Simple procedure for the synthesis of arylmethylenemalononitrile without catalyst

Article abstract of DOI:10.1081/SCC-200064966

Knoevenagel condensation of malononitrile with aromatic aldehydes can be achieved at room temperature in the absence of catalysts in short time, and the products of arylmethylenemalononitriles were isolated in a practically pure form without further purification. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200064966

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Simple Procedure
for the Synthesis of
Arylmethylenemalononitrile
Without Catalyst
Xiang‐Shan Wang a b c , Zhao‐Sen Zeng a , Yu‐Ling Li a
c , Da‐Qing Shi a c , Shu‐Jiang Tu a c , Xian‐Yong Wei b
& Zhi‐Min Zong b
a Department of Chemistry, Xuzhou Normal
University, Xuzhou Jiangsu, China
b School of Chemical Engineering, China University
of Mining and Technology, Xuzhou Jiangsu, China
c Key Laboratory of Biotechnology on Medical Plant,
Xuzhou Jiangsu, China
Published online: 16 Aug 2006.
To cite this article: XiangShan Wang , ZhaoSen Zeng , YuLing Li , DaQing Shi ,
ShuJiang Tu , XianYong Wei & ZhiMin Zong (2005) Simple Procedure for the Synthesis
of Arylmethylenemalononitrile Without Catalyst, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 35:14,
1915-1920, DOI: 10.1081/SCC-200064966
To link to this article: http://dx.doi.org/10.1081/SCC-200064966
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Synthetic Communicationsw, 35: 1915–1920, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200064966
Simple Procedure for the Synthesis
of Arylmethylenemalononitrile
Without Catalyst
Xiang-Shan Wang
Department of Chemistry, Xuzhou Normal University, Xuzhou Jiangsu,
China, School of Chemical Engineering, China University of Mining and
Technology, Xuzhou Jiangsu, China and Key Laboratory of
Biotechnology on Medical Plant, Xuzhou Jiangsu, China
Zhao-Sen Zeng
Department of Chemistry, Xuzhou Normal University,
Xuzhou Jiangsu, China
Yu-Ling Li, Da-Qing Shi, and Shu-Jiang Tu
Department of Chemistry, Xuzhou Normal University, Xuzhou Jiangsu,
China and Key Laboratory of Biotechnology on Medical Plant, Xuzhou
Jiangsu, China
Xian-Yong Wei and Zhi-Min Zong
School of Chemical Engineering, China University of Mining and
Technology, Xuzhou Jiangsu, China
Abstract: Knoevenagel condensation of malononitrile with aromatic aldehydes can be
achieved at room temperature in the absence of catalysts in short time, and the products
of arylmethylenemalononitriles were isolated in a practically pure form without further
purification.
Keywords: Arylmethylenemalononitrile, malononitrile, Knoevenagel condensation
Received in Japan January 17, 2005
Address correspondence to Xiang-Shan Wang, Department of Chemistry, Xuzhou
Normal University, Xuzhou Jiangsu 221116, China. E-mail: xswang1974@yahoo.com
1915

1916
X.-S. Wang et al.
Arylmethylenemalononitriles are an important precursor of potentially
bioactive pyrimidine derivatives,[1] and also are versatile tools for the construc-
tion of a variety of novel complex heterocycles.[2] They can be prepared via
Knoevenagel condensation,[3–14] which is one of the most common
synthetic methods of effecting carbon–carbon bond formation between
malononitrile and various aromatic aldehydes. The reaction is usually
catalyzed by various amines or their corresponding ammonium salts.[3]
Subsequently, the use of Al2O3,[4] silica gel functionalized with amino
groups,[5] BiCl3,[6] CdI2,[7] TiCl4 base,[8] K3PO4,[9] KF/Al2O3,[10] zeolite,[11]
xonntlite,[12] anion-exchange resin,[13] and many other methods[14] have
been reported. More recently, Knoevenagel reactions under solvent-free
conditions carried out by microwave irradiation,[15] by PEG400 and
anhydrous K2CO3,[16] and by grinding methods[17] has rapidly increased.
To our surprise, we found by chance that when aromatic aldehydes and
malononitrile are added together in ethanol (Scheme 1), this reaction can be
easily achieved at room temperature without catalysts in a few minutes or
within a few hours. We have examined the reaction by various aromatic
aldehydes containing electron-withdrawing or electron-donating groups as
reactants; they all gave the expected result with good to excellent yield for
almost all the tested substrates. The results are summarized in Table 1.
From Table 1, we can see that the electronic effect of substituents is the key
element for the rates of the reaction and the product yield. The derivatives
of benzaldehyde bearing electron-withdrawing substituents such as –Cl and
–NO2 gave higher reaction rates and yields than those with electron-releasing
groups such as –N(CH3)2 and –OCH3. We cannot exactly explain the reason
why a longer reaction time was necessary and gave lower yield for the
reactants with 4-hydroxybenzaldehyde and 3-methoxy-4-hydroxybenzalde-
hyde. Allthemeltingpointsoftheknowncompoundsconformtothereferences;
the structures of the new compounds are characterized by IR and 1H NMR.
In conclusion, we found a simple method for the synthesis of arylmethy-
lenemalononitrile. This method has the advantages of an easy workup and
milder reaction conditions.
EXPERIMENTAL
Melting points were determined on XT-5 microscopic melting-point
spectrometer and are uncorrected. IR spectra were recorded on a Tensor 27
Scheme 1.

