Efficient synthesis of β-acetamido ketones catalyzed by cobalt sulfate heptahydrate under ultrasound irradiation

Article abstract of DOI:10.2174/157017812799304088

Ultrasound-promoted synthesis of β-acetamido ketones catalyzed by cobalt sulfate heptahydrate via one-pot multi-component reaction coupling of aromatic aldehyde, acetophenone and acetyl chloride in acetonitrile was carried out in excellent yields at 25-28 °C, providing an efficient synthesis of these compounds. The use of ultrasound increased the rate of reactions compared with reactions under reflux condition.

Full text of DOI:10.2174/157017812799304088

Letters in Organic Chemistry, 2012, 9, 45-50
45
Efficient Synthesis of ꢀ-Acetamido Ketones Catalyzed by Cobalt Sulfate
Heptahydrate Under Ultrasound Irradiation
Bao-Hua Chena,b,c, Ji-Tai Li*,a, Guo-Feng Chena and Ya-Li Songb,c
aCollege of Chemistry and Environmental Science, Hebei University, Baoding 071002, P.R. China
bCollege of Pharmaceutical Sciences, Hebei University, Baoding 071002, P.R. China
cKey Laboratory of Pharmaceutical Quality Control of Hebei Province, Baoding 071002, P.R. China
Received July 07, 2011: Revised November 04, 2011: Accepted November 04, 2011
Abstract: Ultrasound-promoted synthesis of ꢀ-acetamido ketones catalyzed by cobalt sulfate heptahydrate via one-pot
multi-component reaction coupling of aromatic aldehyde, acetophenone and acetyl chloride in acetonitrile was carried out
o
in excellent yields at 25-28 C, providing an efficient synthesis of these compounds. The use of ultrasound increased the
rate of reactions compared with reactions under reflux condition.
Keywords: ꢀ-Acetamido ketones, cobalt sulfate heptahydrate, condensation, synthesis, ultrasound irradiation.
INTRODUCTION
CeCl3•7H2O [5], FeCl3•6H2O [6], ZrOCl2•8H2O [7], ZnO
[8], Mg(HSO4)2 [9], SiCl4-ZnCl2 [10], Cu(BF4)2 [11],
heteropoly acids [12], Amberlyst-15 [13], silica sulfuric acid
[14], ionic liquid [15] and some other catalysts [16], has
been reported. In spite of their potential utility, some of the
reported methods suffer from draw-backs such as low yields,
longer reaction time, expensive catalyst, requiring an inert
atmosphere and harsh reaction conditions. Therefore, the
development of simple, efficient and general methodology
for the reaction is still desirable.
Multi-component reactions (MCRs) have emerged as a
useful tool in modern synthetic organic chemistry and
proved to be remarkably successful in generating molecular
complexity in a single synthetic operation. Through MCRs,
complicated molecules can be achieved in a very fast,
efficient and time saving manner without the isolation of any
intermediate. So the discovery of novel MCRs is of great
interest for the chemists owing to their exceptional synthetic
efficiency [1].
Ultrasound irradiation has been considered as a clean and
useful protocol and widely used in organic synthesis in the
last decades [17]. The most important effect of ultrasound by
passing its waves through a liquid medium is the generation
of many cavities. This leads to development of high
temperatures and high pressures within the cavities during
their collapse. The success and advantages of sonochemical
reactions include shorter reaction times, higher yields and
milder reaction conditions in comparison to classical
methods [18].
ꢀ-Acetamido ketones are valuable intermediates in
organic synthesis and medicinal chemistry, and their
skeletons exist in a large number of biologically or
pharmacologically important compounds. For example, ꢀ-
acetamido ketones can be used in the preparation of 1,3-
aminoalcohols, ꢀ-amino acids, and various bioactive
molecules such as antibiotic nikkomycin or neopolyoximes
[2]. Therefore, the synthesis of ꢀ-acetamido ketones has
gained considerable attention in recent years. Several
strategies have been developed for the preparation of ꢀ-
acetamido ketones, and one of them is the Dakin-West
reaction using ꢁ-amino acids and acetic anhydride [3]. Later
on, Iqbal et al. proposed another procedure for the formation
of these compounds through the condensation of aromatic
aldehyde, acetophenone and acetyl chloride in acetonitrile
catalyzed by CoCl2 or montmorillonite K-10 using one-pot
multi-component reaction [4]. Subsequently, new and
efficient methods for this multi-component reaction were
investigated.
Cobalt sulfate heptahydrate (CoSO4•7H2O), as an
inexpensive commercial available solid, is a water-soluble
cobalt salt with a variety of industrial uses and easy to
handle, and also used as an efficient catalyst in organic
synthesis [19]. In this article, we report an efficient and
convenient procedure for the synthesis of ꢀ-acetamido
ketones using cobalt sulfate heptahydrate as catalyst by one-
pot multi-component reaction under ultrasound irradiation
(Scheme 1).
