Tri-lacunary polyoxometalates of Na8H[PW9O 34] as heterogeneous Lewis base catalysts for Knoevenagel condensation, cyanosilylation and the synthesis of benzoxazole derivatives

Article abstract of DOI:10.1016/j.apcata.2014.01.017

We reported for the first time the development of tri-lacunary polyoxometalates (POMs) of Na₈H[A-PW₉O₃₄] ·7H₂O and Na₈H[B-PW₉O ₃₄]·19H₂O (Na-A-PW₉ and Na-B-PW ₉) as highly selective and efficient heterogeneous Lewis base catalysts for Knoevenagel condensation, cyanosilylation of various aldehydes and ketones and the synthesis of benzoxazole derivatives at 25 C under mild conditions. Since both Na-A-PW₉ and Na-B-PW₉ display no characteristic porosity, it is proposed that the catalytic reactions proceed not only on the surface and interface, but also in the bulk phase. The catalysts can be easily recovered and reused for at least six times without obvious decrease of catalytic activities and the structures of the catalysts remain unchanged after recycling. The easy preparation, high efficiency, reusability of the heterogeneous catalysts of Na-A-PW₉ and Na-B-PW₉ exhibit great potential for further application.

Full text of DOI:10.1016/j.apcata.2014.01.017

Accepted Manuscript
Title: Tri-Lacunary Polyoxometalates of Na8H[PW9O34] as
Heterogeneous Lewis Base Catalysts for Knoevenagel
Condensation, Cyanosilylation and the Synthesis of
Benzoxazole Derivatives
Author: Shen Zhao Yang Chen Yu-Fei Song
PII:
S0926-860X(14)00021-0
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2014.01.017
APCATA 14655
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
22-8-2013
21-12-2013
9-1-2014
Please cite this article as: S. Zhao, Y. Chen, Y.-F. Song, Tri-Lacunary Polyoxometalates
of Na8H[PW9O34] as Heterogeneous Lewis Base Catalysts for Knoevenagel
Condensation, Cyanosilylation and the Synthesis of Benzoxazole Derivatives, Applied
Catalysis A, General (2014), http://dx.doi.org/10.1016/j.apcata.2014.01.017
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Tri-Lacunary Polyoxometalates of Na8H[PW9O34] as Heterogeneous
Lewis Base Catalysts for Knoevenagel Condensation, Cyanosilylation
and the Synthesis of Benzoxazole Derivatives
Shen Zhao1, Yang Chen1, Yu-Fei Song*
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing,
100029, P. R. China.
Tel/Fax: +86-10-64431832; Email: songyufei@hotmail.com or songyf@mail.buct.edu.cn.
Abstract
We reported for the first time the development of tri-lacunary polyoxometalates (POMs) of
Na8H[A-PW9O34]·7H2O and Na8H[B-PW9O34]·19H2O (Na-A-PW9 and Na-B-PW9) as highly
selective and efficient heterogeneous Lewis base catalysts for Knoevenagel condensation,
cyanosilylation of various aldehydes and ketones and the synthesis of benzoxazole derivatives at
25oC under mild conditions. Since both Na-A-PW9 and Na-B-PW9 display no characteristic
porosity, it is proposed that the catalytic reactions proceed not only on the surface and interface,
but also in the bulk phase. The catalysts can be easily recovered and reused for at least six times
without obvious decrease of catalytic activities and the structures of the catalysts remain
unchanged after recycling. The easy preparation, high efficiency, reusability of the heterogeneous
catalysts of Na-A-PW9 and Na-B-PW9 exhibit great potential for further application.
Keywords: Polyoxometalates, Lanthanides, Cyanosilylation, Lewis acids
Page 1 of 18

