Efficient synthesis of β-acetamido ketones by silver(i) triflate-catalyzed multicomponent reactions

Article abstract of DOI:10.5012/bkcs.2012.33.11.3559

An efficient one-pot synthesis of β-acetamido ketones was accomplished by AgOTf-catalyzed multicomponent reactions of substituted acetophenones with aromatic aldehydes and acid chloride in acetonitrile in high yields. The methods offer several significant

Full text of DOI:10.5012/bkcs.2012.33.11.3559

Efficient Synthesis of β-Acetamido Ketones
Bull. Korean Chem. Soc. 2012, Vol. 33, No. 11 3559
http://dx.doi.org/10.5012/bkcs.2012.33.11.3559
Efficient Synthesis of β-Acetamido Ketones by Silver(I) Triflate-Catalyzed
Multicomponent Reactions
*
Rameshwar Prasad Pandit and Yong Rok Lee
*
School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Korea. E-mail: yrlee@yu.ac.kr
Received July 1, 2012, Accepted August 9, 2012
An efficient one-pot synthesis of β-acetamido ketones was accomplished by AgOTf-catalyzed multicomponent
reactions of substituted acetophenones with aromatic aldehydes and acid chloride in acetonitrile in high yields.
The methods offer several significant advantages of easy handling, mild reaction conditions, and use of
effective and non-toxic catalyst.
Key Words : Silver triflate, Multicomponent reaction, β-Acetamido ketone
Introduction
synthetic method that provides a variety of β-acetamido
ketones has led us to looking into more convenient and
safely usable catalysts. Among these, we think silver (I) tri-
flate is a viable alternative, and may be a promising catalyst
for the synthesis of β-acetamido ketones due to its easy
availability, sustainability, non-toxicity, and environmentally
Multicomponent reactions (MCRs) have emerged as an
efficient and powerful tool for the construction of complex
1
molecules in organic synthesis. In particular, MCRs are
very useful to generate diverse combinatorial libraries for
2
22
friendly properties. We report herein an silver (I) triflate-
drug discovery.
The synthesis of β-acetamido ketones using MCR proto-
col has gained considerable attention in the synthesis of a
variety of molecules as valuable building blocks for the
catalyzed one-pot multicomponent reaction of acetophenones,
arylaldehydes, and acetyl chloride in acetonitrile for the
synthesis of biologically interesting β-acetamido ketones
(Scheme 1).
3 4
preparation of 1,3-amino acids, 1,3-amino alcohols, as well
as a structural unit of natural peptide antibiotics nikko-
5
mycins or neopolyoxines. Several methods for the synthesis
Results and Discussion
of acetamido ketones have been reported through Michael
6
addition to α,β-unsaturated ketones, acylation of β-amino-
The reaction of acetophenone (1a, 1.0 mmol) with benz-
aldehyde (2a, 1.1 mmol) and acetyl chloride (3, 2.0 mmol)
in acetonitrile (5 mL) was first examined in the presence of
several silver catalysts (Table 1). With AgO and Ag2Ofor 12 h
at room temperature, the desired product 4a was produced in
82 and 85% yield, respectively. With Ag2CO3 for 6 h,
compound 4a was also isolated in 86% yield, whereas that
with AgNO3 (20 mol %) or AgOAc (10 mol %) for 12 h was
produced in only 35% and 40% yield, respectively. Importantly,
the best yield (91%) was obtained in the presence of 10
7 8
ketones, photoisomerization of phthalimides, and Darkin-
9
West reaction. Among these, the known effective method
for the synthesis of acetamido ketones is Dankin-West
reaction, which involves the condensation of α-amino acids
with acetic anhydride in the presence of base via an
10
azalacetone intermediate. Recently, another new procedure
for the formation of β-acetamido ketones through the MCRs
of acetophenone, arylaldehyde, and acetyl chloride in
11-21
acetonitrile has been developed.
This reaction has been
extensively studied with the use of a variety of catalysts and
11
12
13
reagents such as CoCl2, FeCl3, CeCl3·7H2O, Sc(OTf)3,
14
Table 1. Reaction of acetophenone (1a), benzaldehyde (2a), and
acetyl chloride (3) in acetonitrile under several silver catalysts
15
16
17
ZrOCl2·8H2O, NaHSO4·H2O, Fe(HSO4)3, silica sup-
18 19
ported sulfuric acid, H3PW12O40, Montmorillonite K-10
20
21
clay, and Amberlyst-15.
Although numerous methods for the synthesis of β-
11-21
acetamido ketones have been reported,
there is still
demand for simpler, less toxic, more effective, and milder
catalysts. Our interest in developing a mild and efficient
Entry
Catalyst
Condition
Yield
1
2
3
4
5
6
7
AgO (20 mol %)
rt, 12 h
rt, 12 h
rt, 6 h
82
85
86
35
40
91
85
Ag2O (20 mol %)
Ag2CO3 (20 mol %)
AgNO3 (20 mol %)
AgOAc (10 mol %)
AgOTf (10 mol %)
AgOTf (5 mol %)
rt, 12 h
rt, 12 h
rt, 6 h
rt, 6 h
Scheme 1

3560 Bull. Korean Chem. Soc. 2012, Vol. 33, No. 11
Rameshwar Prasad Pandit and Yong Rok Lee
mol % of AgOTf. The use of 5 mol % of AgOTf gave
product 4a in 85% yield. The product 4a was determined by
analysis of spectral data and compared directly with the
reported data. Recently, it has been suggested that metal
triflates may be catalytically active through the formation of
TfOH, although the pathway of TfOH from metal triflates
In order to establish the generality of this methodology,
additional reactions of several substituted acetophenones
with arylaldehydes and acetyl chloride in acetonitrile were
carried out in the presence of 10 mol % of AgOTf. The
results are summarized in Table 2. Reactions of acetophe-
none (1a) with arylaldehydes 2b-2e bearing electron-
donating groups at ortho, meta or para position on the
benzene ring at room temperature for 1-6 h produced 4b-4e
in 80-90% yield (entries 1-4). Interestingly, with 2-hydroxy-
bezaldehyde (2f), β-acetamido ketone 4f with an acetyloxy
group on the aromatic benzene ring was observed in 65%
23
was not addressed. In order to check a catalytic activity of
TsOH, the use of 5 mol % of TfOH at room temperature for
12 h provided the desired product 4a in 45% yield. We found
that AgOTf is more efficient than TfOH for the formation of
4a.