The one-pot synthesis of the title compounds from
aromatic aldehyde, acetophenone, acetyl chloride and
acetonitrile catalyzed by various catalysts, such as
RESULTS AND DISCUSSION
The synthesis of ꢀ-acetamido ketones using cobalt sulfate
heptahydrate as catalyst was carried out by one-pot
condensation of aromatic aldehyde, acetophenone and acetyl
chloride in acetonitrile. To optimize the reaction conditions,
the condensation of 4-chlorobenzaldehyde (1b, 2 mmol),
*Address correspondence to this author at the College of Chemistry and
Environmental Science, Hebei University, Wusi East Road No.180, Baoding
071002, P.R. China. Tel: +86-312-5079361; Fax: +86-312-5079628; Email-
address: lijitai@hbu.cn
© 2012 Bentham Science Publishers
1875-6255/12 $58.00+.00

46 Letters in Organic Chemistry, 2012, Vol. 9, No. 1
Chen et al.
O
CH3CONH
O
O
H
CH3
CoSO4
7H2O
R1
R1
R2
+
R2
CH3COCl, CH3CN, u.s.
1a-o
Scheme 1. One-pot synthesis of ꢀ-acetamido ketones catalyzed by cobalt sulfate heptahydrate.
2
3a-o
acetophenone (2b, 2 mmol) and acetyl chloride (1 mL, 14
mmol) in acetonitrile (6 mL) was selected as model reaction.
Using this system, we did a series of experiments to prepare
ꢀ-acetamido ketones under ultrasound irradiation. The
results are summarized in Table 3 (Method B).
As shown in Table 1, without ultrasound under reflux
condition by stirring alone for 8 h, the yields of the model
reaction using various amount of CoSO4•7H2O were
obtained and compared. From the results, it can be
concluded that the optimum amount of the catalyst was 30
mol% and the yield of 3b was only 66% (Entry 3).
In order to verify the effect of ultrasound irradiation, a
series of experiments for the condensation of aromatic
aldehydes, acetophenones, acetyl chloride and acetonitrile to
form ꢀ-acetamido ketones 3(a-o) were also completed under
silent condition (Table 3, method A). As shown in Table 3,
aromatic aldehydes or acetophenone in benzene ring with
electron-rich and electron-poor substituents reacted to afford
the corresponding ꢀ-acetamido ketones in high yields (86-
Table 1. The Effect of Catalyst Amount on the Yield of 3b
Under Reflux Condition without Ultrasounda
o
91%) at 25-28 C within 2 h under ultrasound irradiation.
Entry
CoSO4•7H2O, mol%
Isolated yield, %
While in the absence of ultrasound the same reaction was
refluxed for 8 h to provide the ꢀ-acetamido ketones in low
yields (39-63%). It is apparently that ultrasound irradiation
accelerated the condensation and improved the result.
1
2
3
4
5
10
20
30
40
0
58
63
66
Cavitation is the origin of sonochemistry. Cavitation is
the production of microbubbles in a liquid when a large
negative pressure is applied to it. These cavities can collapse
violently with the release of large amounts of energy in and
around these microbubbles. When the compression of
bubbles occurs during cavitation, heating is more rapidly
produced than thermal transport, creating a short lived
localized hot spot, inducing molecular fragmentation, and
highly reactive species are locally produced, which are
responsible for the chemical effects of ultrasound on
homogeneous solutions [21]. In some case, sonication can
probably provide more efficient stirring. All of these can
cause the reaction to take place rapidly.
60
no product
aThe reactions under reflux were performed for 8 h.
The effect of the amount of catalyst and reaction time on
the yield of 3b under ultrasound irradiation was also
observed. As shown in Table 2, the reaction was carried out
using 20 mol% CoSO4•7H2O at 25-28 oC for 2 h under
ultrasound irradiation, 3b can be obtained in 91% yield. It is
clear that sonication can decrease the amount of catalyst,
reduce the reaction time and improve the yield of 3b. The
effect of reaction temperature on the yield was not obvious,
o
25-28 C was the appropriate temperature for the conden-
sation.
In preliminary experiment, we tried to prepare 3a
according to the reported one-pot method in the literature
[12b], but the result was poor, 3a was afforded in 30% yield
only at r.t. for 1 h. Then we decided to investigate the
reaction catalyzed by cobalt sulfate heptahydrate under
ultrasound. The yield and reaction time of 3a catalyzed by
From the results above, a typical experimental procedure
was chosen as following: aromatic aldehyde (1, 2 mmol),
acetophenone (2, 2 mmol), acetyl chloride (1 mL, 14 mmol),
acetonitrile (6 mL) and CoSO4•7H2O (0.4 mmol, 20 mol%).
Table 2. The Effect of Reaction Conditions on the Yield of 3b Under Ultrasound Irradiation
Entry
CoSO4•7H2O, mol%
Temperature, oC
Time, h
Isolated yield, %
1
2
3
4
5
6
7
8
20
10
20
30
20
0
25-28
25-28
25-28
25-28
25-28
25-28
38-40
18-20
1
2
2
2
3
2
2
2
80
80
91
90
88
no product
91
20
20
89

Efficient Synthesis of ꢀ-Acetamido Ketones
Letters in Organic Chemistry, 2012, Vol. 9, No. 1
47
Table 3. The Preparation of ꢀ-Acetamido Ketones Catalyzed by Cobalt Sulfate Heptahydrate Under Different Conditionsa
Isolated yield, %
Entry
R1
R2
Product
m.p., oC [Lit.]
