One-pot synthesis of β-acetamido-β-arylpropiophenone employing trifluoroacetic acid as an efficient catalyst

Article abstract of DOI:10.1007/s11164-011-0288-9

Trifluoroacetic acid as an efficient catalyst promoting the Dakin-West reaction at ambient temperature is reported for the first time in this paper. A few efficacious auxiliary catalysts were also developed for the Dakin-West reaction. A variety of substi

Full text of DOI:10.1007/s11164-011-0288-9

Res Chem Intermed (2011) 37:811–820
DOI 10.1007/s11164-011-0288-9
One-pot synthesis of b-acetamido-b-arylpropiophenone
employing trifluoroacetic acid as an efficient catalyst
•
Xing-Hua Zhang Li Fan Jian Liu Da-Cheng Yang
•
•
Received: 8 December 2010 / Accepted: 17 January 2011 / Published online: 2 February 2011
Ó Springer Science+Business Media B.V. 2011
Abstract Trifluoroacetic acid as an efficient catalyst promoting the Dakin–West
reaction at ambient temperature is reported for the first time in this paper. A few
efficacious auxiliary catalysts were also developed for the Dakin–West reaction.
A variety of substituted aryl aldehydes and aryl ketones were found to be applicable
to the preparation of some new b-acetamido-b-arylpropiophenones. This procedure
has several advantages such as high yields, short reaction time, and smaller amount
(0.30 mol%) of catalyst.
Keywords Trifluoroacetic acid Á b-Acetamido ketones Á One-pot Á
3-Nitroacetophenone
Introduction
b-Acetamido ketones are versatile intermediates in that their skeletons exist in a
number of biologically or pharmacologically important compounds [1, 2]. Examples
include the preparation of 1,3-amino alcohols [3, 4], b-amino acids [5], c-lactams
[6], and antibiotic nikkomycins or neopolyoxines [7, 8]. Moreover, it has recently
been reported that b-acetamido ketones can act as a-glucosidase inhibitors [9]. This
class of compounds is usually prepared by acylation of b-amino ketones [10],
Michael addition of a,b-unsaturated ketones [11], or photoisomerization of
phthalimides [12]. However, the most classical and facile method for the synthesis
of b-acetamido ketones is the Dakin–West reaction. As a representative of
multicomponent reactions, it plays a pivotal role in the building of complex organic
molecules. A modified procedure involves a one-pot condensation of a ketone with
an aldehyde and acetonitrile in the presence of acetyl chloride [13]. Several catalysts
X.-H. Zhang Á L. Fan Á J. Liu Á D.-C. Yang (&)
School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China
e-mail: hxydc@swu.edu.cn
123

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X.-H. Zhang et al.
have been exploited for the synthesis of b-acetamido ketones, for example silica
sulfuric acid [14], K5CoW12O40Á3H2O [15], H6P2W18O62 [16], ZrOCl2Á8H2O [17],
cyanuric chloride [18], selectfluor [19], SnCl2Á2H2O [20], NaHSO4ÁH2O [21],
Montmorillonite K10 [22], etc. Although these catalysts are effective, they still
suffer from disadvantages. Some are required in large amounts [14, 17, 20], some
need a high temperature (80 °C) [14, 16, 21], some require column chromatography
for separation of products [17, 20, 22], and others are expensive [15, 16], etc.
Consequently, the development of new and efficient catalysts has become
mandatory.
Trifluoroacetic acid (TFA) is a readily available organic acid. In recent years,
TFA has been a useful intermediate in the synthesis of fluorine-containing organic
compounds and an important starting material for fluoropolymers. TFA is also
important in the synthesis of amino acids [23] and deprotection of peptides [24]. As
a strongly acidic catalyst, TFA has been extensively used in alkylation [25],
acylation of aromatic compounds, and olefin polymerization. As far as we are aware
TFA has not been used for synthesis of b-acetamido ketones. Herein, it was our
intent to utilize TFA in the Dakin–West reaction for the first time.
