Efficient synthesis of β-acetylamino ketones using silica-supported sodium hydrogen sulfate as a heterogeneous catalyst

Article abstract of DOI:10.1080/00397910701410467

Silica-supported sodium hydrogen sulfate (NaHSO4·SiO2) efficiently catalyzes the four-component reaction of aryl aldehydes, enolisable ketones, acetyl chloride, and acetonitrile to form the corresponding β-acetylamino ketones at room temperature. The cata

Full text of DOI:10.1080/00397910701410467

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Efficient Synthesis of β‐Acetylamino Ketones
using Silica‐Supported Sodium Hydrogen
Sulfate as a Heterogeneous Catalyst
N. Vijaya Kumari a , Lingaiah Nagarapu a & Shivaraj b
a Organic Division II, Indian Institute of Chemical Technology, Hyderabad,
India
b Department of Chemistry, Osmania University, Hyderabad, India
Published online: 11 Jul 2007.
To cite this article: N. Vijaya Kumari , Lingaiah Nagarapu & Shivaraj (2007): Efficient Synthesis of
β‐Acetylamino Ketones using Silica‐Supported Sodium Hydrogen Sulfate as a Heterogeneous Catalyst,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:14, 2325-2329
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Synthetic Communicationsw, 37: 2325–2329, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701410467
Efficient Synthesis of b-Acetylamino
Ketones using Silica-Supported Sodium
Hydrogen Sulfate as a Heterogeneous
Catalyst
N. Vijaya Kumari and Lingaiah Nagarapu
Organic Division II, Indian Institute of Chemical Technology,
Hyderabad, India
Shivaraj
Department of Chemistry, Osmania University, Hyderabad, India
.
Abstract: Silica-supported sodium hydrogen sulfate (NaHSO4 SiO2) efficiently
catalyzes the four-component reaction of aryl aldehydes, enolisable ketones, acetyl
chloride, and acetonitrile to form the corresponding b-acetylamino ketones at room
temperature. The catalyst is inexpensive and ecofriendly and works under hetero-
geneous conditions.The present methodology offers several advantages such as
excellent yields, simple procedure, short reaction times (1–3 h), and mild conditions.
Keywords: b-acetylamino ketones, heterogeneous catalyst, short reaction times,
silica-supported sodium hydrogen sulfate
Heterogeneous catalysts have attracted attention in recent years because of
economic and environmental considerations. The catalyst are generally
inexpensive and easily available and can be conveniently handled and
removed from the reaction mixture, thus making the experimental procedure
simple and ecofriendly. Recently, we have utilized different heterogeneous
catalysts successfully for various chemical transformations.[1] This prompted
Received in India December 4, 2006
Address correspondence to Lingaiah Nagarapu, Organic Division II, Indian Institute
of Chemical Technology, Hyderabad 500 007, India. E-mail: nagarapu2@yahoo.co.in
2325