Table 2. Additional AgOTf-catalyzed one-pot multicomponent reactions for the synthesis of a variety of β-acetamido ketones
Entry Acetophenones Arylaldehydes Time (h) Products (%)

Efficient Synthesis of β-Acetamido Ketones
Bull. Korean Chem. Soc. 2012, Vol. 33, No. 11 3561
Scheme 2
Scheme 4
1
yield (entry 5). The structure of 4f was identified by H
15
NMR analysis and by comparison with the reported data.
mechanism and the role of acid chloride in the reaction, we
examined further reactions without acid chloride. Important-
ly, without any acid chloride, no products were isolated at
room temperature or at reflux for 12 h. No products under
such a reaction condition imply the pivotal role of acetyl
chloride in this multicomponent reaction. Thus, acetophe-
none (1a) in the presence of AgOTf through Lewis acid-
catalyzed enol formation first gives to an enol 6. Subsequent
attack by 6 to benzaldehyde (2a) and acid chloride (3) may
generate a β-acyloxy ketone 7. The nucleophilic attack by
nitrogen on an acetonitrile to 7 may provide a stable cation
intermediate 8, which on further reaction with water during
the work-up may lead to the formation of final product 4a.
Finally, to investigate diastereoselectivity of this methodo-
logy, we have tried other multicomponent reaction. Reaction
of propiophenone (9) with benzaldehyde (2a) and acetyl
chloride (3) in acetonitrile in the presence of 10 mol % of
AgOTf at room temperature for 12 h, two diastereoisomers
10a and 10b were produced in 81% yield with a ratio of
84:16 (Scheme 4). In this case, the anti-diastereoisomer 10a
was isolated as a major component. This result did not show
any increase of diastereoselectivity by comparing with
1
H NMR spectrum of 4f showed a characteristic methyl peak
of an acetyloxy group on the benzene ring at δ 2.34 as a
singlet. With arylaldehydes 2g-2h with electron-withdraw-
ing groups on the benzene ring, the products 4g-4h were
produced in 93 and 91% yield, respectively (entries 6-7).
With 1-naphthaldehyde, product 4i was also produced in
95% yield (entry 8). In this case, the reaction time was
longer (12 h). Treatment of 4-methylacetophenone (1b) with
benzaldehyde or arylaldehydes bearing electron-donating
groups or electron-withdrawing groups on the benzene ring
in acetonitrile for 6 h provided the desired products 4j-4m in
90-95% yield (entries 9-12). Similarly, reactions of 4-meth-
oxyacetophenone (1c) with arylaldehydes bearing electron-
donating groups or electron-withdrawing groups on the
benzene ring in acetonitrile for 6 h gave β-acetamido ketones
4n-4q in 80-88% yield (entries 13-16). Reaction of 1c with
1-naphthaldehyde and acetyl chloride in acetonitrile afford-
ed product 4r in 96% yield (entry 17). These reactions
provided a rapid route to the synthesis of a variety of β-
acetamido ketones in good yield.
To expand the utility of this methodology, another multi-
component reaction of acetophenone (1a) with terephth-
aldehyde (2j) and acetyl chloride (3) in acetonitrile under 10
mol % of AgOTf at room temperature was carried out
(Scheme 2). In this reaction, the desired symmetric product
5 was produced in 91% yield. The product 5 was determined
by analysis of spectral data and compared directly with the
20
reported work.
In summary, we have developed an efficient and general
synthesis of a variety of β-acetamido ketones by AgOTf-
catalyzed one-pot multicomponent reaction of substituted
acetophenones with aromatic aldehydes and acid chloride in
acetonitrile. The advantages of these methodologies are easy
handling, mild reaction conditions, and use of an effective
and non-toxic catalyst. These AgOTf-catalyzed reactions
provided the desired β-acetamido ketones in high yield.
24
reported data.
The formation of 4a can be also explained by the plausible
mechanism as shown in Scheme 3. For understanding the
Experimental Section
All the experiments were carried out under nitrogen
atmosphere. Merck precoated silica gel plates (Art. 5554)
with fluorescent indicator were used for analytical TLC.
Flash column chromatography was performed using silica
1
13
gel 9385 (Merck). H NMR and C NMR spectra were
recorded on a Varian VNS (300 and 75 MHz, respectively)
spectrometer in CDCl3 using δ = 7.24 and 77.0 ppm as the
solvent chemical shift. The IR spectra were recorded on a
Jasco FTIR 5300 spectrophotometer. The HRMS were carried
out at the Korea Basic Science Institute.
