Studying catalytic activity of ternary mixed-metal Keggin H7SiV3W9O40 as a versatile acid catalyst for the synthesis of β-acetamido ketones

Article abstract of DOI:10.1002/aoc.5350

One-pot four-component condensation of an aromatic aldehyde with an enolisable ketone and acetyl chloride is investigated in the presence of H₇SiV₃W₉O₄₀ in acetonitrile. The prepared catalyst was characterized by standard techniques such as XRD, SEM, and FT-IR to verify the Keggin structure of nanocatalyst. Furthermore, findings revealed a very good catalytic activity for the applied vanadium substituted heteropolyacid in this acid catalyzed condensation reaction. A series of Keggin Si and V-substituted heteropolyacids were compared for the synthesis of β-acetamido-β-(4-chlorophenyl)propiophenone, which showed a better catalytic activity for H₇SiV₃W₉O₄₀ and H₄SiW₁₂O₄₀ than the lacunary and mixed metal Keggin H₄SiW₉Mo₃O₄₀ and H₅SiW₉Mo₂VO₄₀. In addition, effect of the nitrilating agent was also demonstrated in this catalytic system and findings show less proficiency for PhCN compared to acetonitrile. Moreover, propiophenone as an α-substituted enolisable ketone was reacted with some aromatic aldehydes and the anti isomer is detected as the major diastereomer. Therefore, H₇SiV₃W₉O₄₀ can be introduced as a new effective, inexpensive, and eco-friendly catalyst for the introduced four-component condensation reaction.

Full text of DOI:10.1002/aoc.5350

Received: 23 August 2019
DOI: 10.1002/aoc.5350
Revised: 12 October 2019
Accepted: 15 October 2019
F U L L P A P E R
Studying catalytic activity of ternary mixed‐metal Keggin
H7SiV3W9O40 as a versatile acid catalyst for the synthesis of
β‐acetamido ketones
Reza Tayebee1
| Akbar Pejhan2
1 Department of Chemistry, School of
Sciences, Hakim Sabzevari University,
Sabzevar 96179‐76487, Iran
2 Cellular and Molecular Research Center,
Sabzevar University of Medical, Sciences,
Sabzevar, Iran
One‐pot four‐component condensation of an aromatic aldehyde with an
enolisable ketone and acetyl chloride is investigated in the presence of
H7SiV3W9O40 in acetonitrile. The prepared catalyst was characterized by stan-
dard techniques such as XRD, SEM, and FT‐IR to verify the Keggin structure of
nanocatalyst. Furthermore, findings revealed a very good catalytic activity for
the applied vanadium substituted heteropolyacid in this acid catalyzed conden-
sation reaction. A series of Keggin Si and V‐substituted heteropolyacids were
compared for the synthesis of β‐acetamido‐β‐(4‐chlorophenyl)propiophenone,
which showed a better catalytic activity for H7SiV3W9O40 and H4SiW12O40 than
the lacunary and mixed metal Keggin H4SiW9Mo3O40 and H5SiW9Mo2VO40.
In addition, effect of the nitrilating agent was also demonstrated in this
catalytic system and findings show less proficiency for PhCN compared to ace-
tonitrile. Moreover, propiophenone as an α‐substituted enolisable ketone was
reacted with some aromatic aldehydes and the anti isomer is detected as the
major diastereomer. Therefore, H7SiV3W9O40 can be introduced as a new effec-
tive, inexpensive, and eco‐friendly catalyst for the introduced four‐component
condensation reaction.
Correspondence
Reza Tayebee, Department of Chemistry,
School of Sciences, Hakim Sabzevari
University, Sabzevar, 96179‐76487, Iran.
Email: rtayebee@hsu.ac.ir
Akbar Pejhan, Cellular and Molecular
Research Center, Sabzevar University of
Medical Sciences, Sabzevar, Iran.
Email: pejhana@medsab.ac.ir
Funding information
Hakim Sabzevari University; Research
Councils of Sabzevar University of Medi-
cal Sciences
KEYWORDS
Acetamido ketone, four‐component, H7SiV3W9O40, Heteropolyacid, Keggin
1 | INTRODUCTION
applications like pigments, membranes, and sorbents are
extruded from their versatile nature.[6] However, the most
Heteropolyoxometalates comprise a wide and well‐defined
class of early transitionmetal clusters which are con-
structed from polyoxoanions generated from early
transition metals such as tungsten, molybdenum, and
vanadium.[1] Although, the chemistry of polyoxometalates
is not even new,[2] however, remains as a great and emerg-
ing key area in the progress and development of sophisti-
cated molecules.[3] These magic compounds are known
with a great variety of structures, applications, properties,
and have been considered as intermediate structures
between molecules and oxide solids.[4,5] Therefore, various
important application of these materials remains in the
area of catalysis.[7]
Mixed‐addenda
vanadium
substituted
polyoxometalates with the general formula of
H3 + nSiM12‐nVnO40 (M = Mo and W; n = 1–6) are well
known, as an important sub‐group of Keggin
heteropolyoxometalates, which their catalytic activities
remained to be explored. In these compounds one or
three addenda units are generally removed from the
Keggin‐type polyoxometalate to generate the so‐called
n‐
lacunary anions of XM11O39 and A‐XM9O34n‐. These
Appl Organometal Chem. 2019;e5350.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5350

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TAYEBEE AND PEJHAN
incomplete species quickly react with an extensive variety
of metal ions to refill the vacant sites.[8–11] A tungsten‐
based Keggin structure H4SiW12O40 is a stable compound
which can be prepared in high yield with excellent purity
from relatively low‐cost precursors. This compound can
be subsequently modified to replace three corner‐sharing
tungsten atoms with vanadium (Scheme 1). The resulting
compound H7SiV3W9O40 is stable over a wide range of
temperatures and pHs.
