Three-component one-pot reaction for the synthesis of β-amide ketones

Article abstract of DOI:10.2478/s11696-013-0313-0

β-amide ketones were synthesised by a three-component one-pot reaction of phenylacetylene, aldehydes, and amides in anhydrous acetonitrile containing trifluoroacetic acid and acetic acid in the presence of AlCl₃ catalyst. The title compound structures were identified by ¹H NMR, ¹³C NMR, MS, and elemental analysis.

Full text of DOI:10.2478/s11696-013-0313-0

Chemical Papers 67 (5) 532–537 (2013)
DOI: 10.2478/s11696-013-0313-0
ORIGINAL PAPER
Three-component one-pot reaction for the synthesis
of β-amide ketones
b
aYan-Ping Luo*, Qiong Chen
aKey Laboratory of Protection and Development Utilisation of Tropical Crop Germplasm Resources, Hainan University,
Ministry of Education, HaiKou 570228, China
bKey Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry,
Central China Normal University, Wuhan 430079, China
Received 18 August 2012; Revised 5 November 2012; Accepted 7 November 2012
β-amide ketones were synthesised by a three-component one-pot reaction of phenylacetylene,
aldehydes, and amides in anhydrous acetonitrile containing trifluoroacetic acid and acetic acid in
the presence of AlCl3 catalyst. The title compound structures were identified by 1H NMR, 13C
NMR, MS, and elemental analysis.
c
ꢀ 2013 Institute of Chemistry, Slovak Academy of Sciences
Keywords: β-amide ketones, one-pot reaction, synthesis
Introduction
In these reactions, only —C(O)NH2 was involved
in cyclisation. Due to the properties of amide situ-
ated between those of amine and urea, it was pre-
dicted that, by replacing urea with amides in the
three-component reactions for the synthesis of oxazine
derivatives, the diversity of the synthesis of oxazine
heterocycles could be increased. However, when the
aldehydes, alkynes, and amides were subjected to the
conditions detailed in the literature (Huang, 2005),
open-ring group IV products (β-amide ketones) were
obtained smoothly; instead of the anticipated group
III compounds (Fig. 1). Hence, this study describes
the discovery of a new method to synthesise β-amide
ketones from aldehydes, phenylacetylene, and amides.
β-Amide ketones exhibit excellent pharmacological
activity (Kikuchi et al., 2005; Lee et al., 2010). Many
methods are used to synthesise β-amide ketones, par-
ticularly by multi-component reactions (MCR), such
as the Dakin–West reaction (Dakin & West, 1928),
and four-component reactions of aldehydes, ketones,
acyl chlorides, and acetonitrile in the presence of
Brønsted acid or Lewis acid catalysts (Bahulayan et
al., 2003; Khodaei et al., 2005; Pandey et al., 2005;
Bhat et al., 2005; Rafiee et al., 2006). The development
of new methods for the synthesis of β-amide ketones is
of great significance for synthetic and medicinal chem-
istry.
In the literature, the three-component reactions
of aldehydes, alkynes and amines provide access to
propargylamines, whilst the three-component one-pot
reactions involving aldehydes, alkynes, and urea or
thiourea yield heterocyclic compounds (Sun et al.,
2012; Samai, 2010 et al.; Du et al., 2008; Ramu et
al., 2007). For example, Pan’s group had synthesised
2-amino-1,3-oxazines III (R2 = NH2) by using multi-
component reactions (Fig. 1) (Huang et al., 2005).
Experimental
All chemical reagents were commercially available
and treated by standard methods prior to use. Sol-
vents were dried routinely and redistilled. 1H NMR
spectra were recorded on a Mercury-Plus 400 spec-
trometer (Varian, USA) in CDCl3 with TMS as the
internal reference. MS spectra were determined us-
ing a Finnigan Trace MS organic mass spectrometer
*Corresponding author, e-mail: yanpluo@yahoo.com.cn

Y. P. Luo, Q. Chen/Chemical Papers 67 (5) 532–537 (2013)
533
Fig. 1. Different products of three-component reactions.
(Finnigan, USA), and signals were given in m/z. Ele-
mentary analyses were performed on a Vario EL III el-
ementary analysis instrument (Elementar, Germany).
Melting points were measured using a Buchi B-545
melting point apparatus (Buchi, Switzerland) and are
uncorrected.
for 209 variables and 2952 contributing reflections.
Maximum shift/error = 0.000, max/min residual elec-
tron density = 0.212/–0.192 e A−3. Hydrogen atoms
˚
were observed and refined with a fixed value of their
isotropic displacement parameter.