A
B
a
b
c
d
e
f
H
4-Cl
H
H
3a
3b
3c
3d
3e
3f
51
63
45
40
39
44
42
45
48
43
48
50
44
46
43
90
91
88
88
86
89
91
91
91
88
90
89
87
88
89
101-103(102-104) [11]
145-147(146-148) [11]
103-105(105-108)[15]
185-187(186-188) [11]
138-140(139-140) [11]
147-149(148-150) [11]
112-114(112-114) [11]
73-75(74-76) [12b]
118-120(116-118) [12b]
215-217
3-Cl
H
2-NO2
3-NO2
4-NO2
4-CH3O
H
H
H
H
g
h
i
H
3g
3h
3i
4-NO2
4-NO2
4-NO2
4-NO2
4-NO2
4-NO2
4-CH3O
4-CH3O
4-Cl
j
2-NO2
4-NO2
4-OH
4-CH3O
H
3j
k
l
3k
3l
185-187(187-188) [12c]
130-132
m
n
o
3m
3n
3o
89-91(87-89) [12b]
128-130(130) [7]
4-Cl
59-61(59-61) [20]
aMethod(A) refluxing for 8 h and (B) ultrasound irradiation at 25-28 oC for 2 h.
CoSO4•7H2O under ultrasound were compared with various
catalysts and conditions reported in some previous works. As
shown in Table 4, the yield of 3a catalyzed by cobalt sulfate
heptahydrate under ultrasound irradiation is, in general,
similar or higher than those described in literatures (except
for Entry 2), and the reaction time is also reduced from 4-8
to 2 h (except for Entry 7). We can deduce that the present
method represented a better procedure for the synthesis of ꢀ-
acetamido ketones.
EXPERIMENTAL SECTION
Melting points were uncorrected. The H NMR and 13C
NMR spectra were measured on a Bruker AVANCE 600
(600 MHz) spectrometer using TMS as the internal standard
and CDCl3 as a solvent. MS were determined on Shimadzu
GCMS-QP2010 spectrometer (ESI). Sonication was
performed in Shanghai Branson-BUG40-06 ultrasonic
cleaner (with a frequency of 40 kHz and a nominal power
250 W).
1
In conclusion, we have developed an efficient procedure
for the preparation of ꢀ-acetamido ketones via multi-
component reaction in the presence of cobalt sulfate
heptahydrate under ultrasound irradiation. This method has
many advantages such as short reaction time, mild
conditions and high yields, which make it a useful strategy
for the synthesis of ꢀ-acetamido ketones.
General Procedure for the Synthesis of ꢀ-Acetamido
Ketones
A 25 mL round-bottomed flask was charged with
aromatic aldehyde (1, 2 mmol), acetophenone (2, 2 mmol),
acetyl chloride (1 mL, 14 mmol), acetonitrile (6 mL) and the
Table 4. Comparison Among Synthesis of 3a via One-Pot Reaction Using Various Catalysts
Entry
Catalyst
Temperature, oC
Time, h
Yield, %
1
2
3
4
5
6
7
8
FeCl3•6H2O
CeCl3•7H2O
ZrOCl2•8H2O
SelectfluorTM
Mont. K10
r. t.
r. t.
r. t.
r. t.
70
8
88 [6]
96 [5]
90[7]
7
5
4
74 [16d]
80 [4c]
90 [8]
91 [14]
90
7
ZnO
80
6
65 min
2
Silica sulfuric acid
CoSO4•7H2O
80
25-28

48 Letters in Organic Chemistry, 2012, Vol. 9, No. 1
Chen et al.
given amount of CoSO4•7H2O was added. The reaction flask
was located in the cleaner bath, where the surface of
reactants is slightly lower than the level of the water.
Observation of the surface of the reaction solution during
vertical adjustment of vessel depth will show the optimum
position by the point at which maximum surface disturbance
occurs. The reaction temperature was controlled by addition
or removal of water from ultrasonic bath. The mixture was
Hz, 2H, Ar-H), 7.70 (d, J=7.8 Hz, 1H, Ar-H), 7.92 (d, J=7.3
Hz, 2H, Ar-H), 7.94 (s, 1H, Ar-H). 13C NMR: ꢀ 23.3, 42.3,
47.4, 125.1, 128.3, 128.4, 128.8, 129.8, 133.5, 133.9, 136.3,
136.7, 148.4, 198.6.
