An efficient and eco-friendly solvent-free synthesis of β-acetamido ketones using l-proline as a green and reusable catalyst

Article abstract of DOI:10.14233/ajchem.2013.13244

A simple and efficient catalytic protocol for the synthesis of β-acetamido ketones via the one-pot, four component condensation of aryl aldehydes, enolizable aryl ketones, acetyl chloride and acetonitrile using L-proline is reported. The present method of

Full text of DOI:10.14233/ajchem.2013.13244

Asian Journal of Chemistry; Vol. 25, No. 4 (2013), 1934-1936
http://dx.doi.org/10.14233/ajchem.2013.13244
An Efficient and Eco-Friendly Solvent-Free Synthesis of β-Acetamido
Ketones Using L-Proline As a Green and Reusable Catalyst
*
M. ROSHANI , S. ALLAMEH and E. DARKOOTI
Department of Chemistry, Mashhad Branch, Islamic Azad University, 91735-413, Mashhad, Iran
*
Corresponding author: E-mail: drmina.roshani@yahoo.com
Received: 14 December 2011;
(
Accepted: 8 October 2012)
AJC-12253
A simple and efficient catalytic protocol for the synthesis of β-acetamido ketones via the one-pot, four component condensation of aryl
aldehydes, enolizable aryl ketones, acetyl chloride and acetonitrile using L-proline is reported. The present method offers several advantages
such as high yields, short reaction times, recovery and reusability of catalyst and easy workup procedures.
Key Words: β-Acetamido ketones, Enolizable aryl ketones, Aryl aldehydes, Reusable catalyst.
1
9
2
and co-workers. A few catalysts including CoCl , cobalt(II)
INTRODUCTION
20
21
22
23
24
25
acetate , SiO -H
2
2
SO
4 3
, triflate salts , zeolite , iodine , Bicl ,
Most attention has been focused on the use of proline due
to its ready availability in either L- or D-form and the highly
26
27
ZrOCl ·8H O and heteropolyacids have already been applied
2 2
1
-3
for the synthesis of β-acetamido ketones, using this method.
Although various procedures are reported for synthesis of β-
acetamido ketones, some drawbacks such as low yields,
prolonged reaction time, use of costly reagents or catalysts
and use of toxic organic solvents, exist. Thus, the development
of an environmentally benign methodology for the synthesis
of β-acetamido ketone derivatives is in great demand.
It is therefore of interest to examine the behavior of L-
proline as catalyst in solvent-free conditions for synthesis of
β-acetamido ketones. To the best of our knowledge, conden-
sation of aryl aldehydes, enolizable aryl ketones, acetyl
chloride and acetonitrile in the presence of a catalytic amount
of L-proline for the synthesis of β-acetamido ketones has not
been reported in literature. In this paper we wish to report the
use of L-proline for synthesis of β-acetamido ketone deriva-
tives (Scheme-I).
versatile nature of its reactivity . The natural amino acid
L-proline is one such small molecule, which given rich dividends
in ees and yields in several asymmetric transformation, such
4
5
6
asAldol , Mannich and Michael reactions, Robinson annula-
7
tions , synthesis of amino acids α-amination of aldehydes
8
9
10
11
and ketones , α-oxidation and α-alkylation of aldehydes .
β-Acetamido ketones are versatile intermediates, in that
their skeletons exist in a number of biologically or pharmaco-
12,13
logically active compounds . They could easily be converted
14
to 1,3-amino alcohols , which are utilized for the synthesis of
1
5
several antibiotics . β-Acetamido ketones are usually prepared
16
through of β-aminoketones , Michael addition to α,β-unsat-
17
18
urated ketones or photoisomerization of phthalimides . The
best-known route for the synthesis of these compounds is the
one-pot condensation of an aldehyde, an enolizable ketone,
acetyl chloride and acetonitrile, originally reported by Iqbal
O
O
H
(1)
O
HN
CH3
L-proline
X
+
CH COCl
+
CH CN
3
3
O
solvent-free/110 ºC
(
3)
(4)
Y
X
CH3
(5)
(
2)
Y
Scheme-I