analysis was performed on a BRUKER D8 ADVANCE
X‐ray diffractometer using a Cu tube operated at 40 kV
and 40 mA in the 2θ range of 4–40°. Electron microscopy
was performed on a Phillips XL‐30 scanning electron
1
microscope (SEM). HNMR spectra were recorded on a
BrukerAVANCE 200‐MHz instrument. All catalysts were
prepared and characterized according to literature proce-
dures.[27–30]
β‐Acetamido ketones are versatile mediators in the
synthesis of many important biological and pharmacolog-
ical stuffs such as neopolyoxins, nucleoside antibiotics,
nikkomycins, and various antibiotic drugs.[12–15] Aside
Dakin–West reaction,[16] one‐pot multi‐component
coupling of an aromatic aldehyde, an enolizable ketone,
and acetyl chloride in the presence of acetonitrile is
the simplest method for the preparation of β‐acetamido
ketones.[17] A number of catalysts such as mont-
morillonite K10 clay,[18] silica sulfuric acid,[19] and
heteropolyacids[20] have been used to prepare these
important organic compounds.
In continuation of our efforts on using
heteropolyoxometalates in multi‐component condensa-
tion reactions,[21–26] we developed the applicability of
strong super‐acidic vanadium (V) substituted Keggin‐type
heteropolyacid, H7SiV3W9O40, as a nanocatalyst for the
efficient and facile synthesis of β‐acetamido ketones by
one‐pot condensation of an aromatic aldehyde, an
enolizable ketone, and acetyl chloride in acetonitrile
(Scheme 1).
2.2 | Synthesis of ternary mixed metal
H7SiV3W9O40
A classic well‐known method was performed for the
preparation of H7SiV3W9O40 from sodium vanadate pre-
cursor.[20,29] Sodium vanadate (1.9 g; 15.5 mmol) was
dissolved in 300 ml of water. Na10[α‐SiW9O34].18H2O
(145 g; 52 mmol) was mixed with the stirred solution
and 185 ml of 6 M sulfuric acid was subsequently added
to this solution under stirring for 45 min. pH was
adjusted between 6–7 by solid potassium carbonate.
After addition of solid potassium chloride (80 g), an
orange potassium salt was precipitated. Further purifica-
tion was achieved via re‐crystallized in water. Calcd
(Found): K, 9.34 (9.12); V, 5.16 (5.28); Si, 0.96 (1.12);
W, 56.48 (56.73); H2O, 6.14 (6.32). FT‐IR (cm−1): 1003
(w), 960 (s), 902 (vs), 805 (vs), 741 (vs). Then, the potas-
sium salt (15 g; 5 mmol) was dissolved in 65 ml of water
in a separatory funnel. Thereafter, diethyl ether was
added, followed by slow addition of 100 mL concen-
trated HCl. The heavy phase was collected and diethyl
ether was evaporated under vacuum. The obtained solid
was dissolved in a little amount of water. Finally, the
heteropolyacid nanoparticles were slowly crystallized at
room temperature.
2 | EXPERIMENTAL
2.1 | Materials and methods
All reagents and starting materials were commercially
available and used as received. β‐Acetamido ketones were
characterized by comparison of their physical and spec-
tral data with known reported samples in the literature.
Progress of the reactions was monitored by TLC by using
Silica gel 60 (70–230 mesh). Infrared spectra were
recorded (KBr pellets) on an 8700 Shimadzu Fourier
Transform spectrophotometer. X‐ray powder diffraction
2.3 | General procedure for the
preparation of β‐acetamido ketones
Aromatic aldehyde (1 mmol), acetyl chloride (2 mmol),
and acetophenone (1 mmol) were mixed in 4 ml of
acetonitrle in the presence of the desired heteropolyacid
(2.5 mol%) at 80 °C. Progress of the reaction was moni-
tored by TLC. After completion of the reaction, the reac-
tion mixture was filtered and the corresponding solid
crude product was washed with ice‐water and petroleum
ether. The pure product could be obtained by re‐
crystallization from ethanol‐water mixture. All products
1
were characterized by FT‐IR and H NMR spectroscopy
and their melting points were compared with those
SCHEME
1
General formulation for the preparation of
substituted β‐acetamido ketones.
reported in the literature.

TAYEBEE AND PEJHAN
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2.4 | Spectral data for some selected
β‐acetamido ketones
2.4.7 | [(1S, 2R)‐2‐Methyl‐1‐ (2‐nitrophe-
nyl) 3‐oxo‐3‐diphenylpropyl] acetamide
1H NMR (CDCl3 + DMSO (d6), 200 MHz): δ 0.87 (d, 3H),
1.56 (s, 3H), 3.99–4.14 (m, 1H), 5.67 (dd, 1H, ‐CHCO),
7.31–7.82 (m, 7H), 7.98–8.14 (d, 1H), 8.44 (d, 1H). FT‐IR
(KBr, cm−1): 3263, 3058, 1978, 1646, 1528, 1454, 1355,
1295, 971, 711.
2.4.1 | β‐Acetamido‐β‐(phenyl)
propiophenone
1H NMR (CDCl3, 200 MHz): δ 2.02 (s, 3H), 3.34 (dd, 1H),
3.66 (dd, 1H), 5.61 (m, 1H), 7.32 (s, 1H), 7.57 (d,
J = 9.1 Hz, 5H), 7.76 (d, J = 9.1 Hz, 5H). FT‐IR (KBr,
cm−1): 3253, 3046, 1666, 1624, 1576, 1288, 1083, 878, 820.