Results and discussion
To optimize the reaction conditions, 3-nitroacteophenone (1 mmol), 4-methylbenz-
aldehyde (1 mmol), acetyl chloride (0.4 mL), and acetonitrile (3 mL) were selected
as model substrates. Reactions were performed under different conditions to
examine the effects of different amounts of TFA (Table 1). In the absence of
catalyst, the b-acetamido ketone product was obtained only in 19.2% yield. When
TFA was added as catalyst to the reaction mixture, the yield was over 80.0%. As can
be seen from entry 3, the best yield was 98.6%, for reaction in the presence of
0.30 mol% TFA for 4.5 h. It is worth mentioning that the yield of product in the
model reaction did not improve obviously with increasing of amount of TFA and the
product could not be separated easily when the amount of TFA exceeded
0.30 mol%. So the optimized amount of catalyst was 0.30 mol% in Scheme 1.
To evaluate the effect of the solvent, the reaction was carried out under similar
reaction conditions but using different organic solvents. Various solvents, for
example methanol, chloroform, and dichloromethane, were used, as shown in
Table 2. No reaction was observed in methanol whereas reaction in chloroform and
dichloromethane was completed with moderate yield. Unexpectedly, the best result
was obtained when acetonitrile was used as solvent. Therefore, all the following
Table 1 Effect of the amount
of TFA on the model reaction
Entry
TFA (mol%)
Time (h)
Yield (%)a
1
2
3
4
0.00
0.15
0.30
0.45
4.5
4.5
4.5
4.5
19.2
80.1
98.6
93.5
a
Isolated yield
123

One-pot synthesis of b-acetamido-b-arylpropiophenone
813
O
O
NHAc
TFA
r.t.
O2N
CHO
+
H3C
O2N
CH3
CH3CN
+
AcCl
Scheme 1 Model reaction
Table 2 Effect of solvents on the model reaction
Entry
Solvent
Time (h)
Yield (%)a
1
2
3
4
a
CH3OHb
CH2Clb2
CHClb3
4.5
4.5
4.5
4.5
None
70.0
58.6
95.6
CH3CNc
Isolated yield
b
c
CH3CN used was 0.041 g (1 mmol), solvent used was 3 mL
CH3CN used was 3 mL
Table 3 Effect of the acyl chlorides and sulfochlorides
Entry
Auxiliary catalyst
Time (h)
Yield (%)
1
2
3
4
5
6
7
a
CH3COCl
4.5
4.5
4.5
4.5
4.5
4.5
4.5
95.6a
60.0b
30.0b
85.0b
None
None
None
ClCH2COCl
ClCH2CH2COCl
ClCH2CH2CH2COCl
p-CH3C6H4SO2Cl
p-NO2C6H4SO2Cl
p-CH3CONHC6H4SO2Cl
Isolated yield
b
Not isolated yield
reactions were carried out in the presence of TFA in acetonitrile at ambient
temperature.
To investigate the range of the acyl chloride, the model reaction was also carried
out with different acyl chlorides and sulfochlorides. The results in Table 3 showed
that the reaction proceeded effectively in the presence of both acetyl chloride and
chlorobutyryl chloride, affording the corresponding b-acetamido ketones in good
yields, whereas chloroacetyl chloride and chloropropionyl chloride did not work
well enough. Surprisingly, sulfochlorides did not obviously promote the reaction.
To expand the scope of the TFA-catalyzed multi-component one-pot reaction, a
variety of aromatic aldehydes and ketones containing both electron-donating and
withdrawing substituents were used to produce the corresponding b-acetamido
ketones. The experimental results in Table 4 revealed that these chose reactants
afforded good to excellent yields under the optimized reaction conditions. It was
123

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X.-H. Zhang et al.