Crystallographic data reported in this manuscript
have been deposited with Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC-
869792.
General procedure for synthesis of title com-
pounds (IVa–IVq)
A solution of benzaldehyde (1 mmol), phenylacety-
lene 0.11g (1.1 mmol), and acetamide or benzamide
(1.5 mmol) in anhydrous acetonitrile (6 mL) contain-
ing AcOH (1 mL), and trifluoroacetic acid (3 mL) in
the presence of 5 mole % AlCl3 catalyst was refluxed
until the reaction was completed, as indicated by TLC
analysis. The reaction mixture was diluted with wa-
ter; the resulting solid was collected by filtration and
directly subjected to silica gel column chromatogra-
phy using petroleum ether–ethyl acetate (ϕr = 5 : 1)
as eluent to give the title compounds IVa–IVq.
Results and discussion
In accordance with the conditions detailed in the
literature (Huang et al., 2005), 4-chlorobenzaldehyde
reacted with phenylacetylene and acetamide to yield
18 % β-amide ketones, and no other products were iso-
lated. Various other solvent systems, such as toluene,
THF, 1,4-dioxane, DMF, CH3CN, and AcOH were em-
ployed; however, according to thin layer chromato-
graphic (TLC) analysis, the reactions did not pro-
X-ray diffraction
Table 1. Effect of Lewis acids on reaction; solvent system used:
CH3CN–AcOH–TFA (ϕr = 6 : 1 : 3)
Orthorhombic blocks of IVc (0.20 mm × 0.20 mm
× 0.10 mm) were mounted on a quartz fibre with
protection oil. Cell dimensions and intensities were
measured at (297
2) K on a Bruker SMART
CCD area-detector diffractometer (Bruker, Germany)
with graphite-monochromated MoKα radiation (λ =
0.71073 A); θmax = 26.00◦; 24483 measured reflec-
˚
tions; 2952 independent reflections (Rint = 0.0352)
of which 2471 had |Fo| > 2|Fo|. Data were corrected
for Lorentz and polarisation effects and for absorp-
tion (Tmin = 0.9804; Tmax = 0.9901). The struc-
ture was solved by direct methods using SHELXS-97
software (Sheldrick, 1997); all other calculations were
performed with Bruker SAINT System and Bruker
SMART programs, Bruker (2003). Full-matrix least-
squares refinement based on F2 using the weight of
1/[σ2(F2o) + (0.0668P)2 + 0.7878P] gave the final val-
ues of R = 0.0490, ωR = 0.1300, and GOF(F) = 1.067
Entry
Lewis acid
Isolated yield/%
1
2
3
4
5
6
7
CuBr2
ZnCl2
NiCl2
BaCl2
InCl3
AlCl3
TiCl4
38
50
34
43
41
56
55

534
Y. P. Luo, Q. Chen/Chemical Papers 67 (5) 532–537 (2013)
Table 2. Characterisation data of compounds IVa–IVq
wi(calc.)/%
wi(found)/%
Yield
M.p.
Entry
Compound
R1
R2
C
H
N
%
33
26
48
59
56
49
50
56
31
38
29
37
41
47
68
25
36
◦C
1
2
IVa
IVb
IVc
IVd
IVe
IVf
C4H9
C5H11
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Ph
72.84
72.73
73.53
73.64
71.56
71.70
67.66
67.59
67.66
67.59
58.97
58.97
58.97
58.80
58.97
58.84
76.84
76.67
76.84
76.71
77.26
77.18
72.71
72.63
65.38
65.22
65.91
65.74
71.63
71.49
80.22
80.07
80.44
80.36
8.56
8.67
8.87
8.80
5.65
5.52
5.34
5.36
5.34
5.63
4.66
4.78
4.66
4.73
4.66
4.49
6.81
6.59
6.81
6.63
7.17
7.23
6.44
6.29
5.16
5.31
5.53
5.49
5.11
4.98
5.81
5.92
6.16
6.28
5.66
5.59
5.36
5.34
4.91
4.88
4.64
4.55
4.64
4.58
4.05
4.18
4.05
4.11
4.05
4.12
4.98
5.03
4.98
5.05
4.74
4.65
4.71
4.57
8.97
8.76
5.12
5.22
4.18
4.03
4.25
4.34
4.08
3.99
101–103
86–88
3
2-F-C6H4
105–107
140–142
154–155
165–166
114–116
166–168
108–110
115–117
103–105
116–118
161–163
154–156
201–203
160–161
177–178
4
2-Cl-C6H4
4-Cl-C6H4
2-Br-C6H4
3-Br-C6H4
4-Br-C6H4
3-CH3-C6H4
4-CH3-C6H4
4-C2H5-C6H4
3-OCH3-C6H4
4-NO2-C6H4
2-Thienyl
5
6
7
IVg
IVh
IVi
8
9
10
11
12
13
14
15
16
17
IVj
IVk
IVl
IVm
IVn
IVo
IVp
IVq
4-Oxochromen-3-yl
C6H5
4-CH3-C6H4
Ph
ceed, while in trifluoroacetic acid (TFA) alone, evi-
dence of reactions was observed by TLC analysis af-
ter 48 h, indicating that TFA played an important
role in the three-component reactions. Next, we ex-
perimented with different ratios of THF–AcOH, and
found that when the TFA–AcOH volume ratio was
3 : 1 the yield was increased to 49 %.
