Silica-supported perchloric acid (HClO4-SiO2): An efficient catalyst for the preparation of β-amido carbonyl compounds using multicomponent reactions

Article abstract of DOI:10.1080/00397910802218728

A new, one-pot, efficient, three-component condensation of benzaldehyde derivatives, enolizable ketones, acetyl chloride, and acetonitrile or benzonitrile in the presence of silica-supported perchloric acid as an effective catalyst for the synthesis of β-

Full text of DOI:10.1080/00397910802218728

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Silica-Supported Perchloric
Acid (HClO4-SiO2): An Efficient
Catalyst for the Preparation of
β-Amido Carbonyl Compounds
Using Multicomponent
Reactions
Hamid Reza Shaterian a , Asghar Hosseinian a &
Majid Ghashang a
a Department of Chemistry, Faculty of Sciences,
University of Sistan and Baluchestan, Zahedan, Iran
Version of record first published: 14 Oct 2008
To cite this article: Hamid Reza Shaterian, Asghar Hosseinian & Majid Ghashang
(2008): Silica-Supported Perchloric Acid (HClO4-SiO2): An Efficient Catalyst for the
Preparation of β-Amido Carbonyl Compounds Using Multicomponent Reactions,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:21, 3766-3777
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Synthetic Communications1, 38: 3766–3777, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802218728
Silica-Supported Perchloric Acid (HClO4-SiO2):
An Efficient Catalyst for the Preparation of
b-Amido Carbonyl Compounds Using
Multicomponent Reactions
Hamid Reza Shaterian, Asghar Hosseinian, and Majid Ghashang
Department of Chemistry, Faculty of Sciences, University of Sistan and
Baluchestan, Zahedan, Iran
Abstract: A new, one-pot, efficient, three-component condensation of benzalde-
hyde derivatives, enolizable ketones, acetyl chloride, and acetonitrile or benzo-
nitrile in the presence of silica-supported perchloric acid as an effective catalyst
for the synthesis of b-amido carbonyl compounds is described. The present
methodology offers several advantages, such as good yields, short reaction times,
and simple workup procedure.
Keywords: b-Amido carbonyl compounds, diastereoselectivity, heterogeneous
catalyst, multicomponent reaction, silica-supported perchloric acid
INTRODUCTION
Multicomponent reactions (MCRs) are emerging as an efficient and
powerful tool in modern synthetic organic chemistry, allowing the facile
reaction of several new bonds in a one-pot transformation from three or
more reactants.[1] Multicomponent, one-pot syntheses are highly impor-
tant because of their wide range of applications in pharmaceutical chem-
istry for production of structural scaffolds and combinatorial libraries
for preparation of drug-like molecules with several levels of structural
Received April 24, 2008.
Address correspondence to Hamid Reza Shaterian, Department of Chemistry,
Faculty of Sciences, University of Sistan and Baluchestan, P.O. Box 98135-674,
Zahedan, Iran. E-mail: hrshaterian@hamoon.usb.ac.ir
3766

b-Amido Carbonyl Compounds
3767
diversity.[1] b-Acetamido ketones and esters are valuable building blocks
for a number of biologically and pharmaceutically bioactive important
compounds.[2,3] They could easily be converted to 1,3-amino alcohols,
which are precursors for the synthesis of several antibiotics such as
nikkomycins or neopolyoxins.[4]
The common procedure for the synthesis of this class of compounds
is the Dakin–West reaction,[5] which involves the condensation of
a-amino acids with acetic anhydride in the presence of a suitable base.[5]
These reactions produce a-acetamido ketones through an intermediate
azalactone.[5]
Iqbal et al. reported a multicomponent reaction for the synthesis of
b-acetamido ketones through the condensation of acetophenone, an aryl
aldehyde, and acetyl chloride in acetonitrile in the presence of cobalt (II)
chloride[6,7] or montmorillonite K-10 clay[8] as catalyst. Other catalysts
such as silica sulfuric acid,[9] BiCl3 generated from BiOCl,[10] ZrOCl2 ꢀ
8H2O,[11] heteropoly acid,[12] H3PW12O40,[13] sulfuric acid absorbed on
silica gel,[14] Sc(OTf)3,[15] K5CoW12O40 ꢀ 3H2O,[16] CeCl3 ꢀ 7H2O,[17]
ZnO,[18] iodine,[19] Amberlyst-15,[20] sulfated zirconia,[21] iron(III) chlor-
ide,[22] p-TSA,[23] Mg(HSO4)2,[24] Fe(HSO4)3[25] and ZnO nanoparticles[26]
have been used for the transformation. However, some of these catalysts
suffer from the drawbacks of prolonged reaction times, toxic reagents,
and low yields. The recovery and reusability of the catalyst is also a pro-
blem. Therefore, introducing clean processes and utilizing ecofriendly
heterogeneous and green catalysts received attention. The demand for
an environmentally benign procedure with heterogeneous catalyst[27]
prompt us to develop a safe alternative method for the synthesis of
b-amido carbonyl compounds, and we chose silica-supported perchloric
acid as catalyst for this purpose (Scheme 1).
Silica-supported perchloric acid as a solid acid catalyst was prepared
from the reaction of silica gel with perchloric acid.[28,29] This catalyst is
safe, easy to handle, and environmentally benign with fewer disposal
problems.
Scheme 1. One-pot preparation of b-acetamido or b-benzamido ketones by using
HClO4-SiO2 as catalyst.