Scheme 3. A plausible mechanism for the formation of 4a in the
presence of AgOTf.
General Procedure for the Synthesis of Acetamido

3562 Bull. Korean Chem. Soc. 2012, Vol. 33, No. 11
Rameshwar Prasad Pandit and Yong Rok Lee
1
Keones 4a-4r. To a solution of 1a, 1b or 1c (1.0 mmol) with
arylaldehyde (1.1 mmol) and acetyl chloride (0.15 mL, 2.0
mmol) in acetonitrile (5 mL) was added AgOTf (25 mg, 10
mol %) and the reaction mixture was stirred at room temper-
ature for 1-12 h. After completion of reaction as indicated by
TLC, water (20 mL) was added. The mixture was extracted
with ethyl acetate (15 mL × 3) and extract was washed with
saturated sodium bicarbonate (25 mL). The combined organic
layers were dried over anhydrous magnesium sulfate to give
residue which was purified by column chromatography on
silica gel using hexane/EtOAc (1:2) to give product.
118-119 °C ; H NMR (300 MHz, CDCl3) δ 7.88 (2H, d, J =
7.5 Hz), 7.54 (1H, dd, J = 7.5, 7.2 Hz), 7.42 (2H, t, J = 7.5
Hz), 6.83 (2H, s), 6.76-6.73 (1H, m), 6.62 (1H, d, J = 7.8 Hz,
NH), 5.35-5.51 (1H, m), 3.80 (6H, s), 3.71 (1H, dd, J = 17.1,
13
5.1 Hz), 3.38 (1H, dd, J = 16.8, 6.6 Hz), 1.99 (3H, s);
C
NMR (75 MHz, CDCl3) δ 198.4, 169.7, 148.9, 148.2, 136.6,
133.8, 133.4, 128.6, 128.6, 128.1, 128.1, 118.6, 111.1, 110.4,
55.8, 55.8, 49.8, 43.6, 23.1; IR (KBr) 3247, 3076, 1681,
−1
1637, 1519, 1253, 1026, 751 cm .
N-{1-(1-Acyloxyphenyl)-3-oxo-3-phenylpropyl}aceta-
mide (4f): Yellow solid. Yield (211 mg, 65%). mp 56-58 °C;
12
N-(3-Oxo-1,3-diphenylpropyl)acetamide (4a): A white
1
H NMR (300 MHz, CDCl3) δ 7.92 (2H, d, J = 8.1 Hz),
1
solid. Yield (243 mg, 91%). mp 103-105 °C; H NMR (300
7.59-7.54 (1H, m), 7.47-7.38 (3H, m), 7.31-7.26 (1H, m),
7.19 (1H, t, J = 7.5 Hz), 7.07 (1H, d, J = 7.8 Hz), 6.46 (1H,
d, J = 7.5 Hz, NH), 5.75-5.68 (1H, m), 3.64 (1H, dd, J =
16.2, 5.4 Hz), 3.44 (1H, dd, J = 16.5, 6.9 Hz), 2.34 (3H, s),
MHz, CDCl3) δ 7.81 (1H, d, J = 7.8 Hz), 7.47 (1H, m), 7.35
(2H, dd, J = 8.4, 7.2 Hz), 7.28-7.11 (5H, m), 6.73 (1H, d, J =
7.5 Hz, NH), 5.51-5.44 (1H, m), 3.65 (1H, dd, J = 16.8, 5.1
13
Hz), 3.34 (1H, dd, J = 16.8, 6.0 Hz), 1.91 (3H, s); C NMR
13
1.96 (3H, s), C NMR (75 MHz, CDCl3) δ 198.1, 169.9,
(75 MHz, CDCl3) δ 197.4, 169.7, 141.3, 136.2, 132.9, 128.2,
128.2, 128.1, 128.1, 127.7, 127.7, 126.9, 126.3, 126.3, 49.4,
43.7, 22.5; IR (KBr) 3285, 3083, 1649, 1549, 1202, 989,
169.4, 148.3, 136.6, 133.5, 132.9, 128.8, 128.8, 128.7,
128.2, 128.2, 127.5, 126.3, 123.0, 44.8, 42.7, 23.2, 21.0; IR
(KBr) 3281, 3065, 2933, 1762, 1656, 1545, 1448, 1369,
−1
750, 696 cm .
−1 +
1202, 1003, 755, 692 cm ; HRMS (EI) m/z (M ) calcd for
12
N-(3-Oxo-3-phenyl-1-p-tolylpropyl)acetamide (4b):
C19H19NO4: 325.1314. Found: 325.1314.