In the literature (Bahulayan et al., 2003; Khodaei
et al., 2005; Pandey et al., 2005; Bhat et al., 2005;
Rafiee et al., 2006), where aldehydes reacted with
ketones, acyl chlorides and acetonitrile to yield β-
acetamido ketones, Lewis acid catalyst played an im-
portant role, hence we considered using a Lewis acid
catalyst to improve the reaction yields. Various Lewis
acid catalysts were screened (Table 1). In the presence
of anhydrous aluminum chloride as the Lewis acid cat-
alyst, the reaction yield was 56 % (Entry 6), but the
yields were lower when other catalysts were used (En-
tries 1–5, 7).
Various aldehydes, amides, and phenylacetylene
with the AlCl3 catalyst were investigated. The com-
position and properties of the corresponding products
are summarised in Tables 2 and 3. For aliphatic alde-
hydes, the yields were lower (Entries 1–2); for aromatic
aldehydes, the substituents on the aromatic ring af-
fected the yields. When the substituents were electron-

Y. P. Luo, Q. Chen/Chemical Papers 67 (5) 532–537 (2013)
535
Table 3. Spectral data of compounds IVa–IVq; spectra are given in the supplementary data, Figs. S1–S17
Compound
Spectral data
IVa
1H NMR (CDCl3) δ: 7.46–7.97 (m, 5H, ArH), 6.33 (s, 1H, NH), 4.34 (d, J = 4.5 Hz, 1H, CH), 3.35 (dd, J = 17.1 Hz,
J = 4.3 Hz, 1H, CH), 3.15 (dd, J = 17.1 Hz, J = 5.5 Hz, 1H, CH), 1.98 (s, 3H, CH3), 1.73–1.49 (m, 2H, CH2), 1.30
(d, J = 3.2 Hz, 4H, 2 × CH2), 0.87 (t, J = 6.7 Hz, 3H, CH3)
13C NMR (CDCl3) δ: 199.3, 169.6, 136.6, 133.3, 128.6, 127.9, 46.5, 41.9, 33.5, 28.5, 23.3, 22.3, 13.9
MS, m/z (Ir/%): 248 ([M – 1]+, 55), 105 (100), 91 (34), 77 (94)
IVb
1H NMR (CDCl3) δ: 7.97–7.46 (m, 5H, ArH), 6.27 (s, 1H, NH), 4.34 (s, 1H, CH), 3.34 (dd, J = 17.0 Hz, J = 3.9 Hz,
1H, CH), 3.14 (dd, J = 17.0 Hz, J = 5.3 Hz, 1H, CH), 1.98 (s, 3H, CH3), 1.76–1.52 (m, 2H, CH2), 1.37–1.27 (m,
6H, 3 × CH2), 0.86 (t, J = 6.3 Hz, 3H, CH3)
13C NMR (CDCl3) δ: 199.3, 169.6, 136.6, 133.3, 128.5, 127.9, 46.5, 41.9, 33.7, 31.4, 26.0, 23.3, 22.4, 13.9
MS, m/z (Ir/%): 262 ([M + 1]+, 4), 105 (47), 77 (32), 43 (100)
IVc
IVd
IVe
IVf
1H NMR (CDCl3) δ: 7.91–6.96 (m, 9H, ArH), 6.87 (m, 1H, NH), 5.54 (dd, J = 13.5 Hz, J = 5.7 Hz, 1H, CH), 3.75
(dd, J = 17.0 Hz, J = 5.0 Hz, 1H, CH), 3.42 (dd, J = 17.0 Hz, J = 6.0 Hz, 1H, CH), 2.03 (s, 3H, CH3)
13C NMR (CDCl3) δ: 198.3, 169.5, 163.1, 160.7, 136.4, 133.6, 128.7, 128.2, 128.1, 128.0, 115.5, 115.3, 49.3, 43.1, 23.3
MS, m/z (Ir/%): 285 ([M]+, 3), 242 (100), 179 (8), 138 (72), 124 (63), 105 (70)