1. Introduction
Polyoxometalates (POMs) are one category of anionic metal-oxides of V, Mo, W and Nb etc. in
their highest oxidation states, and they are thermally and oxidatively stable compared with
commonly used organic ligands.[1] The chemical properties of POMs such as redox potential,
electron-transfer properties, acidities, and solubility etc. can be finely tuned by adjusting the metal
ions and counters ions, which endow POMs to be superior catalysts for oxidative and acid
catalysis.[2-10] Compared with the full-occupied POMs, the negatively charged POMs can act as
Lewis base catalysts since the constituent oxygen atoms become more basic with the increase of
the negative charges of POMs. As a result, lacunary POMs including mono-, di-, and tri-lacunary
POMs could be good candidates as base catalysts. Up to now, Mizuno and co-workers have
developed a series of base POMs catalysts for Knoevenagel condensation, cyanosilylation, carbon
dioxide fixation, N-silylation of indole derivatives with hydrosilanes, dehydration of primary
amides to nitriles and hydrosilylation. [11-17] Inspired by the work of Mizuno and co-workers, we
have developed the heterogeneous POMs catalysts of Na-A-PW9 and Na-B-PW9 for Knoevenagel
condernsation, cyanosilylation and the synthesis of benzoxazole derivatives.
Knoevenagel condensation of carbonyl compounds with active methylene compounds is one of
the most significant reactions for the formation of C-C bonds, which has been widely applied in
the synthesis of important intermediates or products for perfumes, pharmaceuticals and calcium
antagonists, and polymers.[18-20] Cyanosilylation of aldehydes and ketones with trialkylsilyl
cyanides (TMSCNs) is of significance in organic synthesis because this reaction not only creates a
new C-C bond, but also protects an alcohol function. Cyanohydrins produced by this method can
be transformed into a variety of building blocks, such as α-hydroxy acids, α-hydroxy ketones and
β-amino alcohols,[21-23] which are widely applied in chemical industry. The benzoxazole
derivatives are important structural motif in many biologically active natural products and
pharmaceutical compounds, which can be used as cytotoxic agents, cathepsin S inhibitors, HIV
reverse transcriptase inhibitors, estrogen receptor agonists, selective peroxisome proliferator
activated receptor antagonists, anticancer agents, orexin-1 receptor antagonists and herbicides and
fluorescent whitening agent dyes.[24-32] Due to the wide application of these compounds in
industry as chemical intermediates and pharmaceutical agents, a number of catalytic systems have
been developed for Knoevenagel condensation,[33-41] cyanosilylation[42-49] and the synthesis of
Page 2 of 18

benzoxazole derivatives[50-57]. However, the reported catalytic systems show the following
disadvantages: 1) the used catalysts are difficult to recover and reuse for the reported
homogeneous systems; 2) the catalytic efficiency and the yields are not satisfactory in most cases
for the heterogeneous catalytic systems; 3) for Knoevenagel condensation and the synthesis of
benzoxazole derivatives, the reaction temperature is normally refluxing temperature; for
Knoevenagel condensation and cyanosilylation reactions, toxic solvents such as CH2Cl2, CHCl3,
CH2CH2Cl2, DMF or toluene etc are used. As such, it is necessary to develop easy-prepared,
environment-friendly, reusable, selective and efficient catalyic systems that can be applied for the
above three reactions under mild conditions.
In this paper, the tri-lacunary POMs of Na8H[A-PW9O34] ·7H2O and Na8H[B-PW9O34]·19H2O
(denoted as Na-A-PW9 and Na-B-PW9) have been applied as highly selective and efficient
catalysts for Knoevenagel condensation, cyanosilylation and the synthesis of benzoxazole
o
derivatives at 25 C under mild conditions (Scheme 1). Furthermore, the catalysts can be easily
recovered and reused for at least six times without obvious decrease of catalytic activities and the
molecular structures of POMs catalysts remain untouched.
Scheme 1. Schematic representation of Knoevenagel condensation, cyanosilylation and the synthesis of
benzoxazole derivatives by applying Na-A-PW9 and Na-B-PW9 as base catalysts.
2. Experimental Section
2.1. Chemical materials
Cyclohexanone (99%), cyclooctanone (99%), 2-adamantanone (98%), 2-heptanone (99%),
Page 3 of 18

