Journal of Molecular Catalysis A: Chemical 264 (2007) 22–25
Short communication
Potassium dodecatungstocobaltate trihydrate (K5CoW12O40·3H2O):
A mild and efficient reusable catalyst for the synthesis of -acetamido
ketones under solvent-free conditions
Lingaiah Nagarapu ∗ , Srinivas Kantevari, Venkata Narasimhaji Cheemalapati,
Satyender Apuri, N. Vijaya Kumari
Organic Chemistry Division II, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 11 August 2006; received in revised form 30 August 2006; accepted 2 September 2006
Available online 8 September 2006
Abstract
A simpler and greener protocol has been developed for the preparation of -acetamido ketones by a one-pot reaction of aryl aldehydes, enolisable
ketones, acetyl chloride and acetonitrile in the presence of potassium dodecatungstocobaltate trihydrate [K5 CoW12 O40 ·3H2 O (0.01 mol%)] as a
heterogeneous catalyst in a solvent-free media at room temperature. The present methodology offers several advantages such as excellent yields,
simple procedure, short reaction times (1–2 h) and milder conditions and the catalyst exhibited remarkable reusable activity.
© 2006 Elsevier B.V. All rights reserved.
Keywords: Potassium dodecatungstocobaltate trihydrate; -Acetamido ketones; Solvent-free media; Room temperature; Reusable activity
1. Introduction
-Acetamido ketones I are fascinating compounds due to
their multifunctional nature and are important synthons for a
variety of specialty chemicals [1]. They are usually prepared
through acylation of -amino ketones [2], Michael addition to
␣,-unsaturated ketones [3] or photoisomerization of phthalimides [4]. The most interesting reaction for the synthesis of
these compounds is by multicomponent coupling involving aldehyde, enolisable ketone, acetyl chloride and acetonitrile as first
reported by Iqbal and co-workers [5a–d].
The multicomponent reactions leading to the formation of
-acetylamino ketones can be catalyzed by catalysts such as
Montmorillonite K10, CoCl2 , cobalt (II) acetate supported on
∗
Corresponding author. Tel.: +91 40 27160123; fax: +91 40 27193382.
E-mail address: nagarapu2@yahoo.co.in (L. Nagarapu).
1381-1169/$ – see front matter © 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2006.09.001
polyaniline, bismuth oxychloride [5e]. -Acetylamino ketones
have also been synthesized using Cu(OTf)2 , Zn(II), Bi(III),
Sn(II), Sc(III), triflates, BF3 , CuCl2 , BiCl3 , LaCl3 , LiClO4 ,
InCl3 [6], H2 SO4 /SiO2 [7] and zeolite H [8] (reported as a
reusable catalyst). Recently, heteropoly acids (HPAs) have been
reported [9] as solid green Bronsted acids for a one-pot synthesis of -acetylamino ketones by Dakin-West reaction. However,
the reported procedures have one or the other disadvantages.
Thus, there is a need for development of an alternative route
to construct the -acetamido ketone derivatives. During the
course of our studies directed towards the development of practical, and environmental friendly procedures for some important
transformations [10], we developed for the first time the applicability of a novel recyclable heterogeneous catalyst, potassium
dodecatungstocobaltate trihydrate [K5 CoW12 O40 ·3H2 O, a heteropoly acid (HPA)] for efficient, convenient and facile preparation of -acetamido ketones by a one-pot reaction of aryl
aldehydes, enolisable ketones, acetyl chloride and acetonitrile
in the presence of potassium dodecatungstocobaltate trihydrate
[K5 CoW12 O40 ·3H2 O (0.01 mol%)] as a heterogeneous catalyst
in a solvent-free media at room temperature (Scheme 1 and
Table 1). To our knowledge, however, the generality and applicability of K5 CoW12 O40 ·3H2 O to accomplish these reactions
have not appeared so far.
23
L. Nagarapu et al. / Journal of Molecular Catalysis A: Chemical 264 (2007) 22–25
Scheme 1.