3768
H. R. Shaterian, A. Hosseinian, and M. Ghashang
RESULTS AND DISCUSSION
First, we optimized the amount of silica-supported perchloric acid as
catalyst in the reaction of benzaldehyde, acetophenone, acetyl chloride,
and acetonitrile (Table 1). The amount of silica-supported perchloric acid
was 5 mol%.
Thus, we continued preparation of b-amido ketones in an optimum
model experiment: aldehydes (1 equiv), enolizable ketone (1 equiv), acetyl
chloride (0.5 mL), acetonitrile [reactant as well as solvent (2 mL)], or
benzonitrile (2 mL) in the presence of silica-supported perchloric acid
(5 mol%) (Scheme 1, Table 2).
As shown in Table 2, aromatic aldehydes and acetophenone deriva-
tives with both electron-withdrawing and electron-donating substituents
afforded the corresponding b-amido ketones without the formation of
any side products, in high to excellent yields at reflux conditions
(Table 2, entries 1–26). Phenolic –OH groups under the present reaction
conditions were converted to acetate (–OAc) groups (Table 2, entries 17,
18, and 21).
Under the optimized reaction conditions, by using benzonitrile in
place of acetonitrile, aldehydes were transformed to their corresponding
b-benzamido ketones in high yield (Table 2, entries 2, 5, 7, and 9).
We also studied the multicomponent reaction of aromatic aldehydes,
other enolizable ketones (methyl acetoacetate, ethyl acetoacetate, and
propiophenone), and acetonitrile in the presence of acetyl chloride and
HClO4-SiO2 (5 mol%) as catalyst under reflux conditions (Scheme 2).
In all cases, mixtures of syn and anti diastereomers were obtained,
while the diastereoselectivity depended upon the nature of the reactants
(Scheme 2, Table 3). The amount of these syn and anti products was
Table 1. Optimization the amount of silica-supported perchloric acid as catalyst
for preparation of N-(3-oxo-1,3-diphenylpropyl) acetamide under reflux
conditions
Entry
HClO4-SiO2 (mol%)
Time (h)
Yield (%)a
1
2
3
4
5
6
10
5
2.5
1
0.6
—
2
91
89
72
60
45
—
2.5
4.5
7
8.5
12
aIsolated products.

