1-n-butyl-3-methylimmidazolium tetrafluoroborate-promoted green synthesis of 5-arylidene barbituric acids and thiobarbituric acid derivatives

Article abstract of DOI:10.1080/00397910500288254

The room temperature ionic liquid 1-n-butyl-3-methylimmidazolium tetra-fluoroborate ([bmim]BF₄) was used to promote the synthesis of 5-arylidene barbituric acids and thiobarbituric acid derivatives under the solid-state conditions of grinding or microwave irradiation without organic solvent. The yields were 77.9-96.2%. It is shown that the proposed method is fast, efficient, and environmentally benign. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1080/00397910500288254

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1‐n‐Butyl‐3‐Methylimmidazolium
Tetrafluoroborate–Promoted
Green Synthesis of 5‐Arylidene
Barbituric Acids and
Thiobarbituric Acid Derivatives
Chun Wang a , Jing‐jun Ma a , Xin Zhou a , Xiao‐huan
Zang a , Zhi Wang a , Yong‐jun Gao a & Peng‐lei Cui a
a College of Sciences, Agricultural University of
Hebei, Baoding, China
Version of record first published: 22 Aug 2006.
To cite this article: Chun Wang , Jing‐jun Ma , Xin Zhou , Xiao‐huan Zang , Zhi
Wang , Yong‐jun Gao & Peng‐lei Cui (2005): 1‐n‐Butyl‐3‐Methylimmidazolium
Tetrafluoroborate–Promoted Green Synthesis of 5‐Arylidene Barbituric Acids and
Thiobarbituric Acid Derivatives, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 35:21, 2759-2764
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Synthetic Communicationsw, 35: 2759–2764, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500288254
1-n-Butyl-3-Methylimmidazolium
Tetrafluoroborate–Promoted Green
Synthesis of 5-Arylidene Barbituric Acids
and Thiobarbituric Acid Derivatives
Chun Wang, Jing-jun Ma, Xin Zhou, Xiao-huan Zang,
Zhi Wang, Yong-jun Gao, and Peng-lei Cui
College of Sciences, Agricultural University of Hebei,
Baoding, China
Abstract: The room temperature ionic liquid 1-n-butyl-3-methylimmidazolium tetra-
fluoroborate ([bmim]BF4) was used to promote the synthesis of 5-arylidene barbituric
acids and thiobarbituric acid derivatives under the solid-state conditions of grinding or
microwave irradiation without organic solvent. The yields were 77.9–96.2%. It is
shown that the proposed method is fast, efficient, and environmentally benign.
Keywords: 5-Arylidene barbituric acid, 5-arylidene thiobarbituric acid, ionic liquid,
synthesis
The derivatives of 5-arylidene barbituric acids are an important class of
hypnotic and sedative compounds; the arylidene thiobarbituric acid deriva-
tives are valuable intermediates in synthesis of arylthiobarbituric derivatives,
heterocyclic compounds, and as medicinal antioxidants, organic thermal
stabilizers, and charge-generating agents. It is well known that 5-arylidene
barbituric acids and thiobarbituric acids derivatives could be prepared by
the Knoevenagel condensation reaction of carbonyl compounds with
barbituric acid or 2-thiobarbituric acid in homogeneous systems[1,2] or
Received in Japan May 8, 2005
Address correspondence to Chun Wang, College of Sciences, Agricultural
University of Hebei, Baoding 071001, China. E-mail: wangc69@yahoo.com.cn
2759

2760
C. Wang et al.
under solvent-free conditions.[3,4] However, these methods have not been
entirely satisfactory and are associated with shortcomings such as longer
reaction time, lower yields, and production of waste organic solvent.
There has been a growing interest in using ionic liquids as green media in
organic synthesis and these are foreseen as an active area of research in the
future because of their negligible vapor pressure, tunable polarity, high
thermal stability, good solvating ability, and ease of recyclability.[5–7]
Microwave-assisted synthesis also received considerable attention in recent
years because of its rate enhancement when compared with conventional
heating.[8,9]
In continuation our endeavor in green chemistry,[10,11] herein we report a
simple and efficient procedure for the preparation of 5-alkylene barbituric
acids derivatives under the solid-state conditions of grinding or microwave
irradiation in room temperature ionic liquid 1-n-butyl-3-methylimmidazolium
tetrafluoroborate ([bmim]BF4) (Scheme 1).
EXPERIMENTAL
Melting points were recorded on an electrothermal apparatus and are uncor-
1
rected. H NMR (400 MHz) and 12C NMR (100 MHz) spectra were deter-
mined with a JEOL-JNM-GSX 400 spectrometer (DMSO-d6) using TMS as
internal standard. IR spectra (cm21) were measured with a Jasco FT/IR-800
spectrometer. UV spectra were measured with UV-1100 photemeter.
[bmim]BF4 were synthesized according to the literature.[12]
General Procedure
Synthesis Under Grinding Conditions
The mixture of 2.2 mmol of aromatic aldehydes 1, 2 mmol of barbituric acid or
2-thiobarbituric acid 2 and, 0.2 mL of [bmim]BF4 were ground with an agate
mortar and pestle for 5 min and kept standing at room temperture for 2 h.
The products were washed with 5 mL of water, 2 mL of diethyl ether, and
Scheme 1.