2.4.8 | N‐1‐[2‐Methyl‐3‐oxo‐1‐phenylbutyl]
acetamide
2.4.2 | β‐Acetamido‐β‐(4‐chlorophenyl)
propiophenone
1
M. p. 125–128 °C, H NMR (CDCl3, 200 MHz): δ 7.23–
1H NMR (CDCl3, 200 MHz): δ 2.00 (s, 3H), 3.41 (dd, 1H),
3.71 (dd, 1H), 5.55 (m, 1H), 7.02 (m, 5H), 7.44 (m, 3H),
7.84 (d, 2H). FT‐IR (KBr, cm−1): 3265, 3083, 1678, 1641,
1556, 1244, 1104, 887, 824, 683.
7.31 (m, 5H), 7.12 (d, J = 7.8 Hz, 1H), 5.17 (dd, J = 5.8
and 9.1 Hz, 1H), 3.13 (dd, J = 6.9 and 14.2 Hz, 1H),
2.07 (d, J = 10.2 Hz, 6H), 1.15 (d, J = 7.1 Hz, 3H). 13C
NMR (75 MHz, CDCl3): δ 213.3, 169.9, 140.5, 128.4,
127.3, 126.2, 55.4, 51.2, 29.6, 23.3, 15.3. FT‐IR (KBr,
cm−1): 3291, 1717, 1653, 1554, 1377, 1305, 1132, 758.
2.4.3 | β‐Acetamido‐β‐(3‐nitrophenyl)
propiophenone
2.4.9 | N‐1‐[2‐Methyl‐1‐(4‐methylphenyl)‐
3‐oxobutyl]acetamide
1H NMR (CDCl3, 200 MHz): δ 1.87 (s, 3H), 3.11 (d, 1H),
3.52 (d, 1H), 5.50 (s, 1H), 7.32 (m, 5H), 7.80 (d, 2H),
8.00 (d, 2H). FT‐IR (KBr, cm−1): 3290, 3023, 2245, 1681,
1649, 1544, 1440, 1216, 987, 752, 680, 546.
1
M. p. 132–134 °C, H NMR (CDCl3, 200 MHz): δ 7.11 (s,
4H), 6.92 (d, J = 8.3 Hz, 1H), 5.12 (dd, J = 5.8 and
9.1 Hz,1H), 3.09 (dd, J = 6.6 and 13.1 Hz,1H), 2.32 (s,
3H), 2.17–1.94 (m, 6H), 1.15–1.08 (m, 3H). 13C NMR
(75 MHz, CDCl3): δ 183.8, 169.5, 137.9, 137.1, 129.4,
126.8, 126.2, 55.2, 51.3, 29.6, 23.3, 21.0, 15.2. FT‐IR
(KBr, cm−1): 3295, 2987, 1703, 1654, 1556, 1452, 1424,
1375, 1304, 1135, 725, 546.
2.4.4 | β‐Acetamido‐β‐(2‐hydroxyphenyl)
propiophenone
1H NMR (CDCl3, 200 MHz): δ 2.00 (s, 3H), 3.49 (d, 1H),
3.68 (d, 1H), 6.88 (s, 1H), 7.50–7.70 (m, 5H), 7.95 (d,
2H), 8.23 (d, 2H). FT‐IR (KBr, cm−1): 3286, 2843, 1679,
1639, 1595, 1502, 1446, 1341, 1288, 851, 748, 681, 587.
2.4.10 | N‐1‐[2‐Oxocyclohexyl]‐1‐
phenylmethyl]acetamide
2.4.5 | β‐Acetamido‐β‐(4‐nitrophenyl)
propiophenone
1
M.p. 219–222 °C, H NMR (CDCl3, 200 MHz): δ 8.50 (d,
J = 8.3 Hz, 1H), 7.32–7.14 (m, 5H), 6.24 (s, 1H), 5.73 (d,
J = 8.25 Hz, 1H), 2.71 (s, 1H), 2.59 (d, J = 5.4 Hz, 2H),
2.41 (d, J = 5.3 Hz, 2H), 2.25 (m, 4H), 2.1 (s, 3H). FT‐IR
(KBr, cm−1): 3273, 1694, 1636, 1549, 1367, 1232, 694.
1H NMR (CDCl3, 200 MHz): δ 2.01 (s, 3H, CH3), 3.38 (dd,
1H), 3.85 (dd, 1H), 5.60 (m, 1H), 7.20–7.55 (m,7H), 7.87
(d, 2H), 9.19 (br, 1H, NH). FT‐IR (KBr, cm−1): 3285,
1683, 1648, 1522, 1350, 1300, 752.
2.4.6 | β‐Acetamido‐β‐(4‐methoxyphenyl)
propiophenone
2.4.11 | N‐1‐[(4‐Nitrophenyl)‐1‐[2‐
oxocyclohexyl]methyl]acetamide
1H NMR (CDCl3, 200 MHz): δ 2.09 (s, 3H), 2.48 (s, 3H),
3.51 (dd, 1H), 3.84 (dd, 1H), 5.59 (m, 1H), 7.39 (s, 1H),
7.54 (m, 5H), 7.97 (m, 4H). FT‐IR (KBr, cm−1): 3263,
3054, 1672, 1633, 1581, 1291, 1081, 878, 819.