Table 1
Optimization in the one-pot reaction of p-chloro benzaldehyde, acetophenone, acetyl chloride and acetonitrile
Entry
Catalyst (mol%)
Time (h)
Yield (%)
1
2
3
4
K5 CoW12 O40 ·3H2 O (0.01)
K5 CoW12 O40 ·3H2 O (0.05)
K5 CoW12 O40 ·3H2 O (0.1)
K5 CoW12 O40 ·3H2 O (0.15)
1.0
2.0
1.0
3.0
92
78
96
84
The use of heterogeneous catalysts in different areas of
the organic synthesis has now reached significant levels, not
only for the possibility to perform environmentally benign synthesis, but also for the good yields, frequently accompanied
by heteropoly acids (HPAs) and related compounds is a field
of increasing importance [11]. HPAs have several advantages
as catalysts which make them economically and environmentally attractive. On one hand, HPAs have a very strong Bronsted acidity approaching the super acid region; on the other,
they are efficient oxidants, exhibiting fast reversible multielectron redox transformations under rather mild conditions. Their
acid–base and redox properties can be varied over a wide range
by changing the chemical composition. Solid HPAs possess a
discrete ionic structure, comprising fairly mobile basic structural units – heteropolyanions and counter ion (H+ , H3 O+ ,
H5 O2 + , etc.) – unlike the network structure of, e.g. zeolites
and metal oxides. This unique structure manifests itself to
exhibit an extremely high proton mobility and a ‘pseudoliquid phase’ [12], while heteropolyanions can stabilize cationic
organic intermediates [13]. On top of that, HPSD have a very
high solubility in polar solvents and fairly high thermal stability in the solid state. These properties render HPAs potentially
promising acid, redox, and bifunctional catalysts in homogeneous as well as in heterogeneous systems. HPAs are widely
used as model systems for fundamental research, providing
unique opportunities for mechanistic studies on the molecular
level. At the same time, they have become increasingly important for applied catalysis. In the last two decades, the broad
utility of HPA acid and oxidation catalysis has been demonstrated in a wide variety of synthetically useful selective transformation of organic substrates [14]. Several new industrial
processes based on heteropolyanion catalysis, such as oxidation of methacrolein, hydration of olefins, polymerization of
tetrahydrofuran, etc., have been developed and commercialized
[15].
2. Results and discussion
In a typical procedure (Section 5.2), the reaction of enolisable ketones, acetyl chloride, acetonitrile with various aromatic
aldehydes in presence of 0.01 mol% of K5 CoW12 O40 ·3H2 O
[16] proceeded smoothly at room temperature in 1–2 h to
afford excellent yields of -acetamido ketones (Table 2). The
major advantages of K5 CoW12 O40 ·3H2 O, shorter reaction
times (1–2 h) and the products can be isolated without chromatography, affording -acetamido ketones in high purity. It
is noteworthy that the reported CoCl2 catalyzed reaction, even
Table 2
Synthesis of -acetylamino ketones
(K5 CoW12 O40 ·3H2 O (0.01 mol%))
at
room
temperature
using
No
R1
X
R2
Time (h)
syn/anti
Yield (%)a
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
H
2-Cl
4-Cl
2,4-di Cl
4-Br
2-NO2
3-NO2
4-OCH3
2-OH
2,3,4-tri OCH3
4-CN
4-CH3
H
H
4-Br
4-Cl
4-F
4-CH3
H
H
H
H
H
H
H
H
H
H
H
H
CH3
COOCH3
COOCH3
COOCH3
COOCH3
COOCH3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CH3
CH3
CH3
CH3
CH3
1.0
1.0
1.0
1.5
1.0
2.0
2.0
1.5
2.0
2.0
2.0
1.5
2.0
2.0
2.0
2.0
2.0
2.0
–
–
–
–
–
–
–
–
–
–
–
–
8:92
28:72
20:80
15:85
7:93
30:70
86
89
92
91
90
79
78
83
76
71
78
80
70
69
77
73
80
76
a Yields refer to pure products and all products were characterized by comparison of their physical data and 1 H NMR, IR spectral data with those of authentic
samples.