1
Off-white solid. Yield (253 mg, 90%). mp 170 °C; H NMR
N-{1-(4-Bromophenyl)-3-oxo-3-phenylpropyl}acetamide
12
(4g): White solid. Yield (321 mg, 93%). mp 148-150 °C;
(300 MHz, CDCl3) δ 7.89 (1H, d, J = 7.8 Hz), 7.54 (1H, dd,
J = 7.3, 7.2 Hz), 7.42 (2H, dd, J = 8.4, 6.9 Hz), 7.21 (2H, dd,
J = 9.3, 8.1 Hz), 7.09 (2H, d, J = 7.5 Hz), 6.59 (1H, d, J = 7.5
Hz, NH), 5.47-5.53 (1H, m), 3.72 (1H, dd, J = 17.1, 4.8 Hz),
3.40 (1H, dd, J = 16.8, 6.3 Hz), 2.27 (3H, s), 1.99 (3H, s);
1
H NMR (300 MHz, CDCl3) δ 7.86 (1H, d, J = 8.4 Hz),
7.58-7.52 (1H, m), 7.45-7.37 (4H, m), 7.18 (2H, d, J = 7.5
Hz), 6.82 (1H, d, J = 7.8 Hz, NH), 5.51-5.45 (m, 1H), 3.70
(1H, dd, J = 17.1, 5.1 Hz ), 3.38 (1H, dd, J = 17.4, 6.0 Hz),
13
13
1.99 (s, 3H); C NMR (75 MHz, CDCl3) δ 198.4, 169.7,
C NMR (75 MHz, CDCl3) δ 198.5, 169.6, 138.1, 137.1,
136.7, 133.5, 129.4, 129.4, 128.7, 128.7, 128.2, 128.2,
126.5, 126.5, 49.8, 43.5, 23.4, 21.1; IR (KBr) 3288, 3078,
140.3, 136.5, 133.8, 131.8, 131.8, 128.9, 128.9, 128.4,
128.4, 128.2, 128.2, 121.3, 49.4, 43.1, 23.5; IR (KBr) 3287,
-1
1651, 1545, 1207, 990, 751 cm .
−1
3077, 1650, 1546, 1362, 1291, 1001, 752 cm .
N-{1-(2,5-Dimethylphenyl)-3-oxo-3-phenylpropyl}aceta-
mide (4c): Off-white solid. Yield (260 mg, 88%). mp 103-
N-{1-(4-Nitrophenyl)-3-oxo-3-phenylpropyl}acetamide
12
1
(4h): Off-white solid. Yield (284 mg, 91%). mp 153 °C ; H
NMR (300 MHz, CDCl3) δ 8.11 (1H, d, J = 8.7 Hz), 7.85
(2H, d, J = 8.4 Hz), 7.59-7.53 (1H, m), 7.50-7.40 (4H, m),
1
105 °C; H NMR (300 MHz, CDCl3) δ 7.88 (2H, d, J = 6.9
Hz), 7.55-7.50 (1H, m), 7.44-7.38 (2H, m), 7.05-7.00 (2H,
m), 6.39 (1H, d, J = 7.8 Hz), 6.26 (1H, d, J = 6.0 Hz, NH),
5.70-5.63 (1H, m), 3.62 (1H, dd, J = 16.5, 5.7 Hz), 3.42 (1H,
dd, J = 16.2, 7.2 Hz), 2.34 (3H, s), 2.24 (3H, s), 1.95 (3H, s);
7.01 (1H, s, NH), 5.66-5.60 (1H, m), 3.77 (1H, dd, J = 17.4,
13
4.8 Hz), 3.46 (1H, dd, J = 17.4, 5.4 Hz), 2.04 (s, 3H);
C
NMR (75 MHz, CDCl3) δ 197.3, 170.2, 149.2, 146.8, 136.1,
133.8, 128.7, 128.7, 128.0, 128.0, 127.5, 127.5, 123.6,
123.6, 49.1, 43.2, 22.9; IR (KBr) 3303, 3068, 1651, 1525,
13
C NMR (75 MHz, CDCl3) δ 197.9, 169.7, 139.2, 136.6,
135.4, 133.1, 132.4, 130.5, 128.5, 128.0, 126.2, 46.4, 43.5,
22.8, 21.0, 18.8; IR (KBr) 3290, 3068, 2925, 1683, 1646,
−1
1353, 1210, 991, 845, 693 cm .
−1
1549, 1372, 1298, 1209, 995, 758, 694, 618 cm ; HRMS
N-{1-(Naphthalen-1-yl)-3-oxo-3-phenylpropyl}acetamide
(4i): Off-white solid. Yield (301 mg, 95%). mp 170-172 °C;
+
(EI) m/z (M ) calcd for C19H21NO2: 295.1572. Found 295.1570.
1
N-{1-(4-Methoxyphenyl)-3-oxo-3-phenylpropyl}aceta-
H NMR (300 MHz, CDCl3) δ 8.11 (1H, d, J = 8.4 Hz), 7.84
12
mide (4d): Off-white solid. Yield (240 mg, 81%). mp 110-
(3H, dd, J = 8.1, 6.9 Hz), 7.73 (1H, d, J = 8.1 Hz), 7.56-7.46
(4H, m), 7.40-7.33 (3H, m), 6.58 (1H, d, J = 7.5 Hz, NH),
6.38-6.32 (1H, m), 3.82 (1H, dd, J = 16.8, 5.1 Hz), 3.62 (1H,
1
111 °C; H NMR (300 MHz, CDCl3) δ 7.84 (2H, d, J = 7.5
Hz), 7.49 (1H, dd, J = 7.5, 7.2 Hz), 7.37 (2H, dd, J = 7.5, 7.2
Hz), 7.18 (2H, d, J = 8.7 Hz), 6.75 (2H, d, J = 8.4 Hz), 6.62
(1H, d, J = 7.7 Hz, NH), 5.47- 5.41 (1H, m), 3.68-3.63 (4H,
ds, J = 5.1 Hz), 3.33 (1H, dd, J = 16.8, 6.3 Hz), 1.93 (3H, s);
13
dd, J = 16.5, 6.3 Hz), 1.98 (3H, s); C NMR (75 MHz,
CDCl3 and DMSO-d6) δ 197.1, 169.0, 136.8, 136.3, 133.4,
132.8, 130.4, 128.3, 128.2, 128.2, 127.7, 127.7, 127.6,
126.0, 125.3, 124.8, 122.9, 122.8, 45.3, 43.0, 22.5; IR (KBr)
3290, 3061, 1681, 1651, 1547, 1366, 1276, 995, 779, 690
13
C NMR (75 MHz, CDCl3) δ 198.8, 169.8, 158.9, 136.7,
133.6, 133.1, 128.8, 128.8, 128.2, 128.2, 127.9, 127.9,
114.1, 114.1, 55.3, 49.7, 43.4, 23.4; IR (KBr) 3301, 3076,
−1
+
cm ; HRMS (EI) m/z (M ) calcd for C21H19NO2: 317.1416.