b-Amido Carbonyl Compounds
3769
Table 2. Preparation of b-amido ketones from aldehydes and enolizable ketones
in the presence of aceyl chloride, nitrile, and HClO-SiO2 under reflux conditions
Time Yield
(h) (%)a Mp (ꢁC) (lit.mp)[ref]
Entry
b-Amido ketone(s)
1
2
3
4
5
6
7
8
9
X ¼ H, Y ¼ H, R ¼ Me
2.5
2.0
2.0
2.5
2.5
3.0
4.0
3.5
3.5
89 102–104 (103–105)[12]
90 153–155 (153–154)[22]
89 129–131 (130)[10]
X ¼ H, Y ¼ H, R ¼ Ph
X ¼ H, Y ¼ OMe, R ¼ Me
X ¼ 4-Cl, Y ¼ H, R ¼ Me
X ¼ 4-Cl, Y ¼ H, R ¼ Ph
X ¼ 4-NO2, Y ¼ H, R ¼ Me
X ¼ 4-NO2, Y ¼ H, R ¼ Ph
X ¼ 3-NO2, Y ¼ H, R ¼ Me
X ¼ 3-NO2, Y ¼ H, R ¼ Ph
94 149–151 (149–150)[11]
89 179–181 (180–182)[22]
82 141–144 (153)[22]
78 143–145 (142–144)[22]
82 135–137 (139–140)[11]
79 192–194 (194–195)[11]
10
2.0
91 120–121 (120–121)[22]
11
12
13
14
15
16
X ¼ 4-Cl, Y ¼ Cl, R ¼ Me
X ¼ 4-F, Y ¼ Cl, R ¼ Me
2.5
2.0
1.5
1.5
1.5
91 141–143 (143–145)[13]
87 108–110 (108–110)[14]
90 119–121 (121–123)[14]
90 109–111 (110–112)[11]
93 117–119 (ꢂ)
X ¼ H, Y ¼ Me, R ¼ Me
X ¼ 4-OMe, Y ¼ H, R ¼ Me
X ¼ 2,3-Dimethoxy, Y ¼ H, R ¼ Me
X ¼ 2,3-Dimethoxy, Y ¼ Me, R ¼ Me 1.5
90 108–111 (108–111)24
17
18
1.2
92 129–132 (129–132)24
1.0
89 89–93 (ꢂ)
19
20
21
22
23
24
25
26
X ¼ 2,5-Dimethoxy, Y ¼ H, R ¼ Me
X ¼ 4-Me, Y ¼ H, R ¼ Me
X ¼ 4-OAc, Y ¼ H, R ¼ Me
X¼3-NO2, Y¼Me, R¼Me
X ¼ 4-Me, Y ¼ Me, R ¼ Me
X ¼ H, Y ¼ NO2, R ¼ Me
2.0
2.0
1.0
3.5
2.0
2.0
2.0
2.0
90 153–156 (ꢂ)
89 10–112 (112)[11]
85 120–122 (ꢂ)
87 94–97 (94–97)[24]
91 103–105 (103–105)[24]
93 74–76 (74–76)[12]
90 80–83 (83–85)[12]
94 116–118 (116–119)[13]
X ¼ 4-Me, Y ¼ NO2, R ¼ Me
X ¼ 4-Cl, Y ¼ NO2, R ¼ Me
aYields refer to the pure isolated products. All known products have been reported pre-
viously in the literature and were characterized by comparison of IR and NMR spectra with
authentic samples.[6–26]

3770
H. R. Shaterian, A. Hosseinian, and M. Ghashang
Scheme 2. Diastereoselective preparation of b-acetamido ketones=esters by using
HClO-SiO2 as catalyst.
determined by 1H NMR spectra; the coupling constant between H-2 and
H-3 is 6–9 Hz for an anti isomer and 2–5 Hz for a syn isomer.[6–8,23]
As shown in Table 3, the anti diastereomer was the major product.
Methyl acetoacetate and ethyl acetoacetate afforded the corresponding
b-acetamido ketoesters in good yields with high diastereoselectivity.
CONCLUSION
In summary, we have demonstrated a new and important catalytic activ-
ity of silica-supported perchloric acid as an inexpensive, commercially
Table 3. Diastereoselective preparation of b-acetamido ketones=esters from the
reaction of enolizable ketones=esters with aryl aldehydes, acetyl chloride, and
acetonitrile (reactant as well as solvent) using HClO-SiO2 as catalyst under reflux
conditions
Productsb
Time Yield Anti Syn
(%)a (%)
Entry
b-acetamido ketones=esters
(h)
(%)
1
2
3
4
5
6
7
8
9
10
R1 ¼ Me, R2 ¼ CO2 Me, X ¼ H
R1 ¼ Me, R2 ¼ CO2 Me, X ¼ 4-Cl
R1 ¼ Me, R2 ¼ CO2 Me, X ¼ 2,4-Dichloro
R1 ¼ Me, R2 ¼ CO2 Me, X ¼ 4-Me
R1 ¼ Me, R2 ¼ CO2 Me, X ¼ 2-NO2
R1 ¼ Me, R2 ¼ CO2 Et, X ¼ H
R1 ¼ Me, R2 ¼ CO2 Et, X ¼ 4-Cl
R1 ¼ Ph, R2 ¼ Me, X ¼ H
2.5
2.5
2.5
2.5
2.5
3.0
3.0
3.5
3.5
3.5
89
93
90
92
86
91
92
85
91
88
68
70
77
73
82
76
72
57
65
60
32
30
23
27
18
24
28
43
35
40
R1 ¼ Ph, R2 ¼ Me, X ¼ Cl
R1 ¼ Ph, R2 ¼ Me, X ¼ 2,4-Dichloro
aYields are reported after aqueous workup.
bRatio obtained from 1H NMR of the crude reaction mixture. All syn and anti diastereo-
mers have been reported previously in the literature, thus we compared 1H NMR spectra
with authentic samples.[6–8,23]