Compound 3e
ꢀ-Acetamido-ꢀ-(3-nitrophenyl)propiophenone, white
1
solid. H NMR: ꢀH1.99 (s, 3H, CH3), 3.62 (dd, J=5.4 and
o
16.8 Hz, 1H, CH2), 3.71 (dd, J=6.4 and 16.9 Hz, 1H, CH2),
5.95 (d, J=6.5 Hz, 1H, CH), 7.06 (d, J=6.2 Hz, 1H, NH),
7.39 (t, J=15.2 Hz, 1H, Ar-H), 7.45 (t, J=15.2 Hz, 2H, Ar-
H), 7.57 (t, J=11.3 Hz, 2H, Ar-H), 7.70 (d, J=7.8 Hz, 1H,
Ar-H), 7.93 (t, J=14.5 Hz, 3H, Ar-H). 13C NMR: ꢀ 22.8,
44.0, 45.7, 124.3, 128.0, 128.1, 128.8, 128.9, 133.4, 133.5,
136.6, 138.6, 148.4, 169.6, 196.1.
irradiated by ultrasound at 25-28 C (bath temperature, the
temperature inside the reactor was also the same) in the
water bath of the ultrasonic cleaner for the period as
indicated in Table 3. The reaction was monitored by TLC
(petroleum ether: ethyl acetate = 3:1, V/V). After the
completion of the reaction, the mixture was poured into 50
mL water and neutralized by diluted sodium hydroxide
solution. The solid was filtered and washed with water. The
crude product was further purified by column
chromatography on silica gel (200–300 mesh), eluted with
Compound 3f
ꢀ-Acetamido-ꢀ-(4-nitrophenyl)propiophenone, white
1
o
solid. H NMR: ꢀH 2.05 (s, 3H, CH3), 3.49 (dd, J=5.6 and
petroleum ether (b.p. 60-90 C) or a mixture of petroleum
17.5 Hz, 1H, CH2), 3.79 (dd, J=5.2 and 17.5 Hz, 1H, CH2),
5.63-5.67 (m, 1H, CH), 7.07 (d, J=8.1 Hz, 1H, NH), 7.45 (t,
J=15.6 Hz, 2H, Ar-H), 7.52 (d, J=8.7 Hz, 2H, Ar-H), 7.59 (t,
J=9.4 Hz, 1H, Ar-H), 7.88 (d, J=7.4 Hz, 2H, Ar-H), 8.13 (d,
J=8.8 Hz, 2H, Ar-H). 13C NMR: ꢀ 23.3, 42.7, 49.2, 123.8,
127.4, 128.1, 128.9, 134.0, 136.2, 147.1, 148.7, 169.8, 198.0.
ether and ethyl acetate (1/2, V/V). The authenticity of the
unknown compounds 3j and 3l were established by their
spectral data of 1H NMR, 13C NMR and MS; the rest known
1
compounds were established by their spectral data of H
NMR, 13C NMR and their melting points compared with that
reported in literatures.
Compound 3a
Compound 3g
ꢀ-Acetamido-ꢀ-(phenyl)propiophenone, white solid. 1H
NMR: ꢀH 1.80 (s, 3H, CH3), 3.40 (dd, J=5.7 and 16.9 Hz,
1H, CH2), 3.54 (dd, J=8.4 and 16.9 Hz, 1H, CH2), 5.37-5.40
(m, 1H, CH), 6.71 (s, 1H, NH), 7.22-7.36 (m, 5H, Ar-H),
7.52 (t, J=15.4 Hz, 2H, Ar-H), 7.63 (t, J=14.8 Hz, 1H, Ar-
H), 7.95 (d, J=7.4 Hz, 2H, Ar-H). 13C NMR: ꢀ 23.1, 45.1,
49.4, 127.1, 127.3, 128.5, 128.7, 129.2, 133.7, 137.0, 143.5,
168.8, 197.6.
ꢀ-Acetamido-ꢀ-(4-methoxyphenyl)propiophenone,
white solid. H NMR: ꢀH 1.95 (s, 3H, CH3), 3.36-3.40 (m,
1
1H, CH2), 3.67-3.71 (m, 1H, CH2), 3.73 (s, 3H, CH3O), 5.50
(d, J=6.2 and 13.9 Hz, 1H, CH), 6.8 (d, J=7.8 Hz, 2H, Ar-H),
6.87-6.90 (m, 1H, NH), 7.24 (d, J=8.8 Hz, 2H, Ar-H), 7.42
(t, J=14.5 Hz, 2H, Ar-H), 7.54 (t, J=14.4 Hz, 1H, Ar-H),
7.89 (d, J=8.1 Hz, 2H, Ar-H). 13C NMR: ꢀ 23.4, 43.5, 49.6,
55.2, 114.0, 127.8, 128.2, 128.7, 133.2, 133.4, 136.7, 158.8,
169.5, 198.5.
Compound 3b
Compound 3h
ꢀ-Acetamido-ꢀ-(4-chlorophenyl)propiophenone, white
solid. H NMR: ꢀH 2.00 (s, 3H, CH3), 3.42 (dd, J=5.8 and
1
ꢀ-Acetamido-ꢀ-(phenyl)-4-nitropropiophenone, white
1
17.1 Hz, 1H, CH2), 3.73 (dd, J=4.9 and 17.1 Hz, 1H, CH2),
5.53 (d, J=7.8 Hz, 1H, CH), 6.75 (d, J=7.4 Hz, 1H, NH),
7.27 (s, 4H, Ar-H), 7.46 (t, J=15.2 Hz, 2H, Ar-H), 7.58 (t,
J=14.6 Hz, 1H, Ar-H), 7.89 (d, J=7.7 Hz, 2H, Ar-H). 13C
NMR: ꢀ 23.4, 43.0, 49.3, 127.9, 128.1, 128.7, 128.8, 133.1,
133.7, 136.5, 139.6, 198.4.
solid. H NMR: ꢀH 2.01 (s, 3H, CH3), 3.47 (dd, J=6.7 and
16.7 Hz, 1H, CH2), 3.83 (dd, J=5.3 and 16.6 Hz, 1H, CH2),
5.53 (dd, J=6.8 and 12.8 Hz, 1H, CH), 6.47 (d, J=7.0 Hz,
1H, NH), 7.26-7.33 (m, 5H, Ar-H), 8.06 (d, J=8.8 Hz, 2H,
Ar-H), 8.28 (d, J=8.8 Hz, 2H, Ar-H). 13C NMR: ꢀ 23.4, 44.1,
50.3, 123.9, 126.6, 127.9, 128.9, 129.2, 140.2, 141.0, 150.5,
169.6, 196.8.