Found: 317.1414.
−1
1647, 1538, 1234, 1032, 745 cm .
N-{1-(3,4-Dimethoxyphenyl)-3-oxo-3-phenylpropyl}-
N-{3-Oxo-1-phenyl-3-p-tolylpropyl}acetamide (4j):
12
acetamide (4e): Off-white solid. Yield (261 mg, 80%). mp
1
Off-white solid. Yield (264 mg, 94%). mp 115-116 °C; H

Efficient Synthesis of β-Acetamido Ketones
Bull. Korean Chem. Soc. 2012, Vol. 33, No. 11 3563
−1 +
548 cm ; HRMS (EI) m/z (M ) calcd for C19H21NO3:
NMR (300 MHz, CDCl3) δ 7.72 (2H, d, J = 8.1 Hz), 7.14-
7.26 (7H, m), 6.78 (1H, d, J = 7.2 Hz, NH), 5.51-5.45 (1H,
m), 3.63 (1H, dd, J = 16.8, 5.9 Hz), 3.32 (dd, J = 16.8, 6.0
311.1521. Found: 311.1519.
N-{1-(2,5-Dimethylphenyl)-3-(4-methoxyphenyl)-3-oxo-
propyl}acetamide (4o): Off-white solid. Yield (273 mg,
13
Hz ), 2.32 (3H, s), 1.93 (3H, s); C NMR (75 MHz, CDCl3)
1
84%). mp 122-123 °C; H NMR (300 MHz, CDCl3) δ 7.86
δ 197.6, 170.2, 144.2, 141.0, 133.9, 129.2, 129.2, 128.5,
128.5, 128.2, 128.2, 127.2, 126.5, 126.5, 49.9, 43.5, 23.2,
21.6; IR (KBr) 3274, 3081, 2928, 1681, 1646, 1557, 1407,
(2H, d, J = 9 Hz), 7.08 (1H, s), 7.00 (1H, d, J = 7.8 Hz),
6.92-6.84 (3H, m), 6.64 (1H, d, J = 7.2 Hz, NH), 5.69-5.62
(1H, m), 3.81 (3H, s), 3.53 (1H, dd, J = 15.9, 6.0 Hz), 3.32
(1H, dd, J = 15.9, 6.9 Hz), 2.34 (3H, s), 2.23 (3H, s), 1.90
−1 +
1370, 1297, 1181, 994, 810, 703 cm ; HRMS (EI) m/z (M )
calcd for C18H19NO2: 281.1416. Found: 281.1416.
13
(3H, s); C NMR (75 MHz, CDCl3) δ 196.3, 169.5, 163.4,
N-{3-Oxo-1,3-di-p-tolylpropyl}acetamide (4k): Off-white
1
solid. Yield (265 mg, 90%). mp 109-110 °C; H NMR (300
139.4, 135.3, 132.3, 130.4, 130.3, 130.3, 129.6, 127.9,
126.2, 113.6, 113.6, 55.2, 46.6, 43.1, 22.8, 20.9, 18.7; IR
(KBr) 3334, 3010, 2931, 2841, 1662, 1601, 1516, 1264,
MHz, CDCl3) δ 7.79 (2H, d, J = 8.4 Hz), 7.24-7.17 (4H, m),
7.08 (2H, d, J = 7.8 Hz), 6.63 (1H, d, J = 7.2 Hz, NH), 5.51-
5.48 (1H, m), 3.68 (1H, dd, J = 16.2, 4.5 Hz), 3.37 (1H, dd, J
−1 +
1174, 1026, 989, 833, 592 cm ; HRMS (EI) m/z (M ) calcd
13
= 16.5, 6.0 Hz), 2.38 (3H, s), 2.27 (3H, s), 1.99 (3H, s); C
for C20H23NO3: 325.1678. Found: 325.1675.
NMR (75 MHz, CDCl3) δ 197.8, 169.6, 144.1, 138.3, 136.8,
134.2, 129.3, 129.3, 129.2, 129.2, 128.2, 128.2, 126.5,
126.5, 49.7, 43.5, 23.1, 21.6, 20.9; IR (KBr) 3259, 3068,
2925, 1655, 1544, 1421, 1366, 1292, 1190, 995, 814, 724
N-{1-(4-Bromophenyl)-3-(4-methoxyphenyl)-3-oxoprop-
yl}acetamide (4p): White solid. Yield (330 mg, 88%). mp
1
155-157 °C; H NMR (300 MHz, CDCl3) δ 7.80 (2H, d, J =
8.7 Hz), 7.42 (2H, d, J = 8.4 Hz), 7.21 (2H, d, J = 8.4 Hz),
6.92 (2H, d, J = 9.0 Hz), 6.86 (1H, s, br, NH), 5.53-5.46 (1H,
m), 3.87 (3H, s), 3.67 (1H, dd, J = 17.1, 5.1 Hz), 3.34 (1H,
−1
+
cm ; HRMS (EI) m/z (M ) calcd for C19H21NO2: 295.1572.
