Knoevenagel condensation of aromatic aldehydes with active methylene compounds using a catalytic amount of iodine and K2CO3 at room temperature

Article abstract of DOI:10.1080/00397910701397375

A convenient method for Knoevenagel condensation of aromatic aldehydes with malononitrile or ethyl cyanoacetate has been developed using the inexpensive and environmentally friendly reagent I2/K2CO3 at room temperature. The method is mild and simple with

Full text of DOI:10.1080/00397910701397375

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Knoevenagel Condensation of Aromatic
Aldehydes with Active Methylene Compounds
using a Catalytic Amount of Iodine and K CO
2
3
at Room Temperature
a
a
Yi‐Ming Ren & Chun Cai
a
Chemical Engineering College, Nanjing University of Science and
Technology, Nanjing, China
Version of record first published: 03 Jul 2007.
To cite this article: Yi‐Ming Ren & Chun Cai (2007): Knoevenagel Condensation of Aromatic Aldehydes with
Active Methylene Compounds using a Catalytic Amount of Iodine and K CO at Room Temperature, Synthetic
2
3
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:13,
209-2213
2
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Synthetic Communications , 37: 2209–2213, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701397375
Knoevenagel Condensation of Aromatic
Aldehydes with Active Methylene
Compounds using a Catalytic Amount of
Iodine and K CO at Room Temperature
2
3
Yi-Ming Ren and Chun Cai
Chemical Engineering College, Nanjing University of Science and
Technology, Nanjing, China
Abstract: A convenient method for Knoevenagel condensation of aromatic aldehydes
with malononitrile or ethyl cyanoacetate has been developed using the inexpensive and
environmentally friendly reagent I
2 2 3
/K CO at room temperature. The method is mild
and simple with good to high product yields.
Keywords: aromatic aldehydes, Knoevenagel condensation, methylene compounds,
molecular iodine
INTRODUCTION
The Knoevenagel condensation is one of the most useful and widely employed
methods for carbon–carbon formation in organic synthesis, with numerous
[
1]
applications in the synthesis of fine chemicals
[
hetero Diels–Alder
reactions, and carbocyclic as well as heterocyclic compounds of biological
2]
[3]
[4]
significance. The reactions are usually catalyzed by bases such as amines,
[6]
ammonia, or sodium ethoxide in organic solvents. Lewis acids, surfactants,
[
zeolites, and ionic liquids have also been employed to catalyze the reactions.
[5]
7]
[8]
[9]
Recently, the use of molecular iodine has received considerable
attention because it is an inexpensive, nontoxic, readily available catalyst
Received September 27, 2006
Address correspondence to Chun Cai, Chemical Engineering College, Nanjing Uni-
versity of Science and Technology, Nanjing 210094, China. E-mail: c.cai@mail.njust.
edu.cn
2
209

2
210
Y.-M. Ren and C. Cai
Scheme 1.
for various organic transformations to afford the corresponding products in
excellent yields with high selectivity. The mild Lewis acidity associated
with iodine enhance its use in organic synthesis of several organic transform-
ations, using stoichiometric levels to catalytic amounts. Owing to numerous
advantages associated with this ecofriendly element, iodine has been
[
10]
explored as a powerful catalyst for various organic transformations.
viously, Yu-Qing Cao and coworkers
Pre-
had reported a new method for prep-
[11a]
aration of some arylidene derivatives by Knoevenagel condensation of
aromatic aldehydes with active methylene compounds under solvent-free con-
ditions using PEG400 and K CO as catalysts, but it needed a long reaction
2
3
time and had to have a high reaction temperature. Now we report a facile
method for the synthesis of arylidene derivatives from aromatic aldehydes
and malononitrile or ethyl cyanoacetate using I and K CO as the catalysts
2
2
3
in EtOH or DMF at room temperature (Scheme 1).
RESULTS AND DISCUSSION
First, the condensation of p-chlorobenzaldehyde with malononitrile using
molecular iodine as catalyst was examined with several inorganic alkali
catalysts, and the results are summarized in Table 1. As shown in Table 1,
Table 1. Effect of the alkalies on the condensation of p-chloroben-
a
zaldehyde with malononitrile
b
Entry
Alkali
Reaction time (min)
Yield(%)
1
2
3
4
5
—
NaOH
KOH
60
30
60
30
3
50
52
40
87
95
Na
2
CO
CO
3
K
2
3
c
60
60
30
90
6
NaHCO
3
a
Mmol ration of p-chlorobenzaldehyde/malononitrile/I
2
/alkali is
1
room temperature.
0.0/12.0/0.3/0.3. The reaction was accomplished in EtOH at
b
Isolated yields.
Without iodine.
c

