Simple and efficient procedure for the one-pot synthesis of β-acetamido-β-aryl-propiophenones by molecular iodine-catalyzed tandem reaction

Article abstract of DOI:10.1080/00397910701234982

Molecular iodine efficiently catalyzes the four-component tandem reaction of araldehydes, arylmethyl ketones, acetyl chloride, and acetonitrile to afford the corresponding β-acetamido-β-aryl-propiophenones. The new protocol gives high yields of the produc

Full text of DOI:10.1080/00397910701234982

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Simple and Efficient Procedure
for the One‐Pot Synthesis of
β‐Acetamido‐β‐aryl‐propiophenones by
Molecular Iodine–Catalyzed Tandem Reaction
a
a
a
M. A. Pasha , V. P. Jayashankara & N. Ramachandraswamy
a
Department of Studies in Chemistry, Central College Campus, Bangalore
University, Bangalore, India
Published online: 11 May 2007.
To cite this article: M. A. Pasha , V. P. Jayashankara & N. Ramachandraswamy (2007) Simple and Efficient
Procedure for the One‐Pot Synthesis of β‐Acetamido‐β‐aryl‐propiophenones by Molecular Iodine–Catalyzed
Tandem Reaction, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 37:9, 1551-1556, DOI: 10.1080/00397910701234982
To link to this article: http://dx.doi.org/10.1080/00397910701234982
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Synthetic Communications , 37: 1551–1556, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701234982
Simple and Efficient Procedure for the
One-Pot Synthesis of b-Acetamido-
b-aryl-propiophenones by Molecular
Iodine–Catalyzed Tandem Reaction
M. A. Pasha, V. P. Jayashankara, and N. Ramachandraswamy
Department of Studies in Chemistry, Central College Campus, Bangalore
University, Bangalore, India
Abstract: Molecular iodine efficiently catalyzes the four-component tandem reaction
of araldehydes, arylmethyl ketones, acetyl chloride, and acetonitrile to afford the cor-
responding b-acetamido-b-aryl-propiophenones. The new protocol gives high yields of
the products, and the reactions go to completion within 10–15 min on a hot plate at
80–858C.
Keywords: b-acetamido-b-aryl-propiophenones, acetonitrile, acetyl chloride,
arylaldehydes, arylmethyl ketones, iodine
INTRODUCTION
b-Acetamido-b-aryl-propiophenones are versatile intermediates in that their
skeletons exist in a number of biologically or pharmacologically important
[
compounds. The best known route for the synthesis of these compounds
1]
[
2]
is the Dakin–West reaction,
which involves the condensation of an
b-amino acid with acetic anhydride in the presence of a base via an intermedi-
ate azalactone to give the b-acetamido-b-aryl-propiophenones.
Recently, the synthesis of b-acetamido-b-aryl-propiophenones has
gained acceptance and popularity among the synthetic chemist community;
Received in India September 28, 2006
Address correspondence to M. A. Pasha, Department of Studies in Chemistry,
Central College Campus, Bangalore University, Bangalore 560 001, India. E-mail:
m_af_pasha@yahoo.co.in
1
551

1
552
M. A. Pasha, V. P. Jayashankara, and N. Ramachandraswamy
thus, the preparation of this type of molecules is of much importance.
Consequently, a few methods have been reported with reagents such as
[
silica–sulphuric acid, Lewis acids,
3]
[4,5]
[6]
montmorillonite K-10 clay, and
[
7]
heteropoly acids. The existing methods involve expensive reagents and
strongly acidic conditions, require longer reaction duration and high tempera-
ture, and give unsatisfactory yields. The products, incompatible with other
functional groups, involve cumbersome product isolation and environmental
pollution. Improvements in the synthesis have been sought continuously;
therefore, there is a need for simple and environmentally friendly processes
for the synthesis of b-acetamido-b-aryl-propiophenones. To avoid these limit-
ations, we started searching for new catalysts with high catalytic activity, easy
availability, short reaction time, and simple workup. Molecular iodine
attracted our attention. Recently, we have reported the synthesis of N,N’-dis-
ubstituted ureas/thioureas catalyzed by molecular iodine and a-iodoacetates
[8]
from alkenes/ammonium acetate/I2.
RESULTS AND DISCUSSION
In continuation of the search for simple, nonhazardous methods for the trans-
formations in organic synthesis using iodine, herein we report a highly
versatile and efficient one-pot synthesis of b-acetamido-b-aryl-propiophe-
nones by a four-component tandem reaction of araldehyde, arylmethyl
ketone, acetyl chloride, acetonitrile, and a catalytic amount of iodine. In an
experiment, the reaction mixture was taken in a 50-mL, round-bottomed
flask and heated for 10–15 min on a hot plate at 80–858C under solvent-
free conditions to get b-acetamido-b-aryl-propiophenones in good to
excellent yield as shown in Scheme 1.
To demonstrate the protocol, we selected 4-nitrobenzaldehyde (1 mmol)
as the model substrate and treated it with acetophenone (1 mmol), acetyl
chloride, and acetonitrile in the presence of iodine (0.25 mmol) for 15 min
to get the desired b-acetamido-b-(4-nitrophenyl)-propiophenone in 85%
yield (entry 3, Table 1). The results of the reactions of different araldehydes,
arylmethyl ketones, acetyl chloride, and acetonitrile are summarized in
Table 1. Several interesting features of the preparation of b-acetamido-b-
aryl-propiophenones are apparent from Table 1. More important, the
Scheme 1.

