Exploitation of the catalytic efficacy of Mg/Al hydrotalcite for the rapid synthesis of 2-aminochromene derivatives via a multicomponent strategy in the presence of microwaves

Article abstract of DOI:10.1016/j.tetlet.2008.11.114

Mg/Al hydrotalcite, a heterogeneous base catalyst, was found to be highly effective for the synthesis of 2-aminochromenes via a multicomponent reaction of aromatic aldehydes, malononitriles and 1-naphthol under microwaves. The reaction is rapid, clean and

Full text of DOI:10.1016/j.tetlet.2008.11.114

Tetrahedron Letters 50 (2009) 719–722
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Tetrahedron Letters
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Exploitation of the catalytic efficacy of Mg/Al hydrotalcite for the rapid
synthesis of 2-aminochromene derivatives via a multicomponent strategy
in the presence of microwaves
Mandar P. Surpur, Siddheshwar Kshirsagar, Shriniwas D. Samant *
Organic Chemistry Research Laboratory, University Institute of Chemical Technology, N. M. Parekh Road, Matunga, Mumbai 400 019, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Mg/Al hydrotalcite, a heterogeneous base catalyst, was found to be highly effective for the synthesis of 2-
aminochromenes via a multicomponent reaction of aromatic aldehydes, malononitriles and 1-naphthol
under microwaves. The reaction is rapid, clean and gives the products in high yields. The catalyst is reus-
able; however, there was reduction in the yield of the product.
Received 16 October 2008
Revised 19 November 2008
Accepted 28 November 2008
Available online 3 December 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
2
-Aminochromenes
Hydrotalcite
Microwaves
1
. Introduction
One-pot multicomponent reactions have emerged as an effec-
lished the synthesis of dihydroquinazolinone derivatives using this
one-pot multicomponent dry media reaction approach under
3
microwaves. 2-Aminochromenes are widely employed as pig-
ments, cosmetics, potential agrochemicals and also as components
tive tool for atom economic and benign synthesis by virtue of their
convergence, productivity, facile execution and generation of
highly diverse and complex products from easily available starting
materials in a single operation.1 There has been a tremendous
development in three- and four-component reactions, and efforts
are still being made to find and develop new multicomponent reac-
1
2–14
of many natural products.
The development of an efficient
methodology for the synthesis of 2-amino-chromenes is highly
essential. The most straightforward synthesis of this heterocyclic
system involves a three-component coupling of aromatic aldehyde,
malononitrile and activated phenol. Traditionally, this condensa-
2
15
tions. Multicomponent reactions are now being tailored and fine
tion was catalyzed by a base such as piperidine. A few diverse
tuned for synthesizing various heterocyclic scaffolds for diverse
applications. Heterogeneous catalysts are vital in green synthesis
due to their easy recovery and subsequent reuse. Our research
group has been developing efficient and environmentally benign
protocols using various heterogeneous catalysts.3 Hydrotalcites
catalysts have been employed for this multicomponent reaction.
1
6
17
Recently, basic alumina, cetyl trimethyl ammonium chloride,
1
8
19
20
NaOH, InCl3, and I
/K
2 2
CO
3
have been used as catalysts for this
multicomponent reaction. Very recently, nanosized magnesium
oxide has also been shown as an effective catalyst for this reac-
–6
2
1
(
HTs) possess strong surface basicity and are useful catalysts for
some selective oxidation reactions. HTs and modified HTs have
been used for the epoxidation of olefins and ,b-unsaturated ke-
tion. However, all these methods include some or other draw-
backs such as prolonged reaction time, tedious catalyst
preparation and workup, and exhaustive usage of energy sources
and solvents. The first sequential reaction in this multicomponent
condensation is the Knoevenagel condensation of an aldehyde and
malononitrile. Usually, this reaction is catalyzed by a mild base,
and very recently it has also been shown that this reaction pro-
ceeds in water under thermal or microwave conditions.22 It ap-
pears that the catalyst does play a pivotal role in catalyzing the
addition of the arylidene malononitrile intermediate to the ortho
position of 1-naphthol, which is also the rate-determining step of
the reaction.
a
7,8
9
tones using hydrogen peroxide, oxidation of alcohols and the
Bayer–Villager reaction using peracids.10
Microwave heating has been known for long for acceleration of
reactions. Cyclocondensation reactions in ‘dry media’ leading to
heterocyclic systems have been performed under microwave irra-
diation. The reactions carried out in a neat or solvent-free state un-
der microwave irradiation help to generate products not attainable
through classical heating methods. A large number of heterocycles
11
have been synthesized by this approach. Our group recently pub-
In continuation of our efforts to develop efficient environmen-
tally benign protocols for the synthesis of various heterocycles,
we report herein our results with Mg/Al hydrotalcite that effi-
*
Corresponding author. Fax: +91 022 24145614/16.
E-mail address: samantsd@yahoo.com (S.D. Samant).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.11.114