Table 4 Experimental results under the optimum conditions
Entry
R1
R2
Time (h)
Yield (%)
M.p. ( °C)
1
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
3-NO2
4-Br
4-CH3
3-CH3
4-OCH3
3-OCH3
3,4,5-triOCH3
H
5.0
4.5
5.5
5.0
5.5
5.0
7.0
6.5
5.5
4.0
5.5
4.0
6.5
6.0
8.0
6.0
5.5
8.0
5.5
92.6
98.6
88.0
86.2
84.6
96.0
87.5
86.9
84.5
88.0
83.1
79.4
87.9
94.7
85.8
80.0
85.0
83.5
85.0
125.1–126.8
150.1–152.5
155.2–157.4
95.4–96.2
2
3
4
5
148.5–150.3
132.1–133.2
128.0–129.0
147.4–149.1
178.1–179.9
149.5–151.2
207.7–208.9
204.9–206.4
202.4–204.1
174.8–176.5
193.0–195.0
198.0–200.4
161.6–164.0
132.5–134.5
137.9–139.7
6
7
4-Cl
8
3-Cl
9
2-Cl
10
11
12
13
14
15
16
17
18
19
3-F
4-NO2
3-NO2
4-Br
3,4-diCl
2,4-diCl
3-OCH3-4-OH
3,4-diCl
3-F
3,4-diCl
4-OCH3
3,4-diCl
O
O
NHAc
TFA(0.30 mol%)
CHO
R1
R2
CH3CN
+
R1
R2
+
r.t.
AcCl
Scheme 2
also found that substituent groups in the meta position resulted in shorter reaction
times than those in the para position (entries 1 and 2, 3 and 4, 7 and 8, 11 and 12),
and that substituents groups on the acetophenone ring did not affect the reaction
time obviously (entries 14, 17, 19). Furthermore, for substituents in the para
position, aromatic aldehydes with weak electron-withdrawing groups reacted faster
than the others (for example entries 1, 3, 7, 11 and 13). With liquid aldehydes and
aldehydes with substituents in the meta position, usually no solid was observed after
completion of the reaction (entries 4, 8, 10), with the exception of entry 2. When
phenylacetaldehyde reacted with 3-nitroacteophenone and acetonitrile, the title
product was obtained in trace amount (monitored by TLC). It is noteworthy that no
acetylation of an aromatic hydroxyl group was observed and the corresponding
b-acetamido ketones were isolated in an excellent yield (entry 16) in Scheme 2.
In the course of our work, the effect of hydrogen chloride and concentrated
hydrochloric acid on the model reaction were also examined carefully, but the
results demonstrated that in the presence of hydrogen chloride or hydrochloric acid
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One-pot synthesis of b-acetamido-b-arylpropiophenone
CF3COO
815
CF3COOH
+
H
OH
OH
O
H
Ar'
Ar'
Ar'
CH2
O
O
O
Cl
O:
O
CH3
H3C
Cl
O
CH3
H
Ar
Ar
H
Ar
H
Cl
O
CH3
CH3
O
O
CH3
+
N
O
N
Ar
O
H
Ar
O
CH3
Ar
O
CH3
NCCH3
CH3
O
CH3
O
O
N
CH3
-H+
NHAc
Ar
Hydrolysis
O
N
O
CH3
H-OH
Ar
HO
Ar'
Ar
Ar'
Ar'
H2C
Fig. 1
acetyl chloride in the model reaction could not react thoroughly (only approxi-
mately 50%, monitored by TLC) within the same time, and there were some side
products. Besides, the same reactants did not react when catalyzed by sulfochlorides
without acetyl chloride. So, we consider TFA as the real catalyst of this reaction. On
the basis of all the above results, we propose the mechanism as follows in Fig. 1.
Conclusion
In summary, we discovered that TFA was a readily available and efficient catalyst
for the one-pot synthesis of b-acetamido ketones. Especially, we found a few
effective auxiliary catalysts for the first time. This methodology offers another
choice to prepare b-acetamido ketones with several advantages, for example
excellent yields, simple procedure, short reaction time, and mild conditions.
Experimental
General methods
Melting points were detected using an X-6 sophisticated micro-melting-point
1
apparatus and were uncorrected. H NMR spectra were recorded in DMSO-d6 on a
Bruker AV-3000 spectrometer, and chemical shifts (d) were expressed in ppm,
123

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X.-H. Zhang et al.
downfield from the TMS used as the internal standard. Coupling constant (J) values
were in Hz. The progress of the reactions was monitored by TLC using several
solvent systems with different polarities. All solvents and reagents were of chemical
grade or analytical grade.