Knoevenagel Condensation of Aromatic Aldehydes
2211
K CO was more satisfactory to obtain excellent yields in a short time (entry
2
3
5
time was needed using NaOH and KOH as catalysts (entries 2 and 3), because
) than other inorganic alkalies. A low yield was obtained and a long reaction
[11a]
NaOH and KOH were too strong of bases to result in more by-products.
Na CO and NaHCO also had good yields under the same reaction conditions
2
3
3
(entries 4 and 6), but they both needed a longer reaction time than K CO .
2 3
However, a long reaction time was needed and low yield was obtained
without any base (entry 1) or without molecular iodine (entry 5).
Then, to generalize our reagent system, we investigated the Knoevenagel
condensation of various aromatic aldehydes with malononitrile or ethyl cya-
noacetate (Table 2). Table 2 shows that aromatic aldehydes, having
different substituents such as chloro, nitro, methoxy, and methyl, were
converted to the corresponding arylidene derivatives in high yields.
However, the aromatic aldehydes with electron-withdrawing groups such as
Table 2.
temperature
2 2 3
I /K CO -catalyzed Knoevenagel condensation in EtOH at room
a
Reaction
time (min)
Yield
b
(%)
Entry
Ar
Ph
X
mp (8C) (mp lit.)
[
11a]
3a
CN
CN
12
3
80
95
82–83 (81–82)
161–162 (161–162)
[
11a]
3b
4-ClPh
c
3
95
d
4
0
2
6
70
[
[
11a]
11a]
3
3
3
c
d
e
4-NO
3-NO Ph
2
Ph
CN
CN
CN
93
90
86
160–161 (159–160)
102–103 (103–104)
135–137 (134.5–
2
4-MePh
10
[
11b]
1
35.0)
[
[
[
11a]
11a]
11a]
3
3
3
3
3
3
3
3
3
3
3
f
4-OHPh
4-MeOPh
4-(Me )NPh
CN
CN
16
14
24
60
50
25
30
70
70
70
70
86
80
75
80
85
87
94
85
186–188 (186–187)
113–115 (113–114)
178–179 (179–180)
g
h
i
2
CN
[
11a]
Ph
4-ClPh
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
48–49 (48–50)
88–90 (89–90)
[
11a]
j
[
[
11a]
11a]
k
l
4-NO
3-NO
2
Ph
Ph
168–169 (167–169)
132–133 (134–135)
2
[
11b]
m
n
o
p
4-MePh
4-OHPh
4-MeOPh
90–91 (91.5–92.5)
167–169 (168–169)
e
[11a]
81
89
e
[11a]
79–80 (79–80)
122–124 (123–125)
e
[11a]
4-(Me )NPh COOEt
2
75
a
Mmol ratio of aldehyde/malononitrile or ethyl cyanoacetate/I /K CO is 10.0/
2
2
3
1
2.0/0.3/0.3. The reaction was accomplished in EtOH at room temperature.
b
Isolated yields.
The reaction was accomplished in DMF.
c
d
The reaction was accomplished under solvent-free conditions.
e
2 2 3
Mmol ration of aldehyde/ethyl cyanoacetate/I /K CO is 10.0/12.0/0.6/0.6.

2
212
Y.-M. Ren and C. Cai
chloro and nitro proceeded at faster rates than those with electron-donating
groups such as methoxy and methyl. The reactions with malononitrile were
also faster than with ethyl cyanoacetate. A longer reaction time will be
necessary and lower yield was obtained under solvent-free conditions than
in the solvent EtOH or DMF (entry 3b). However, the reaction failed to
proceed with ketones because of their hindered and unfavorable electronic
[
12]
structure.
In conclusion, we have developed a simple, inexpensive, and effective
method for Knoevenagel condensation of aromatic aldehydes with active
methylene compounds with molecular iodine in the presence of K CO at
2
3
room temperature. Further study on the synthetic application of the present
reaction is now in progress.
EXPERIMENTAL
Typical Procedure of Condensation of p-Chlorobenzaldehyde with
Malononitrile
To a solution of p-chlorobenzaldehyde (10 mmol) and malononitrile (12 mmol)
in EtOH or DMF (1 mL) were added I (0.3 mmol) and K CO (0.3 mmol). The
2
2
3
mixture was stirred at room temperature. After 3 min, the solid produced was
treated with Na S O solution (5%) and EtOH (5%). The solid product 3b
2
2 3
1
1.807 g, 95%) was identified by H NMR and comparison with an authentic
(
[11a]
sample. It needed no further purification. MP 160–1618C (lit.
mp 160–
1
2
1
1
618); IR (KBr, cm ): 3032, 2225, 1654, 1554, 1308, 780. H NMR
(
300 MHz, CDCl , d): 7.49 (d, J ¼ 8.4 Hz, 2H, ArH), 7.71 (s, 1H, CH 55 ),
3
7
.83 (d, J ¼ 8.7 Hz, 2H, ArH). Similarly, the compounds 3a and 3c–3p were
1
synthesized and were confirmed by comparison of H NMR data with those
[
13]
described in the literature
and authentic samples.
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