Green Synthesis of Barbituric Acid Derivatives
2761
5 mL of boiling water respectively. The products 3a–3p were given as shown
in Table 1.
Synthesis Under Microwave-Irradiation Conditions
The mixture of 2.2 mmol of aromatic aldehydes 1, 2 mmol of barbituric acid or
2-thiobarbituric acid 2, and 0.2 mL of [bmim]BF4 was mixed thoroughly in a
10-mL beaker. The mixture was subjected to microwave irradiation for 20 s
(160 W); then, the products were washed with 5 mL of water, 2 mL of
diethyl ether, and 5 mL of boiling water respectively. The products 3a–3p
were given as shown in Table 1.
From Table 1, we can see that a wide range of aromatic aldehydes, which
contain either electron-donating groups or electron-withdrawn groups, can
undergo the condensation reaction with reasonably high yields. In contrast,
the yields of the products were very low if ionic liquid was not added to the
mixture of reactants, such as the yield of 3h (25% and 21% under grinding
and microwave irradiation condition respectively without ionic liquid).
In conclusion, we have developed a simple and efficient method for the
preparation of 5-alkylene barbituric acids derivatives with high yield, time
savings, and minimal environment impact.
Table 1. Condensation reaction of aromatic aldehydes and barbituric acid or 2-thio-
barbituric acid
Yield Yield
(%)b
Entry
Ar
X
mp (8C)
mp (8C)[Lit]
(%)a
3a
3b
3c
3d
3e
3f
4-(CH3)2NC6H4
3-O2NC6H4
4-ClC6H4
O
O
O
O
O
O
O
S
272–273
242–243
292–293
267–268
.300
287–289
251–253
258–259
261–263
247–248
.300
284–285
.300
234–236
.300
264–266
274–276[4]
245–245.5[4]
298.5–300.5[4]
267.5–268[4]
.300[4]
96.2
78.7
77.9
91.9
95.2
93.1
79.8
87.8
91.5
92.5
94.2
91.5
92.8
91.8
92.4
95.9
98.7
89.4
81.8
92.3
98.2
95.4
87.3
95.3
89.7
94.6
90.1
90.6
85.7
89.4
94.4
96.1
2-CH3OC6H4
4-HOC6H4
4-CH3OC6H4
C6H5CH55CH
4-(CH3)2NC6H4
3-O2NC6H4
287–289[4]
2504
3g
3h
3i
257–258.3[13]
261.5–264.5[13]
246–247[13]
.300[13]
S
3j
2-O2NC6H4
S
3k
3l
3,4-(OCH2O)C6H3
2-CH3OC6H4
4-ClC6H4
S
S
288.5–289.5[13]
.300[13]
3m
3n
3o
3p
S
2- ClC6H4
4-CH3OC6H4
C6H5CH55CH
S
234–235.5[13]
.300[13]
S
S
264.5–265.5[13]
aYields of grinding reaction.
bYields of microwave irradiation reaction.