2-octanone (98%), 2-nonanone (98%), 2-decanone (97%), hexanal (99%), heptanal (99%), octanal
(98%), nonanal (99%), decanal (96%), cyclohexanecarboxaldehyde (98%), benzaldehyde (98%),
2-methylbenzaldehyde (98%), 3-methylbenzaldehyde (97%), 4-methylbenzaldehyde (98%),
2-methoxybenzaldehyde (98%), 3-methoxybenzaldehyde (98%), 4-methoxybenzaldehyde (98%),
2-chlorobenzaldehyde (97%), 3-chlorobenzaldehyde (97%), 4-chlorobenzaldehyde (98%),
2-bromobenzaldehyde (98%), 3-bromobenzaldehyde (97%), 4-bromobenzaldehyde (99%),
2-nitrobenzaldehyde (98%), 3-nitrobenzaldehyde (99%), 4-nitrobenzaldehyde (99%),
thiophene-2-carboxylaldehyde (97%), pyridine-3-carboxylaldehyde (97%), ethyl cyanoacetate
(98%), malononitrile (99%), trimethylsilyl cyanide (TMSCN, 97%), 2-aminophenol (98%), and
solvents were purchased from Alfa Acesa. Analytical phosphoric acid (H3PO4, 85%), acetic acid
(CH3COOH), and sodium tungstate dihydrate (Na2WO4·2H2O) were obtained from Energy
Chemical in Shanghai. All the chemicals and solvents were used without further purification.
2.2. Measurements
Fourier transform infrared (FT-IR) spectra were recorded on a Bruker Vector 22 infrared
spectrometer using KBr pellet method. Powder X-ray diffraction (XRD) patterns were recorded on
a Rigaku XRD-6000 diffractometer under the following conditions: 40 kV, 30 mA, Cu Kα
radiation (λ = 0.154 nm). Inductively coupled plasma–atomic emission spectroscopy (ICP-AES)
analysis was performed using a Shimadzu ICPS-7500 spectrometer. 1H-NMR spectra were
recorded on a Bruker 400 MHz NMR spectrometer. The products of the catalytic reactions were
analyzed by Agilent 7820A gas chromatography (GC) system using a 30 m 5% phenylmethyl
silicone capillary column with an ID of 0.32 mm and 0.25 µm coating (HP-5). Yields were
determined by GC analysis using reference standards. Assignments of corresponding products
were analysed by 1H-NMR.
2.3. Synthesis and characterization of Na-A-PW9 and Na-B-PW9
The synthesis and characterization of Na-A-PW9 and Na-B-PW9 is according to the literature
method.[58,59] The TGA and ICP analysis suggest the formula can be determined as
Na8H[A-PW9O34]·7H2O and Na8H[B-PW9O34]·19H2O, respectively.
2.4 Procedure for cyanosilylation of aldehyeds and ketones
In a typical experiment, 1 mmol aldehyde or ketone, 1.5 mmol methylene compound (ethyl
cyanoacetate or malononitrile), 0.25 mol% Na-A-PW9 or Na-B-PW9 as catalyst and 0.2 ml
Page 4 of 18

o
methanol were placed in a 20 ml glass bottle at 25 C and the reaction mixture was kept stirring
vigorously. The reaction was effectively quenched after 6 hours. The resulting oily products were
extracted by diethyl ether, analyzed by GC, and identified by 1H-NMR. The yields were
determined by reference standards. After completion of the reaction, the catalysts can be
recovered by centrifugation, washed with acetone, and dried in air.
Detailed procedure for cyanosilylation of aldehydes and ketones, and for synthesis of
benzoxazole derivatives can be found in supporting information.
3. Results and discussion
3.1. Effect of catalysts on the Knoevenagel condensation
Table 1. Effect of different catalysts on the Knoevenagel condensation of benzaldehyde with ethyl cyanoacetate.a
Entry
1
2
3
4
5
6
7
8
Catalyst
Na-A-PW9
Na-B-PW9
Yield (%)
80
83
1
1
31
1
16
60
10
40
1
H3PW12O40·xH2O (H-PW12)
Na3[PW12O40]·13H2O (Na-PW12)
K7[PW11O39]·13H2O (K-PW11)
H4SiW12O40·xH2O (H-SiW12)
K8[SiW11O39] (K-SiW11)
Na10[SiW9O34] (Na-SiW9)
K2[{WO(O2)2(H2O)}2(μ-O)]·2H2O (K-W2)
Na2WO4·2H2O
9
10
11
12
13
14
WO3
Na2HPO4
NaH2PO4
None
1
1
1
a
Reaction conditions: benzaldehyde (1 mmol), catalyst (2.25 mol% to benzaldehyde based on W), ethyl
cyanoacetate (1.5 mmol), 0.2 ml methanol, 25 oC, 6 hours.
Initially, the Knoevenagel condensation of benzaldehyde with ethyl cyanoacetate catalyzed by
Na-A-PW9 and Na-B-PW9 at 25 oC in methanol has been carried out, and good yields of 80% and
83% can be afforded (Table 1, Entries 1 and 2). In contrast, the Keggin POMs of
H3PW12O40·xH2O and Na3[PW12O40]·13H2O (H-PW12 and Na-PW12) are not effective (Entries 3
and 4); the mono-lacunary POM of K7[PW11O39]·13H2O (K-PW11) exhibits much lower yield of
31% (Entry 5). From tmolecular structure point of view, the tri-lacunary POMs of Na-A-PW9 and
Na-B-PW9 contain nine negative charges and three lacunary sites when compared with those of
mono-lacunary Keggin POMs, and as a result, the former one can abstract the protons from ethyl
cyanoacetate easily than the latter one.
When the heteroatom changes from P to Si, the Keggin cluster of H4SiW12O40·xH2O (H-SiW12)
is not effective (Entry 6), and the mono-lacunary POM of K8[SiW11O39] (K-SiW11) and the
Page 5 of 18