b-Acetamido-b-aryl-propiophenones
1553
Table 1. Condensation of arylaldehydes, arylmethyl ketones, acetyl chloride, and
acetonitrile to get b-acetamido-b-aryl-propiophenones
Melting point (8C)
b
Time Yield
(min) (%) Found Reported
0
a
c
Entry
1
R
H
R
Product
H
10
15
90
102–4 104–6
2
3
4-OCH3
4-NO2
H
86 116–17 115–17
H
15
85
152 151–3
4
5
3-NO2
4-Cl
H
H
15
10
85 112–15 112–15
85
145 146–8
6
7
8
9
4-F
H
Cl
Cl
10
10
10
15
10
10
80 110–11 109–11
H
92
90
90
114 114–15
124–5 125–7
140–2 141–3
4-OCH
3
4-Cl Cl
4-F Cl
1
1
0
1
88 108–10 108–10
H
NO2
91
75–6
74–6
(
continued)

1
554
M. A. Pasha, V. P. Jayashankara, and N. Ramachandraswamy
Table 1. Continued
Melting point (8C)
b
Time Yield
(min) (%) Found Reported
0
a
c
Entry
R
R
Product
12
13
14
4-OCH
3
NO
2
13
10
10
85
87–8
87–9
4-Cl NO2
86 116–18 116–18
4-CH
3
NO
2
84
84–5
83–5
a
All the products are known, characterized by IR and NMR spectral analysis, and
compared with the authentic samples.
b
Isolated yields.
Melting points of compounds are consisted with reported values (Refs. 3, 6, and 7).
c
substituents such as OCH , Cl, F, and NO are unaffected under the present
2
3
reaction conditions. Further, it has been found that the conventional Lewis
acids such as ZnCl , CuCl , FeCl , NiCl , CoCl , MnCl , and AlCl have
poor effect; the yields were also not satisfactory.
2
2
3
2
2
2
3
The mechanismmay involve the enolicformof the ketone, which attacks the
activated aldehyde to provide b-acetoxy ketone. The acetate group of b-acetoxy
ketone is displaced by the nucleophilic nitrogen of the nitrile to provide a stable
Scheme 2.

b-Acetamido-b-aryl-propiophenones
1555
carbocation, which may react in a Ritter fashion with water to provide the
b-acetamido-b-aryl-propiophenones as shown in Scheme 2.
EXPERIMENTAL
Melting points were determined on a B u¨ chi melting-point apparatus. IR
1
spectra were recorded on Nicolet 400D FT-IR spectrophotometer. H NMR
1
3
and C NMR were recorded on 200-MHz Brucker spectrometer, and GC
mass spectra on a Shimadzu GC-MS QP 5050A. Elemental analysis was
performed on a Themo Finnigan Flash EA 1112 CHNS analyzer. All aralde-
hydes, arylmethyl ketones, acetyl chloride, acetonitrile, and iodine were
commercial products and were used without further purification.
Procedure for b-Acetamido-b-(4-nitrophenyl)-propiophenones
4
-Nitrobenzaldehyde (1.51 g, 10 mmol), acetophenone (1.2 g, 10 mmol),
acetyl chloride (0.3 mL), acetonitrile (2 mL), and iodine (0.25 mmol) were
taken in a 50-mL, round-bottomed flask and heated at 80–858C for 15 min.
After the completion of the reaction (monitored with thin-layer
chromatography, TLC), the reaction mixture was poured into ice-cold
water, filtered, washed with 10% Na S O solution, and recrystallized from
2
2 3
EtOAc–pet. ether to afford b-acetamido-b-(4-nitrophenyl)-propiophenone
2.64 g, 85%).
(
Data
b-Acetamido-b-(4-nitrophenyl)-propiophenone (entry 3, Table 1): H NMR
1
(
200 MHz, CDCl ) d 8.16 (d, J ¼ 8.4 Hz, 2H), 7.89 (d, J ¼ 9.6 Hz, 2H),
3
7
.62–7.46 (m, 5H), 7.02 (d, J ¼ 9.0 Hz, 1H), 5.66 (s, 1H), 3.80 (dd,
J ¼ 4.8 and 17.6 Hz, 1H), 3.50 (dd, J ¼ 5.2 and 17.6 Hz, 1H), 2.0 (s, 3H).
1
3
C NMR (200 MHz, CDCl ): d ¼ 195.38, 168.93, 147.34, 137.3, 135.4,
3
1
32.5, 132.49,127.8, 127.7, 127.1, 127.05, 123.35, 44.83, 42.89, 21.76; IR
21
KBr): 3310, 1686, 1645, 1580, 1513, 1352, 1300, 751 cm . Anal. calcd.
(
for C H N O : C, 65.38; H, 5.16; N, 9.00. Found: C, 65.19; H, 5.08; N,
1
7 16 2 4
8
.95. MS: m/z ¼ 311 (Mþ).
ACKNOWLEDGMENTS
One of the authors, Jayashankara V. P., thanks Jagadhguru Sri Sri Sri Balagan-
gadharanatha Swamiji of Adichunchanagiri Muth, Nagamangala (Taluk),
Mandya (district), Karnataka, India, for his blessings; Mrs. Faheemunnisa,

1
556
M. A. Pasha, V. P. Jayashankara, and N. Ramachandraswamy
assistant mistress, Government Model Higher Primary School, Aswathnagar,
Bangalore, Karnataka, India, for the encouragement; and Sophisticated Instru-
ment Facility (SIF) and Department of Organic Chemistry, Indian Institute of
Science, Bangalore, for recording NMR spectra.
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