Silica sulphuric acid: An efficient and recyclable catalyst for the synthesis of β-acetamido ketones in single pot

Article abstract of DOI:10.1081/SCC-200057240

An efficient method has been developed for the synthesis of β-acetamido ketones by a multicomponent condensation route using sulphuric acid on silica gel as an inexpensive catalyst. Catalyst was recycled without loss of activity. Copyright Taylor & Franci

Full text of DOI:10.1081/SCC-200057240

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Silica Sulphuric Acid: An
Efficient and Recyclable
Catalyst for the Synthesis of
β‐Acetamido Ketones in Single
Pot
a
a
a
T. Yakaiah , G. Venkat Reddy , B. P. V. Lingaiah
,
a
a
B. Narsaiah & P. Shanthan Rao
a
Fluoroorganic Division, Indian Institute of Chemical
Technology, Hyderabad, India
Version of record first published: 16 Aug 2006.
To cite this article: T. Yakaiah , G. Venkat Reddy , B. P. V. Lingaiah , B. Narsaiah & P.
Shanthan Rao (2005): Silica Sulphuric Acid: An Efficient and Recyclable Catalyst for
the Synthesis of β‐Acetamido Ketones in Single Pot, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 35:10,
1307-1312
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w
Synthetic Communications , 35: 1307–1312, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200057240
Silica Sulphuric Acid: An Efficient and
Recyclable Catalyst for the Synthesis of
b-Acetamido Ketones in Single Pot
T. Yakaiah, G. Venkat Reddy, B. P. V. Lingaiah, B. Narsaiah, and
P. Shanthan Rao
Fluoroorganic Division, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: An efficient method has been developed for the synthesis of b-acetamido
ketones by a multicomponent condensation route using sulphuric acid on silica gel
as an inexpensive catalyst. Catalyst was recycled without loss of activity.
Keywords: Acetonitrile, acetophenones, acetyl chloride, aromatic aldehydes, silica
sulphuric acid
INTRODUCTION
Solid acid catalysts play a prominent role in organic synthesis under hetero-
geneous conditions. The importance of these catalysts is growing because
of their ecofriendly nature as attention is directed toward the development
of clean and green technologies for important organic molecules to promote
environmental safety. In general, solid acid catalysts are mainly based on
[2–10]
[11]
clay
and silica.
In terms of convenience, silica-based catalysts are
inexpensive, easy to prepare, and insoluble in most of the organic solvents,
which means they have the advantage of recovery and recycle from various
reactions. Therefore, silica sulphuric acid is extensively studied and found
[11a]
useful in many reactions such as nitration of aromatic compound,
Received in India January 18, 2005
Address correspondence to B. Narsaiah, Fluoroorganic Division, Indian Institute of
Chemical Technology, Hyderabad 500 007, India. Fax: þ91-040-27160387; E-mail:
narsaiah@iict.res.in
1
307

1308
T. Yakaiah et al.
[
11b]
[11c]
oxidation of thiols to disulphides,
three component Biginelli reaction,
and so on. Based on these facts, we propose to use silica sulphuric acid as a
catalyst for multicomponent condensation reaction. Earlier studies to obtain
[12]
b-acetamido ketones mainly used cobalt (II) chloride
as catalyst;
however, search for an efficient and economically viable catalyst for
complex reactions is ongoing among chemists. It is prerequisite that the
catalyst should activate aldehyde, acetonitrile, and enolisable ketone one
after the other to facilitate the reaction in a multicomponent reaction. In our
findings, we identified silica sulphuric acid as a suitable catalyst for preparation
of b-acetamido ketones by multicomponent condensation reaction in a single
pot and are report our results here for the first time.
In a typical reaction, the enolizable ketone (acetophenone) was reacted
with various aldehydes in presence of acetyl chloride in acetonitrile
medium using silica sulphuric acid as a catalyst. The catalyst is the source
of protons, which protonates aldehyde and acetonitrle to form a six-
membered transition state. Subsequently, a nucleophile of enolizable ketone
attacks methine carbon and forms b-acetamido ketones. The formation of
silica–sulphuric acid and probable mechanism for multicomponent conden-
sation is schematically drawn below in Scheme 1.
The role of substituents in enolizable ketone (acetophenone) and
aldehydes on the rate of reaction and yield of products is studied in detail.
In the case of enolizable ketone, it is found that the electron-withdrawing
groups in para position enhances the rate of reaction and yield in comparison
to electron-donating groups. We attribute this to the electron-withdrawing
groups in para position promoting enolization of active methyl group to facili-
tate the reaction, resulting high yield and low reaction time. In the case of
aldehydes, electron-withdrawing groups in para position promote reaction
whereas electron-releasing groups are detrimental to the reaction. It is
confirmed when the reaction is carried out with aldehydes that have
Scheme 1.