tri-lacunary Na10[SiW9O34] (Na-SiW9) give relatively lower yields of 16% and 60%, respectively
(Entries 7 and 8). The yield can be increased by replacing the P with Si, which is in line with the
acid strength order of H4SiW12O40 > H3PW12O40. Contrast experiments indicate that
K2[{WO(O2)2(H2O)}2(μ-O)]·2H2O (K-W2), WO3, Na2HPO4 and NaH2PO4 are not effective for
such Knoevenagel condensation (Entries 9-13). Sodium tungstate Na2WO4·2H2O (Entry 10)
exhibits much lower yield of 40% than those by Na-A-PW9 and Na-B-PW9. Moreover, the
reaction does not proceed without catalysts (Entry 14).
3.2. Knoevenagel condensation of various aldehydes and ketones catalyzed by Na-PW9
Table 2. Knoevenagel condensation of various aldehydes with ethyl cyanoacetate catalyzed by Na-A-PW9.a
Entry
Donor
Acceptor
Product
Yield (%)b
E/Zc
1
2
3
4
5
6
7
8
X = H
X = H
80 (76)
99 (97)
>99.9 (99)
89 (85)
>99.9 (98)
95 (92)
87 (83)
99/1
70/30
70/30
70/30
70/30
70/30
70/30
99/1
X = 2-Me
X = 3-Me
X = 4-Me
X = 2-MeO
X = 3-MeO
X = 4-MeO
X = 2-Cl
X = 2-Me
X = 3-Me
X = 4-Me
X = 2-MeO
X = 3-MeO
X = 4-MeO
X = 2-Cl
96 (92)
9
X = 3-Cl
X = 4-Cl
X = 2-Br
X = 3-Br
X = 3-Cl
X = 4-Cl
X = 2-Br
X = 3-Br
>99.9 (99)
>99.9 (98)
97 (96)
>99.9 (98)
>99.9 (99)
>99.9 (98)
>99.9 (99)
>99.9 (98)
99/1
99/1
99/1
99/1
99/1
95/5
95/5
95/5
10
11
12
13
14
15
16
X = 4-Br
X = 4-Br
X = 2-NO2
X = 3-NO2
X = 4-NO2
X = 2-NO2
X = 3-NO2
X = 4-NO2
17
18
>99.9 (98)
>99.9 (98)
99/1
99/1
19
20
21
R = n-C5H11
R = n-C6H13
R = n-C7H15
R = n-C5H11
R = n-C6H13
R = n-C7H15
>99.9 (99)
92 (90)
81 (79)
80/20
80/20
80/20
22
86 (83)
85/15
a Reaction conditions: substrate (1 mmol), Na-A-PW9 (0.25 mol% to substrate), ethyl cyanoacetate (1.5 mmol), 0.2
o
ml methanol, 25 C, 6 hours. Yields were determined by GC analysis using reference standards. Assignments of
1
b
c
corresponding products were analyzed by H and 13C-NMR. The values in parentheses are the isolated yields.
E/Z = E isomers of corresponding Knoevenagel condensation products/ Z isomers of corresponding Knoevenagel
condensation products.
The Knoevenagel condensation of various aldehydes with ethyl cyanoacetate catalyzed by
o
Na-A-PW9 at 25 C in methanol has been carried out. All the corresponding products can be
afforded in high yields as shown in Table 2. For the aromatic aldehydes, benzaldehyde can be
converted to the corresponding product in good yield of 80% (Entry 1). Methyl substituted
Page 6 of 18

aromatic
aldehydes
including
2-methylbenzaldehyde,
3-methyl-benzaldehyde,
and
4-methylbenzaldehyde can be converted to the corresponding products in high yields of 99%,
>99.9%, and 89% (Entries 2-4), respectively. In terms of methoxy substituted aromatic aldehydes,
such as 2-methoxylbenzaldehyde, 3-methoxy benzaldehyde, and 4-methoxybenzaldehyde, the
corresponding products can be obtained in high yield of >99.9%, 95%, and 87% (Entries 5-7). The
above results show that electron-donating group substituted aromatic aldehydes give high yields.
For the electron-withdrawing group substituted aromatic aldehydes including
2-chlorobenzaldehyde, 3-chlorobenzaldehyde, 4-chloro -benzaldehyde, 2-bromobenzaldehyde,
3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaledhyde, and
4-nitrobenzaldehyde, excellent yields of 96%, >99.9%, >99.9%, 97%, >99.9%, >99.9%, >99.9%,
>99.9%, and >99.9% can be achieved (Entries 8-16). The Knoevenagel condensation of
thiophene-2-carboxaldehyde and pyridine-3-carboxaldehyde can give excellent yields of both
above 99.9% (Entries 17 and 18). In the case of aliphatic aldehydes, the Knoevenagel
condensation of hexanal, heptanal and octanal aldehydes afford the yields of >99.9%, 92% and
81%, respectively (Entries 19-21). It can be seen that the catalytic activities of alkyl aldehydes
decrease accordingly with the increase of alkyl chains. The cyclic aliphatic aldehyde of
cyclohexanecarboxaldehyde proceeds efficiently with good yield of 86% (Entry 22).
It is important to identify the E/Z (E/Z = E isomers of corresponding products/ Z isomers of
corresponding products) of corresponding Knoevenagel condensation products. Take
4-methylbenzaldehyde for example (Fig S3), the yield of 89% can be obtained from the GC
spectra using reference standards. The 1H-NMR spectrum in CDCl3 reveal that two signals at 4.19
(1.4H) and 1.30 ppm (2.1H) with the respective intensity ratio of 2: 3, assigning to the hydrogen
atoms in –COOCH2CH3 of the E-isomer product. At the same time, the signals at 3.37 (0.6H) and
1.10 ppm (0.9H) with the respective intensity ratio of 2: 3 are assigned to the hydrogen atoms in
–COOCH2CH3 of the Z-isomer product. The E/Z of 70/30 can be obtained from the respective
integral area ratio of the two groups of peaks in 1H-NMR spectrum. In the case of
4-bromobenzaldehyde (Fig S4), the yield of >99.9% can be obtained from the GC spectra. The
E/Z of 99/1 can be obtained from the respective integral area ratio of the two groups of peaks in
1H-NMR spectrum in CDCl3. The E/Z of the Knoevenagel condensation products in Table 2 can
be obtained through the above method, which is indicated in Table 2. Similar catalytic results
Page 7 of 18