Found: 295.1573.
13
dd, J = 16.8, 5.8 Hz), 2.03 (3H, s); C NMR (75 MHz,
N-{1-(2,5-Dimethylphenyl)-3-oxo-3-p-tolylpropyl}aceta-
mide (4l): White solid. Yield (293 mg, 95%). mp 136-138
CDCl3) δ 196.8, 169.7, 164.0, 140.5, 131.7, 131.7, 130.5,
130.5, 129.6, 128.4, 128.4, 121.2, 114.0, 114.0, 55.6, 49.5,
42.7, 23.4; IR (KBr) 3276, 3076, 2839, 1670, 1640, 1603,
1
°C; H NMR (300 MHz, CDCl3) δ 7.78 (2H, d, J = 8.4 Hz),
7.21 (2H, d, J = 7.8 Hz), 7.06-7.00 (2H, m), 6.93 (1H, d, J =
7.8 Hz), 6.28 (1H, d, J = 6.3 Hz, NH), 5.68-5.62 (1H, m),
3.53 (1H, dd, J = 16.2, 5.7 Hz), 3.38 (1H, dd, J = 16.2, 6.9
−1
1549, 1368, 1261, 1174, 1031, 832, 751, 605 cm ; HRMS
+
(EI) m/z (M ) calcd for C18H18BrNO3: 375.0470. Found:
13
Hz), 3.37 (3H, s), 2.35 (3H, s), 2.24 (3H, s), 1.95 (3H, s); C
375.0467.
NMR (75 MHz, CDCl3) δ 197.7, 169.3, 144.1, 139.2, 135.6,
134.3, 132.7, 130.7, 129.3, 129.3, 128.3, 128.3, 128.2,
126.2, 46.8, 43.2, 23.2, 21.6, 21.1, 18.9; IR (KBr) 3296,
3040, 2922, 1652, 1544, 1437, 1361, 1288, 1217, 994, 805,
N-{3-(4-Methoxyphenyl)-1-(4-nitrophenyl)-3-oxoprop-
yl}acetamide (4q): Yellow solid. Yield (295 mg, 87%). mp
1
60-62 °C; H NMR (300 MHz, CDCl3) δ 8.11 (2H, d, J = 9.0
Hz), 7.83 (2H, d, J = 9.0 Hz), 7.47 (2H, d, J = 9.0 Hz), 7.07
(1H, d, J = 7.8 Hz, NH), 6.88 (2H, d, J = 9.0 Hz), 5.62-5.56
(1H, m), 3.83 (3H, s), 3.70 (1H, dd, J = 17.4, 5.1 Hz), 3.38
−1
+
750 cm ; HRMS (EI) m/z (M ) calcd for C20H23NO2:
309.1729. Found: 309.1728.
13
(1H, dd, J = 17.4, 5.4 Hz), 2.03 (3H, s); C NMR (75 MHz,
N-{1-(4-Bromophenyl)-3-oxo-3-p-tolylpropyl}acetamide
1
(4m): White solid. Yield (360 mg, 92%). mp 145-146 °C; H
CDCl3) δ 195.9, 170.0, 164.1, 149.3, 146.8, 130.4, 130.4,
129.2, 127.5, 127.5, 123.7, 123.7, 113.9, 113.9, 55.5, 49.4,
42.6, 23.1; IR (KBr) 3283, 3071, 2936, 1671, 1600, 1519,
NMR (300 MHz, CDCl3) δ 7.76 (2H, d, J = 8.1 Hz), 7.39
(2H, d, J = 8.7 Hz), 7.16-7.24 (4H, m), 6.82 (1H, d, J = 7.5
Hz, NH), 5.45-5.51 (1H, m), 3.67 (1H, dd, J = 17.1, 4.8 Hz),
3.35 (1H, dd, J = 17.4, 5.7 Hz), 2.38 (3H, s), 2.00 (3H, s);
−1
1348, 1259, 1173, 1025, 836, 700 cm ; HRMS (EI) m/z
+
(M ) calcd for C18H18N2O5: 342.1216. Found: 342.1212.
13
C NMR (75 MHz, CDCl3) δ 198.0, 169.8, 144.7, 140.4,
N-{3-(4-Methoxyphenyl)-1-(naphthalen-1-yl)-3-oxoprop-
yl}acetamide (4r): Off-white solid. Yield (333 mg, 96%).
134.1, 131.7, 131.7, 129.5, 129.5, 128.4, 128.4, 128.3,
128.3, 121.2, 49.4, 42.9, 23.4, 21.8; IR (KBr) 3272, 3073,
2924, 1645, 1546, 1420, 1371, 1298, 1215, 1089, 999, 817,
1
mp 175-176 °C; H NMR (300 MHz, CDCl3) δ 8.11 (1H, d,
J = 8.7 Hz), 7.83 (3H, d, J = 8.7 Hz), 7.72 (1H, d, J = 8.1
Hz), 7.56-7.45 (3H, m), 7.36 (1H, dd, J = 8.1, 7.2 Hz), 6.84
(2H, d, J = 9.0 Hz), 6.67 (1H, d, J = 7.5 Hz, NH), 6.36-6.29
(1H, m), 3.76 (1H, dd, J = 16.2, 5.1 Hz), 3.81 (3H, s), 3.54
−1
+
745 cm ; HRMS (EI) m/z (M ) calcd for C18H18BrNO2:
359.0521. Found: 359.0521.
N-{3-(4-Methoxyphenyl)-3-oxo-1-p-tolylpropyl}acetamide
1
(4n): Yellow solid. Yield (289 mg, 80%). mp 58-60 °C; H
13
(1H, dd, J = 16.2, 6.6 Hz), 1.99 (3H, s); C NMR (300
NMR (300 MHz, CDCl3) δ 7.89 (2H, d, J = 8.7 Hz), 7.20
(2H, d, J = 7.8 Hz), 7.09 (2H, d, J = 8.4 Hz), 6.90 (2H, d, J =
8.7 Hz), 6.84 (1H, d, J = 7.8 Hz, NH), 5.53-5.47 (1H, m),
3.84 (3H, s), 3.66 (1H, dd, J = 16.5, 5.4 Hz), 3.33 (1H, dd, J
MHz, CDCl3) δ 197.2, 169.4, 163.9, 136.4, 134.1, 130.9,
130.6, 130.6, 129.9, 129.1, 128.5, 126.8, 125.9, 125.3,
123.7, 123.2, 113.9, 113.9, 55.6, 46.6, 42.3, 23.5; IR (KBr)
3294, 3064, 2838, 1674, 1638, 1603, 1541, 1418, 1306,
13
= 16.5, 6.3 Hz), 2.28 (3H, s), 1.98 (3H, s); C NMR (75
−1 +
1258, 1174, 1024, 780, 608 cm ; HRMS (EI) m/z (M )
MHz, CDCl3) δ 196.7, 169.8, 163.6, 138.4, 136.7, 130.4,
130.4, 129.7, 129.1, 129.1, 126.4, 126.4, 113.7, 113.7, 55.3,
49.8, 43.3, 23.0, 20.9; IR (KBr) 3276, 3063, 2931, 2842,
1671, 1647, 1600, 1550, 1367, 1259, 1173, 1027, 824, 600,
calcd for C22H21NO3: 347.1521. Found: 347.1519.
N,N'-{1,1'-(1,4-Phenylene)bis(3-oxo-3-phenylpropane-
24
1,1-diyl}diacetamide (5): To a solution of 1a (120 mg, 1.0
mmol), terephthaldehyde (2j, 67 mg, 0.5 mmol) and acetyl

3564 Bull. Korean Chem. Soc. 2012, Vol. 33, No. 11
Rameshwar Prasad Pandit and Yong Rok Lee
chloride (0.3 mL, 4.0 mmol) in acetonitrile (5 mL) was
added AgOTf (25 mg, 10 mol %) and the reaction mixture
was stirred at room temperature for 12 h. After completion
of reaction as indicated by TLC, water (20 mL) was added.
The mixture was extracted with ethyl acetate (20 mL × 3)
and the extract was washed with saturated sodium bicarbo-
nate (25 mL). The combined organic layers were dried over
anhydrous magnesium sulfate to give residue which was
recrystalized from ethanol to give pure product 5 (207 mg,
No. RTI04-01-04 from the Regional Technology Innovation
Program of the Ministry of Commerce, Industry, and Energy
(MOCIE).
References
1. (a) Tietze, L. F.; Brasche, G.; Gericke, K. M. Domino Reactions in
Organic Synthesis; WILEY-VCH Verlag GmbH & Co. KGaA:
Weinheim, 2006. (b) Zhu, J.; Bienayme, H. Multicomponent
Reactions; Wiley: Weinheim, 2005.
1
91%) as an off-white solid. mp 190-191°C; H NMR (300
2. (a) Barry, B. T.; Dennis, G. H. Chem. Rev. 2009, 109, 4439. (b)
Magedov, I. V.; Manpadi, M.; Ogasawara, M. A.; Dhawan, A. S.;
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M.; Uglinskii, P. Y.; Elias, E. M.; Knee, E. J.; Tongwa, P.; Antipin,
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MHz, DMSO-d6) δ 8.26 ( 2H, d, J = 8.1 Hz), 7.95 (4H, d, J =
7.5 Hz), 7.63 (2H, dd, J = 7.5, 7.2 Hz), 7.51 (4H, d, J = 7.8,
7.2 Hz), 7.29 (2H, s, NH), 5.38-5.31 (2H, m), 3.56-3.33 (4H,
13
m), 1.77 (6H, s); C NMR (75 MHz, DMSO-d6) δ 197.0,
168.2, 141.5, 136.5, 133.1, 128.6, 127.9, 126.5, 48.6, 44.4,
22.5; IR (KBr) 3256, 3067, 1682, 1647, 1547, 1370, 1270,
4. (a) Barluenga, J.; Viado, A. L.; Aguilar, E.; Fustero, S.; Olano, B.
J. Org. Chem. 1993, 58, 5972. (b) Enders, D.; Moser, M.; Geibel,
G.; Laufer, M. C. Synthesis 2004, 2040.
−1
996 cm .
20
N-(2-Methyl-3-oxo-1,3-diphenylpropyl)acetamide (10).
5. (a) Kobinata, K.; Uramoto, M.; Nishii, M.; Kusakabe, H.; Nakamura,
G.; Isono, K. Agric. Biol. Chem. 1980, 44, 1709 (b) Fiedler, E.;
Fiedler, H.-P.; Gerhard, A.; Keller-Schierlein, W.; Köenig, W. A.;
Zäehner, H. Arch. Microbiol. 1976, 107, 249.