M.p. 193–195 °C, 1H NMR (CDCl3, 200 MHz): δ 8.31–8.23
(m, 2H), 7.75–7.60 (m, 2H), 5.42 (s, 1H), 2.21–2.23 (m,
8H), 1.80 (s, 3H). FT‐IR (KBr, cm−1): 3380, 2943, 1656,
1610, 1525, 1341, 1224, 855, 692.

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TAYEBEE AND PEJHAN
2H), 7.41–7.57 (m, 3H), 7.87–7.91 (d, 2H). 13C NMR
(75 MHz, CDCl3): δ 14.1, 20.8, 23.1, 45.5, 54.8, 126.7,
128.2, 128.6, 129.2, 133.0, 136.4, 136.9, 137.4, 169.7,
201.8. FT‐IR (KBr, cm−1): 3242, 3055, 1679, 1637, 1552,
1374, 1291, 973, 712. Anal. Calcd for C19H21O2N: C,
77.25; H, 7.16; N, 4.74; Found: C, 77.22; H, 6.96; N, 4.43.
2.4.12 | N‐1‐[2‐Methyl‐3‐oxo‐1,3‐
diphenylpropyl)]acetamide
1
M. p. 141–143 °C, H NMR (DMSO, 200 MHz): δ 8.41 (d,
J = 7 Hz, 1H), 8.1 (s, 1H), 7.75–7.55 (m, 4H), 7.41–7.33
(m, 5H), 5.11 (s, 1H), 1.82 (s, 1H), 1.68 (s, 3H), 0.80 (s,
3H). FT‐IR (KBr, cm−1): 2977, 1671, 1657, 1546, 1457,
1369, 975, 707, 609.
anti‐Isomer: white crystals, m.p. 165 °C, 1H NMR
(CDCl3, 200 MHz): δ 1.36–1.39 (d, J = 7.1 Hz,3H), 2.11
(s, 3H), 4.0–4.2 (m, 1H), 5.35–5.42 (dd, J = 3.8 Hz,1H),
7.13–7.50 (m, 9H), 7.73–7.79 (d, J = 7.4 Hz, 2H).
syn‐Isomer: white crystals. M.p. 123 °C. 1H NMR
(CDCl3, 200 MHz): δ 1.19–1.22 (d, J = 6.9 Hz, 3H), 2.02
(s, 3H), 4.02–4.12 (m, 1H), 5.46–5.52 (t, J = 7.7 Hz, 1H),
5.95–6.04 (d, J = 5.9 Hz, 1H), 7.21–7.62 (m, 8H), 7.92–
8.03 (d, J = 7.2 Hz, 2H).
3 | RESULTS AND DISCUSSION
3.1 | Characterization of Keggin
H7SiV3W9O40 nanoparticles
FT‐IR spectroscopy is a powerful method to investigate
structure of heteropoly anions and can detect the hydro-
gen bond system. The four characteristic vibration modes
of Keggin heteropolyacids appear at 1100–800 cm−1
which can be used for their identification.[31] Figure 1
shows the FT‐IR spectrum of H7SiV3W9O40 with three
bands at 965, 914 and 785 cm−1, which are ascribed to
νas(M–Od), νas (Si–Oa) and νas(M‐Oc‐M) modes, respec-
tively. The νas(M–Ob–M) bands are too weak and over-
lapped with νas(M‐Oc‐M). These characteristic peaks
indicated that this vanadium‐substituted heteropoly acid
possesses a Keggin structure.[32] The vibrations around
1620 and 3400 cm−1can be attributed to the bending
vibration of H–O–H and stretching vibration of O‐H
bonds, respectively.[32]
2.4.13 | N‐1‐[2‐Methyl‐1‐(2‐nitrophenyl)‐3‐
oxo‐3‐phenylpropyl]acetamide
1
M. p. 123–125 °C, H NMR (DMSO, 200 MHz): δ 8.54–
8.64 (m, 1H), 8.12–7.97 (m, 1H), 7.83–7.34 (m, 8H), 5.67
(dd, J = 7.7 and 13.4 Hz, 1H), 4.11–3.94 (m, 1H), 1.52
(s, 3H), 0.88 (d, J = 7 Hz, 3H). FT‐IR (KBr, cm−1): 3268,
3051, 1972, 1641, 1529, 1454, 1351, 1299, 978, 719.
1
anti‐Isomer: off white crystals, m.p. 135–137 °C, H
NMR (CDCl3, 200 MHz): δ 1.41–1.47 (d, J = 7.1 Hz,
3H), 2.11 (s, 3H), 4.11–4.42 (m, 1H), 5.78–5.84 (dd,
J = 3.6 Hz, 1H), 7.25–7.97 (m, 10H). syn‐Isomer: oily,
1H NMR (CDCl3, 200 MHz): δ 1.22–1.28 (d, 3H), 2.05 (s,
3H), 4.41–4.49 (m, 1H), 5.72–5.79 (t, 1H), 6.64–6.67 (d,
1H), 7.34–7.95 (m, 9H).
To further investigate the structure and phase of
Keggin H7SiV3W9O40 nanoparticles, the powder X‐ray
diffraction (XRD) was measured, as shown in Figure 2.
The XRD pattern confirmed four groups of peaks in the
2.4.14 | N‐[2‐Methyl‐1‐(4‐methyl‐phenyl)‐
3‐oxo‐3‐phenylpropyl]acetamide
anti‐Isomer: white crystals, m.p. 170 °C. 1H NMR (CDCl3,
200 MHz): δ 1.32–1.37 (d, 3H), 2.11 (s, 3H), 2.23 (s, 3H),
4.02–4.12 (m, 1H), 5.31–5.39 (m, 1H), 7.03–7.07 (d, 2H),
7.13–7.17 (d, 2H), 7.33–7.58 (m, 4H), 7.74–7.81 (d, 2H).