could be obtained using Na-B-PW9 as catalyst (Table S2).
Table 3. Knoevenagel condensation of various aldehydes and ketones with malononitrile catalyzed by Na-A-PW9.a
Entry
Donor
Acceptor
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
X = H
X = H
92 (89)
98 (94)
>99.9 (97)
99 (96)
>99.9 (98)
86 (83)
>99.9 (98)
>99.9 (98)
>99.9 (97)
>99.9 (98)
>99.9 (98)
>99.9 (97)
>99.9 (96)
99 (95)
X = 2-Me
X = 3-Me
X = 4-Me
X = 2-MeO
X = 3-MeO
X = 4-MeO
X = 2-Cl
X = 3-Cl
X = 4-Cl
X = 2-Br
X = 3-Br
X = 2-Me
X = 3-Me
X = 4-Me
X = 2-MeO
X = 3-MeO
X = 4-MeO
X = 2-Cl
X = 3-Cl
X = 4-Cl
X = 2-Br
X = 3-Br
X = 4-Br
X = 4-Br
X = 2-NO2
X = 3-NO2
X = 4-NO2
X = 2-NO2
X = 3-NO2
X = 4-NO2
>99.9 (97)
99 (97)
17
18
98 (95)
98 (95)
19
20
21
22
23
R = n-C5H11
R = n-C6H13
R = n-C7H15
R = n-C8H17
R = n-C9H19
R = n-C5H11
R = n-C6H13
R = n-C7H15
R = n-C8H17
R = n-C9H19
>99.9 (98)
98 (96)
97 (95)
91 (88)
87 (82)
24
98 (94)
25
26
27
28
R = n-C5H11
R = n-C6H13
R = n-C7H15
R = n-C8H17
R = n-C5H11
R = n-C6H13
R = n-C7H15
R = n-C8H17
>99.9 (96)
99 (97)
99 (95)
98 (93)
29
99 (97)
30
99 (95)
a
Reaction conditions: substrate (1 mmol), Na-A-PW9 (0.25 mol% to substrate), malononitrile (1.5 mmol), 0.2 ml
methanol, 25 oC, 6 hours. Yields were determined by GC analysis using reference standards. Assignments of
corresponding products were analyzed by 1H and 13C-NMR. b The values in parentheses are the isolated yields.
To extend the application scope, Knoevenagel condensation of various aldehydes and ketones
o
with malononitrile has been investigated by Na-A-PW9 at 25 C. All the corresponding products
can be afforded in good yields (Table 3). Since the electron-withdrawing ability of -CN is stronger
than that of -COOEt, the methylene group in malononitrile is more active than that in ethyl
cyanoacetate. The catalytic results show that benzaldehyde can be converted to the corresponding
product in good yield of 92% (Entry 1). Methyl-substituted aromatic aldehydes can be converted
Page 8 of 18