Vol. 25, No. 4 (2013)
Synthesis of β-Acetamido Ketones Using L-Proline As a Green and Reusable Catalyst 1935
Initially, in order to find the optimal amount of catalyst,
the reaction of p-nitrobenzaldehyde (1 mmol), acetophenone
(Table-2). Unlike some previously reported methods, the
present method does not require toxic organic solvents to
produce the β-acetamido ketone derivatives. All the products
were characterized by NMR, IR and melting point and also
by comparison with the data reported in literature.
(
(
1 mmol), acetyl chloride (1.5 mmol 0.3 mL) and acetonitrile
3 mL) under solvent-free condition at 110 ºC in the presence
of various amount of L-proline were used as a model reaction.
The best result has been obtained at 35 mol % of catalyst
The suggested mechanism of the reaction can be followed
according to the steps in Scheme-II.
(
Table-1).
We also investigated the reusability of the catalyst. For
this purpose after completion of the model reaction, the cold
water was added. The catalyst is soluble in cold water and
could therefore be recycled as the filtrate. The catalyst was
recovered by evaporation of the water and washed with
diethylether and reused in model reaction without appreciable
reduction in the catalytic activity.
TABLE-1
COMPARISION OF THE AMOUNT OF L-PROLINE AND
YIELDS FOR SYNTHESIS OF N-[1-(4-NITROPHENYL)-
3-OXO-3-PHENYLPROPYL]ACETAMID (5h)
Entry
Catalyst (mol %)
Time (min)
Yield (%)
1
2
3
4
5
6
0
300
120
80
Nil
30
46
72
85
70
5
15
30
35
40
30
EXPERIMENTAL
30
40
Melting points were determined on an Electrothermal type
9
100 melting point apparatus. IR spectra were recorded using
1
The generality of this process was demonstrated by the
wide range of substituted aryl aldehydes and enolizable aryl
ketones to synthesize the corresponding products in high yields
a 4300 Shimadzu spectrophotometer with KBr plates. H NMR
spectra were recorded on a Bruker DR X500 spectrometer.
The products (5a-l) were isolated and characterized by
TABLE-2
SYNTHESIS OF β-ACETAMIDO KETONES USING L-PROLINE UNDER SOLVENT-FREE CONDITIONS
Entry
X
Y
H
Product
5a
Time (min)
Yield (%)
67
m.p. (ºC)
103-105
295-297
145-146
239-242
160-162
137-140
115-117
152-154
209-211
107-110
140-143
115-118
Lit. m.p. (ºC)
19
19
19
19
19
19
19
19
19
19
1
2
3
4
5
6
7
8
9
H
50
40
25
25
25
30
30
25
45
40
25
25
104-105
295-296
149-150
239-240
162-164
139-140
119-121
155-156
210-211
109-110
–
2-Cl
H
5b
5c
85
4-Cl
H
90
3-Br
4-Br
2-NO2
3-NO2
4-NO2
4-Me
4-OMe
4-Cl
H
5d
5e
80
H
89
H
5f
63
H
5g
74
H
5h
5i
85
H
45
10
11
12
H
5j
55
4-Cl
4-NO2
5k
5l
92
4-Cl
94
–
Y
Y
HN
O
H
+
COOH
N
H
+
N
CH3
H
CH3
H
-H O
2
OH COOH
CH3
Y
COO-
O
OH+
COO-
H
+
CH COH
H
COO-
H
3
N +
X
CH COCl
N +
3
X
X
Y
Y
+
CH -CN
COO-
H
3
CH CONH
3
O
CH CN
N +
3
H O
2
X
X
Y
Y
Scheme-II

1
936 Roshani et al.
Asian J. Chem.
comparison of physical and spectral data with those of known
samples.
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2
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1
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1
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2
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1
1
-1
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4
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2
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4
2
3 2 2
.2 (s, 3H, CH ), 3.7 (dd, 1H, CH ), 3.9 (dd, 1H, CH
2
1
4
-1
disc, νmax, cm ): 3295 (NH
2
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2
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2
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It should be noted that, this method is effective for the
preparation of β-acetamido ketones from the one-pot, four
component condensation of aryl aldehydes, enolizable aryl
ketones, acetyl chloride and acetonitrile using L-proline.
2