b-Amido Carbonyl Compounds
3771
available, and noncorrosive catalyst for the synthesis of b-amido keto-
nes=esters in high to excellent yields. The simple experimental procedure
combined with the easy workup are the strong features of the presented
method.
EXPERIMENTAL
All reagents were purchased from Merck and Aldrich and used without
further purification. All yields refer to isolated products after purifica-
tion. Silica-supported perchloric acid was prepared according to the
reported procedure.[29] Products were characterized by comparison with
1
authentic samples and by spectroscopic data (IR, H NMR, 13C NMR
spectra). The NMR spectra were recorded on a Bruker Avance DEX
500- and 300-MHz instrument. The spectra were measured in CDCl3
(and DMSO-d6) relative to TMS (0.00 ppm). Elemental analyses for C,
H, and N were performed using a Heraeus CHN–O–Rapid analyzer.
IR spectra were recorded on a Jasco Fourier transform infrared spectro-
scopy (FT-IR) 460 Plus spectrophotometer. Mass spectra were recorded
on a Agilent Technologies 5973 network mass selective detector (MSD)
operating at an ionization potential of 70 eV. Melting points were deter-
mined in open capillaries with a Buchi 510. Thin-layer chromatography
(TLC) was performed on silica-gel PolyGram SIL G=UV 254 plates.
Typical Experimental Procedure for the One-Pot Preparation of
N-(3-Oxo-1,3-diphenylpropyl) Acetamide (Table 2, Entry 1)
A solution of the benzaldehyde (1 mmol), acetophenone (1 mmol), acetyl
chloride (0.5 mL), and acetonitrile in the presence of silica-supported
perchloric acid (0.1 g, 5 mol%) was heated at 80 ꢁC under reflux condi-
tions. The reaction mixture was stirred for the appropriate time (Table 2).
The progress of the reaction was followed by TLC. After completion of
the reaction, the reaction mixture was filtered, and the heterogeneous cat-
alyst was separated. Then, the residue solution was poured into 50 mL of
ice water. The solid was separated and dissolved in dichloromethane
(5 mL). Silica gel (2 g) was added to the solution. Evaporation of the sol-
vent afforded a presorbed material, which was purified by column chro-
matography [petroleum ether (60–80 ꢁC)=ethyl acetate (8=2)]. Solvent
was evaporated under reduced pressure to give the desired pure N-(1,3-
diphenyl-3-oxo-propyl) acetamide in 89% yield. White crystals (Table 2,
1
entry 1): H NMR (300 MHz, CDCl3): d ¼ 2.03 (s, 3H), 3.45 (dd, J ¼ 6.0
and 16.9 Hz, 1H), 3.77 (dd, J ¼ 5.2 and 16.9 Hz, 1H), 5.58 (dd, J ¼ 5.6 and