24
L. Nagarapu et al. / Journal of Molecular Catalysis A: Chemical 264 (2007) 22–25
Table 3
Reuse of the catalyst for synthesis of 5c (Table 2, entry 3)
5. Experimental
Entry
Time (h)
Yield (%)a
0
1
2
3
4
5
6
7
1.0
1.0
1.0
1.5
2.0
2.0
2.5
3.0
92
92
91
89
88
87
88
87
a
Isolated yields.
though carried at room temperature, required longer periods,
i.e. 5 days and also required a nonaqueous workup [5b]. The
use of Montmorillonite K10 required a high temperature
(70 ◦ C) [5a]. Polyaniline supported cobalt (II) acetate required
a nitrogen atmosphere [5c]. Zeolite H catalyzed reaction, even
though carried out at room temperature required 8–12 h [8],
does not require inert atmosphere, reusable, aqueous workup,
but our protocol has several advantages, as it does not need an
inert atmosphere or a high temperature, involves an aqueous
workup and above all requires very short reaction times (1–2 h).
The reaction involving acetophenone gave products with only
one asymmetric centre (5a–i). The reaction involving propiophenone (5m) and methyl acetoacetate (5n) however, led to
diastereomeric mixtures. The ratio of these diastereomers was
determined by 1 H NMR spectroscopy (Section 5.3). As can be
seen from Table 2, the major diastereomer was anti in all cases.
3. Reusability of catalyst
In addition, we investigated the reusability and recycling of K5 CoW12 O40 ·3H2 O. At first, we put 0.01 mol% of
K5 CoW12 O40 ·3H2 O, p-chloro benzaldehyde, acetophenone,
acetyl chloride and acetonitrile together, and then the mixture
was stirred at room temperature. When the reaction was completed, the catalyst was separated by simple filtration by diluting
with acetonitrile and recovered K5 CoW12 O40 ·3H2 O was reused
in subsequent reactions without significant decrease in activity
even after seven runs (Table 3).
4. Conclusion
In conclusion, this paper describes a convenient and efficient process for the synthesis of -acetamido ketones through
the four-component coupling of various aromatic aldehydes, enolisable ketone, acetyl chloride and acetonitrile using
K5 CoW12 O40 ·3H2 O as a solid support at room temperature.
Present methodology offers very attractive features such as
reduced reaction times, higher yields and will have wide scope in
organic synthesis. This simple procedure combined with easy of
recovery and reuse of the catalyst makes this method economic,
benign, and a waste-free chemical process for the synthesis of
-acetamido ketones. We believe that this procedure is convenient, economic, and a user-friendly process for the synthesis of
-acetamido ketones.
All of the products were characterized by a comparison of
their spectral and physical data with those of authentic samples.
All yields refer to isolated products. NMR spectra were recorded
on a Varian 200 MHz or Bruker 300 MHz. IR spectra were run
on a Perkin-Elmer bio-spectrometer. Mass spectra were recorded
on VG micromass 7070H or a Finnigan Met 1020B at 70 eV. The
purity of the substances and the progress of the reactions were
monitored by TLC on silica gel.
5.1. Preparation of the catalyst [16]
The synthesis of potassium dodecatungstocobaltate trihydrate (K5 CoW12 O40 ·3H2 O) starts with the preparation of
sodium tungstodicobalt(II)ate from cobaltous acetate (5.0 g,
0.02 mol) and sodium tungstate (39.6 g, 0.12 mol) in acetic acid
and water at pH 6.5–7.5. The sodium salt is then converted to
the potassium salt by treatment with potassium chloride (26 g).
Finally the cobalt(II) complex is oxidized to the cobalt(III) complex by potassium persulfate (20 g) in 80 mL of 2 M H2 SO4 .
The crystals of K5 CoW12 O40 ·20H2 O were dried at 200 ◦ C, after
recrystallization with methanol, and potassium dodecatungstocobaltate trihydrate (K5 CoW12 O40 ·3H2 O) were obtained.