to the corresponding products in high yields of above 98% (Entries 2-4). In terms of
methoxy-substituted aromatic aldehydes, such as 2-methoxylbenzaldehyde,
3-methoxybenzaldehyde, and 4-methoxybenzaldehyde etc, the corresponding products can be
obtained in high yield of >99.9%, 86%, and >99.9%, respectively (Entries 5-7). Therefore, good
yields can be achieved by Na-A-PW9 with either electron-donating or electron-withdrawing
groups substituted aromatic aldehydes as substrates (Entries 8-18). For aliphatic aldehydes,
Knoevenagel condensation of hexanal, heptanal, octanal, nonanal, and decanal gives the yield of
>99.9%, 98%, 97%, 91%, and 87%, respectively (Entries 19-23). For alkyl ketones excellent
yields of ≥ 98% can be afforded (Entries 25-28). Knoevenagel condensation of cyclic ketones
including cyclohexanone and 2-admantanone affords the yields of ~99% (Entries 29-30). Similar
catalytic results can be obtained with Na-B-PW9 as catalyst (Table S3). As such, highly selective
and efficient Knoevenagel condensation of various aldehydes and ketones can be realized by
applying Na-A-PW9 and Na-B-PW9 as catalysts.
The more unreactive donors of cyanoacetic acid, phenylacetonitrile and chloroacetonitrile have
been tried catalyzed by Na-A-PW9 and Na-B-PW9. However, the POMs catalysts of Na-A-PW9
and Na-B-PW9 are not effect for the Knoevenagel condensation of aldehydes and ketones with
more unreactive donors of cyanoacetic acid, phenylacetonitrile and chloroacetonitrile.
3.3. Cyanosilylation of various aldehydes and ketones catalyzed by Na-PW9
o
Cyanosilylation of various aldehydes and ketones catalyzed by Na-A-PW9 at 25 C in ethyl
acetate reveals that all the corresponding cyanohydrins can be afforded in high yields. For
aromatic aldehydes, benzaldehyde can be converted to the corresponding cyanohydrin in excellent
yield of >99.9% (Table 4, Entry 1). Methyl-substituted aromatic aldehydes can be converted to
the corresponding cyanohydrins in high yields of >99% (Entries 2-4). For methoxy-substituted
aromatic aldehydes including 2-methoxylbenzaldehyde, 3-methoxybenzaldehyde and
4-methoxybenzaldehyde, the corresponding cyanohydrins can be obtained in high yields of
>99.9%, 98% and 93%, respectively (Entries 5-7). The above results suggest that cyanosilylation
of electron-donating group substituted aromatic aldehydes gives high yields of the corresponding
cyanohydrins. In the case of electron-withdrawing groups substituted aromatic aldehydes,
excellent yields above 93% can be achieved (Entries 8-16). Cyanosilylation of
Page 9 of 18

thiophene-2-carboxaldehyde can give high yield of 81% (Entry 17).
Table 4. Cyanosilylation of various aldehydes and ketones catalyzed by Na-A-PW9.a
Entry
Substrate
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
X = H
X = H
>99.9 (98)
>99.9 (97)
>99.9 (97)
>99.9 (98)
>99.9 (98)
98 (96)
93 (90)
>99.9 (97)
94 (90)
X = 2-Me
X = 3-Me
X = 4-Me
X = 2-MeO
X = 3-MeO
X = 4-MeO
X = 2-Cl
X = 2-Me
X = 3-Me
X = 4-Me
X = 2-MeO
X = 3-MeO
X = 4-MeO
X = 2-Cl
X = 3-Cl
X = 3-Cl
10
11
12
13
14
15
16
X = 4-Cl
X = 2-Br
X = 3-Br
X = 4-Br
X = 2-NO2
X = 3-NO2
X = 4-NO2
X = 4-Cl
X = 2-Br
X = 3-Br
X = 4-Br
X = 2-NO2
X = 3-NO2
X = 4-NO2
96 (91)
96 (92)
99 (94)
97 (92)
93 (88)
>99.9 (97)
99 (96)
17
81 (77)
18
19
20
21
22
R = n-C5H11
R = n-C6H13
R = n-C7H15
R = n-C8H17
R = n-C9H19
R = n-C5H11
R = n-C6H13
R = n-C7H15
R = n-C8H17
R = n-C9H19
>99.9 (98)
98 (96)
95 (92)
95 (93)
94 (91)
23
24
25
>99.9 (98)
>99.9 (96)
92 (88)
a Reaction conditions: substrate (1 mmol), Na-A-PW9 (0.25 mol% to substrate), TMSCN (1.5 mmol), 0.2 ml ethyl
acetate, 25 oC, 6 hours. Yields were determined by GC analysis using reference standards. Assignments of
corresponding products were analyzed by 1H and 13C-NMR. b The values in parentheses are the isolated yields.
In the case of hexanal, heptanal, octanal, nonanal, decanal, and cyclohexanecarboxaldehyde,
cyanosilylation of these alkiphatic aldehydes gives the yields of >99.9%, 98%, 95%, 95%, 94%
and >99.9%, respectively (Entries 18-23). For cyclohexanone and 2-admantanone, the yields are
>99.9 and 92%, respectively (Entries 24-25). Similar catalytic results can be achieved with
Na-B-PW9 as catalyst (Table S4). The above results indicate that Na-A-PW9 and Na-B-PW9 are
highly selective and efficient for cyanosilylation reaction too.
3.4. Synthesis of benzoxazole derivatives catalyzed by Na-PW9
Page 10 of 18