3772
H. R. Shaterian, A. Hosseinian, and M. Ghashang
13.1 Hz, 1H), 6.90 (d, J ¼ 6.3 Hz, 1H), 7.24–7.60 (m, 8H), 7.91 (d,
J ¼ 7.5 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3): d ¼ 23.5, 43.3, 50.0,
126.6, 127.5, 128.2, 128.7, 128.8, 133.6, 136.7, 141.6, 169.6, 199.3 ppm;
IR (KBr, cmꢂ1): 3286, 3091, 1693, 1650, 1556, 1273, 1066, 753, 691.
The desired pure products were characterized by comparison of their
physical data with those of known b-amido carbonyl compound.[6–25]
The Spectral Data of Some Representative b-Amido Ketones/Esters
N-[1-(2,3-Dimethoxyphenyl)-3-oxo-3-phenylpropyl] Acetamide
(Table 2, Entry 15)
1H NMR (500MHz, CDCl3): d ¼ 1.99 (s, 3H), 3.40 (dd, J ¼ 6.0 and 15.7Hz,
1H), 3.55 (dd, J ¼ 6.6 and 15.7 Hz, 1H), 3.85 (s, 3H), 3.97 (s, 3H), 5.73 (dd,
J ¼ 6.4 and 14.3 Hz, 1H), 6.85 (m, 3H), 6.98 (t, J ¼ 8.0 Hz, 1H), 7.43
(t, J ¼ 7.7 Hz, 2H), 7.54 (t, J ¼ 7.4 Hz, 1H), 7.95 (d, J ¼ 7.6 Hz, 2H) ppm;
13C NMR (125MHz, CDCl3): d ¼ 23.4, 43.7, 47.1, 55.7, 60.7, 111.7,
119.5, 124.1, 128.3, 128.6, 133.4, 134.5, 136.5, 146.2, 152.6, 169.2,
198.8 ppm; IR (KBr, cmꢂ1): 3257, 3069, 2937, 1685, 1639, 1560, 1480,
1449, 1372, 1282, 1220, 1084, 1052, 1003, 756, 690; mass [m=z (%)]:
327.2 (Mþ, 10.30), 284.3 (100), 237.2 (14.91), 208.2 (21.80), 180.2
(20.96), 166.2 (73.63), 105.2 (59.40), 77.2 (31.39), 51.2 (5.36), 43.2 (1.63).
Found: C, 69.55; H, 6.40; N, 4.35. C19H21NO4 requires C, 69.71; H, 6.47;
N, 4.28%.
N-[1-(2,3-Dimethoxyphenyl)-3-oxo-3-(4-methylphenyl)propyl]
Acetamide (Table 2, Entry 16)
1H NMR (500 MHz, CDCl3): d ¼ 1.99 (s, 3H), 2.38 (s, 3H), 3.42 (dd,
J ¼ 6.4 and 15.6 Hz, 1H), 3.51 (dd, J ¼ 6.2 and 15.6 Hz, 1H), 3.72 (s,
3H), 3.84 (s, 3H), 5.68 (dd, J ¼ 6.4 and 14.8 Hz, 1H), 6.72 (dd, J ¼ 2.8
and 8.8 Hz, 1H), 6.78 (d, J ¼ 8.8 Hz, 1H), 6.87–6.86 (m, 2H), 7.22 (d,
J ¼ 7.9 Hz, 2H), 7.82 (d, J ¼ 8.0 Hz, 2H) ppm; 13C NMR (125 MHz,
CDCl3): d ¼ 21.6, 23.4, 42.9, 47.9, 55.7, 55.8, 111.7, 112.7, 114.9, 128.3,
129.3, 129.7, 134.3, 144.0, 150.7, 153.6, 169.1, 198.2 ppm; IR (KBr,
cmꢂ1): 3301, 3081, 2941, 1686, 1651, 1610, 1552, 1503, 1466, 1372,
1284, 1225, 1047, 807, 714; Mass [m=z (%)]: 341.2 (Mþ, 19), 299.2 (21),
298.2 (100), 251.2 (23), 208.1 (20), 180.2 (30), 166.1 (70), 151.1 (15),
136.1 (13), 119.1 (65), 105.1 (14), 91.2 (27), 77.2 (12), 43.2 (20). Found:
C, 70.32; H, 6.71; N, 4.07. C20H23NO4 requires C, 70.36; H, 6.79; N,
4.10%.