Compound 3c
Compound 3i
ꢀ-Acetamido-ꢀ-(3-chlorophenyl)propiophenone, white
solid. H NMR: ꢀH 2.01 (s, 3H, CH3), 3.41 (dd, J=5.6 and
1
ꢀ-Acetamido-ꢀ-(4-chlorophenyl)-4-nitropropiophen-
one, white solid. H NMR: ꢀH 2.01 (s, 3H, CH3), 3.46 (dd,
1
17.2 Hz, 1H, CH2), 3.71 (dd, J=5.2 and 17.2 Hz, 1H, CH2),
5.53 (d, J=8.0 Hz, 1H, CH), 6.94 (s, 1H, NH), 7.18-7.23 (m,
3H, Ar-H), 7.33 (s, 1H, Ar-H), 7.45 (t, J=15.4 Hz, 2H, Ar-
H), 7.57 (t, J=14.8 Hz, 1H, Ar-H), 7.89 (d, J=7.4 Hz, 2H,
Ar-H). 13C NMR: ꢀ 23.3, 43.3, 49.4, 124.9, 126.7, 127.5,
128.1, 128.8, 129.9, 133.7, 134.4, 136.4, 143.5, 169.8, 198.0.
m/z (ESI): 302 [M]+, 324 [M+Na]+.
J=6.5 and 17.1 Hz, 1H, CH2), 3.80 (dd, J=5.3 and 17.1 Hz,
1H, CH2), 5.51 (dd, J=6.3 and 13.4 Hz, 1H, CH), 6.66 (d,
J=7.8 Hz, 1H, NH), 7.28 (s, 4H, Ar-H), 8.06 (d, J=8.8 Hz,
2H, Ar-H), 8.28 (d, J=8.8 Hz, 2H, Ar-H). 13C NMR: ꢀ 23.3,
43.9, 49.4, 124.0, 128.0, 129.0, 129.2, 133.6, 138.9, 140.7,
150.5, 169.7, 196.5.
Compound 3d
Compound 3j
ꢀ-Acetamido-ꢀ-(2-nitrophenyl)propiophenone, white
solid. H NMR: ꢀH 1.99 (s, 3H, CH3), 3.62 (dd, J=5.4 and
ꢀ-Acetamido-ꢀ-(2-nitrophenyl)-4-nitropropiophenone,
white solid. H NMR: ꢀH 1.78 (s, 3H, CH3), 3.36 (d, J=14.1
1
1
16.7 Hz, 1H, CH2), 3.71 (dd, J=6.4 and 16.8 Hz, 1H, CH2),
5.94-5.97 (m, 1H, CH), 7.09 (s, 1H, NH), 7.39 (t, J=15.4 Hz,
1H, Ar-H), 7.45 (t, J=15.2 Hz, 2H, Ar-H), 7.57 (t, J=13.4
Hz, 1H, CH2), 3.51 (dd, J=3.3 and 18.0 Hz, 1H, CH2), 3.75
(dd, J=9.8 and 18.0 Hz, 1H, CH), 5.74-5.77 (m, 1H, NH),
7.52-7.55 (m, 1H, Ar-H), 7.72-7.78 (m, 2H, Ar-H), 7.95 (d,

Efficient Synthesis of ꢀ-Acetamido Ketones
Letters in Organic Chemistry, 2012, Vol. 9, No. 1
49
J=8.2 Hz, 1H, Ar-H), 8.24 (d, J=8.8 Hz, 2H, Ar-H), 8.35 (d,
J=8.8 Hz, 2H, Ar-H). 13C NMR: ꢀ 22.9, 44.7, 45.1, 124.3,
124.6, 128.8, 129.0, 130.0, 134.1, 138.5, 141.3, 148.5, 150.5,
169.3, 195.9. m/z (ESI): 358 [M]+.
REFERENCES
[1]
(a) Nishiyama, Y.; Katahira, C.; Sonoda, N. A new method for the
synthesis of 1,3-oxathiolan-2-ones by the reaction of epoxides with
sulfur and carbon monoxide. Tetrahedron Lett., 2004, 45, 8539-
8540. (b) Tu, S.J.; Jiang, B.; Jia, R.H.; Zhang, J.Y.; Zhang, Y. An
efficient and expeditious microwave-assisted synthesis of 4-
azafluorenones via a multi-component reaction. Tetrahedron Lett.,
2007, 48, 1369-1374. (c) Yonggui, C.; Steven, T.S.; Jean, M.J.F.
