiangsu Normal University (No. 09XLA17, No.
09XLB05) for financial support.
Entry
T (ºC)
r.t
Isolated yield (%)
1
2
3
4
5
6
Nrb
Nrb
64
60
80
90
88
100
110
88
86
aReaction condition: 4-nitroacetophenone (1 mmol), 3,4-
dimethoxybenzaldehyde (1 mmol) and urea (4 mmol) in [Bpy]BF4 at
different temperature for 6 h catalyzed by 0.4 mol % of I. bNo reaction.
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