General procedure for the synthesis of b-acetamido ketones
To a solution of an aldehyde (1.0 mmol), an enolizable ketone (1.0 mmol), and
acetyl chloride (0.4 mL) in acetonitrile (2.0 mL), TFA (0.30 mol%) was added
dropwise and the reaction mixture was stirred for 0.5 h at 0 °C, and then at ambient
temperature (approx. 33 °C). The progress of the reaction was monitored by TLC.
On completion, the reaction mixture was poured into ice water (20.0 mL), then the
solution was adjusted to pH 7 with saturated NaHCO3, which resulted in
precipitation of the desired b-acetamido ketone. The precipitate was filtered and
washed with diethyl ether (1.0 mL). The crude product obtained was recrystallized
from a mixture of ethyl acetate and ethyl ether to afford analytically pure product.
Eighteen title compounds are new and were characterized by 1H NMR and 13C NMR.
Spectral data for the new products
b-Acetamido-b-(4-methylphenyl)-3-nitropropiophenone (1)
1H NMR (300 MHz, DMSO-d6,): 1.76 (s, 3H, COCH3), 2.25 (s, 3H, CH3), 3.46 (dd,
J = 5.40 and 17.1 Hz, 1H, CH2), 3.62 (dd, J = 8.40 and 17.1 Hz, 1H, CH2),
5.28–5.35 (m, 1H, CHN), 7.10 (d, J = 7.80 Hz, 2H, Ar–H), 7.24 (d, J = 7.80 Hz,
2H, Ar–H), 7.81 (t, J = 8.10 Hz, 1H, Ar–H), 8.40 (d, J = 6.60 Hz, 2H, Ar–H), 8.45
(d, J = 8.10 Hz, 1H, Ar–H), 8.61 (s, 1H, Ar–H). 13C NMR(75 MHz, DMSO-
d6):196.3, 168.8, 148.5, 140.1, 138.2, 136.4, 134.7, 131.0, 129.2, 127.8, 127.0,
122.8, 48.1, 45.3, 23.0, 21.0.
b-Acetamido-b-(3-methylphenyl)-3-nitropropiophenone (2)
1H NMR (300 MHz, DMSO-d6): 1.78 (s, 3H, COCH3), 2.27 (s, 3H, CH3), 3.47 (dd,
J = 8.40 and 17.1 Hz, 1H, CH2), 3.64 (dd, J = 5.70 and 17.1 Hz, 1H, CH2),
5.28–5.35 (m, 1H, CHN), 7.02 (d, J = 6.90 Hz, 1H, Ar–H,), 7.16–7.18 (m, 3H, Ar–
H), 7.81 (t, J = 8.10 Hz, 1H, Ar–H,), 8.36–8.46 (m, 3H, NH, Ar–H), 8.60 (s, 1H,
Ar–H). 13C NMR (75 MHz, DMSO-d6): 196.3, 168.9, 148.4, 143.1, 138.2, 137.7,
134.7, 131.0, 128.6, 128.0, 127.8, 124.4, 122.8, 49.3, 45.3, 23.0, 21.5.
b-Acetamido-b-(4-methoxylphenyl)-3-nitropropiophenone (3)
1H NMR (300 MHz, DMSO-d6): 1.78 (s, 3H, COCH3), 2.27 (s, 3H, CH3), 3.43-3.41
(m, 1H, CH2), 3.60-3.70 (m, 1H, CH2), 5.28–5.35 (m, 1H, CHN), 6.86 (d,
J = 7.80 Hz, 2H, Ar–H), 7.27–7.32 (m, 3H, Ar–H), 7.64–7.72 (m, 1H, Ar–H), 8.27
(d, J = 7.50 Hz, 1H, Ar–H), 8.41 (d, J = 8.10 Hz,1H, NH), 8.72 (s, 1H, Ar–H).13C
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One-pot synthesis of b-acetamido-b-arylpropiophenone
817
NMR (75 MHz, DMSO-d6): 196.3, 168.9, 158.6, 148.4, 138.2, 135.0, 134.7, 131.0,
128.3, 127.8, 122.7, 114.0, 55.5, 48.9, 45.3, 22.9.
