Efficient method for synthesis of the derivatives of 5-arylidene barbituric acid catalyzed by aminosulfonic acid with grinding

Article abstract of DOI:10.1080/00397910500451324

Aminosulfonic acid is an environmentally friendly catalyst. Grinding a mixture of aromatic aldehydes, barbituric acid, and H₂NSO ₃H at room temperature (without any solvent) gave 5-arylidene barbituric acid in high yields, providing a simple and efficient route to synthesis of these compounds. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500451324

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Efficient Method for Synthesis of the
Derivatives of 5‐Arylidene Barbituric Acid
Catalyzed by Aminosulfonic Acid With
Grinding
Ji‐Tai Li a , Hong‐Guang Dai a , Da Liu a & Tong‐Shuang Li a
a College of Chemistry and Environmental Science, Hebei University, Key
Laboratory of Analytical Science and Technology of Hebei Province, Baoding,
China
Version of record first published: 16 Aug 2006.
To cite this article: Ji‐Tai Li , Hong‐Guang Dai , Da Liu & Tong‐Shuang Li (2006): Efficient Method for
Synthesis of the Derivatives of 5‐Arylidene Barbituric Acid Catalyzed by Aminosulfonic Acid With Grinding,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
36:6, 789-794
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Synthetic Communicationsw, 36: 789–794, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500451324
Efficient Method for Synthesis of the
Derivatives of 5-Arylidene Barbituric Acid
Catalyzed by Aminosulfonic Acid
With Grinding
Ji-Tai Li, Hong-Guang Dai, Da Liu, and Tong-Shuang Li
College of Chemistry and Environmental Science, Hebei University,
Key Laboratory of Analytical Science and Technology of
Hebei Province, Baoding, China
Abstract: Aminosulfonic acid is an environmentally friendly catalyst. Grinding a
mixture of aromatic aldehydes, barbituric acid, and H2NSO3H at room temperature
(without any solvent) gave 5-arylidene barbituric acid in high yields, providing a
simple and efficient route to synthesis of these compounds.
Keywords: Aminosulfonic acid, aromatic aldehyde, 5-arylidene barbituric acid,
barbituric acid, grinding method
INTRODUCTION
Some barbituric acid derivatives have been widely used as sedative, hypnotic,
anticonvulsant, antispasmodic, and local anaesthetic agents.[1] Benzylidene
barbituric acids are useful as potential organic oxidizers, for the preparation
of oxadeazaflavines, and for the asymmetrical synthesis of disulfides.[2]
Some of them have been recently studied as nonlinear optical materials.[3]
Over the past few years, many synthetic methods[3–7] for preparation of
these compounds have been reported, such as infrared irradiation[3] and
Received in Japan July 15, 2005
Address correspondence to Ji-Tai Li, College of Chemistry and Environmental
Science, Hebei University , Hezuo Road No. 88, Baoding 071002, China. Fax: þ86-
312-5079628; E-mail: lijitai@yahoo.com.cn
789

790
J.-T. Li et al.
microwave irradiation.[4] However, many of these procedures involve
expensive reagents, higher temperatures, and lower yields.
Aminosulfonic acid[8] has been extensively used as a catalyst for many
organic reactions, such as the esterification of carboxylic acids; the
oxidation of aromatic aldehydes to carboxylic acids; the preparation of
amines by decarbonylation of carboxamides with sodium hypochlorite; the
synthesis of anthroquinonecarboxamides from anthroquinonecarboxylic
acids; synthesis of dihydropyrimidinones via condensation of aldehydes,
b-keto esters, and urea[9]; and synthesis of bis(indolyl)methanes from indole
and aromatic aldehydes[10]
.
The grinding method is used more and more frequently in organic
synthesis in the past three decades. Compared with traditional methods, this
method is more convenient and easily controlled. A great number of
organic reactions can be carried out in higher yields, shorter times, or
milder conditions by the grinding method. It can even set off some
reactions that cannot be carried out under traditional conditions.[11]
All of these results spurred us to study the possibility of Knoevenagel
condensation of aromatic aldehydes with barbituric acid catalyzed by amino-
sulfonic acid without solvent. Herein, we report the condensation using
aminosulfonic acid as catalyst under solvent-free conditions by the grinding
method at room temperature (Scheme 1).
RESULTS AND DISCUSSION
As shown in Table 1, the effects of different catalysts, such as potassium acid
phthalate, NH4Cl, 4-CH3C6H4SO3H, and NH2SO3H, on the reaction were
examined. Among these catalysts, aminosulfonic acid was found to be an
excellent catalyst in terms of yield and cost. So, we chose aminosulfonic
acid as the catalyst for synthesis of 5-arylidene barbituric acid by the
grinding method.
We studied the influence of the amount of the catalyst on the yield. As
shown in Table 2, increasing the quantity of the catalyst can improve the
reaction yields. For example, without catalyst the yield is 35%, whereas
using 100% mol H2NSO3H, the yield of 3i is 96% for the same period
(120 min) using the grinding method.
Scheme 1.