2762
C. Wang et al.
3a: 1H NMR (DMSO-d6, 400 MHz) d: 3.12 (s, 6H), 6.80 (d, J ¼ 9.2 Hz,
2H), 8.15 (s, 1H), 8.42 (d, J ¼ 9.5 Hz, 2H), 10.90 (s, 1H), 11.03 (s, 1H); 13C
NMR (DMSO-d6, 100 MHz) d: 39.65, 109.53, 111.18, 119.97, 139.03, 150.29,
154.16, 155.47, 162.69, 164.68; IR (KBr): 3549, 3200, 1730, 1680, 1655,
1608, 1377 cm21
.
3b: 1H NMR (DMSO-d6, 400 MHz) d: 7.64–8.32 (m, 4H), 8.90 (s, 1H),
11.36 (s, 1H), 11.51 (s, 1H); 13C NMR (DMSO-d6, 100 MHz) d: 121.79,
125.77, 126.50, 129.78, 134.81, 131.85, 147.52, 150.67, 151.78, 161.90,
163.24.
1
3c: H NMR (DMSO-d6, 400 MHz) d: 7.54 (d, J ¼ 8.6 Hz, 2H), 8.08
(d, J ¼ 8.6 Hz, 2H), 8.25 (s, 1H), 11.27 (s, 1H), 11.41 (s, 1H); 13C NMR
(DMSO-d6, 100 MHz) d: 119.67, 128.07, 131.57, 134.65, 136.70, 150.13,
152.95, 161.55, 163.17; IR (KBr): 3213, 3094, 1755, 1701, 1669, 1550 cm21
.
1
3d: H NMR (DMSO-d6, 400 MHz) d: 3.88 (s, 3H), 6.98 (t, J ¼ 7.6 Hz,
1H), 7.11 (d, J ¼ 8.2 Hz, 1H), 7.50–7.54 (m, 1H), 8.01 (dd, J ¼ 1.2 Hz,
7.5 Hz, 1H), 8.50 (s, 1H), 11.16 (s, 1H), 11.34 (s, 1H); 13C NMR (DMSO-
d6, 100 MHz) d: 55.89, 110.97, 118.57, 119.46, 121.50, 132.44, 134.09,
149.88, 150.22, 158.99, 161.42, 163.39; IR (KBr): 3200, 3085,1715, 1695,
1650, 1580 cm21
.
1
3e: H NMR (DMSO-d6, 400 MHz) d: 6.88 (d, J ¼ 118.1 Hz, 2H), 8.21
(s, 1H), 8.33 (d, J ¼ 8.1 Hz, 2H), 10.82 (s, 1H), 11.12 (s, 1H), 11.25
(s, 1H); 13C NMR (DMSO-d6, 100 MHz) d: 114.22, 115.52, 123.82, 138.30,
150.22, 155.55, 162.29, 163.03, 164.11; IR (KBr): 3274, 3090, 1718, 1697,
1670, 1614, 1535, 1219, 1186 cm21
.
1
3f: H NMR (DMSO-d6, 400 MHz) d: 3.86 (s, 3H), 7.15 (d, J ¼ 8.3 Hz,
2H), 8.43 (d, J ¼ 8.3 Hz, 2H), 8.24 (s, 1H), 11.04 (s, 1H), 11.17 (s, 1H); IR
(KBr): 3200, 3085, 1715, 1695, 1650, 1580, 1418 cm21
.
3g: 1H NMR (DMSO-d6, 400 MHz) d: 7.43–7.67 (m, 5H), 7.68 (d, 1H),
8.00 (d, 1H), 8.43 (m, 1H), 11.22 (s, 1H), 11.27 (s, 1H); 13C NMR (DMSO-d6,
100 MHz) d: 116.02, 124.59, 128.90, 129.56, 131.48, 135.62, 150.73, 152.96,
154.07, 163.39, 163.53.
3h: 1H NMR (DMSO-d6, 400 MHz) d: 3.15 (s, 6H), 6.81 (d, J ¼ 9.4 Hz,
2H), 8.14 (s, 1H), 8.45 (d, J ¼ 9.4 Hz, 2H), 12.02 (s, 1H), 12.12 (s, 1H); 13C
NMR (DMSO-d6, 100 MHz) d: 94.21, 109.68, 111.93, 120.83, 140.18, 155.22,
156.61, 160.89, 163.47, 177.93; IR: 3065, 1649, 1527, 1485, 1458,
1359 cm21
.
3i: 1H NMR (DMSO-d6, 400 MHz) d: 7.78 (s, 1H), 7.89 (t, J ¼ 8.0 Hz),
7.97 (d, J ¼ 7.4 Hz, 1H), 9.32 (d, J ¼ 7.4 Hz, 1H), 10.13 (s, 1H), 11.71
(s, 1H); 13C NMR (DMSO-d6, 100 MHz) d: 173.0, 162.9, 178.2, 147.6,
145.7, 137.1, 135.0, 133.6, 130.8, 128.5, 123.9; IR (KBr): 3447, 3069,
1711, 1660, 1610, 1585, 1523, 1386, 1352 cm21
.
1
3j: H NMR (DMSO-d6, 400 MHz) d: 7.62 (d, J ¼ 7.7 Hz, 1H), 7.69
(t, J ¼ 8.4 Hz, 1H), 7.79 (t, J ¼ 7.5 Hz, 1H), 8.24 (d, J ¼ 8.4 Hz, 1H), 8.63
(s, 1H), 12.33 (s, 1H), 12.56 (s, 1H); 13C NMR (DMSO-d6, 100 MHz)
d: 120.48, 123.96, 130.27, 130.36, 131.44, 133.65, 146.16, 153.18, 159.05,