b-Acetamido-b-(3-methoxylphenyl)-3-nitropropiophenone (4)
1H NMR (300 MHz, CDCl3): 2.04 (s, 3H, COCH3), 3.49 (dd, J = 6.60 and 17.1 Hz,
1H, CH2), 3.85 (dd, J = 9.30 and 17.1 Hz, 1H, CH2), 3.79 (s, 1H, OCH3),
3.83–3.88 (m, 1H, CH2), 5.50–5.56 (m, 1H, CHN), 6.41 (d, J = 7.80 Hz, 1H, Ar–
H,), 6.80 (d, J = 8.40 Hz, 1H, Ar–H,), 6.89–6.93 (m, 2H, Ar–H), 7.23–7.27 (m, 1H,
Ar–H), 7.67 (t, J = 7.80 Hz, 1H, Ar–H), 8.24 (d, J = 7.80 Hz, 1H, Ar–H), 8.41 (d,
J = 7.80 Hz, 1H, NH), 8.72 (s, 1H, Ar–H).13C NMR (75 MHz, CDCl3): 196.0,
184.8, 169.6, 141.9, 137.3, 133.7, 130.0, 129.9, 127.7, 123.0, 118.7, 112.8, 112.7,
55.2, 50.1, 43.8, 23.4
b-Acetamido-b-(3,4,5-trimethoxylphenyl)-3-nitropropiophenone (5)
1H NMR(300 MHz, CDCl3): 2.04 (s, 3H, COCH3), 3.43–3.41 (m, 1H, CH2),
3.65–3.84 (m, 1H, CH2,OCH3), 5.43–5.49 (m, 1H, CHN), 6.41 (d, J = 7.50 Hz, 1H,
Ar–H), 6.56 (s, 1H, Ar–H), 7.68 (t, J = 7.80 Hz, 1H, Ar–H), 8.27 (d, J = 7.80 Hz,
1H, Ar–H), 8.42 (d, J = 9.60 Hz, 1H, NH), 8.73 (s, 1H, Ar–H). 13C NMR (75 MHz,
CDCl3): 196.0, 168.6, 153.4, 148.4, 137.7, 136.2, 133.7, 130.0, 127.6, 123.0, 104.0,
60.7, 56.1, 50.6, 44.0, 23.3.
b-Acetamido-b-phenyl-3-nitropropiophenone (6)
1H NMR (300 MHz, DMSO-d6): 1.78(s, 3H, COCH3), 3.47–3.55 (m, 1H, CH2),
3.60–3.69 (m, 1H, CH2), 5.33–5.40 (m, 1H, CHN), 7.22–7.38 (m, 5H, Ar–H), 7.82
(t, J = 8.10 Hz, 1H, Ar–H), 8.32–8.62 (m, 3H, Ar–H, NH), 8.63 (s, 1H, Ar–H).
b-Acetamido-b-(4-chlorophenyl)-3-nitropropiophenone (7)
1H NMR (300 MHz, CDCl3): 2.04(s, 3H, COCH3), 3.51 (dd, J = 5.40 and 17.4 Hz,
1H, CH2), 3.83 (dd, J = 6.60 and 17.4 Hz, 1H, CH2), 5.51–5.58 (m, 1H, CHN),
6.49 (d, J = 7.50 Hz, 1H, Ar–H), 7.27–7.30 (m, 4H, Ar–H), 7.69 (t, J = 7.80 Hz,
1H, Ar–H), 8.24 (d, J = 7.20 Hz, 1H, Ar–H), 8.43 (d, J = 9.60 Hz, 1H, NH),
8.72(s, 1H, Ar–H).13C NMR(75 MHz, DMSO-d6): 196.3, 168.9, 148.4, 142.2,
138.1, 134.7, 131.9, 131.0, 129.0, 128.6, 127.9, 122.8, 48.7, 45.0, 23.0.
b-Acetamido-b-(3-chlorophenyl)-3-nitropropiophenone (8)
1H NMR (300 MHz, CDCl3): 2.05(s, 3H, COCH3), 3.51 (dd, J = 5.70 and 16.5 Hz,
1H, CH2), 3.83 (dd, J = 5.10 and 16.5 Hz, 1H, CH2), 5.55–5.57 (m, 1H, CHN),
6.56 (d, J = 6.60 Hz, 1H, Ar–H), 7.25–7.27 (m, 2H, Ar–H), 7.34 (s, 1H, Ar–H),
7.69 (t, J = 7.80 Hz, 1H, Ar–H), 8.25 (d, J = 7.80 Hz, 1H, Ar–H), 8.43 (d,
J = 8.10 Hz, 1H, NH), 8.72 (s, 1H, Ar–H). 13C NMR(75 MHz, CDCl3): 195.6,
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X.-H. Zhang et al.