b-Amido Carbonyl Compounds
3773
N-[1-(4-Acethoxy-2-methoxyphenyl)-3-oxo-3-(4-methylphenyl)propyl]
Acetamide (Table 2, Entry 18)
1H NMR (500 MHz, CDCl3): d ¼ 1.98 (s, 3H), 2.27 (s, 3H), 2.39 (s, 3H),
3.38 (dd, J ¼ 5.7 and 16.6 Hz, 1H), 3.65 (dd, J ¼ 5.0 and 16.7 Hz, 1H),
3.77 (s, 3H), 5.51 (d, J ¼ 6.2 Hz, 1H), 6.82 (d, J ¼ 7.7 Hz, 1H), 6.87 (d,
J ¼ 8.1 Hz, 1H), 6.93 (d, J ¼ 8.1 Hz, 1H), 6.96 (s, 1H), 7.23 (d, J ¼ 7.5 Hz,
2H), 7.79 (d, J ¼ 7.4 Hz, 2H) ppm; 13C NMR (125 MHz, CDCl3):
d ¼ 20.6, 21.6, 23.3, 43.0, 49.9,55.9, 111.5, 118.4, 122.7, 128.2, 129.3,
134.1, 140.1, 144.4, 151.0, 169.0, 169.5, 191.0, 198.0 ppm; IR (KBr,
cmꢂ1): 3261, 3252, 3076, 2946, 1768, 1679, 1649, 1608, 1547, 1512,
1466, 1422, 1372, 1265, 1200, 1126, 1035, 1013, 845, 789, 674, 603; mass
[m=z (%)]: 369.3 (Mþ, 6.84), 326.2 (24.66), 268.2 (8.89), 208.1 (11.55),
206.1 (12.59), 194.1 (13.90), 173.1 (22.11), 171.1 (62.91), 153.2 (21.96),
152.2 (100), 151.2 (71.54), 119.2 (41.58), 109.2 (9.12), 91.2 (19.81), 77.2
(7.10), 65.2 (9.95), 51.2 (8.80), 43.2 (35.97). Found: C, 68.19; H, 6.12;
N, 3.73. C21H23NO5 requires C, 68.28; H, 6.28; N, 3.79%.
N-[1-(2,5-Dimethoxyphenyl)-3-oxo-3-phenylpropyl] Acetamide
(Table 2, Entry 19)
1H NMR (500 MHz, CDCl3): d ¼ 2.00 (s, 3H), 3.46 (dd, J ¼ 6.6 and
15.8 Hz, 1H), 3.56 (dd, J ¼ 6.1 and 15.7 Hz, 1H), 3.73 (s, 3H), 3.85 (s,
3H), 5.69 (dd, J ¼ 2.3 and 6.5 Hz, 1H), 6.73 (dd, J ¼ 3.0 and 8.9 Hz,
1H), 6.79 (d, J ¼ 8.9 Hz, 1H), 6.83 (d, J ¼ 8.4 Hz, 1H), 6.87 (d, J ¼ 3.0 Hz,
1H), 7.43 (t, J ¼ 7.6 Hz, 2H), 7.55 (t, J ¼ 7.3 Hz, 1H), 7.92 (d, J ¼ 7.4 Hz,
2H) ppm; 13C NMR (125 MHz, CDCl3): d ¼ 23.5, 43.0, 48.0, 55.7, 55.8,
111.7, 112.8, 115.0, 128.2, 128.6, 129.5, 133.2, 136.8, 150.8, 153.6,
169.0, 198.6 ppm; IR (KBr, cmꢂ1): 3296, 3086, 1689, 1649, 1558, 1505,
1774, 1296, 1226, 1047, 807, 754; mass [m=z (%)]: 327.2 (Mþ, 17), 285.2
(19), 284.2 (100), 237.1 (16), 208.1 (17), 180.2 (27), 166.1 (62), 151.1
(13), 136.1 (12), 105.1 (45), 77.2 (23), 43.2 (14). Found: C, 69.56; H,
6.39; N, 4.34. C19H21NO4 requires C, 69.71; H, 6.47; N, 4.28%.
N-[1-(4-Acethoxyphenyl)-3-oxo-3-phenylpropyl] Acetamide
(Table 2, Entry 21)
1H NMR (500 MHz, CDCl3): d ¼ 2.01 (s, 3H), 2.28 (s, 3H), 3.44 (dd,
J ¼ 6.1 and 17.0 Hz, 1H), 3.73 (dd, J ¼ 5.2 and 17.0 Hz, 1H), 5.56 (dd,
J ¼ 5.8 and 13.6 Hz, 1H), 6.73 (d, J ¼ 8.0 Hz, 1H), 7.03 (d, J ¼ 8.5 Hz,
2H), 7.35 (d, J ¼ 8.5 Hz, 2H), 7.46 (t, J ¼ 7.7 Hz, 2H), 7.58 (t, J ¼ 7.4 Hz,

