Solvent-free bentonite-catalyzed condensation of malonic acid and aromatic aldehydes under microwave irradiation

Article abstract of DOI:10.1039/b009803p

Solvent-free condensation between malonic acid and aromatic aldehydes in the presence of bentonite was investigated. Various diacids were obtained in good to moderate yields and in very short short reaction times under microwave irradiation. The method showed simplicity in performance, non-aqueous work-up, no side products and low cost.

Full text of DOI:10.1039/b009803p

View Article Online / Journal Homepage / Table of Contents for this issue
Solvent-free bentonite-catalyzed condensation of malonic acid and
aromatic aldehydes under microwave irradiation
a
b
b
b
b
André Loupy, Suk-Jin Song, Sun-Mee Sohn, Young-Mee Lee and Tae-Woo Kwon*
1
a
Laboratoire des Réactions Sélectives sur Supports, associé au CNRS, UMR 8615—ICMO,
Université Paris-Sud, Bâtiment 410, F-91405 Orsay Cedex, France.
E-mail: aloupy@icmo.u-psud.fr
Department of Chemistry, Kyungsung University, Daeyoen-dong, Pusan 608-736, Korea.
E-mail: twkwon@star.kyungsung.ac.kr
b
Received 4th December 2000, Accepted 3rd April 2001
First published as an Advance Article on the web 3rd May 2001
Solvent-free condensation between malonic acid and aromatic aldehydes is studied in the presence of bentonite.
Various diacids are prepared in good to moderate yields and in very short reaction times under microwave
irradiation.
Introduction
(1)
1
Recently, microwave-assisted solvent-free synthesis in organic
reactions has been of growing interest as an efficient, economic
2
and clean procedure (‘green chemistry’). Over the past few
years, a considerable number of reactions have been developed
in which inorganic solid supports such as aluminas, silica gels
and montmorillonites appeared to be useful in terms of mild-
3
ness of conditions, yield and convenience. We have shown
earlier that diethyl malonate, ethyl cyanoacetate, malonic acid
and several different types of aldehyde could be efficiently
condensed in chlorobenzene or in ‘dry media’ in the presence
The best results (in italics) were obtained with the mixture of
composition 1c : malonic acid = 1 : 3 w/w for an irradiation
time of 5 min in the presence of bentonite (entry 4, 86%).
Irradiation time also significantly affected the yields. Thus,
increasing the reaction time up to 5 min enhanced the yield
4–6
of basic alumina. In the present communication, we report
our results on this environmentally benign approach for
the bentonite-catalyzed condensation between malonic acid
and various aromatic aldehydes such as benzaldehyde,
o- or p-tolualdehyde, 2-chlorobenzaldehyde, p-anisaldehyde,
(
entries 4, 5 and 6). However we could not improve the yield
even after prolonged irradiation (9–15 min, entries 7 and 8). In
the absence of bentonite, the formation of product was very
low (entry 9).
After we had optimized the reaction conditions, we investi-
gated the effect of the amount of bentonite on the reaction
of p-tolualdehyde 1c and malonic acid under microwave
irradiation (Table 2).
Table 2 shows that the yields were highly dependent on the
quantity of support. In the absence of bentonite, only traces of
product were detected (entry 1). Maximum yield was obtained
when the mass ratio of bentonite and malonic acid was 1.4 : 1
(entry 4). However, isolated yields were decreased when using
larger amounts of support (entries 5, 6).
1
-naphthaldehyde and 2-furaldehyde under microwave
irradiation in ‘dry media’.
Results and discussion
We first examined the relative concentration effects between
p-tolualdehyde 1c and malonic acid under microwave
conditions [eqn. (1)] (Table 1).
The main products under these conditions were the
diacids 2.
Table 1 Effect of the relative amounts of p-tolualdehyde 1c and malonic acid under microwave irradiation in the presence of bentonite (bentonite :
malonic acid = 1.38 : 1)
p-Tolualdehyde
Malonic acid
g (mmol)
a
Entry
g (mmol)
Equiv.
Equiv.