1H NMR (CDCl3) δ: 7.90–7.15 (m, 9H, ArH), 7.06 (s, 1H, NH), 5.82 (d, J = 6.2 Hz, 1H, CH), 3.76 (dd, J = 16.7 Hz,
J = 5.7 Hz, 1H, CH), 3.46 (dd, J = 16.7 Hz, J = 5.4 Hz, 1H, CH), 2.04 (s, 3H, CH3)
13C NMR (CDCl3) δ: 198.7, 169.5, 138.0, 136.3, 133.6, 132.4, 129.8, 128.7, 128.2, 128.1, 126.9, 114.2, 47.7, 41.4, 23.3
MS, m/z (Ir/%): 302 ([M]+, 1), 266 (100), 207 (13), 154 (52), 145 (84), 105 (69)
1H NMR (CDCl3) δ: 7.90–7.25 (m, 9H, ArH), 7.07 (s, 1H, NH), 5.54 (dt, J = 8.0 Hz, J = 5.5 Hz, 1H, CH), 3.76
(dd, J = 17.2 Hz, J = 5.1 Hz, 1H, CH), 3.42 (dd, J = 17.2 Hz, J = 5.8 Hz, 1H, CH), 2.05 (s, 3H, CH3)
13C NMR (CDCl3) δ: 198.3, 169.6, 139.5, 136.3, 133.7, 133.1, 128.7, 128.6, 128.0, 127.9, 49.2, 42.9, 23.4
MS, m/z (Ir/%): 302 ([M]+, 26), 258 (100), 241 (21), 153 (78), 137 (65), 105 (81), 77 (88)
1H NMR (CDCl3) δ: 7.91–7.10 (m, 9H, ArH), 7.08 (s, 1H, NH), 5.77 (d, J = 5.7 Hz, 1H, CH), 3.78 (dd, J = 16.6 Hz,
J = 5.7 Hz, 1H, CH), 3.44 (dd, J = 16.6 Hz, J = 5.2 Hz, 1H, CH), 2.04 (s, 3H, CH3)
13C NMR (CDCl3) δ: 198.8, 169.32, 139.7, 136.4, 133.6, 133.2, 128.9, 128.7, 128.4, 128.2, 127.5, 122.7, 50.1, 41.4,
23.4
MS, m/z (Ir/%): 346 ([M]+, 1), 266 (29), 184 (22), 146 (94), 105 (100), 77 (68)
IVg
IVh
IVi
1H NMR (CDCl3) δ: 7.91–7.15 (m, 9H, ArH), 6.96 (s, 1H, NH), 5.54 (s, 1H, CH), 3.73 (dd, 1H, J = 16.6 Hz, J =
5.7 Hz, CH), 3.43 (dd, 1H, J = 16.6 Hz, J = 5.2 Hz, CH), 2.04 (s, 3H, CH3)
13C NMR (CDCl3) δ: 197.8, 169.7, 143.5, 136.2, 133.6, 130.3, 130.1, 129.4, 128.6, 128.0, 125.2, 122.6, 49.1, 43.1, 23.2
MS, m/z (Ir/%): 346 ([M]+, 4), 302 (52), 105 (88), 77 (100)
1H NMR (CDCl3) δ: 7.91–7.21 (m, 9H, ArH), 6.87 (s, 1H, NH), 5.52 (d, J = 7.5 Hz, 1H, CH), 3.75 (dd, J = 17.2 Hz,
J = 4.8 Hz, 1H, CH), 3.42 (dd, J = 17.2 Hz, J = 5.8 Hz, 1H, CH), 2.04 (s, 3H, CH3)
13C NMR (CDCl3) δ: 198.3, 169.6, 140.0, 136.2, 133.7, 131.6, 128.7, 128.2, 128.0, 121.1, 49.1, 42.8, 23.4
MS, m/z (Ir/%): 347 ([M + 1]+, 6), 345 ([M – 1]+, 10), 304 (100), 302 (76), 105 (44)
1H NMR (CDCl3) δ: 7.90–6.84 (m, 9H, ArH), 6.79 (s, 1H, NH), 5.51 (d, J = 6.7 Hz, 1H, CH), 3.69 (dd, J = 16.7 Hz,
J = 5.4 Hz, 1H, CH), 3.40 (dd, J = 16.7 Hz, J = 6.1 Hz, 1H, CH), 2.30 (s, 3H, CH3), 1.97 (s, 3H, CH3)
13C NMR (CDCl3) δ: 198.3, 169.4, 140.7, 138.2, 136.5, 133.3, 128.6, 128.4, 128.1, 128.0, 127.2, 123.3, 49.9, 43.3,
23.3, 21.4
MS, m/z (Ir/%): 281 ([M]+, 44), 238 (100), 207 (30), 134 (68), 120 (69), 105 (80)
IVj
1H NMR (CDCl3) δ: 7.93–7.19 (m, 9H, ArH), 6.77 (s, 1H, NH), 5.53 (d, J = 6.7 Hz, 1H, CH), 3.76 (dd, J = 16.9 Hz,