13C NMR (75 MHz, CDCl3): δ 16.5, 20.8, 23.3, 44.3, 55.5,
126.4, 128.3, 128.5, 129.1, 133.5, 136.5, 136.7, 137.7,
169.9, 204.7. FT‐IR (KBr, cm−1): 3311, 2989, 1683, 1648,
1543, 1365, 1141, 972, 702. Anal. Calcd for C19H21O2N:
C, 77.25; H, 7.16; N, 4.74; Found: C, 77.22; H, 7.13; N,
4.49.
syn‐Isomer: white crystals, m.p. 124 °C. 1H NMR
(CDCl3, 200 MHz): δ 1.21–1.25 (d, J = 6.97 Hz, 3H),
1.98 (s, 3H), 2.27 (s, 3H), 4.02–4.15 (m, 1H), 5.40–5.48 (t,
J = 7.62 Hz, 1H), 5.94–6.05 (d, J = 7.68 Hz, 1H), 7.05–
7.13 (d, J = 7.82 Hz, 2H), 7.21–7.30 (d, J = 7.96 Hz,
FIGURE
nanoparticles
1
FT‐IR spectrum of Keggin H7SiV3W9O40

TAYEBEE AND PEJHAN
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TABLE 1 Comparing catalytic activity of some heteropolyacids
in the synthesis of β‐acetamido‐β‐(4‐chlorophenyl)propiophenone
Catalyst Time Yield
Heteropolyacid Structure
(mol%) (hr) (%)
H7SiV3W9O40
V substituted Keggin 10
0.5
1
98
75
95
67
H5SiVW9Mo2O40 mixed metal Keggin
10
10
H4SiW12O40
Keggin
0.5
1
H4SiW9Mo3O40 mixed metal lacunary 10
Keggin
H4SiW11MoO40 Mo substituted mixed 10
metal Keggin
0.5
82
4‐chlorobenzaldehyde (1 mmol), acetyl chloride (2 mmol), acetophenone
(1 mmol) in acetonitrle (4 ml) were treated with a desired amount of
heteropolyacid at 80 °C. Progress of the reaction was monitored by TLC.
FIGURE 2 XRD pattern of Keggin H7SiV3W9O40 nanoparticles
heteropolyacids are more effective catalysts than
Mo‐included ones. Moreover, H4SiW12O40 behaved
almost similar to H7SiV3W9O40. Different observed reac-
tivity patterns would be explained considering various
factors which affect Bronsted and Lewis acidity of
heteropolyacids. Strong Bronsted acidity of these pseudo
liquid phase super‐acidic materials originates from good
mobility of the dissociated protons on the surface of crys-
tal structure. These protons include both un‐hydrated
protons localized at the peripheral oxygen atoms and
combined hydrogens with the heteropolyanion.[34–36]
Therefore, silicon as the heteroatom and transition metals
such as vanadium and molybdenum strongly affect crys-
tal structure and mobility of the mentioned protons.
Another important aspect of this study refers to compari-
son of the rarely studied and less effective quaternary
heteropolyacid (H5SiW9Mo2VO40) with the ternary coun-
terparts. In addition, less catalytic activity of
H4SiW9Mo3O40 and H5SiW9Mo2VO40 would be explained
considering coordination of CH3CN to the Lewis acid
sites of Mo containing heteropolyacids, which may
reduce Lewis/Bronstead acidity and, therefore, catalytic
activity of these compounds toward the condensation
reaction.
ranges of 2θ, 7–10°, 16–20°, 25–35°, and 35–40°, which
are in agreement with the characteristic diffractions of
Keggin structure.[33] This result indicated that the
nanomaterial had a high crystallinity. Size and morphol-
ogy of nanoparticles were further studied with FESEM.
Figure 3 describes that the Keggin H7SiV3W9O40 nano-
particles were semi‐spherical in shape in the nano range
with a uniform size and good dispersibility.
3.2 | Catalytic tests
In the first attempt we tried to compare reactivity of a
range of mixed metal substituted Keggin and lacunary
heteropolyacids. Table 1 compares reactivity of some
Keggin‐type Si and V‐substituted single or mixed metal
heteropolyacids in the four component condensation of
4‐chlorobenzaldehyde, acetophenone, and acetyl chloride
in
CH3CN.
Obviously,
tungsten
substituted
Then, effect of the presence of catalyst was investi-
gated in the four‐component coupling of benzaldehyde,
acetophenone, and acetyl chloride in acetonitrile. Find-
ings revealed that Keggin H7SiV3W9O40 nanoparticles
behaved as an active catalyst, due to its bi‐functional
nature originating from their strong acidic protons and
presence of vanadium (V) transition metal ion, as effec-
tive electron acceptor resource.[37] The four‐component
coupling
condensation
of
4‐chlorobenzaldehyde,
acetophenone, and acetyl chloride was performed in ace-
tonitrile in the absence of catalyst. Findings revealed that
the reaction could not be productive, and no reaction was
FIGURE 3 FESEM image and size distribution of Keggin
H7SiV3W9O40 nanoparticles

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TAYEBEE AND PEJHAN
TABLE 4 Effect of some solvents on the progress of the conden-
sation reaction
happened even after prolonged reaction time (5 hr), indi-
cating that this is a heteropolyacid catalyzed reaction
(Table 2). According to the reactivity pattern observed
for various heteropolyoxometalates in Table 1,
H7SiV3W9O40 was selected as the best catalyst and effi-
ciency of the present method was evaluated considering
some influencing parameters such as catalyst amount
and temperature. Table 2 describes effect of different
mol% of H7SiV3W9O40. The best result was achieved with
10 mol% of this catalyst. 98% of product was attained with
4‐chlorobenzaldehyde after 0.5 hr and higher mol% of
catalyst led to a decreased yield.