Table 5. Synthesis of benzoxazole derivatives through various aldehydes with 2-aminophenol catalyzed by
Na-A-PW9.a
Entry
Substrate
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
X = H
X = H
93 (89)
89 (85)
87 (82)
89 (86)
>99.9 (97)
99 (96)
>99.9 (98)
>99.9 (97)
>99.9 (98)
>99.9 (98)
94 (90)
99 (95)
>99.9 (97)
99 (96)
X = 2-Me
X = 3-Me
X = 4-Me
X = 2-MeO
X = 3-MeO
X = 4-MeO
X = 2-Cl
X = 3-Cl
X = 4-Cl
X = 2-Br
X = 3-Br
X = 2-Me
X = 3-Me
X = 4-Me
X = 2-MeO
X = 3-MeO
X = 4-MeO
X = 2-Cl
X = 3-Cl
X = 4-Cl
X = 2-Br
X = 3-Br
X = 4-Br
X = 4-Br
X = 2-NO2
X = 3-NO2
X = 4-NO2
X = 2-NO2
X = 3-NO2
X = 4-NO2
97 (95)
99 (96)
17
84 (80)
18
19
20
21
22
R = n-C5H11
R = n-C6H13
R = n-C7H15
R = n-C8H17
R = n-C9H19
R = n-C5H11
R = n-C6H13
R = n-C7H15
R = n-C8H17
R = n-C9H19
>99.9 (98)
>99.9 (97)
98 (95)
>99.9 (98)
>99.9 (97)
a
Reaction conditions: substrate (1 mmol), Na-A-PW9 (0.25 mol% to substrate), 2-aminophenol (1 mmol), 0.2 ml
o
acetonitrile, 25 C, 6 hours. Yields were determined by GC analysis using reference standards. Assignments of
corresponding products were analyzed by 1H and 13C-NMR. b The values in parentheses are the isolated yields.
The benzoxazole derivatives can be obtained in excellent yields using Na-A-PW9 as catalyst at
o
25 C under mild conditions. For aromatic aldehydes, benzaldehyde can be converted to the
corresponding benzoxazole in the yield of 93% (Table 5, Entry 1). Methyl-substituted aromatic
aldehydes can be converted to the corresponding benzoxazole derivatives in the good yields of
~87%
(Entries
2-4).
For
methoxy-substituted
aromatic
aldehydes
including
the
2-methoxylbenzaldehyde,
3-methoxybenzaldehyde
and
4-methoxybenzaldehyde,
corresponding benzoxazole derivatives can be obtained in the excellent yields of ~99%, (Entries
5-7). The above results indicate that electron-donating substituted aromatic aldehydes give high
yields of the corresponding benzoxazole derivatives.
For 2-chloro-benzaldehyde,
3-chlorobenzaldehyde, 4-chloro-benzaldehyde, 2-bromobenzaldehyde, 3-bromobenzaldehyde,
4-bromo-benzaldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaledhyde and 4-nitrobenzaldehyde, the
yields of >99.9, >99.9%, >99.9, 94%, 99%, >99.9, 99%, 97% and 99% can be achieved,
respectively, using Na-A-PW9 as catalyst (Entries 8-16). In the case of aliphatic aldehydes,
excellent yields of the corresponding benzoxazole derivatives can be obtained in high yields and
Page 11 of 18

selectivities under mild conditions. (Entries 18-22).
3.5. Recovery and Reuse of Na-PW9
The POMs catalyst of Na-A-PW9 can be recovered successfully after Knoevenagel
condensation, cyanosilylation and the synthesis of benzoxazole derivatives. The yields of
corresponding products remain unchanged (Fig 1A) and the initial kinetic contact does not
decrease obviously (Fig 1B). It has been demonstrated that Na-A-PW9 can be reused for at least
six times without obvious loss of activities, and the yields for catalyst recovery of Na-A-PW9 are
above 96% (Fig 1C). FT-IR spectra of the fresh and reused Na-A-PW9 samples exhibit the same
absorption peaks (Fig 1D).[58,59] Powder X-ray diffraction (XRD) patterns of the fresh and
reused Na-A-PW9 samples are almost the same (Fig 1E). All these results indicate that the
structure of Na-A-PW9 remains unchanged after reaction.
Figure 1. Catalyst recycling experiments and the characterization of the reused POMs catalyst of Na-A-PW9.
3.6. Heterogeneous and Proposed Mechanism
To confirm the catalysis is truly heterogeneous, Knoevenagel condensation of benzaldehyde
with ethyl cyanoacetate has been selected as an example by applying Na-A-PW9 as catalyst at 25
oC in methanol. When the product yield reaches about 50%, Na-A-PW9 is removed from the
reaction mixture by filtration, and the reaction is allowed to proceed with the filtrate under the
same conditions. It can be found that no product can be obtained by adding more ethyl
Page 12 of 18