One-pot multi-component asymmetric Cascade reactions catalyzed
by soluble star polymers with highly branched non-interpentrating
catalytic cores. J. Am. Chem. Soc., 2008, 130, 6322-6323. (d)
Kumar, A.; Sharma, S.; Maurya, R.A. A novel multi-component
reaction of indole, formaldehyde, and tertiary aromatic amines.
Tetrahedron Lett., 2009, 50, 5937-5940.
Compound 3k
ꢀ-Acetamido-ꢀ-(4-nitrophenyl)-4-nitropropiophenone,
1
white solid. H NMR: ꢀH 2.08 (s, 3H, CH3), 3.57 (dd, J=5.9
and 17.7 Hz, 1H, CH2), 3.88 (dd, J=5.0 and 17.7 Hz, 1H,
CH2), 5.65-5.69 (m, 1H, CH), 6.66 (d, J=8.0 Hz, 1H, NH),
7.54 (d, J=8.7 Hz, 2H, Ar-H), 8.07 (d, J=8.8 Hz, 2H, Ar-H),
8.18 (d, J=7.2 Hz, 2H, Ar-H), 8.31 (d, J=8.8 Hz, 2H, Ar-H).
13C NMR: ꢀ 23.4, 43.4, 49.2, 124.0, 124.1, 127.5, 129.2,
140.4, 147.3, 147.8, 150.8, 169.7, 196.3.
[2]
(a) Enders, D.; Moser, M.; Geibel, G.; Laufer, M.C. Diastereo- and
enantioselective synthesis of differently N,O-protected 1,3-amino
alcohols with three neighbouring stereogenic centers. Synthesis,
2004, 2040-2046. (b) Kobinata, K.; Uramoto, M.; Nishii, M.;
Kusakabe, H.; Nakamura, G.; Isono, K. Neopolyoxins A, B, and C,
new chitin synthetase inhibitors. Agric. Biol. Chem., 1980, 44,
1709-1711. (c) Barluenga, J.; Viado, A.L.; Aguilar, E.; Fustero, S.;
Olano, B. 1,3-Amino alcohols from 4-amino-1-aza dienes.
Diastereo- and enantioselective approach to the four
diastereoisomers of the N-terminal amino acid component of
nikkomycins B and BX. J. Org. Chem., 1993, 58, 5972-5975.
(a) Darkin, H.D.; West, R. A general reaction of amino acids. II. J.
Biol. Chem., 1928, 78, 745-746. (b) Buchanan, G.L. The Dakin-
West reaction. Chem. Soc. Rev., 1988, 17, 91-109.
(a) Bhatia, B.; Reddy, M.M.; Iqbal, J. Cobalt catalysed three
component coupling involving ketones or ketoesters, aldehyde and
acetonotrile: a novel one pot synthesis of ꢀ-acetamido ketones. J.
Chem. Soc., Chem. Commun., 1994, 6, 713-714. (b) Rao, I.N.;
Prabhakaran, E.N.; Das, S.K.; Iqbal, J. Cobalt-catalyzed one-pot
three-component coupling route to ꢀ-acetamido carbonyl
compounds: a general synthetic protocol for ꢁ-lactams. J. Org.
Chem., 2003, 68, 4079-4082. (c) Bahulayan, D.; Das, S.K.; Iqbal, J.
Montmorillonite K10 Clay: An efficient catalyst for the one-pot
stereoselective synthesis of ꢀ-acetamido ketones. J. Org. Chem.,
2003, 68, 5735-5738.
Compound 3l
ꢀ-Acetamido-ꢀ-(4-hydroxyphenyl)-4-nitropropioph-
enone, white solid. 1H NMR: ꢀH 1.92 (s, 3H, CH3), 3.45 (dd,
J=6.2 and 16.9 Hz, 1H, CH2), 3.72 (dd, J=7.5 and 16.8 Hz,
1H, CH2), 5.37-5.54 (m, 1H, CH), 6.75 (d, J=8.4 Hz, 1H,
NH), 7.02-7.96 (m, 4H, Ar-H), 8.13-8.32 (m, 5H, Ar-
H+OH). 13C NMR: ꢀ 22.0, 40.1, 47.1, 115.5, 121.7, 123.8,
128.0, 129.4, 139.3, 141.2, 150.1, 169.4, 196.1. m/z (ESI):
329 [M]+.
[3]
[4]
Compound 3m
ꢀ-Acetamido-ꢀ-(4-methoxyphenyl)-4-nitropropiophe-
1
none, white solid. H NMR: ꢀH1.99 (s, 3H, CH3), 3.44 (dd,
J=7.1 and 16.5 Hz, 1H, CH2), 3.76 (s, 3H, CH3O), 3.80 (dd,
J=5.4 and 16.4 Hz, 1H, CH2), 5.46 (dd, J=7.2 and 12.8 Hz,
1H, CH), 6.50 (d, J=7.6 Hz, 1H, NH), 6.84 (d, J=8.7 Hz, 2H,
Ar-H), 7.24 (d, J=8.7 Hz, 2H, Ar-H), 8.07 (d, J=7.0 Hz, 2H,
Ar-H), 8.27 (d, J=7.0 Hz, 2H, Ar-H). 13C NMR: ꢀ 23.4, 44.4,
49.9, 55.3, 114.2, 123.9, 127.9, 129.2, 132.3, 141.1, 150.4,
159.2, 169.6, 196.8. m/z (ESI): 343 [M]+.