169.8, 148.4, 142.8, 137.6, 134.6, 133.6, 130.0, 129.9, 127.8, 126.8, 126.7, 124.9,
122.9, 49.3, 43.7, 23.3.
b-Acetamido-b-(2-chlorophenyl)-3-nitropropiophenone (9)
1H NMR (300 MHz, CDCl3): 2.06(s, 3H, COCH3), 3.58 (dd, J = 5.70 and 16.5 Hz,
1H, CH2), 3.83 (dd, J = 6.00 and 16.5 Hz, 1H, CH2), 5.83–5.90 (m, 1H, CHN),
6.68 (d, 1H, J = 7.80 Hz, Ar–H), 7.17–7.26 (m, 2H, Ar–H), 7.35–7.38 (m, 1H, Ar–
H), 7.42–7.47 (m, 1H, Ar–H), 7.68 (t, J = 7.80 Hz, 1H, Ar–H), 8.26 (d,
J = 7.50 Hz, 1H, Ar–H), 8.42 (d, J = 7.80 Hz, 1H, NH), 8.75 (s, 1H, Ar–H).13C
NMR(75 MHz, CDCl3): 195.6, 168.9, 148.4, 140.4, 137.9, 134.5, 132.1, 130.8,
129.6, 128.9, 128.0, 127.7, 127.6, 122.8, 46.6, 43.9, 22.9.
b-Acetamido-b-(3-fluorophenyl)-3-nitropropiophenone (10)
1H NMR (300 MHz, CDCl3): 2.05(s, 3H, COCH3), 3.50 (dd, J = 6.30 and 17.1 Hz,
1H, CH2), 3.83 (dd, J = 5.10 and 17.1 Hz, 1H, CH2), 5.55–5.61 (m, 1H, CHN),
6.56 (d, J = 7.80 Hz, 1H, Ar–H), 6.92–6.99 (m, 1H, Ar–H), 7.05–7.14 (m, 2H,
Ar–H), 7.27–7.34 (m, 1H, Ar–H), 7.69 (m, 1H, Ar–H), 8.25 (d, J = 8.10 Hz, 1H,
Ar–H), 8.42 (d, J = 8.10 Hz, 1H, NH), 8.72(s, 1H, Ar–H).13C NMR (75 MHz,
CDCl3): 195.8, 169.7, 161.3, 148.4, 143.1, 137.6, 133.6, 130.4, 130.1, 127.8, 122.9,
122.1, 114.8, 113.8, 46.6, 43.9, 22.9.
b-Acetamido-b-(4-nitrophenyl)-3-nitropropiophenone (11)
1H NMR (300 MHz, DMSO-d6): 1.83(s, 3H, COCH3), 3.60 (dd, J = 5.10 and
18.0 Hz, 1H, CH2), 3.77 (dd, J = 8.40 and 18.0 Hz, 1H, CH2), 5.42–5.49 (m, 1H,
CHN), 7.66 (d, J = 8.40 Hz, 2H, Ar–H), 7.84 (t, J = 8.40 Hz, 1H, Ar–H), 8.20
(d, J = 8.40 Hz, 2H, Ar–H), 8.40 (d, J = 7.80 Hz, 1H, NH), 8.49 (m, 2H, Ar–H),
8.66(s, 1H, Ar–H). 13C NMR (75 MHz, DMSO-d6): 195.6, 169.2, 151.2, 148.4,
146.9, 138.0, 134.6, 131.0, 128.4, 128.0, 123.9, 122.8, 48.9, 44.6, 23.0.