Time (t/min)
Yield 2c (%)
1
2
3
4
5
6
7
8
9
0.20 (1.67)
0.20 (1.67)
0.20 (1.67)
0.20 (1.67)
0.20 (1.67)
0.20 (1.67)
0.20 (1.67)
0.20 (1.67)
0.20 (1.67)
1.5
1
3
1
1
1
1
1
1
0.12 (0.11)
0.26 (2.51)
0.06 (0.56)
0.52 (5.01)
0.52 (5.01)
0.52 (5.01)
0.52 (5.01)
0.52 (5.01)
0.52 (5.01)
1
1.5
1
3
3
3
3
3
3
5
5
5
5
1
3
9
15
15
32
9
86
28
37
74
65
b
5 (neat)
3
a
b
Yield of isolated product based on p-tolualdehyde. No bentonite was used.
1
220
J. Chem. Soc., Perkin Trans. 1, 2001, 1220–1222
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b009803p

View Article Online
Table 4 Bentonite-catalyzed condensation between various aldehydes
and malonic acid (amounts of products) under microwave irradiation
for 5 minutes
Table 2 Effect of the amount of bentonite on the reaction of
p-tolualdehyde 1c (0.20 g) and malonic acid (3 equiv., 0.52 g) under
microwave irradiation (5 min)
a
Entry
Bentonite/g
Yield 2c (%)
Mp (θ/ЊC)
Yield
2 (%)
Aldehyde
Product
Found
Lit. [ref.]
1
2
3
4
5
6
0
3
55
80
86
73
52
0.24
0.36
0.73
1.45
2.18
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
2f
193–195
195–196
205–208
184–187
194 (decomp.)
198–200
196 (decomp.)
194–196 [8]
193–194 [6]
207–210 [9]
185–188 [8]
196 [10]
199–203 [11]
197 (decomp.) [12]
79
82
86
88
94
94
75
a
Yield of isolated product based on p-tolualdehyde.
1
1
f
g
2g
Table
3
Comparison between classical heating and microwave
irradiation (MW) in the absence or presence of bentonite at 80 ЊC for
the reaction of benzaldehyde 1a (1.8 mmol, 0.20 g) and malonic acid
Table 5 Microwave-irradiated condensation between benzaldehyde 1a
and malonic acid using various solid supports
(
3 equiv., 5.4 mmol, 0.56 g)
a
Ratio
Heating time (t/min)
b
b
Solid support
2a
3a
Classical
heating
Yield
2a (%)
a
Entry
Bentonite/g
MW
Bentonite
Silica gel
K10
92 (79)
95 (74)
98 (80)
88 (63)
8
5
2
1
2
3
4
5
0
0
0.80
0.80
0.80
5
0
5
Trace
9
74
KSF
12
5
900
a
1
Ratios were determined by H integration using 300 MHz NMR
b
5
79
spectroscopy. In parentheses, yield of isolated product based on
benzaldehyde.
a
b
Oil-bath with reflux condenser (bath temperature = 80 ЊC). Yield of
isolated product based on benzaldehyde.
1
3
Table 6 Some characteristics of the supports
In order to check the possible intervention of specific (not
purely thermal) microwave effects, the reaction was performed
in one case under similar experimental conditions (weight of
reactants, time and temperature) using a thermostatted oil-bath
H Hammett
acidity
Surfacearea/
2 Ϫ1
o
Solid support
m g
Bentonite
Silica gel
K10
ϩ1.5 to Ϫ3.0
ϩ6.8 to ϩ4.0
Ϫ5 to Ϫ6
Ϫ8
500–700
500–600
220–270
20–40
(
conventional heating). The temperature was measured in the
reaction medium using a thermometer either under microwave
irradiation (at the end of the reaction) or under classical
heating (Table 3).
KSF
For comparison, the mixtures were heated (80 ЊC) to the
temperature attained by the bentonite just after microwave
irradiation for 5 min (78–80 ЊC). As shown in Table 3, we could
not isolate a product in the absence of bentonite (entries 1 and
two main properties: their acidity as evaluated in the solid state
by Ho Hammett functions and their capacity in absorbing
organic molecules as connected to their specific areas.
Acidity seems not to be the only important factor. In fact,
K10 and bentonite lead to closely related results, which are very
different from those with KSF, a clay with rather similar acidity
2
). Under the same conditions with bentonite the thermal acti-
vation (80 ЊC) did not give good yields (entry 3). Microwave
irradiation allowed a drastic reduction of reaction time as
comparable yields were obtained using 5 min of irradiation in
a domestic microwave oven (entry 5), while under classical
heating the reaction time required 900 min of stirring at 80 ЊC
even with lower yields (entry 4).