J = 3.0 Hz, 1H, CH), 3.43 (dd, J = 16.8 Hz, J = 6.1 Hz, 1H, CH), 2.30 (s, 3H, CH3), 2.02 (s, 3H, CH3)
13C NMR (CDCl3) δ: 197.9, 169.5, 138.0, 136.7, 136.3, 133.1, 129.0, 128.4, 127.9, 126.3, 49.4, 43.5, 23.0, 20.8
MS, m/z (Ir/%): 281 ([M]+, 11), 238 (100)
IVk
1H NMR (CDCl3) δ: 7.97–7.12 (m, 9H, ArH), 6.78 (d, J = 7.2 Hz, 1H, NH), 5.53 (d, J = 7.3 Hz, 1H, CH), 3.71
(dd, J = 16.7 Hz, J = 5.3 Hz, 1H, CH), 3.41 (dd, J = 16.8 Hz, J = 6.2 Hz, 1H, CH), 2.58 (q, J = 7.5 Hz, 2H, CH2),
1.97 (s, 3H, CH3), 1.18 (t, J = 7.6 Hz, 3H, CH3)
13C NMR (CDCl3) δ: 198.4, 169.4, 143.3, 138.2, 136.5, 133.3, 128.6, 128.0, 126.4, 125.8, 49.7, 43.3, 28.3, 23.3, 15.4
MS, m/z (Ir/%): 296 ([M + 1]+, 9), 252 (54), 148 (36), 134 (44), 105 (100), 77 (73)
IVl
1H NMR (CDCl3) δ: 7.91–6.75 (m, 10H, ArH, NH), 5.53 (d, J = 7.8 Hz, 1H, CH), 3.77 (s, 3H, OCH3), 3.76–3.67
(m, 1H, CH), 3.42 (dd, J = 16.9 Hz, J = 6.0 Hz, 1H, CH), 2.03 (s, 3H, CH3)
13C NMR (CDCl3) δ: 198.3, 169.5, 159.6, 142.6, 136.5, 133.4, 129.6, 128.6, 128.0, 118.6, 112.6, 112.4, 55.1, 49.8,
43.2, 23.2
MS, m/z (Ir/%): 297 ([M]+, 50), 254 (100), 150 (60), 136 (59), 104 (93), 77 (76)
IVm
IVn
1H NMR (CDCl3) δ: 8.18–7.46 (m, 9H, ArH), 7.04 (s, 1H, NH), 5.67 (s, 1H, CH), 3.83 (d, J = 15.5 Hz, 1H, CH),
3.51 (d, J = 15.8 Hz, 1H, CH), 2.09 (s, 3H, CH3)
13C NMR (CDCl3) δ: 197.7, 169.8, 148.7, 146.8, 135.9, 133.9, 128.8, 127.9, 127.3, 123.7, 49.0, 42.6, 23.3
MS, m/z (Ir/%): 312 ([M]+, 11), 298 (51), 283 (18), 269 (100), 252 (78), 105 (94)
1H NMR (CDCl3) δ: 7.94–6.78 (m, 9H, ArH, NH), 5.96–5.72 (m, 1H, CH), 3.78 (dd, J = 17.3 Hz, J = 4.5 Hz, 1H,
CH), 3.48 (dd, J = 17.3 Hz, J = 5.8 Hz, 1H, CH), 1.99 (s, 3H, CH3)
13C NMR (CDCl3) δ: 198.1, 169.3, 144.7, 136.4, 133.5, 128.7, 128.0, 126.7, 124.4, 77.3, 77.0, 76.7, 45.8, 43.4, 23.2
MS, m/z (Ir/%): 274 ([M + 1]+, 2), 230 (17), 105 (100), 77 (83)

536
Y. P. Luo, Q. Chen/Chemical Papers 67 (5) 532–537 (2013)
Table 3. continued
Compound
Spectral data
IVo
1H NMR (CDCl3) δ: 8.23 (s, 1H, CH), 8.18–7.40 (m, 10H, ArH, NH), 5.56 (d, J = 4.3 Hz, 1H, CH), 3.83 (dd, J =
17.6 Hz, J = 9.1 Hz, 1H, CH), 3.55 (dd, J = 17.6 Hz, J = 4.3 Hz, 1H, CH), 2.03 (s, 3H, CH3)
13C NMR (CDCl3) δ: 197.5, 178.0, 169.3, 156.0, 155.3, 136.2, 133.9, 133.3, 128.5, 127.9, 125.2, 123.9, 121.7, 118.2,
45.0, 41.7, 23.3
MS, m/z (Ir/%): 335 ([M]+, 6), 292 (78), 215 (34), 188 (50), 174 (100), 105 (67)
IVp
IVq
1H NMR (CDCl3) δ: 7.93–7.23 (m, 16H, ArH, NH), 5.77 (d, J = 7.9 Hz, 1H, CH), 3.89 (dd, J = 16.9 Hz, J = 4.9 Hz,