Synthesis of b-Acetamido Ketones in Single Pot
1309
electron-releasing groups such as CH , OCH , and N(CH ) and there is no
3
3
3 2
reaction. The catalyst is recovered and recycled four times for compound 3a
and found to have no loss of activity. The reaction is drawn in Scheme 2
and the number of compounds prepared in this study have been tabulated in
Table 1.
In conclusion, an efficient method for multicomponent condensation
using an inexpensive catalyst has been demonstrated for further applications
in the synthesis of a number of interesting molecules of high value.
EXPERIMENTAL
Melting points were determined in open-glass capillaries on a Mettler FP51
melting point apparatus and are uncorrected. IR spectra were recorded on
1
FT-IR Schimadzu Perkin-Elmer 1310 infrared spectrophotometer. H NMR
spectra were recorded on Varian Gemini (200 MHz) spectrometer and tetra-
1
3
methylsilane (TMS) was used as the internal standard. C NMR spectra
recorded on Varian Gemini (50 MHz) spectrometer. Mass spectra were
recorded on a VG-micromass 7070H instrument 70 ev.
General Procedure for the Synthesis of b-Acetamido Ketones (3)
[
11a]
A freshly prepared, dried solid silica sulphuric acid
(0.4 g) was added to a
stirred solution of substituted aromatic aldehyde (1.8 mmol), substituted acet-
ophenone (1.8 mmol), and acetyl chloride (1.5 mL) in acetonitrile (2.5 mL).
The reaction mixture was heated to 808C and stirred for 2–5 h at the same
temperature. After completion of the reaction, the solid catalyst was filtered
off and the filtrate was concentrated under reduced pressure to afford the
crude product as residue. It was purified by the column chromatography
method using 100–200 mesh silica gel as stationery phase and ethylacetate–
n-hexane (35 : 65) as eluents.
1
3
a: H NMR (200 MHz, CDCl ): d 7.90 (d, J ¼ 7.3 Hz, 2H), 7.58–7.20
3
(
(
(
m, 8H), 6.77 (d, J ¼ 8.9 Hz, 1H), 5.56 (dd, J ¼ 5.7 and 13.4 Hz, 1H), 3.77
dd, J ¼ 5.2 and 16.9 Hz, 1H), 3.43 (dd, J ¼ 6.1 and 16.9 Hz, 1H), 2.0
1
s, 3H); C NMR (50 MHz, CDCl ) d 198.5, 169.45, 140.8, 133.46, 128.6,
3
3
Scheme 2.