(
Table 6). It seems evident that some other factors, certainly
such as surface area, may play a decisive role in the reaction.
The supports with higher surface areas lead to the best results.
They are indicative that the reaction occurs mainly when the
reactions are effectively absorbed on the support, a fact which is
confirmed by the effect of the amount of bentonite (Table 2).
It is evident that very strong specific effects of micro-
waves were operating here to induce enhancements yet to be
1,7
seen in a lot of cases in organic synthesis.
Conclusions
In order to extend the scope of this method, the conden-
sations of aromatic aldehydes with malonic acid in the presence
of bentonite were successfully performed. The results are sum-
marized in Table 4.
It was finally interesting to compare the support influence
according to their acidity. We carried out the reaction using
other solid supports such as silica gel, K10 and KSF (Table 5).
In summary, we have demonstrated the bentonite-catalyzed
condensation between malonic acid and various aldehydes
under irradiation in a domestic microwave oven. This method
offers some advantages in terms of simplicity of performance,
non-aqueous work-up, no side products and low cost. In addi-
tion, the bentonite can be recycled after activation (yields
remained 79% after 3 re-uses) in the reaction of benzaldehyde
1a and malonic acid.
In all cases, diacids 2 were obtained as the major product and
E)-cinnamic acids 3 were detected as minor products in H
1
(
NMR spectra. Clays K10 and bentonite have been shown to be
good supports in terms of yields. The selectivity obtained with
K10 was superior to that with bentonite despite the disadvan-
tages of stronger acidity and higher cost. The product ratio of
diacid 2 and monoacid 3 is shown in Table 5.
In order to try to understand the differences in behaviour
between these solid supports, we indicate in Table 6 some
important characteristics of these supports upon considering
We have also to underline that under our conditions diacids
were selectively obtained, whereas cinnamic acids (monoacids)
14
were obtained in a basic medium (piperidine in pyridine,
15
ethanol or ammonium acetate under solvent-free condi-
16
tions ) under MW irradiation. The two methods appeared to
be complementary. One has finally to quote the large discrep-
17
ancy with the recent result published by Sampath Kumar et al.
who obtained the (E)-cinnamic acids under MW (emitted
J. Chem. Soc., Perkin Trans. 1, 2001, 1220–1222
1221

View Article Online
power = 600 W within 4 min) in the presence of silica gel
activated at 140 ЊC for 3 hours prior to use). Maybe a different
quality of support or, more certainly, higher temperature levels
were involved in their experiments.
Acknowledgements
This work was supported by a grant from the Basic Research
Program of the Korea Science & Engineering Foundation
(
(
2000-2-11400-009-3).
Experimental
References
Mps were taken on a Haake Buchler mp apparatus and are
uncorrected. Infrared spectra were recorded with an infrared
spectrophotometer model Magna-IR 500 and are reported in
wavenumbers. NMR spectra were determined in a d-chloro-
1 (a) A. Loupy, A. Petit, J. Hamelin, F. Texier-Boullet, P. Jacquault
and D. Mathé, Synthesis, 1998, 1213 and references therein; (b) R. S.
Varma, Green Chem., 1999, 1, 43.
2
(a) R. Gedye, F. Smith, K. C. Westaway, H. Ali, L. Baldisera,
L. Laberge and J. Rousell, Tetrahedron Lett., 1986, 27, 279; (b) R. J.
Giguere, R. L. Bray, S. M. Duncan and G. Majetich, Tetrahedron
Lett., 1986, 27, 4945.
form/DMSO-d solution mixture on an FT-NMR Bruker 300
6
(
300 MHz) spectrometer and are reported in ppm using
tetramethylsilane as the internal standard. Bentonite, mont-
morillonite K10, KSF (Aldrich Co.) and silica gel 60 (Merck,
3 (a) A. McKillop and D. W. Young, Synthesis, 1979, 481;
b) P. Laszlo, Acc. Chem. Res., 1986, 19, 121; (c) G. W. Kabalka and
(
7
0–230 mesh ASTM) were activated at 140 ЊC for 3 h prior to
R. M. Ragni, Tetrahedron, 1997, 53, 7999; (d) A. Loupy, Top. Curr.
use. The reactions were carried out in a 2450 MHz commercial
microwave oven (Sam Sung, Model # RE-555 TCW).