b-Acetamido-b-(3-nitrophenyl)-3-nitropropiophenone (12)
1H NMR (300 MHz, DMSO-d6): 1.84 (s, 3H, COCH3), 3.58–3.66 (dd, J = 5.10
and 17.7 Hz,1H, CH2), 3.79–3.87 (dd, J = 8.70and 17.7 Hz, 1H, CH2), 5.45–5.52
(m, 1H, CHN), 7.22–7.39 (m, 1H, Ar–H), 7.62 (t, J = 7.80 Hz, 2H, Ar–H), 8.12
(d, J = 8.70 Hz, 1H, Ar–H), 8.27 (s, 1H, Ar–H), 8.42 (d, J = 7.80 Hz, Ar–H), 8.48
(d, J = 8.40 Hz, Ar–H), 8.66(s, 1H, Ar–H), 8.74(d, J = 6.90 Hz, NH)
13C NMR(75 MHz, DMSO-d6): 195.8, 169.3, 148.4, 148.2, 145.7, 138.0, 134.7,
134.2, 131.0, 130.2, 127.9, 123.9, 122.8, 122.3, 121.8, 48.8, 44.7, 22.9.
b-Acetamido-b-(4-bromophenyl)-3-nitropropiophenone (13)
1H NMR (300 MHz, DMSO-d6): 1.78(s, 3H, COCH3), 3.51 (dd, J = 5.40 and
17.1 Hz,1H, CH2), 3.66 (dd, J = 8.40 and 17.7 Hz, 1H, CH2), 5.28–5.35 (m, 1H,
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One-pot synthesis of b-acetamido-b-arylpropiophenone
819
CH), 7.33 (d, J = 8.40 Hz, 2H, Ar–H), 7.51 (d, J = 8.40 Hz, 2H, Ar–H), 7.82
(t, J = 8.10 Hz, 1H, Ar–H), 8.36 (m, 2H, NH, Ar–H), 8.45–8.49 (m, 1H, Ar–H),
8.63(s, 1H, Ar–H). 13C NMR(75 MHz, DMSO-d6): 196.0, 168.9, 148.4, 142.7,
138.0, 134.6, 131.5, 131.0, 129.4, 127.9, 122.8, 120.4, 48.7, 44.7, 23.0.
b-Acetamido-b-(3,4-chlorophenyl)-3-nitropropiophenone (14)
1H NMR (300 MHz, DMSO-d6): 1.82(s, 3H, COCH3), 3.54–3.62 (m, 1H, CH2),
3.68–3.77 (m, 1H, CH2), 5.31–5.38 (m, 1H, CH), 7.37–7.41 (m, 1H, Ar–H), 7.61 (d,
J = 8.10 Hz, 1H, Ar–H), 7.66 (s, 1H, Ar–H), 7.85 (t, J = 7.80 Hz, 1H, Ar–H), 8.41
(m, 2H, NH, Ar–H), 8.49 (d, J = 7.80 Hz, 1H, Ar–H), 8.67 (s, 1H, Ar–H). 13C
NMR (75 MHz, DMSO-d6): 195.8, 169.1, 148.4, 144.5, 138.0, 134.7, 131.3, 131.0,
130.8, 129.8, 129.2, 127.9, 127.7, 122.8, 48.4, 44.7, 23.0.
b-Acetamido-b-(2,4-chlorophenyl)-3-nitropropiophenone (15)
1H NMR (300 MHz, DMSO-d6): 1.81 (s, 3H, COCH3), 3.44 (dd, J = 4.20 and
17.7 Hz, 1H, CH2), 3.62 (dd, J = 9.00 and 17.7 Hz, 1H, CH2), 5.62–5.69 (m, 1H,
CH), 7.44–7.53 (m, 2H, Ar–H), 7.60 (s, 1H, Ar–H), 7.84 (t, J = 7.80 Hz, 1H, Ar–
H), 8.39–8.50 (m, 3H, NH, Ar–H), 8.68 (s, 1H, Ar–H).13C NMR(75 MHz, DMSO-
d6): 195.6, 169.1, 148.4, 139.8, 137.9, 134.7, 133.0, 132.7, 131.0, 129.6, 129.1,
128.0, 127.9, 122.9, 46.3, 43.7, 22.9.