7
20
M. P. Surpur et al. / Tetrahedron Letters 50 (2009) 719–722
OH
O
NH2
NC
NC
HT/ MW
40 °C
Ar-CHO
+
+
1
CN
Ar
Scheme 1.
Figure 1. Mg/Al HT structure showing the brucite layer and interlayer region.
ciently catalyzed the three-component condensation of aromatic
aldehydes, malonitrile and 1-naphthol in a dry state under sin-
gle-mode microwave irradiation (see Scheme 1).
2. Results and discussion
Mg/Al hydrotalcites of Mg/Al mole ratio 2, 3, and 5 were pre-
pared by a procedure reported in the literature and were character-
2
3
ized by XRD and FT-IR. The HTs are synthetic basic clays which
contain brucite layer structure (Fig. 1).
Table 1
Effect of temperature on the synthesis of 2-aminochromene derivatives via
a
multicomponent condensation of benzaldehyde, malononitrile, and 1-naphthol in
the presence of Mg/Al hydrotalcite under microwave irradiation
S. no.
Temperature (°C)
Time (min)
Yielda (%)
Table 4
Reusability study
1
2
3
4
90
14
9
7
34
62
84
52
120
140
150
Yielda (%)
Run
Time (min)
5
1
2
3
7
9
18
84
79
62
Reaction condition: benzaldehyde (1 mmol), malononitrile (1 mmol), 1-naphthol
1 mmol), (Mg/Al = 3) HT (50% w/w of 1-naphthol), solvent-free.
(
Reaction attempted in a single-mode microwave reactor (Biotage).
a
Reaction condition: benzaldehyde (1 mmol), malononitrile (1 mmol), 1-naphthol
1 mmol), (Mg/Al = 3) HT (50% w/w of 1-naphthol), temp: 140 °C.
Isolated yield.
(
Reaction attempted in a single-mode microwave reactor (Biotage).
a
Isolated yield.
Table 2
Mode in which the reaction is attempted
Medium
Time (min)
Yielda (%)
Table 5
Solvent-free
Solvated (DMF)
7
21
84
60
Synthesis of 2-aminochromenes via a multicomponent condensation of aromatic
aldehydes, malononitrile, and 1-naphthol catalyzed by (Mg/Al = 3) hydrotalcite under
single-mode microwave irradiation
Reaction condition: benzaldehyde (1 mmol), malononitrile (1 mmol), 1-naphthol
1 mmol), (Mg/Al = 3) HT (50% w/w of 1-naphthol), temp: 140 °C.
No.
R
C
Time (min)
Yielda (%)
(
Reaction attempted in a single-mode microwave reactor (Biotage).
a
1
2
3
4
5
6
7
8
9
6
H
5
7
6
6
10
5
24
8
16
8
5
9
84
88
90
72
89
74
76
76
71
88
72
80
Isolated yield.
4-Cl C
4-F C
4-N(CH
4-Br C H5
2-CH3 C6H5
2-Cl C H5
4-OCH
2-NO
4-NO
4-CH
Piperonal
6
H
4
6
H
4
3
)
2
C
6
H
4
Table 3
6
Effect of different hydrotalcites on the three-component coupling of benzaldehyde,
malononitrile, and 1-naphthol at 1400 °C under microwave irradiation
6
Yieldb (%)
3
C
6
H
5
HT
Time (min)
2
C
6
H
H
H
5
Mg/Al: 3
Mg/Al:2a
Mg/Al: 5
7
30
19
84
34
42
10
11
12
2
C
6
5
3
C
6
5
8
Reaction condition: benzaldehyde (1 mmol), malononitrile (1 mmol), 1-naphthol
1 mmol), Mg/Al HT (50% w/w of 1-naphthol), temp: 140 °C.
Reaction condition: aromatic aldehyde (1 mmol); malononitrile (1 mmol); acti-
vated phenol (1 mmol); (Mg/Al = 3) HT 50% w/w of 1-naphthol, temperature 140 °C,
(Microwave, single mode, Biotage); solvent-free.
(
Reaction attempted in a single-mode microwave reactor (Biotage).
a
All products are known and are fully characterized by 1H NMR and IR spectra.
Complete conversion of the reactants not seen on TLC.
Isolated yields.
b
a
Isolated yield.