2326
N. V. Kumari, L. Nagarapu, and Shivaraj
.
us to use silica-supported sodium hydrogen sulfate (NaHSO4 SiO2) for
multicomponent coupling. As a part of our ongoing green technology
program,[2] we disclose here a more practical, one-pot, green alternative for
the synthesis of b-acetylamino ketones (Scheme 1).
b-Acetylamino ketones are usually prepared through acylation of
b-amino ketones,[3] Michael addition to a,b-unsaturated ketones,[4] or photo-
isomerization of phthalimides.[5] The most interesting reaction for the
synthesis of these compounds is multicomponent coupling involving
aldehyde, enolisable ketone, acetyl chloride, and acetonitrile as first
reported by Bahulayan and coworkers.[6] The multicomponent reactions
leading to the formation of b-acetylamino ketones can be catalyzed by
CoCl2,[6b] cobalt(II) acetate supported on polyaniline,[6c] monmorillonite
K10,[6a] and bismuth oxychloride.[6c] b-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,[7a] H2SO4/SiO2,[7b] and zeolite Hb
(reported as a reusable catalyst).[8] Recently, heteropoly acids (HPAs) have
been reported[9] as solid green Brønsted acids for a one-pot synthesis of
b-acetylamino ketones by the Dakin–West reaction. However, the reported
procedures have disadvantages.
In a typical procedure, the reaction of enolisable ketone, acetyl chloride,
and acetonitrile with various aromatic aldehydes in presence of
.
NaHSO4 SiO2 proceded smoothly at room temperature in 1–3 h to afford
excellent yields of b-acetylamino ketones (Table 1). The major advantages
[10]
from the
.
of this is that NaHSO4 SiO2 could conveniently be prepared
readily available ingredients in very short reaction times (1–3 h) and the
isolation of the products can be isolated without chromatography, affording
b-acetylamino ketones in high purity. It is noteworthy that the reported
CoCl2-catalyzed reaction, even though carried out at room temperature,
required longer periods (i.e., 5 days) and also required a nonaqueous
workup.[6b] The use of montmorillonite K10 required a high temperature
(708C).[6a] Polyaniline-supported cobalt (II) acetate required a nitrogen atmo-
sphere.[6c] Zeolite Hb–catalyzed reaction, even though carried out at room
temperature, required 8–12 h,[8] does not require an inert atmosphere, is
reusable, and has an 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 (1–3 h).
The reaction involving acetophenone gave products with only one asymmetric
Scheme 1.

Synthesis of b-Acetylamino Ketones
2327
Table 1. Synthesis of b-acetylamino ketones at room temperature using
.
NaHSO4 SiO2
No.
R1
X
R2
Time (h)
Syn/anti Yield (%)a
5a
5b
5c
5d
5e
5f
H
2-Cl
H
Ph
Ph
3.0
1.0
1.5
2.0
1.0
3.0
3.0
1.0
3.0
3.0
2.0
1.5
2.0
3.0
3.0
3.0
—
—
88
90
93
96
97
78
76
81
78
76
80
83
72
70
75
73
H
4-Cl
2,4-di Cl
4-Br
H
Ph
Ph
—
—
H
H
Ph
Ph
—
—
2-NO2
3-NO2
4-OCH3
2-OH
2,3,4-tri OCH3
4-CN
4-CH3
H
H
5g
5h
5i
H
Ph
Ph
—
—
H
H
H
Ph
Ph
—
—
5j
5k
5l
H
Ph
Ph
—
—
H
CH3
5m
5n
5o
5p
Ph
5:95
20:80
13:87
10:90
H
4-Br
COOCH3
COOCH3
COOCH3
CH3
CH3
CH3
4-Cl
aYields refer to pure products, and all products, were characterized by a comparision
of their physical data and 1H NMR and IR spectral data with those of authentic samples.
center (5a–i). The reaction involving propiophenone (5m) and methyl acetoa-
cetate (5n), however, led to diastereomeric mixtures. The ratio of these dia-
1
stereomers was determined by H NMR spectroscopy. As can be seen from
Table 1, the major diastereomer was anti in all cases.
In conclusion, this article describes a convenient and efficient process
for the synthesis of b-acetylamino ketones through the four-component
coupling of various aromatic aldehydes, enolisable ketone, acetyl chloride,
.
and acetonitrile using NaHSO4 SiO2 as a solid support at room temperature.
The present methodology offers very attractive features such as reduced
reaction times, higher yields, and economic viability of the catalyst when
compared with conventional method as well as with other catalysts and
will have wide scope in organic synthesis. This simple procedure combined
with ease of recovery and reuse of the catalyst makes this method economical
benign, and a waste-free chemical process for the synthesis of b-acetylamino
ketones. We believe that this procedure is convenient, economic, and a user-
friendly process for the synthesis of b-acetylamino ketones.
TYPICAL PROCEDURE
.
To a stirred mixture of NaHSO4 SiO2 (100 mg) in acetonitrile (2.5 mL), an
aldehyde (106 mg), an enolisable ketone (120 mg), and acetyl chloride