To a solution of propiophenone (134 mg, 1.0 mmol) with
benzaldehyde (117 mg, 1.1 mmol) and acetyl chloride (0.15
mL, 2.0 mmol) in acetonitrile (5 mL) was added AgOTf (25
mg, 10 mol %) and the reaction mixture was stirred at room
temperature for 12 h. After completion of reaction as
indicated by TLC, water (20 mL) was added. The mixture
was extracted with ethyl acetate (15 mL × 3) and extract was
washed with saturated sodium bicarbonate (25 mL). The
combined organic layers were dried over anhydrous magne-
sium sulfate to give residue which was purified by column
chromatography on silica gel using hexane/EtOAc (1:1) to
give 10a and 10b.
6. Jeffs, P. W.; Redfearn, R.; Wolffram, J. J. Org. Chem. 1983, 48,
3861.
7. Dallemagne, P.; Rault, S.; Severicourt, M.; Hassan, K. M.; Robba,
M. Tetrahedron Lett. 1986, 27, 2607.
8. Paleo, M. R.; Dominguez, D.; Castedo, L. Tetrahedron Lett. 1993,
34, 2369.
9. Dakin, H. D.; West, R. J. Biol. Chem. 1928, 78, 745.
10. Buchanan, G. L. Chem. Soc. Rev. 1988, 17, 91.
11. Rao, I. N.; Prabhakaran, E. N.; Das, S. K.; Iqbal, J. J Org. Chem.
2003, 68, 4079.
12. Khan, A. T.; Parvin, T.; Choudhury, L. H. Tetrahedron 2007, 63,
5593.
anti-Isomer (10a): White solid (191 mg, 68%); mp 102-
1
104 °C; H NMR (300 MHz, CDCl3) δ 7.84-7.81 (2H, m),
13. Khan, A. T.; Choudhury, L. H.; Parvin, T.; Ali, A. Tetrahedron
Lett. 2006, 47, 8137.
7.52-7.47 (1H, m), 7.41-7.36 (2H, m), 7.27-7.19 (4H, m),
7.17-7.12 (1H, m), 6.17 (1H, d, J = 8.4 Hz, NH), 5.42 (1H,
dd, J = 8.4, 7.5 Hz), 4.05-3.59 (1H, m), 1.91 (3H, s), 1.16
14. Pandey, G.; Singh, R. P.; Garg, A.; Singh, V. K. Tetrahedron Lett.
2005, 46, 2137.
15. Ghosh, R.; Maiti, S.; Chakraborty, A.; Chakraborty, S.; Mukherjee,
A. K. Tetrahedron 2006, 62, 4059.
13
(3H, d, J = 6.9 Hz); C NMR (75 MHz, CDCl3) δ 201.9,
16. Hassankhani, A.; Maghsoodlou, M. T.; Habibi-Khorassani, S. M.;
Hosseini-Mahdiabad, H.; Marandi, G. ARKIVOC 2008, (ii), 134.
17. Shaterian, H. R.; Yarahmadi, H.; Ghashang, M. ARKIVOC 2007,
(xvi), 298.
169.7, 140.4, 136.2, 133.0, 128.6, 128.6, 128.4, 128.4,
128.0, 128.0, 127.3, 126.8, 126.8, 54.9, 45.5, 23.1, 13.8; IR
(KBr) 3297, 3059, 2978, 1674, 1643, 1540, 1291, 968, 703
−1
cm .
18. Khodaei, M. M.; Khosropour, A. R.; Fattahpour, P. Tetrahedron
Lett. 2005, 46, 2105.
syn-Isomer (10b): White solid (37 mg, 13%); mp 170-
1
172 °C; H NMR (300 MHz, CDCl3) δ 7.74-7.70 (2H, m),
19. Rafiee, E.; Shahbazi, F.; Joshaghani, M.; Tork, F. J. Mol. Catal. A:
Chem. 2005, 242, 129.
7.52-7.46 (2H, m), 7.38-7.33 (2H, m), 7.29-7.16 (3H, m),
20. Bahulayan, D.; Das, S. K.; Iqbal, J. J. Org. Chem. 2003, 68, 5735.
21. Das, B.; Reddy, K. R. Helv. Chim. Act. 2006, 89, 3109.
22. Harmata, M., Ed.; Silver in Organic Chemistry; John Wiley &
Sons Inc.: Hoboken, 2010.
7.13-7.08 (1H, m), 5.35 (1H, dd, J = 8.7, 3.9 Hz), 4.11-4.03
13
(1H, m), 2.08 (3H, s), 1.34 (3H, d, J = 7.2 Hz); C NMR (75
MHz, CDCl3) δ 204.9, 169.9, 140.8, 136.3, 133.4, 128.5,
128.5, 128.3, 128.3, 128.1, 128.1, 127.1, 126.2, 126.2, 55.6,
44.3, 23.3, 16.5; IR (KBr) 3298, 3065, 2977, 1682, 1645,
23. (a) Tschan, M. J.-L.; Thomas, C. M.; Strub, H.; Carpentier, J.-F.
Adv. Synth. Catal. 2009, 351, 2496. (b) Rosenfeld, D. C.; Shekhar,
S.; Takemiya, A.; Utsunomiya, M.; hartwig, J. F. Org. Lett. 2006,
8, 4179.
−1
1547, 1303, 969, 707 cm .
24. Shinu, V. S.; Sheeja, B.; Purushothaman, E., Bahulayan, D. Tetra-
hedron Lett. 2009, 50, 4838.
Acknowledgments. This work was supported by grant