[5]
Khan, A.T.; Choudhury, L.H.; Parvin, T. CeCl3·7H2O: an efficient
and reusable catalyst for the reparation of ꢀ-acetamido carbonyl
compounds by multi-component reactions (MCRs). Tetrahedron
Lett., 2006, 47, 8137-8141.
Compound 3n
[6]
[7]
[8]
Khan, A.T.; Parvin, T.; Choudhury, L.H. Iron(III) chloride-
catalyzed convenient one-pot synthesis of ꢀ-acetamido carbonyl
compounds. Tetrahedron, 2007, 63, 5593-5601.
Ghosh, R.; Maiti, S.; Chakraborty, A. ZrOCl2·8H2O: an efficient
Lewis acid catalyst for the one-pot multicomponent synthesis of ꢀ-
acetamido ketones. Tetrahedron, 2006, 62, 4059-4064.
ꢀ-Acetamido-ꢀ-(phenyl)-4-methoxypropiophenone,
1
white solid. H NMR: ꢀH1.99 (s, 3H, CH3), 3.34 (dd, J=5.8
and 16.6 Hz, 1H, CH2), 3.66 (dd, J=5.2 and 16.6 Hz, 1H,
CH2), 3.85 (d, J=10.5 Hz, 3H, CH3O), 5.54 (d, J=6.8 Hz, 1H,
CH), 6.89-6.95 (m, 4H, Ar-H), 7.21 (d, J=7.0 Hz, 1H, NH),
7.32 (d, J=7.4 Hz, 2H, Ar-H), 7.90 (dd, J=8.5 and 31.9 Hz,
3H, Ar-H). 13C NMR: ꢀ 23.4, 26.4, 42.9, 50.1, 55.5, 113.7,
113.9, 126.5, 127.3, 128.6, 129.8, 130.5, 130.6, 141.2, 163.8,
169.5, 197.1.
Maghsoodlou, M.T.; Hassankhani, A.; Shaterian, H.R. Zinc oxide
as an economical and efficient catalyst for the one-pot preparation
of ꢀ-acetamido ketones via
a four-component condensation
reaction. Tetrahedron Lett., 2007, 48, 1729-1734.
[9]
Shaterian, H.R.; Hosseinian, A.; Ghashang, M. One-pot preparation
of ꢀ-amido ketones/esters in a three-component condensation
reaction using magnesium hydrogensulfate as an effective and
reusable catalyst. Can. J. Chem., 2008, 86, 376-383.
Compound 3o
[10]
[11]
[12]
Salama, T.A.; Elmorsy, S.S.; Khalil, A.M.; Ismail, M. A. A SiCl4–
ZnCl2 induced general, mild and efficient one-pot, three-component
synthesis of ꢀ-amido ketone libraries. Tetrahedron Lett., 2007, 48,
6199-6203.
Yadav, J.S.; SubbaReddy, B.; Shankar, V.K. Copper(II)
tetrafluoroborate as mild and versatile catalyst for the rapid
synthesis of ꢀ-acetamido ketones and ketoesters via a three
component reaction. Org. Commun. 2008, 76-83.
(a) Rafiee, E.; Shahbazi, F.; Joshaghani, M. The silica supported
H3PW12O40 (a heteropoly acid) as an efficient and reusable catalyst
for a one-pot synthesis of ꢀ-acetamido ketones by Dakin–West
reaction. J. Mol. Catal. A: Chem., 2005, 242, 129-134. (b) Rafiee,
E.; Torka, F.; Joshaghani, M. Heteropoly acids as solid green
Brønsted acids for a one-pot synthesis of ꢀ-acetamido ketones by
Dakin-West reaction. Bioorg. Med. Chem. Lett., 2006, 16, 1221-
1226. (c) Heravi, M.M.; Ranjbar, L.; Derikvand, F. H6P2W18O62:
An efficient and reusable catalyst for one-pot synthesis of ꢀ-
acetamido ketone and esters. Catal. Commun., 2007, 8, 289-291.
(d) Rafiee, E.; Paknezhad, F.; Shahebrahimi, S.; Joshaghani, M.;
ꢀ-Acetamido-ꢀ-(4-chlorophenyl)-4-methoxypropioph-
1
enone, white solid. H NMR: ꢀH1.97 (s, 3H, CH3), 3.31 (dd,
J=6.0 and 16.8 Hz, 1H, CH2), 3.63 (dd, J=5.4 and 16.8 Hz,
1H, CH2), 3.84 (s, 3H, CH3O), 5.49 (dd, J=5.7 and 13.8 Hz,
1H, CH), 6.89 (d, J=8.9 Hz, 2H, Ar-H), 7.16 (t, J=14.5 Hz,
1H, NH), 7.24 (dd, J=8.6 and 15.8 Hz, 4H, Ar-H), 7.86 (d,
J=8.9 Hz, 2H, Ar-H). 13C NMR: ꢀ 23.3, 42.7, 49.4, 55.5,
113.9, 128.0, 128.7, 129.6, 130.5, 133.0, 140.0, 163.9, 169.7,
196.7.