M. P. Surpur et al. / Tetrahedron Letters 50 (2009) 719–722
721
Table 6
From the XRD spectrum, it was seen that the basal spacing at
0
Effect on the use of different activated phenols in synthesis of 2-amino chromene
derivatives via a multicomponent condensation of benzaldehyde, malononitrile an
activated phenol in the presence of Mg/Al hydrotalcite under single-mode microwave
irradiation
7
.87 ÅA corresponded to the HT phase. In the FT-IR of Mg/Al hydro-
ꢀ1
talcite, the absorption at 3581 cm corresponded to the H-bond-
ing stretching vibration of the OH group in the brucite layer. A
ꢀ1
shoulder present at around 3000 cm was due to H-bonding be-
tween H O and the anions in the interlayer.
Activated phenol
Time (min)
Yieldb (%)
2
1
2
-Naphthol
-Naphthola
7
25
9
84
32
61
The reaction between benzaldehyde, malononitrile, and 1-
naphthol was selected as the model reaction for optimization of
various parameters. The reaction was attempted at different tem-
peratures ranging from 90 to 150 °C (Table 1). It was found that
above and below 140 °C, the yield of the product decreased. When
the reaction was attempted without microwaves at 140 °C, 44%
yield of the product was obtained in 4.5 h. The reaction worked
best at 140 °C under microwave irradiation.
Resorcinol
Reaction condition: benzaldehyde (1 mmol), malononitrile (1 mmol), phenol
1 mmol), (Mg/Al = 3) HT (w.r.t activated phenol), temp: 140 °C.
(
Reaction attempted in a single-mode microwave reactor (Biotage).
a
Complete consumption of reactants not observed on TLC.
Isolated yields.
b
To make the reaction clean and green, the reaction was at-
tempted under dry conditions (neat state) so that the maximum
absorption of microwaves by the reactants occurs, and solvent
usage is kept at a minimum. It was found that under these condi-
tions, complete conversion occurred only in about 7 min as com-
pared to when the reaction was attempted in the presence of a
high boiling solvent like DMF (Table 2).
Table 7
Effect on the use of different active methylene compounds in synthesis of 2-amino
chromene derivatives via a multicomponent condensation of benzaldehyde, malon-
onitrile an activated phenol in the presence of Mg/Al hydrotalcite under single-mode
microwave irradiation
Active methylene compounds
Malononitrile
Time (min)
Yield (%)b
The reaction was carried out using different uncalcined HTs
(
Mg/Al = 2, 3, and 5) at 140 °C (Table 3). The uncalcined HTs (Mg/
7
—
—
84
—
—
a
Ethyl cyanoacetate
Al = 3) gave good yields of the product.
Diethyl malonatea
On calcination at a high temperature, the Lewis basicity of HT
increases, while the Bronsted basicity decreases. The Bronsted ba-
sicity is required for the reaction. It is essentially due to hydroxyl
groups in the brucite layer which are eliminated as water upon cal-
cination. It is reported that calcined HTs contain surface basicity
Reaction condition: benzaldehyde (1 mmol), malononitrile (1 mmol), 1-naphthol
1 mmol), (Mg/Al = 3) HT (50% w.r.t 1-naphthol), temp: 140 °C.
(
Reaction attempted in a single-mode microwave reactor (Biotage).
a
Complete consumption of reactants not observed on TLC.
Isolated yield.
b
ꢀ
2ꢀ
24
due to OH groups, (Mg–O) pairs, and (O ) species. The catalytic
NC
H
+
OH
OH
NC
CN
H
CN
Ar
+
Ar
HT
NC
OH
CN
Ar
H
NH
H
CN
O
Ar
NH2
CN
Ar
O
Scheme 2.

7
22
M. P. Surpur et al. / Tetrahedron Letters 50 (2009) 719–722
activity of calcined HTs was lower than that of the corresponding
uncalcined HTs. The basicity of HT is sensitive to the Mg/Al ratio.
The total basicity of HT increases gradually with the Mg/Al molar
ratio and comes to a maximum value at the Mg/Al ratio of 3.0. Fur-
ther increase in the Mg/Al molar ratio decreases the basicity. The
reaction did not take place in the absence of HT. It was found that
(1 mmol), and Mg/Al HT (0.072 g, 50% w/w of 1-naphthol) was
added. A magnetic stirrer was inserted to bring about stirring
during the reaction. The vial was sealed with an aluminum cap
fitted with a pressure- and temperature-calibrated Teflon seal.
The vial was inserted into the cavity of the microwave reactor,
and the reaction mixture was irradiated with monomode irradi-
ation at 140 °C in a pulsed mode. The progress of the reaction
mixture was monitored by TLC. After the complete consumption
of the reactions, as seen on TLC, the reaction mixture was di-
luted with methanol (4 ml). The reaction mixture was filtered
to separate the catalyst. The filtrate was concentrated under vac-
uum to get the solid product which was purified by recrystalliz-
ing from absolute ethanol.
5
0% of (Mg/Al = 3) HT with respect to 1-naphthol (w/w) was re-
quired to affect the reaction.
The hydrotalcite is a heterogeneous basic catalyst and could
easily be separated from the reaction mixture by simple filtration.
The recovered catalyst was used for successive runs to investigate
its reusability (Table 4). It was observed that there was a decrease
in the yield of the product.
Under the optimized conditions, various substituted aromatic
aldehydes were reacted to obtain the corresponding 2-amino-
chromenes in high yields (Table 5). It was observed that the alde-
hydes containing electron-withdrawing substituents in the para
position reacted faster and gave a high yield of the product as com-
pared to those containing electron-donating substituents.
To further extend the scope of the reaction, the reaction was at-
tempted with various activated phenols (Table 6) as well as other
active methylene compounds (Table 7). It was found that 1-naph-
thol and malononitrile were the best-suited reactants to bring
about this condensation furnishing 2-aminochromene derivatives.
The reaction of benzaldehyde with malononitrile (Knoevenagel
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4
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2
4
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1
described previously and are fully characterized by IR and
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H
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.2. Typical reaction procedure
2
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