cyanoacetate. ICP-AES measurement reveals there is no P and W content in the filtrate. These
results rule out the contribution of P and W species leached into the reaction solution for the
observed catalytic results. Similar catalytic results could be achieved with Na-A-PW9 as catalyst
in cyanosilylation of cyclohexanone in ethyl acetate and in the synthesis of benzoxazole in
acetonitrile. Therefore, the catalytic reaction is truly heterogeneous.
Figure 2. Proposed mechanism of Knoevenagel condensation, cyanosilylation and synthesis of benzoxazole
derivatives catalyzed by the POMs catalysts of Na-A-PW9 and Na-B-PW9.
Accodring to the literature [11-17, 60-62], the mechanism of Knoevenagel condensation,
cyanosilylation and synthesis of benzoxazole derivatives has been proposed (Fig 2): in
Knoevenagel condensation, the oxo ligands at the lacunary sites of Na-A-PW9 and Na-B-PW9 can
activate the methylene compounds, and the next step is the nucleophilic addition to aldehyde or
ketone with the activated methylene compounds to form the corresponding product; in
cyanosilylation, the oxo ligands at the lacunary sites of Na-A-PW9 and Na-B-PW9 can activate the
TMSCN, and the next step is the nucleophilic addition to aldehyde or ketone with the activated
TMSCN to form the corresponding product; in synthesis of benzoxazole derivatives, the reaction
between aldehyde and 2-aminophenol leads to the formation of Schiff base which is stabilized by
the POMs catalysts of Na-A-PW9 and Na-B-PW9. Then intramolecular attack by the second group
on C=N double bond to give the final product.
4. Conclusions
In summary, the development of Na-A-PW9 and Na-B-PW9 as heterogeneous Lewis base
catalysts leads to the highly selective and efficient Knoevenagel condensation, cyanosilylation of
Page 13 of 18

o
various aldehydes and ketones, and the synthesis of benzoxazole derivatives at 25 C. The
catalysts can be easily separated from the reaction mixtures and used for the next run over six
times without obvious decrease of catalytic activities. In addition, the molecular structures of
Na-A-PW9 and Na-B-PW9 remain unchanged, as evidenced by the FT-IR and powder XRD
measurement. The easy preparation, reusability, high selectivity and efficiency of the
heterogeneous catalysts of Na-A-PW9 and Na-B-PW9 provide great potential for their practical
application.
Acknowledgements
This research was supported by National Science Foundation of China (21222104, 21076020), and
the Fundamental Research Funds for the Central Universities (ZZ1227).
Appendix A. Supplementary data
Supplementary data associated with this article can be found in the online version.
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Page 16 of 18

Graphical Abstract:
Tri-Lacunary Polyoxometalates of Na8H[PW9O34] as Heterogeneous Lewis Base
Catalysts for Knoevenagel Condensation, Cyanosilylation and Synthesis of
Benzoxazole Derivatives
Shen Zhao, Yang Chen, Yu-Fei Song*
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical
Technology, Beijing 100029, P. R. China.
We reported for the first time the development of tri-lacunary polyoxometalates (POMs) of
Na8H[A-PW9O34]·7H2O and Na8H[B-PW9O34]·19H2O (Na-A-PW9 and Na-B-PW9) as highly
selective and efficient heterogeneous Lewis base catalysts for Knoevenagel condensation,
cyanosilylation of various aldehydes and ketones and the synthesis of benzoxazole derivatives at
o
25 C under mild conditions. Since both Na-A-PW9 and Na-B-PW9 display no characteristic
porosity, it is proposed that the catalytic reactions proceed not only on the surface and interface,
but also in the bulk phase. The catalysts can be easily recovered and reused for at least six times
without obvious decrease of catalytic activities and the structures of the catalysts remain
unchanged after recycling. The heterogeneous catalysts of Na-A-PW9 and Na-B-PW9 exhibit great
potential for further application.
Page 17 of 18

Highlights:
1. The POMs of Na8H[PW9O34] have been developed as heterogeneous catalysts.
2. The POMs catalysts can catalyze the reactions selectively and efficiently.
3. The POMs catalysts can catalyze the reactions at 25 oC under mild conditions.
4. The POMs catalysts can catalyze the reactions in chloride-free solvents.
Page 18 of 18