Green Synthesis of Barbituric Acid Derivatives
2763
160.50, 178.92; IR (KBr): 3269, 3163, 3030, 1724, 1697, 1630, 1543, 1520,
1442, 1354 cm21
.
3k: 1H NMR (DMSO-d6, 400 MHz) d: 6.20 (s, 2H), 7.10 (d, J ¼ 8.2 Hz,
1H), 7.80 (dd, J ¼ 1.7 Hz, J ¼ 8.2 Hz, 1H), 8.23 (s, 1H), 8.30 (d, J ¼ 1.7 Hz,
1H), 12.31 (s, 1H), 12.41 (s, 1H); 13C NMR (DMSO-d6, 100 MHz) d: 78.84,
102.22, 106.19, 108.49, 115.85, 128.47, 131.39, 148.25, 152.67, 159.88,
162.02, 178.14; IR (KBr): 3231, 3165, 1691, 1670, 1523, 1452, 1386 cm21
.
1
3l: H NMR (DMSO-d6, 400 MHz) d: 3.88 (s, 3H), 6.98 (t, J ¼ 7.6 Hz,
1H), 7.11 (d, J ¼ 8.5 Hz, 1H), 7.53–7.56 (m, 1H), 8.08 (d, J ¼ 8.0 Hz, 1H),
8.53 (s, 1H), 12.27 (s, 1H), 12.41 (s, 1H); 13C NMR (DMSO-d6, 100 MHz)
d: 55.90, 111.01, 118.42, 119.47, 121.34, 132.58, 134.76, 150.56, 159.24,
161.63, 178.53; IR (KBr): 3125, 3072, 1705, 1655, 1595, 1537, 1437,
1390 cm21
.
1
3m: H NMR (DMSO-d6, 400 MHz) d: 7.55 (d, J ¼ 8.6 Hz, 2H), 8.13
(d, J ¼ 8.6 Hz, 2H), 8.26 (s, 1H), 12.36 (s, 1H), 12.48 (s, 1H); 13C NMR
(DMSO-d6, 100 MHz) d: 119.62, 128.08, 131.45, 134.87, 137.10, 159.35,
161.40, 162.85, 178.50; IR (KBr): 3055, 1701, 1657, 1568, 1537, 1421,
1388 cm21
.
1
3n: H NMR (DMSO-d6, 400 MHz) d: 7.37 (t, J ¼ 7.2 Hz, 1H), 7.49
(t, J ¼ 8.4 Hz, 1H), 7.56 (d, J ¼ 8.1 Hz, 1H), 7.82 (d, J ¼ 8.1 Hz, 1H), 8.31
(s, 1H), 12.35 (s, 1H), 12.53 (s, 1H); 13C NMR (DMSO-d6, 100 MHz)
d: 121.63, 126.25, 127.82, 128.86, 131.96, 132.24, 133.381, 150.191,
158.75, 160.81, 178.77; IR (KBr): 3086, 1720, 1680, 1595, 1562, 1454,
1379 cm21
.
3o: 1H NMR (DMSO-d6, 400 MHz) d: 3.89 (s, 3H), 7.08 (d, J ¼ 9.1 Hz,
2H), 8.27 (s, 1H), 8.42 (d, J ¼ 9.1 Hz, 2H), 12.28 (s, 1H), 12.37 (s, 1H); 13C
NMR (DMSO-d6, 100 MHz) d: 55.71, 114.02, 115.52, 125.21, 129.56, 131.73,
134.51, 159.87, 163.90, 178.19; IR (KBr): 3069, 1695, 1651, 1601, 1562,
1522, 1431, 1269 cm21
.
1
3p: H NMR (DMSO-d6, 400 MHz) d: 7.50 (t, J ¼ 3.0 Hz, 3H), 7.69–
7.71 (m, 2H), 7.79 (d, J ¼ 15.4 Hz, 1H), 8.06 (d, J ¼ 11.8 Hz, 1H), 8.45
(dd, J ¼ 15.4 Hz, J ¼ 11.8 Hz, 1H), 12.33 (s, 1H), 12.37 (s, 1H); 13C NMR
(DMSO-d6, 100 MHz) d: 115.81, 124.47, 128.72, 129.25, 131.44, 135.17,
153.68, 154.59, 160.76, 161.27, 178.46; IR (KBr) n: 3074, 1653, 1599,
1556, 1522, 1450, 1379 cm21
.
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