Conditions
Time (hr)
Temperature (°C)
Yield (%)
Solvent‐free
CH2Cl2
H2O
0.5
1
80
98
<15
30
reflux
reflux
reflux
1
MeOH
1
55
Reaction condition is described below Table 1. 10 mol% H7SiV3W9O40 was
used in all cases.
Table 3 shows effect of temperature on the reaction
progress in the presence of 2.5 mol% H7SiV3W9O40. As
is anticipated, yield% was enhanced with the reaction
temperature in the range of 25–80 °C. Therefore, the best
temperature was adjusted under refluxing of acetonitril
for all subsequent reactions.
Then, effect of various solvents was compared with the
solvent‐free case (Table 4). It was found that the reaction
was almost completed after 30 min in the absence of sol-
vent and indeed CH3CN acted as both solvent and primary
reagent in the four component condensation reaction.
Effect of the nitrilating agent was also demonstrated in
this catalytic system. Therefore, the two nitrilatings
agents of CH3CN and PhCN were compared in the pres-
ence of 2.5 mol% of H7SiV3W9O40 (Scheme 2). Obviously,
acetonitrile was more efficient than PhCN and provided
SCHEME 2 Effect of nitrilating agent on the synthesis of β‐
acetamido‐β‐(4‐chlorophenyl)propiophenone.
76% of β‐acetamido‐β‐(4‐chlorophenyl)propiophenone
after 3 hr; while, phenyl cyanide afforded only 28% yield
after 6 hr.
TABLE 5 Synthesis of β‐acetamido‐β‐(4‐chlorophenyl) ketones
TABLE 2 Synthesis of β‐acetamido‐β‐(4‐chlorophenyl)
propiophenone in the presence of different catalytic amounts of
H7SiV3W9O40 in refluxing acetonitrile
Carbonyl
Time
(h)
Yield
(%)
compound
Product
Catalyst
Catalyst (mol%)
Time (hr)
Yield (%)
0.5
98
27
18
24
‐
‐
0.5
2.5
5
5
‐
53
76
78
98
89
H7SiV3W9O40
H7SiV3W9O40
H7SiV3W9O40
H7SiV3W9O40
H7SiV3W9O40
6
3
2
3
10
15
0.5
0.5
Reaction condition is described below Table 1.
5
TABLE 3 Synthesis of β‐acetamido‐ β‐(4‐chlorophenyl)
propiophenone in acetonitrile at different temperatures
Time
(hr)
Yield
(%)
Temperature (°
C)
Catalyst
5
H7SiV3W9O40 (2.5 mol%)
H7SiV3W9O40 (2.5 mol%)
H7SiV3W9O40 (2.5 mol%)
3
5
6
76
48
33
80
50
25
Reaction condition is described below Table 1.
Reaction condition is described below Table 1.

TAYEBEE AND PEJHAN
7 of 10
In another attempt to compare reactivity of
acetophenone with other carbonyl compounds, acetone,
cyclohexanone, and ethyl methyl ketone were substituted
with the former.[18,20] Interestingly, in agreement with
the literature acetophenone was the best for the conden-
sation with 4‐chlorobenzaldehyde and acetyl chloride in
acetonitrle (Table 5).
Effect of different electron releasing/withdrawing
groups on the phenyl ring of aldehyde moiety was inves-
tigated to explore generality and productivity of
H7SiV3W9O40 and the corresponding results are gathered
in Table 6. Thus, applicability and merit of this protocol
was ascertained by performing a range of aromatic alde-
hydes under optimized conditions. Nearly, in all cases,
aromatic aldehydes with substituents carrying either
electron‐withdrawing or electron‐donating groups
reacted successfully and gave smoothly the expected
products in good to excellent yields. However, in some
cases it seems that aromatic aldehydes bearing electron‐
withdrawing groups reacted faster than those involving
electron‐donating groups.
To demonstrate the versatility of this catalyst, it has
been shown that aromatic aldehydes can react with
propiophenone and other R‐substituted ketones to afford
the β‐acetamido ketones in a diastereoselective manner.
Thus, propiophenone as an α‐substituted enolisable
ketone was treated with some aromatic aldehydes under
the optimum conditions (Table 7). It was found that two
TABLE 7 Reaction of some substituted ketones with some aro-
matic aldehydes
Syn: Yield Time M.P.
Entry β‐acetamido ketone
antia (%)
(h)
(°C)
1
38:62 88
1
140–141
TABLE 6 Synthesis of different β‐acetamido‐β‐(aryl)
propiophenones
2
3
36:64 93
39:61 95
1
151–152
120–122
0.7
Aldehyde
Time (h)
Yield (%)
M.P. (°C)
Ref.