5.2. Typical procedure
To a stirred mixture of K5 CoW12 O40 ·3H2 O (0.01 mol%)
in acetonitrile (2.5 mL) were added an aldehyde (106 mg), an
enolisable ketone (120 mg) and acetyl chloride (0.4 mL). The
reaction mixture was stirred at room temperature for 1–2 h. The
mixture was filtered to remove the catalyst and the filtrate was
poured into ice-cold water. The precipitated solid was filtered,
dried, washed with petroleum ether 60–80 ◦ C to remove any
residual starting material and dried. All products were characterized by comparison of their physical constants and spectral
data with those for authentic samples [9].
5.3. Representative spectral data
Compound 5a: mp 101.8–103.4 ◦ C, 1 H NMR (200 MHz,
CDCl3 ), δ: 2.04 (s, 3H, Ac), 3.33 (dd, 1H, J = 6.6 and 9.8 Hz),
3.66 (dd, 1H, J = 6.4 and 9.9 Hz), 5.55 (m, 1H), 6.82 (brs, 1H),
7.45 (d, 5H, J = 9.6 Hz), 7.88 (d, 5H, J = 9.0 Hz); IR (KBr, cm−1 ):
3250, 3030, 1662, 1635, 1574, 1265, 1085. Compound 5c: mp
141.2–143.0 ◦ C, 1 H NMR (300 MHz, CDCl3 ), δ: 2.01 (s, 3H,
Ac), 3.40 (dd, 1H, J = 6.6 and 9.6 Hz), 3.68 (dd, 1H, J = 6.6
and 9.6 Hz), 5.56 (m, 1H), 6.77 (brs, 1H), 7.00 (m, 5H), 7.42
(m, 3H), 7.84 (d, 2H, J = 9.1 Hz); IR (KBr, cm−1 ): 3263, 3080,
1666, 1565, 1250, 1100. Compound 5g: mp 110.0–111.6 ◦ C,
1 H NMR (200 MHz, CDCl ), δ: 2.04 (s, 3H, Ac), 3.23 (dd,
3
1H, J = 6.8 and 10.0 Hz), 3.55 (dd, 1H, J = 6.7 and 9.7 Hz), 5.50
(m, 1H), 6.85(brs, 1H), 7.36 (m, 5H), 7.75–8.05 (m, 4H); IR
(KBr, cm−1 ): 3290, 3025, 2255, 1685, 1545, 1452, 760, 685,
555. Compound 5j: mp 151.3–152.8 ◦ C, 1 H NMR (300 MHz,
CDCl3 ), δ: 2.05 (s, 3H, Ac), 3.33 (dd, 1H, J = 6.7 and 10.5 Hz),
3.68 (dd, 1H, J = 6.8 and 10.0 Hz), 3.82 (s, 9H, OCH3 ), 5.45
L. Nagarapu et al. / Journal of Molecular Catalysis A: Chemical 264 (2007) 22–25
(m, 1H), 6.55 (s, 2H), 6.80 (brs, 1H), 7.45 (t, 2H), 7.65 (t, 1H),
8.05 (d, 2H, J = 9.5 Hz); IR (KBr, cm−1 ): 3270, 3075, 2945,
1695, 1560, 1230, 1125, 750, 680. Compound 5q: 1 H NMR
(300 MHz, CDCl3 ), δ: 2.02 (s, 3H, Ac), 2.15 (s, 3H, CH3 ) 3.80
(s, 3H, OCH3 ), 4.05 (d, 1H, J = 6.5 Hz), 5.75 (dd, 1H, J = 8.6
and 5.3 Hz), 6.85 (brs, 1H), 6.88 (d, 2H, J = 9.4 Hz), 7.28 (d,
2H, J = 9.6 Hz); IR (KBr, cm−1 ): 3275, 1750, 1725, 1658, 1510.
Acknowledgement
[6]
[7]
[8]
[9]
[10]
The authors are thankful to Dr. J.S. Yadav, Director and Dr.
M. Hari Babu, Deputy Director and Head, Organic Chemistry
Division-II, IICT for providing facilities and helpful discussions.
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