b-Acetamido-b-(4-hydroxy-3–methoxyphenyl)-3-nitropropiophenone (16)
1H NMR (300 MHz, DMSO -d6): 1.77 (s, 3H, COCH3), 3.45-3.61 (m, 2H, CH2),
3.75 (s, 1H, OCH3), 5.23–5.30 (m, 1H, CH), 6.66–6.75 (m, 2H, Ar–H), 6.93 (s, 1H,
Ar–H), 7.81 (t, 1H, Ar–H, J = 8.40 Hz), 8.22 (d, 1H, J = 8.10 Hz, Ar–H), 8.37
(d, J = 7.80 Hz, 1H, Ar–H), 8.43–8.46 (m, 2H, NH, Ar–H), 8.60 (s, 1H, Ar–H), 8.84
(s, 1H, Ar–H). 13C NMR(75 MHz, DMSO-d6): 196.5, 168.7, 148.4, 147.8, 146.0,
138.2, 134.7, 133.7, 131.0, 127.8, 122.8, 119.4, 115.5, 111.5, 56.0, 49.3, 45.6, 23.0.
b-Acetamido-b-(3,4-chlorophenyl)-4-bromopropiophenone (17)
1H NMR (300 MHz, DMSO-d6): 1.81 (s, 3H, COCH3), 3.39-3.47 (m, 1H, CH2),
3.54–3.63 (m, 1H, CH2), 5.28–5.37 (m, 1H, CHN), 7.34–7.41 (m, 4H, Ar–H), 7.35
(d, J = 8.10 Hz, 2H, Ar–H),7.58 (s, 1H, Ar–H) 7.60 (d, J = 7.80 Hz, 1H, Ar–H),
7.74 (d, J = 8.70 Hz, 2H, Ar–H), 7.90 (d, J = 7.80 Hz, 2H, Ar–H), 8.38
(d, J = 7.50 Hz, 1H, NH). 13C NMR(75 MHz, DMSO-d6):196.6, 168.8, 150.9,
145.2, 135.9, 132.2, 130.5, 129.7, 127.8, 124.5, 120.8, 120.2, 48.8, 44.8, 23.1.
b-Acetamido-b-(3-fluorophenyl)-3,4-chloropropiophenone (18)
1H NMR (300 MHz, DMSO-d6): 1.80 (s, 3H, COCH3), 3.42 (dd, J = 5.10 and
17.4 Hz, 1H, CH2), 3.57 (dd, J = 8.40 and 17.4 Hz, 1H, CH2), 5.23-5.33 (m, 1H,
CHN), 7.07–7.21 (m, 3H, Ar–H), 7.35–7.38 (m, 1H, Ar–H), 7.80 (d, J = 8.38 Hz,
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1H, Ar–H), 7.93 (d, J = 8.38 Hz, 1H, Ar–H), 8.19 (s, 1H, Ar–H), 8.34
(d, J = 7.35 Hz, 1H, NH).13C NMR(100 MHz, DMSO-d6): 195.1, 168.4, 163.3,
145.7, 136.6, 135.9, 131.7, 130.1, 130.0, 129.9, 127.9, 122.7, 113.6, 113.2, 48.3,
44.2, 22.5.
b-Acetamido-b-(3,4-chlorophenyl)-4-methoxylpropiophenone (19)
1H NMR (300 MHz, DMSO -d6): 1.79 (s, 3H, COCH3), 3.34–3.40 (m, 1H, CH2),
3.52–3.60 (m 1H, CH2), 5.29–5.36 (m 1H, CHN), 7.15 (d, J = 8.70 Hz, 2H, Ar–H),
7.21(s, 1H, Ar–H), 7.25 (d, J = 7.50 Hz, 1H, Ar–H), 7.58 (d, J = 7.50 Hz, 1H, Ar–
H), 7.92 (d, J = 8.70 Hz, 2H, Ar–H,), 8.53 (d, J = 7.50 Hz, 1H, NH). 13C NMR
(75 MHz, DMSO-d6):195.5, 169.1, 163.6, 144.9, 131.2, 130.8, 130.7, 129.8, 129.7,
129.2, 127.7, 114.3, 55.9, 48.7, 44.1, 22.9
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