[18]
1.5
65
80–82
4
5
35:65 97
31:69 92
0.5
0.7
[38]
[39]
[40]
1.5
1.5
2
75
87
75
108–109
114–116
129–131
133–134
152–154
6
7
8
9
30:70 84
27:73 87
33:67 81
36:64 65
0.7
2.5
2.5
2
[41]
0.5
85
186–188
[40]
[40]
[40]
126–128
135–137
219–222
0.6
0.5
0.5
90
98
97
103–105
144–146
109–111
[42]
0.6
93
101–103
[41]
[42]
0.5
0.6
98
95
148–150
10
32:68 69
2
193–195
>300
Aromatic aldehyde (1 mmol), acetyl chloride (2 mmol), acetophenone
(1 mmol) in acetonitrle (4 ml) was treated with 10 mol% of H7SiV3W9O40
at 80 °C. Progress of the reaction was monitored by TLC. Yields refer to
the isolated products.
aRatio of syn:anti isomer was defined based on coupling constants of
methine proton with 1H NMR. 10 mol% of H7SiV3W9O40 was used in all
cases. Yields refer to the isolated products.

8 of 10
TAYEBEE AND PEJHAN
TABLE 8 Comparison of the catalytic efficiency of H7SiV3W9O40
with some reported catalysts in the synthesis of β‐acetamido‐ β‐(4‐
chlorophenyl)propiophenone
benzaldehyde derivatives with ethyl methyl ketone and
cyclohexanone was also investigated. These two ketones
were also effective and the anti‐diastereomers were
obtained as the major products (Table 7, entries 7–10).
Table 8 compares catalytic efficacy and superiority of
H7SiV3W9O40 with some reported methodologies by con-
sideration of yield%, reaction parameters, catalyst
amount, and reaction time. For this purpose, reaction of
4‐chlorobenzaldehyde, acetophenone and acetyl chloride
was monitored in acetonitril as a model reaction. Clearly,
H7SiV3W9O40 was among the best catalysts in this series.
Finally, a reaction pathway is disclosed in Scheme 3.
The mechanism would be involved acylation of the aro-
matic aldehyde with acetyl chloride and production of
an α‐chloroacetate as intermediate (I). Then, this inter-
mediate reacts with acetonitrile to produce the corre-
sponding α‐acetoxy amide, which can combine with the
enolate form of acetophenone to give a six‐membered
Catalyst
Mol%
Time (hr)
Yield %
Ref.
H7SiV3W9O40
ZrOCl2.8H2O
Zn (OTf)2
BF3.OEt2
10
15
0.5
12
98
83
60
78
79
This work
[43]
[44]
[44]
[44]
10
30
100
100
30
CuCl2
30
Reaction condition is described below Table 1.
diastereomeric products can be formed in definite propor-
tions, in which the anti isomer was the major product.
Noteworthy, the ratio of syn: anti isomers can be evaluated
from coupling constant of methine proton (CHCO) by
means of 1H NMR. Furthermore, the reaction of some
SCHEME 3 A plausible reaction
pathway for the condensation of aldehyde,
acetophenone, acetyl chloride, and
acetonitrile.

TAYEBEE AND PEJHAN
9 of 10
[6] D. E. Katsoulis, Chem. Rev. 1998, 98, 359.
imidate ester and, thereafter, the amide product. Proton-
ation of aldehyde also can activate the carbony group
for the nucleophillic attack.[20]
[7] M. Misono, CR. Acad. Sci., Ser. IIc: Chim. 2000, 3, 471.
[8] R. Tayebee, M. Fattahi Abdizadeh, N. Erfaninia, A. Amiri, M.
Baghayeri, R. M. Kakhki, B. Maleki, E. Esmaili, Appl. Organomet.
Chem. 2019, n/a, 4959. https://doi.org/10.1002/aoc.4959
4 | CONCLUSIONS
[9] A. Dolbecq, E. Dumas, C. R. Mayer, P. Mialane, Chem. Rev.
2010, 110, 6009.
In conclusion, the present report introduces catalytic effi-
cacy of H7SiV3W9O40 as a new convenient and effective
mediator for the preparation of various β‐acetamido
ketones. The prepared catalyst is characterized by
standard techniques such as XRD, SEM, and FT‐IR to
verify that the Keggin structure of nanocatalyst is
[10] R. Tayebee, M. Jarrahi, RSC Adv. 2015, 5, 21206.
[11] L. C. W. Baker, D. C. Glick, Chem. Rev. 1998, 98, 3.
[12] J. R. Casimir, C. Turetta, L. Ettouati, J. Paris. Tetrahedron Lett.
1995, 36, 4797.
[13] A. G. Godfrey, D. A. Brooks, L. A. Hay, M. Peters, J. R. McCar-
thy, D. Mitchell, J. Org. Chem. 2003, 68, 2623.
formed.
A series of Keggin Si and V‐substituted
[14] U. Dähn, H. Hagenmaier, H. Höhne, W. König, G. Wolf, H.
heteropolyacids are compared and show a better catalytic
activity for H7SiV3W9O40 and H4SiW12O40 than the
lacunary and mixed metal Keggin H4SiW9Mo3O40 and
H5SiW9Mo2VO40. Another important aspect of this study
refers to comparison of the rarely studied and less effec-
tive quaternary heteropolyacid (H5SiW9Mo2VO40) with
the ternary counterparts. Moreover, less proficiency is
attained for PhCN compared to acetonitrile and conden-
sation of propiophenone leads to the anti isomer as the
major diastereomer.
Zähner, Arch. Microbiol. 1976, 107, 143.
[15] A. K. Tiwari, R. M. Kumbhare, S. B. Agawane, A. Z. Ali, K. V.
Kumar, Bioorg. Med. Chem. Lett. 2008, 18, 4130.
[16] H. Dakin, R. A. West, J. Biol. Chem. 1982, 78, 745.
[17] B. Bhatia, M. M. Reddy, J. Iqbal, J. Chem. Soc., Chem. Commun.
1994, n/a, 713.