Arylmethylenemalononitrile
1917
Table 1. Reaction time, yields, and melting points of the products 3
Mp (8C)
Reported
Time
(h)
Yields
(%)
Entry
Ar
Found
3a
3b
3c
3d
3e
3f
C6H5
4-CH3C6H4
4-CH3OC6H4
3
2
63.6
96.0
75.4
88.4
98.0
92.0
92.0
91.5
75.0
48.5
47.5
91.0
97.3
94.6
92.1
94.6
66.4
89.3
86.9
85.3
94.7
56.0
86.0
82–84
82–83[17]
133–135[13]
111–112[13]
199–201[13]
161–16[13]
95–96[13]
102–104[13]
154–155[13]
180–182[13]
186–187[13]
137–138[17]
120–121[13]
—
131–133
112–114
200–201
159–161
97–98
6
3,4-OCH2OC6H3
4-ClC6H4
2-ClC6H4
6
0.2
0.2
1.5
0.2
8
3g
3h
3i
3-NO2C6H4
2,4-Cl2C6H3
103–105
152–153
181–183
190–191
135–136
119–120
153–155
84–86
4-(CH3)2NC6H4
4-OHC6H4
3j
24
36
0.2
0.2
4
3k
3l
3-CH3O-4-OHC6H3
3-ClC6H4
4-BrC6H4
3m
3n
3o
3p
3q
3r
3s
2-CH3OC6H4
2,3-(CH3O)2C6H3
3,4-Cl2C6H3
—
—
3
101–103
145–147
140–142
138–140
148–150
111–113
137–138
119–121
141–142
0.2
4
—
—
2,4-(CH3O)2C6H3
2-NO2-4-ClC6H3
2-NO2-3,4-(CH3O)2C6H2
2-NO2-3,4-OCH2OC6H2
2-NO2C6H4
1
—
—
4
3t
4
—
—
3u
3v
3w
0.2
4
3,4-(CH3)2C6H3
3,4-(CH3O)2C6H3
—
—
4
spectrometer in KBr. 1H NMR spectra were obtained from solution in CDCl3
with Me4Si as internal standard using a Bruker-400 spectrometer.
A 50-mL flask was charged with malononiteile 3.3 g (50 mmol), aromatic
aldehydes (50 mmol), and ethyl alcohol (25 mL); the mixture was stirred at
room temperature for times listed in Table 1. Without any further purification,
the precipitate was filtered off to give 3.
1
The IR and H NMR of the new compounds are as follows.
3m: IR (KBr, n, cm21): 3092, 3032, 2226, 1578, 1553, 1488, 1407, 1366,
1
1289, 1214, 1070, 1007, 938, 823 cm21. H NMR: 7.69 (d, J ¼ 8.4 Hz, 2H,
ArH), 7.72 (s, 1H, CH55), 7.77 (d, J ¼ 8.4 Hz, 2H, ArH).
3n: IR (KBr, n, cm21): 3046, 2977, 2944, 2223, 1579, 1483, 1465,
1
1433, 1369, 1295, 1254, 1167, 1111, 1021, 755, 616 cm21. H NMR: 3.93
(s, 3H, CH3O), 6.99 (d, J ¼ 8.4 Hz, 1H, ArH), 7.08 (dd, J ¼ 8.0 Hz,
J0 ¼ 1.6 Hz, 1H, ArH), 7.58 (dd, J ¼ 8.0 Hz, J0 ¼ 1.6 Hz, 1H, ArH), 8.19
(d, J ¼ 8.4 Hz, 2H, ArH), 8.31 (s, 1H, CH55).
3o: IR (KBr, n, cm21): 3049, 2970, 2940, 2840, 2226, 1589, 1570, 1481,
1
1428, 1310, 1281, 1223, 1074, 990, 792, 751 cm21. H NMR: 3.91 (s, 3H,