1H, CH), 3.54 (dd, J = 16.9 Hz, J = 5.9 Hz, 1H, CH)
MS, m/z (Ir/%): 329 ([M]+, 1), 224 (100), 105 (94)
1H NMR (CDCl3) δ: 7.93–7.10 (m, 10H, ArH, NH), 5.73–5.70 (m, 1H, CH), 3.85 (dd, J = 16.9 Hz, J = 4.9 Hz, 1H,
CH), 3.49 (dd, J = 16.9 Hz, J = 5.9 Hz, 1H, CH), 2.29 (s, 3H, CH3)
13C NMR (CDCl3) δ: 199.0, 166.6, 137.8, 137.0, 136.5, 134.1, 133.5, 131.5, 129.3, 128.6, 128.5, 128.1, 127.0, 126.3,
50.0, 42.9, 21.0
MS, m/z (Ir/%): 343 ([M]+, 26), 237 (100), 207 (47), 117 (88), 104 (96), 77 (99)
withdrawing groups, the yields were higher (Entries
3–8, 13–15); when the substituents were electron-
donating groups, the yields were lower (Entries 9–
12). For amides, the yields were higher for acetamide
than for benzamide (Entries 16–17). The single-crystal
structure of IVc was determined by X-ray crystallog-
raphy as shown in Fig. 2.
A proposed reaction mechanism of three-com-
ponent one-pot reaction is shown in Fig. 3. Aldehyde
and amide reacted and the intermediate V was formed
under the Lewis acid catalyst condition, followed by
removal of a molecule of water from the intermediateV
to generate intermediateVI (Akiyama et al., 2004;
Dondoni et al., 2004; Kappe, 1997). Subsequently, the
resulting intermediate VI underwent a hetero Diels–
Alder cycloaddition with phenylacetylene, producing
intermediate VII (Barluenga et al., 1995). Finally, a
highly unstable intermediate VII was deprotonated to
the open ring to form β-amido ketones IV upon the
Fig. 2. Crystal structure of compound IVc.
addition of water.
Fig. 3. Possible mechanism of three-component one-pot reaction.

Y. P. Luo, Q. Chen/Chemical Papers 67 (5) 532–537 (2013)
537
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We successfully developed a novel three-component
reaction for the synthesis of β-amide ketones in AlCl3
catalysis.
Acknowledgements. The authors wish to express their grat-
itude for the financial support afforded by the National Nat-
ural Science Foundation of China (Grant Nos. 21172091,
21162007), the Key Projects in the National Science & Tech-
nology Pillar Programme during the 12th Five-Year Plan Pe-
riod (Grant No. 2011BAE06B05) and the National Key Fun-
damental Research Programme (973 Programme) under grant
No. 2010CB126103.
Supplementary data
Supplementary data associated with this article
(Three-component one-pot reaction for the synthesis
of β-amide ketones) can be found in the online version
of this paper (DOI: 10.2478/s11696-013-0313-0).
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