3774
H. R. Shaterian, A. Hosseinian, and M. Ghashang
1H), 7.91 (d, J ¼ 7.7 Hz, 2H) ppm; 13C NMR (125 MHz, DMSO-d6):
d ¼ 20.8, 22.6, 44.5, 48.4, 121.5, 127.7, 128.0, 128.7, 133.2, 136.5, 140.5,
149.2, 168.3, 169.2, 197.0 ppm; IR (KBr, cmꢂ1): 3262, 3085, 2928, 1762,
1699, 1652, 1651, 1509, 1448, 1411, 1365, 1294, 1216, 1200, 911, 759,
691; Mass [m=z (%)]: 352.2 (Mþ, 8), 326.2 (2), 282.2 (100), 240.2 (41),
242.2 (19), 178.2 (20), 167.1 (26), 149.1 (62), 136.2 (37), 122.2 (55),
105.2 (86), 77.2 (40), 57.2 (16), 43.2 (41). Found: C, 70.08; H, 5.78; N,
4.24. C19H19NO4 requires C, 70.14; H, 5.89; N, 4.31%.
N-[1-(3-Nitrophenyl)-3-oxo-3-(4-methylphenyl)propyl] Acetamide
(Table 2, Entry 22)
1H NMR (300 MHz, DMSO-d6): d ¼ 1.97 (s, 3H), 2.36 (s, 3H), 3.43 (dd,
J ¼ 5.5 and 17.4 Hz, 1H), 3.61 (dd, J ¼ 8.3 and 17.4 Hz, 1H), 5.45 (dd,
J ¼ 7.6 and 13.4 Hz, 1H), 7.31 (d, J ¼ 7.9 Hz, 2H), 7.62 (t, J ¼ 7.9 Hz,
1H), 7.86–7.75 (m, 3H), 8.08 (d, J ¼ 8.0 Hz, 1H), 8.22 (s, 1H), 8.49 (d,
J ¼ 7.5 Hz, 1H) ppm; 13C NMR (75 MHz, DMSO-d6): d ¼ 20.7, 22.6,
44.0, 48.5, 121.3, 121.8, 128.1, 129.1, 129.7, 133.7, 133.9, 143.7, 145.6,
147.8, 168.6, 196.1 ppm; IR (KBr, cmꢂ1): 3301, 3069, 1680, 1645, 1606,
1531, 1352, 1202, 1180, 810, 741, 696; mass [m=z (%)]: 326.3 (Mþ, 0.8),
283.2 (20), 267.2 (12), 189.2 (24), 190.2 (17), 165.2 (38), 151.2 (33),
134.2 (13), 119.2 (100), 105.2 (12), 91.2 (43), 77.2 (6), 65.2 (14), 43.2
(26). Found: C, 66.23; H, 5.56; N, 8.51. C18H18N2O4 requires C, 66.25;
H, 5.56; N, 8.58%.
(R)-Methyl 2-((S)-Acetamido(phenyl)methyl)-3-oxobutanoate (Table 3,
Entry 1)
Mixture of diastereomers; data for the major isomer: 1H NMR
(500 MHz, CDCl3): d ¼ 1.97 (s, 3H), 2.11 (s, 3H), 3.71 (s, 3H), 4.07 (d,
J ¼ 5.5 Hz, 1H), 5.72 (dd, J ¼ 5.5 and 9.0 Hz, 1H), 6.91 (d, J ¼ 8.1 Hz,
1H), 7.22–7.30 (m, 5H).
(R)-Ethyl 2-((S)-Acetamido(4-chlorophenyl)methyl)-3-oxobutanoate
(Table 3, Entry 7)
Mixture of diastereomers; data for the major isomer: 1H NMR
(500 MHz, CDCl3): d ¼ 1.25 (t, J ¼ 6.9, 3H), 2.03 (s, 3H), 2.16 (s, 3H),
4.01 (d, J ¼ 5.7 Hz, 1H), 4.12 (q, J ¼ 7.1, 2H), 5.70 (dd, J ¼ 5.7 and
8.9 Hz, 1H), 6.95 (d, J ¼ 8.9 Hz, 1H), 7.20–7.35 (m, 4H).

b-Amido Carbonyl Compounds
3775
N-((1S,2R)-1-(4-Chlorophenyl)-2-methyl-3-oxo-3-phenylpropyl)
acetamide (Table 3, Entry 9)
Mixture of diastereomers; data for the major isomer: 1H NMR
(500 MHz, CDCl3): d ¼ 1.34 (d, J ¼ 7.1 Hz, 3H), 2.08 (s, 3H), 4.00–4.07
(m, 1H), 5.33 (dd, J ¼ 4.2 and 8.6 Hz, 1H), 7.19 (s, 4H), 7.38–7.43 (m,
2H), 7.53 (t, J ¼ 7.1 Hz, 1H), 7.65 (brd, J ¼ 8.5 Hz, 1H), 7.76 (d,
J ¼ 7.9 Hz, 2H).
ACKNOWLEDGMENTS
We are thankful to the Sistan and Baluchestan University Research
Council for partial support of this work.
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