[18] D. Bahulayan, S. K. Das, J. Iqbal, J. Org. Chem. 2003, 68, 5735.
[19] M. M. Khodaei, A. R. Khosropour, P. A. Fattahpour, Tetrahe-
dron Lett. 2005, 46, 2105.
[20] R. Tayebee, S. Tizabi, Chin. J. Catal. 2012, 33, 923.
[21] R. Tayebee, A. F. Lee, L. Frattini, S. Rostami, Catalysts 2019, 9,
409.
ACKNOWLEDGEMENTS
[22] R. Tayebee, A. Pejhan, H. Ramshini, B. Maleki, N. Erfaninia, Z.
Tabatabaie, E. Esmaeili, Appl. Organomet. Chem. 2018, 32, 3924.
Partial financial support from the Research Councils of
Sabzevar University of Medical Sciences and Hakim
Sabzevari University is greatly appreciated.
[23] R. Tayebee, B. Maleki, J. Iran. Chem. Soc. 2017, 14, 1179.
[24] N. M. Ghohe, R. Tayebee, M. M. Amini, A. Osatiashtiani, M. A.
Isaacs, A. F. Lee, Tetrahedron 2017, 73, 5862.
[25] R. Tayebee, M. Jomei, B. Maleki, M. K. Razi, H. Veisi, M.
CONFLICT OF INTEREST
Bakherad, J. Mol. Liq. 2015, 206, 119.
[26] R. Tayebee, M. Ghadamgahi, Arab. J. Chem. 2017, 10, 757.
[27] G. A. Tsigdinos, C. Hallada, J. Inorg. Chem. 1968, 7, 437.
[28] S. Farhadi, M. Taherimehr, Acta Chim. Slov. 2008, 55, 637.
The authors declare that there is no conflict of interests
regarding the publication of this manuscript.
[29] E. Cadot, R. Thouvenot, A. Teze, G. Herve, Inorg. Chem. 1992,
31, 4128.
ORCID
[30] M. H. Alizadeh, S. P. Harmalker, Y. Jeanin, M. T. Pope, J. Am.
Chem. Soc. 1985, 107, 2662.
Reza Tayebee https://orcid.org/0000-0003-1211-1472
[31] W. L. Zhou, J. Liang, L. Zhao, X. L. Wang, K. Z. Shao, Z. M. Su,
Inorg. Chem. Commun. 2014, 47, 48.
REFERENCES
[32] S. But, S. Lis, J. Alloys Compd. 2008, 451, 384.
[1] M. T. Pope, A. Müller, Introduction to Polyoxometalate Chemis-
try: From Topology via self‐Assembly to Applications, Vol. 1‐6,
Dordrecht: Kluwer Academic Publishers, 2002.
[33] Q. Y. Wu, X. G. Sang, B. Liu, V. G. Ponomareva, Mater. Lett.
2005, 59, 123.
[34] U. Thanganathan, J. Mater. Chem. 2011, 21, 456.
[2] J. B. Moffat, in Metal‐Oxygen Clusters: The surface and Catalytic
Properties of Heteropolyoxometalates, (Eds: M. V. Twigg, M. S.
Spencer), Kluwer Academic Publisers, n/a 2002.
[35] J. L. Malers, M. A. Sweikart, J. L. Horan, J. A. Turner, A. M.
Herring, J. Power Sources 2007, 172, 83.
[3] D. L. Long, R. Tsunashima, L. Cronin, Angew. Chem. Int. Ed.
2010, 49, 1736.
[36] Z. Xie, Q. Wu, F. He, L. Ai, Funct. Mater. Lett. 2018, 11,
1850065.
[4] L. Vila‐Nadal, S. G. Mitchell, A. Rodríguez‐Fortea, H. N. Miras,
L. Cronin, J. M. Poblet, Phys. Chem. Chem. Phys. 2011, 13,
20136.
[37] C. Marchal‐Roch, J.‐M. Millet, C. R. Acad, Sci. Paris Sér. Chim.
2001, 4, 321.
[38] M. Safaiee, M. A. Zolfigol, F. Derakhshan‐Panah, M. Mokhlesi,
Iran. J. Catal. 2016, 6, 173.
[5] P. Gourzerh, M. Che, l'actualité Chimique 2006, 298, 923.

10 of 10
TAYEBEE AND PEJHAN
[39] V. Siddaiah, G. L. V. Damu, D. Sudhakar, C. Venkata Rao, V.
Christopher, J. Kor. Chem. Soc. 2008, 52, 712.
How to cite this article: Tayebee R, Pejhan A.
[40] E. Rafiee, F. Tork, M. Joshaghani, Med. Chem. 2006, 16, 1221.
Studying catalytic activity of ternary mixed‐metal
Keggin H7SiV3W9O40 as a versatile acid catalyst for
the synthesis of β‐acetamido ketones. Appl
Organometal Chem. 2019;e5350. https://doi.org/
10.1002/aoc.5350
[41] T. Yakaiah, B. P. V. Lingaiah, G. Venkat Reddy, B. Narsaiah, P.
Shanthan Rao, ARKIVOC (Xiii) 2007, n/a, 227.
[42] Z. Abdi Piralghar, M. M. Hashemi, A. Ezabadi, Poly. Arom.
Compn. 2019, n/a, 1.
[43] R. Ghosh, S. Maiti, A. Chakraborty, S. Chakraborty, A. K.
Mukherjee, Tetrahedron 2006, 62, 4059.
[44] G. Pandey, R. P. Singh, A. Garg, V. K. Singh, Tetrahedron Lett.
2005, 46, 2137.