Chem., 1999, 206, 153.
J. K. Kim, P. S. Kwon, T. W. Kwon, S. K. Chung and J. W. Lee,
Synth. Commun., 1996, 26, 535.
S. Y. Kim, P. S. Kwon, T. W. Kwon, S. K. Chung and Y. T. Chang,
Synth. Commun., 1997, 27, 533.
P. S. Kwon, Y. S. Kim, C. J. Kang, T. W. Kwon, S. K. Chung and
Y. T. Chang, Synth. Commun., 1997, 27, 4091.
(a) S. Deshayes, M. Liagre, A. Loupy, J. L. Luche and A. Petit,
Tetrahedron, 1999, 55, 10851 and quoted references; (b) S. Chatti,
M. Bortolussi and A. Loupy, Tetrahedron, 2000, 56, 5877.
S. Scheler and F. Endermann, S. Afr. Pat. 67 07,085, 16 April 1968
4
5
6
7
A typical procedure for the condensation of malonic acid and
p-tolualdehyde 1c
In a screw-capped vial were placed malonic acid (0.52 g, 5.0
mmol, 3 equiv.), p-tolualdehyde 1c (0.20 g, 1.67 mmol) and
bentonite (0.72 g). The tube was capped and the contents of the
tube were thoroughly mixed with a vortex mixer and then
irradiated in the microwave oven for 5 min at a power of 1050
W. After the reaction the mixture was cooled to room tempera-
ture and washed successively with hexane (3 × 10 mL) and cold
water (3 × 10 mL). The resulting mixture was immersed in ethyl
acetate (2 × 10 mL) for 5 min. After removal of bentonite by
filtration under vacuum, the mixture was evaporated under
reduced pressure to give 2-(4-methylbenzylidene)malonic acid
8
9
(
Chem. Abstr. 1969, 70, 47115b).
K. C. Pandya and R. B. Pandya, Proc. Indian Acad. Sci., Sect. A,
941, 14, 112.
0 D. Molho and M. Giraud, Bull. Soc. Chim. Fr., 1968, 6, 2603.
1
1
11 S. K. Chung, J. W. Lee, N. Y. Shim and T. W. Kwon, Bioorg. Med.
Chem. Lett., 1996, 6, 1309.
1
2 A. I. Kiprianov and T. S. Kusner, J. Gen. Chem. USSR
(
Engl. Transl.), 1936, 6, 641.
2
c as a white solid (0.29 g, 86%). This solid was recrystallized
1
3 P. Diddams, in Solid Supports and Catalysts in Organic Synthesis,
9
1
from hot, distilled water, mp 205–208 ЊC (lit., 207–210 ЊC); H
NMR δ 7.43 (1H, s, vinyl H), 7.39 (2H, d, J 8.07 Hz), 7.06 (2H,
d, J 8.07 Hz) and 2.32 (3H, s, Ar-CH ); C NMR δ 169.05,
ed. K. Smith, Ellis Horwood, Chichester, UK, 1992, ch. 1, pp.
3
–39.
13
3
C
14 A. K. Mitra, A. De and N. Karchaudhuri, Synth. Commun., 1999,
29, 573.
1
66.20, 141.10, 139.59, 130.82, 130.11, 130.03, 127.90, 21.89; IR
1
1
1
5 R. F. Pellon, T. Mamposo, E. Gonzalez and O. Calderon, Synth.
Commun., 2000, 30, 3769.
6 H. M. Sampath Kumar, B. V. Subbareddy, S. Anjaneyulu and
J. S. Yadav, Synth. Commun, 1998, 28, 3811.
7 H. M. Sampath Kumar, B. V. Subbareddy, P. Thirupathi Reddy,
D. Srinivas and J. S. Yadav, Org. Prep. Proced. Int., 2000, 32, 81.
(
1
KBr) ν 3320–2460 (COOH), 1701 (C᎐O), 1610, 1450, 1298,
245 cm .
max
Ϫ1
All other products were identified by comparison with
authentic samples (mp, TLC) and by their H NMR and IR
spectra.
1
1
222
J. Chem. Soc., Perkin Trans. 1, 2001, 1220–1222