5-Arylidene Barbituric Acid Derivatives
791
Table 1. Effects of catalysts on the reaction of 4-ClC6H4CHO and
barbituric acid
Grinding Laying
time, min time, min Yield, %
Entry
Catalysta
1
2
3
4
Potassium acid phthalate
NH4Cl
5
5
5
5
30
30
30
30
23
53
81
80
4-CH3C6H4SO3H
NH2SO3H
aThe amount of catalyst is 100% mol. Barbituric acid, 2 mmol
(256 mg); aldehyde, 2 mmol (281 mg).
As shown in Table 3, increasing the grinding time can improve the
reaction yields. For example, when the grinding time is 1 min, the yield of
3b is 69%, whereas when the grinding time is 10 min, the yield of 3b is 86%.
From the results in Table 1, Table 2, and Table 3, the reaction conditions
we chose were aromatic aldehyde (2 mmol), barbituric acid (2 mmol),
H2NSO3H (2 mmol), and grinding the mixture for 10 min. Under these
reaction conditions, we did a series of experiments for the condensation of
barbituric acid with different aldehydes using the grinding method.
The results are summarized in Table 4. It can easily be seen that the
solvent-free grinding method represented a good procedure in terms of the
high yield, mild reaction condition, and easy workup. For example, under
solvent-free conditions using the grinding method, compounds 3b, 3f, 3i,
and 3j were obtained in high yields (93%, 94%, 96%, 94%). Also, the
present procedure also got a good result on a 100-mmol scale for 1b. The
reaction in the absence of solvent has a high concentration of reactants, and
the surface area of the catalyst increases greatly upon being ground.
The steric hindrance affects the yields too. As shown in Table 4, when the
amount of the catalyst was 100% mol, 3b was obtained in 93% yield within
190 min, but the reaction of babituric acid with 1a gave 3a in only 85%
yield within 250 min.
Table 2. Effects of amount of H2NSO3H on the reaction of 4-(CH3)2
NC6H4CHO and barbituric acid
Grinding time,
min
Laying time,
min
Amount of
catalyst, %mol
Yield,
%
Entry
1
2
3
4
10
10
10
10
120
120
120
120
0
10
35
87
96
96
100
150
Note: Barbituric acid, 2 mmol (256 mg); aldehyde, 2 mmol (298 mg).

792
J.-T. Li et al.
Table 3. Effects of grinding time on the reaction of
4-ClC6H4CHO and barbituric acid catalyzed by 100%
mol NH2SO3H
Grinding time,
min
Laying time,
min
Yield,
%
Entry
1
2
3
4
1
5
30
30
30
30
69
80
86
84
10
15
Note: Barbituric acid, 2 mmol (256 mg); aldehyde,
2 mmol (281 mg).
CONCLUSION
In conclusion, we have found a practical Knoevenagel condensation procedure
for the preparation of 5-arylidene barbituric acid catalyzed by H2NSO3H by
the grinding method.
EXPERIMENTAL
Melting points are uncorrected. 1H NMR spectra were measured on a Bruker
Advance 400 (400-MHz) spectrometer using TMS as internal standard and
DMSO as solvent.
Table 4. Condensation of barbituric acid with aromatic aldehydesa
Laying
time, h
Yield,
%
Entry
Ar
mp,8C (lit.)
a
b
bb
c
3-ClC6H4
4-ClC6H4
4-ClC6H4
4
3
3
4
6
4
6
6
4
2
4
273–275 (274–278)[12]
298–300 (304–308)[12]
298–300 (304–308)[12]
269–271 (265–270)[12]
251–253 (248–250)[12]
282–284 (278–280)[12]
307–309 (298–300)[12]
309–313 (313)[13]
85
93
96
89
47
65
94
87
81
96
94
2,4-Cl2C6H3
3-NO2C6H4
4-CH3C6H4
d
e
f
4-CH3OC6H4
3-CH3O-4-HOC6H3
C6H5CH55CH
4-(CH3)2NC6H4
4-HOC6H4
g
h
i
274–276 (250)[7]
282–284 (278–282)[12]
.350
j
aThe grinding time is 10 min.
bThe reaction was done on a 100-mmol scale.

5-Arylidene Barbituric Acid Derivatives
General Procedure
793
Barbituric acid (2 mmol), aromatic aldehyde (2 mmol), and H2NSO3H
(2 mmol) were added to a mortar. The mixture was ground by mortar and
pestle at room temperature for 10 min and was kept at room temperature in
a desiccator. The mixture was dissolved in DMSO, and the solution was
poured into H2O. The precipitate was washed with boiling H2O and then
washed with EtOH, affording 3a–3j.The authenticity of the products was
1
established by comparing their melting points and H NMR spectra with the
data in the literature.
1
3 h: H NMR (400 MHz, DMSO): dH 7.49–7.73 (6H, m), 8.015 (1H, d,
J ¼ 12 Hz), 8.44 (1H, t, J ¼ 12 Hz), 11.21 (1H, s, NH), 11.26 (1H, s, NH).
1
3j: H NMR (400 MHz, DMSO): dH 6.88 (2H, s), 8.21 (1H, s), 8.33 (2H, s),
10.79 (1H, s, OH), 11.11 (1H, s, NH), 11.24 (1H, s, NH).
ACKNOWLEDGMENTS
Educational Ministry of China, Educational Department of Hebei Province
(2001104), and Natural Science Foundation of Hebei Province (203107),
China, supported the project.
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