2328
N. V. Kumari, L. Nagarapu, and Shivaraj
(0.4 mL) were added. The reaction mixture was stirred at room temperature
for 1–3 h. The mixture was filtered to remove the catalyst, and the filtrate
was poured into ice-cold water. The precipitated solid was filtered (entry a
was not precipitated immediately), dried, washed with petroleum ether 60–
808C to remove any residual starting material, and dried. All products were
characterized by their physical constants and spectral data compared with
those for authentic samples.
REPRESENTATIVE SPECTRAL DATA
1
Compound 5a: Mp 102–1038C, H NMR (200 MHz, CDCl3): d 2.05 (s, 3H,
Ac), 3.30 (dd, 1H, J ¼ 6.5 & 9.6 Hz), 3.65 (dd, 1H, J ¼ 6.6 & 9.7 Hz), 5.55
(m, 1H), 6.85 (brs, 1H), 7.40 (d, 5H, J ¼ 9.4 Hz), 7.85 (d, 5H, J ¼ 9.1 Hz);
IR (KBr, cm21) 3250, 3035, 1665, 1630, 1570, 1265, 1087. Compound 5d:
1
Mp 168–1708C, H NMR (200 MHz, CDCl3): d 2.01 (s, 3H, Ac), 3.35 (dd,
1H, J ¼ 6.6 & 9.9 Hz), 3.70 (dd, 1H, J ¼ 6.8 & 10.0 Hz), 5.70 (m, 1H), 7.05
(brs, 1H), 7.30 (s, 1H), 7.45 (m, 5H), 7.55 (d, J ¼ 9.6 Hz, 1H), 7.80 (d, 1H,
J ¼ 9.4 Hz); IR (KBr, cm21) 3282, 3080, 1688, 1651, 1548, 1232, 753.
Compound 5f: Mp: 190–1928C, 1H NMR (200 MHz, CDCl3): d 2.07
(s, 3H, Ac), 3.33 (dd, 1H, J ¼ 6.8 & 9.8 Hz), 3.77 (dd, 1H, J ¼ 7.0 &
10.0 Hz), 5.56 (m, 1H), 6.85 (brs, 1H), 7.18–7.55 (m, 4H); IR (KBr,
cm21) 3295, 3035, 1652, 1460, 1220, 680, 585. Compound 5j: Mp: 152–
1548C, 1H NMR (200 MHz, CDCl3): d 2.05 (s, 3H, Ac), 3.35 (dd, 1H,
J ¼ 6.8 & 10.0 Hz), 3.75 (dd, 1H, J ¼ 6.8 & 9.9 Hz), 3.85 (s, 9H, OCH3),
5.40 (m, 1H), 6.55 (s, 2H), 6.78 (brs, 1H), 7.45 (t, 2H), 7.60 (t, 1H), 7.90
(d, 2H, J ¼ 9.5 Hz); IR (KBr, cm21) 3272, 3075, 2942, 1690, 1557, 1230,
1123, 752, 682; Compound 5m: 1H NMR (200 MHz, CDCl3): d 2.04
(s, 3H, Ac), 2.18 (s, 3H, CH3) 3.80 (s, 3H, OCH3), 4.08 (d, 1H,
J ¼ 6.0 Hz), 5.75 (dd, 1H, J ¼ 8.6 & 5.5 Hz), 6.80 (brs, 1H), 6.95 (d, 2H,
J ¼ 9.0 Hz), 7.26 (d, 2H, J ¼ 9.2 Hz); IR (KBr, cm21) 3275, 1745, 1720,
1660, 1515.
ACKNOWLEDGMENT
The authors are thankful to M. Hari Babu, deputy director and head,
Organic Chemistry Division II, IICT, for providing facilities and helpful
discussions.
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