ACKNOWLEDGEMENTS
The project was supported by National Natural Science
Foundation of China (20905019) and Natural Science
Foundation of Hebei University (2010-194), P. R. China.

50 Letters in Organic Chemistry, 2012, Vol. 9, No. 1
Chen et al.
Eavani, S.; Rashidzadeh, S. Acid catalysis of different supported
heteropoly acids for a one-pot synthesis of ꢀ-acetamido ketones. J.
Mol. Catal. A: Chem., 2008, 282, 92-98.
Das, B.; Reddy, K.R. Facile one-pot multicomponent synthesis of
ꢀ-acetamido ketones with Amberlyst-15 as heterogeneous catalyst.
Helv. Chim. Acta., 2006, 89, 3109-3111.
a four-component condensation reaction. Appl. Catal., A, 2009,
366, 108-113.
[17]
[18]
(a) Luche, J.L. Synthetic Organic Sonochemistry, Plenum Press:
New York, 1998. (b) Mamaghani, M.; Dastmard, S. An efficient
ultrasound-promoted synthesis of the Baylis-Hillman adducts
catalyzed by imidazole and L-proline. Ultrason. Sonochem., 2009,
16, 445-447.
[13]
[14]
Khodaei, M.M.; Khosropour, A.R.; Fattahpour, P. A modified
procedure for the Dakin-West reaction: an efficient and convenient
method for a one-pot synthesis of ꢀ-acetamido ketones using silica
sulfuric acid as catalyst. Tetrahedron Lett., 2005, 46, 2105-2108.
Davoodnia, A.; Heravi, M.M.; Rezaei-Daghigh, L.; Tavakoli-
Hoseini, N. Brønsted-acidic ionic liquid [HO3S(CH2)4MIM][HSO4]
as efficient and reusable catalyst for one-pot synthesis of ꢀ-
acetamido ketones. Monatsh. Chem., 2009, 140, 1499-1502.
(a) Mirjalili, B.F.; Bamonirib, A.; Zarchi, M.A.K.; Emtiazi, H.
Zr(HSO4)4/SiO2: An effective heterogeneous alternative for one-pot
synthesis of ꢀ-acetamido ketones. J. Iran. Chem. Soc., 2010, 7, 95-
99. (b) Das, B.; Srilatha, M.; Veeranjaneyulu, B.; Rao, B.R. An
efficient, one-pot, multicomponent synthesis of ꢀ-acetamido
carbonyl compounds using cyanuric chloride in an aqueous
medium. Synthesis, 2010, 803-806. (c) Mao, H.; Wan, J.P.; Pan,
Y.J. Facile and diastereoselective synthesis of ꢀ-acetamido ketones
and keto esters via direct Mannich-type reaction. Tetrahedron,
2009, 65, 1026-1032. (d) Shinu, V.S.; Sheeja, B.; Purushothaman,
E.; Bahulayan, D. An efficient green MCR protocol for the
stereoselective synthesis of ꢀ-acetamido ketones catalyzed by
SelectfluorTM. Tetrahedron Lett., 2009, 50, 4838-4843. (e) Nabid,
M.R.; Rezaei, S.J.T. Polyaniline-supported acid as an efficient and
reusable catalyst for a one-pot synthesis of ꢀ-acetamido ketones via
(a) Memarian, H.R.; Farhadi, A.; Sabzyan, H. Ultrasound-assisted
dehydrogenation of 5-acetyl-3,4-dihydropyrimidin-2(1H)-ones.
Ultrason. Sonochem., 2010, 17, 579-586. (b) Mantu, D.;
Moldoveanu, C.; Nicolescu, A.; Deleanu, C.; Mangalagiu, I.I. A
facile synthesis of pyridazinone derivatives under ultrasonic
irradiation. Ultrason. Sonochem., 2009, 16, 452-454. (c) Li, J.T.;
Sun, M.X.; He, G.Y.; Xu, X.Y. Efficient and green synthesis of
bis(indolyl) methanes catalyzed by ABS in aqueous media under
ultrasound irradiation, Ultrason. Sonochem., 2011, 18, 412-414.
Wang, M.; Tian, G.F.; Song, Z.G.; Jiang, H. Cobalt sulfate as a
recyclable catalyst for chemoselective synthesis of diacetates from
aldehydes. Chem. Res. Chin. Univ., 2009, 25, 455-457.
Lu, X.H. Study on the multicomponent reaction catalyzed by solid
acid. Master’s degree thesis, SuZhou University: SuZhou, June
2008.
Mohammadpoor-Baltork, I.; Moghadam, M.; Tangestaninejad, S.;
Mirkhani, V.; Eskandari, Z. Ultrasound promoted selective
synthesis of 2-aryl-5,6-dihydro-4H-1,3-oxazines catalyzed by K-10
and KSF montmorillonite clays: A practical procedure under mild
and solvent-free conditions. Ultrason. Sonochem., 2010, 17, 857-
862.
[15]
[16]
[19]
[20]
[21]