1310
T. Yakaiah et al.
Table 1. Reaction time and yields of b-acetamido ketones (3)
Entry
X
Y
Time (h)
Yield (%)
Mp (8C)
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
H
H
4
75
86
89
87
89
88
76
78
69
104–106
151–153
109–111
114–115
125–127
108–110
121–123
104–106
Liquid
NO
F
2
H
2.5
3.0
3.0
2.0
2.5
5.0
4.5
4.0
H
H
Cl
Cl
Cl
CH
NO2
F
g
h
i
H
3
F
NO
CH3
CH
2
3
All the compounds gave satisfactory elemental data.
2
1
1
1
1
6
28.07, 127.3, 126.4, 49.8, 43.14, 23.37; IR (KBr) Vmax/cm , 3423, 1772,
659, 1500, 1374, 1295, 1188, 1023, 704, 585. MS (m/z): 266 (M-1), 208,
79, 162, 120, 107, 106, 77, 50. Anal. calcd. for C H NO : C, 76.38; H,
1
7
17
2
.41; N, 5.24. Found: C, 76.29; H, 6.37; N, 5.11.
1
3
b: H NMR (200 MHz, CDCl ): d 8.16 (d, J ¼ 8.4 Hz, 2H), 7.89
3
(
d, J ¼ 9.6 Hz, 2H), 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,
(
1
3
1
1
4
1
1
H), 2.0 (s, 3H); C NMR (75 MHz, CDCl3 þ DMSO) d 195.38, 168.93,
47.34, 137.3, 135.4, 132.5, 132.49, 127.8, 127.7, 127.1, 127.05, 123.35,
2
4.83, 42.89, 21.76; IR (KBr) Vmax/cm : 3310, 1686, 1645, 1580, 1513,
1
þ
352, 1300, 751. MS (m/z): 311(M ), 295, 270, 194, 175, 165, 151, 129,
20, 105, 102, 90, 68, 54. Anal. calcd. for C H N O : C, 65.38; H, 5.16;
1
7 16 2 4
N, 9.00. Found: C, 65.19; H, 5.08; N, 8.95.
1
3
c: H NMR (200 MHz, CDCl þ DMSO-d ): d 8.00 (d, 1H, NH), 7.90
3
6
(
d, J ¼ 7.2 Hz, 2H, aromatic H), 7.22–7.60 (m, 5H, aromatic H), 6.90–7.00
m, 2H, aromatic H), 5.40 (q, H, methine H), 3.60 (dd, J ¼ 4.9 and 15.2 Hz,
(
1
H, CH ), 3.30 (dd, J ¼ 5.8 and 15.7 Hz, 1H, CH ), 1.85 (s, 3H, CH ). IR
2
2
3
2
1
KBr) Vmax/cm , 294, 3065, 2362, 1688, 1646, 1546, 1368, 1204, 760,
(
þ
6
C, 71.56; H, 5.65; N, 4.90. Found: C, 71.52; H, 5.59; N, 5.10.
87. MS (m/z): 284(M ), 242, 105, 77, 43. Anal. calcd. for C H FNO :
1
7
16
2
1
3
d: H NMR (200 MHz, CDCl þ DMSO-d ): d 8.10 (d, 1H, NH), 7.90
3
6
(
d, J ¼ 7.8 Hz, 2H, aromatic H), 7.25–7.45 (m, 7H, aromatic H), 5.35
(
q, 1H, methine H), 3.55 (dd, J ¼ 5.1 and 17.4 Hz, 1H, CH ), 3.25 (dd,
2
2
1
J ¼ 7.2 and 18.1 Hz, 1H, CH ), 1.85 (s, 3H, CH ). IR (KBr)Vmax/cm
:
289, 3068, 2369, 1690, 1650, 1558, 1380, 1208, 754, 668. MS (m/z): 301
2
3
3
þ
(
M ), 259, 139, 106, 77, 43. Anal. calcd. for C H ClNO : C, 67.66; H,
1
7
16
2
5
.34; N, 4.64. Found: C, 67.71; H, 5.29; N, 4.68.
1
3
e: H NMR (200 MHz, CDCl þ DMSO-d ): d 8.25 (d, 1H, NH), 8.10
3
6
(
(
d, J ¼ 8.1 Hz, 2H, aromatic H), 7.85 (d, J ¼ 10.2 Hz, 2H, aromatic H), 7.57
d, J ¼ 9.1 Hz, 2H, aromatic H), 7.55 (d, J ¼ 8.6 Hz, 2H, aromatic H), 7.40