1918
X.-S. Wang et al.
CH3O), 3.95 (s, 3H, CH3O), 7.15–7.21 (m, 2H, ArH), 7.85 (dd, J ¼ 7.6 Hz,
J0 ¼ 2.8 Hz, 1H, ArH), 8.26 (s, 1H, CH55).
3p: IR (KBr, n, cm21): 3087, 3036, 2230, 1594, 1546, 1471, 1360, 1285,
1218, 1134, 1032, 952, 910, 883, 821, 699, 665 cm21 1H NMR: 7.63
.
(d, J ¼ 8.4 Hz, 1H, ArH), 7.68 (s, 1H, CH55), 7.81 (dd, J ¼ 8.4 Hz,
J0 ¼ 2.0 Hz, 1H, ArH), 7.94 (d, J ¼ 2.0 Hz, 1H, ArH).
3q: IR (KBr, n, cm21): 3090, 3037, 2976, 2945, 2844, 2222, 1609, 1562,
1492, 1471, 1430, 1356, 1305, 1281, 1212, 1164, 1121, 1038, 1021, 852,
807 cm21 1H NMR: 3.90 (s, 3H, CH3O), 3.91 (s, 3H, CH3O), 6.44
.
(d, J ¼ 2.0 Hz, 1H, ArH), 6.61 (dd, J ¼ 8.8 Hz, J0 ¼ 2.0 Hz, 1H, ArH), 8.18
(s, 1H, CH55), 8.27 (d, J ¼ 8.8 Hz, 2H, ArH).
3r: IR (KBr, n, cm21): 3100, 3051, 2237, 1590, 1561, 1510, 1467, 1342,
1303, 1207, 1109, 1076, 922, 848, 754, 721, 674 cm21. 1H NMR: 7.74 (s, 1H,
ArH), 7.75 (d, J ¼ 8.4 Hz, 1H, ArH), 8.32 (d, J ¼ 8.4 Hz, 1H, ArH), 8.38
(s, 1H, CH55).
3s: IR (KBr, n, cm21): 3052, 2942, 2856, 2235, 1608, 1567, 1523, 1464,
1440, 1365, 1323, 1290, 1227, 1180, 1070, 989, 872, 790, 738 cm21
.
1H NMR: 4.04 (s, 3H, CH3O), 4.05 (s, 3H, CH3O), 7.31 (s, 1H, ArH), 7.80
(s, 1H, ArH), 8.46 (s, 1H, CH55).
3t: IR (KBr, n, cm21): 3049, 2938, 2234, 1610, 1575, 1526, 1505, 1505,
1479, 1434, 1385, 1329, 1153, 1029, 917, 877, 814, 752, 725, 694 cm21
.
1H NMR: 6.28 (s, 2H, OCH2O), 7.19 (s, 1H, ArH), 7.76 (s, 1H, ArH), 8.33
(s, 1H, CH55).
3u: IR (KBr, n, cm21): 3049, 3090, 2240, 1592, 1567, 1522, 1441,
1347, 1210, 1145, 1074, 916, 870, 835, 796, 731, 694, 670 cm21
.
1H NMR: 7.79–7.90 (m, 3H, ArH), 8.36 (d, J ¼ 8.0 Hz, 1H, ArH),
8.45(s, 1H, ArH).
3v: IR (KBr, n, cm21): 3023, 2978, 2945, 2921, 2225, 1588, 1561,
1053, 1447, 1407, 1385, 1311, 1246, 1223, 1128, 1019, 946, 816, 790,
772, 707 cm21 1H NMR: 2.33 (s, 3H, CH3), 2.36 (s, 3H, CH3), 7.29
.
(d, J ¼ 8.0 Hz, 1H, ArH), 7.66–7.69 (m, 3H, ArH þ CH55).
3w: IR (KBr, n, cm21): 3008, 2964, 2935, 2831, 2222, 1601, 1567, 1508,
1441, 1423, 1341, 1272, 1206, 1168, 1143, 1016, 959, 933, 850, 822, 779,
733 cm21 1H NMR: 3.95 (s, 3H, CH3O), 3.98 (s, 3H, CH3O), 6.96
.
(d, J ¼ 8.4 Hz, 1H, ArH), 7.39 (dd, J ¼ 8.4 Hz, J0 ¼ 2.0 Hz, 1H, ArH), 7.64
(s, 1H, CH55), 7.69 (d, J ¼ 2.0 Hz, 2H, ArH).
ACKNOWLEDGMENT
We are grateful to the Foundation (No. QL98001) of the “Surpassing
Project” of Jiangsu Province and Natural Science Foundation
(04KJB150139) of the Education Committee of Jiangsu Province for
financial support.

Arylmethylenemalononitrile
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