Synthesis of b-Acetamido Ketones in Single Pot
1311
(
d, J ¼ 10.6 Hz, 2H, aromatic H), 5.45 (q, 1H, methine H), 3.60 (dd, J ¼ 5.2
and 16.1 Hz, 1H, CH ), 3.30 (dd, J ¼ 6.4 and 17.3 Hz, 1H, CH ), 1.85 (s, 3H,
2
2
2
1
CH ). IR (KBr)Vmax/cm : 3310, 3066, 2369, 1686, 1645, 1580, 1380,
3
þ
1
C H ClN O : C, 58.88; H, 4.35; N, 8.07. Found: C, 58.91; H, 4.33; N, 8.17.
209, 760, 656. MS (m/z): 346 (M ), 304,139,43. Anal. calcd. for
1
7
15
2 4
1
3
f: HNMR (200 MHz, CDCl þ DMSO-d ): d 8.10 (d, 1H, NH), 7.92
3
6
(
d, J ¼ 8.6 Hz, 2H, aromatic H), 7.30–7.50 (m, 4H, aromatic H), 6.90–7.05
m, 2H, aromatic H), 5.40 (q, 1H, methine H), 3.60 (dd, J ¼ 5.4 and
(
1
6.8 Hz, 1H, CH ), 3.30 (dd, J ¼ 6.8 and 18.6 Hz, 1H, CH ), 1.85 (s, 3H,
2
2
2
1
CH ). IR (KBr)Vmax/cm : 3296, 3067, 2370, 1689, 1651, 1549, 1372,
1
for C H ClFNO : C, 63.85; H, 4.72; N, 4.38. Found: C, 63.92; H, 4.69;
3
þ
209, 758, 690. MS (m/z): 320 (M ), 278, 139, 106, 77, 43. Anal. calcd.
1
7
15
2
N, 4.41.
3
1
g: HNMR (200 MHz, CDCl þ DMSO-d ): d 8.10 (d, 1H, NH), 7.75
3
6
(
d, J ¼ 9.9 Hz, 2H, aromatic H), 7.15–7.35 (m, 7H, aromatic H), 5.35
(
q,1H, methine H), 3.49 (dd, J ¼ 6.4 and 19.2 Hz, 1H, CH ), 3.20 (dd,
2
J ¼ 7.4 and 18.9 Hz, 1H, CH ), 2.35 (s, 3H, CH ), 1.80 (s, 3H, CH ). IR
2
3
3
2
KBr)Vmax/cm : 3423, 3071, 2961, 1772, 1659, 1500, 1374, 1295, 1188,
1
(
þ
1023, 704, 585. MS (m/z): 282 (M ), 239, 223, 147, 106, 43. Anal.
calcd. for C H NO : C, 76.84; H, 6.80; N, 4.97. Found: C, 76.79; H, 6.86;
1
8
19
2
N, 5.01.
3
1
h: H NMR (200 MHz, CDCl þ DMSO-d ): d 8.05 (d, 1H, NH), 7.80
3
6
(
d, J ¼ 12.1 Hz, 2H, aromatic H), 7.20–7.40 (m, 4H, aromatic H), 6.90–
7
.05 (m, 2H, aromatic H), 5.40 (q, 1H, methine H), 3.58 (dd, J ¼ 4.8 and
8.2 Hz, 1H, CH ), 3.30 (dd, J ¼ 7.8 and 19.0 Hz, 1H, CH ), 2.40 (s, 3H,
1
2
2
21
CH ), 1.90 (s, 3H, CH ). IR (KBr)Vmax/cm : 3290, 3065, 2958, 2362,
3
3
þ
1688, 1646, 1546, 1367, 1202, 758, 685. MS (m/z): 299 (M ), 257, 191,
119, 43. Anal. calcd. for C H FNO : C, 71.06; H, 6.31; N, 4.87. Found:
1
7
18
2
C, 71.12; H, 6.39; N, 4.91.
1
3
i: H NMR (200 MHz, CDCl þ DMSO-d ): d 8.40 (d, 1H, NH), 8.0
3
6
(
d, J ¼ 8.1 Hz, 2H, aromatic H), 7.75 (d, J ¼ 10.2 Hz, 2H, aromatic H),
7
.55 (d, J ¼ 9.8 Hz, 2H, aromatic H), 7.15 (d, J ¼ 10.6 Hz, 2H, aromatic
H), 5.58 (q, 1H, methine H), 3.62 (dd, J ¼ 4.6 and 18.9 Hz, 1H, CH ),
2
3
.35 (dd, J ¼ 4.9 and 16.2 Hz, 1H, CH ), 2.30 (s, 3H, CH ), 1.90
2
3
2
1
(
s, 3H, CH ). IR(KBr) Vmax/cm : 3310, 3071, 2959, 1686, 1645, 1586,
3
þ
1513, 1352, 1300, 751. MS (m/z): 284 (M ), 165, 77, 43. Anal. calcd.
for C H N O : C, 66.24; H, 5.55; N, 8.58. Found: C, 66.29; H, 5.61;
N, 8.49.
1
8 18 2 4
ACKNOWLEDGMENTS
The authors are thankful to J. S. Yadav, Director, IICT, and Sri S. Narayan
Reddy, Head, Fluoroorganics, IICT, Hyderabad for constant encouragement
and financial support from the industry-sponsored project.

1312
T. Yakaiah et al.
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