P4VPy–CuO nanoparticles as a novel and reusable catalyst: application at the protection of alcohols, phenols and amines

Article abstract of DOI:10.1007/s13738-016-0887-x

P₄VPy–CuO nanoparticles were synthesized using ultrasound irradiations. Relevant properties of the synthesized nanoparticles were investigated by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and Fourier transform infrared spectroscopy. After identification, the prepared reagent was used for the promotion of different types of protection reactions of alcohols, phenols and amines. Easy workup, short reaction times, excellent yields, relatively low cost and reusability of the catalyst are the striking features of the reported methods.

Full text of DOI:10.1007/s13738-016-0887-x

J IRAN CHEM SOC
DOI 10.1007/s13738-016-0887-x
ORIGINAL PAPER
P4VPy–CuO nanoparticles as a novel and reusable catalyst:
application at the protection of alcohols, phenols and amines
Farhad Shirini1 · Abdollah Fallah‑Shojaei1 · Masoumeh Abedini1 · Laleh Samavi1
Received: 23 January 2016 / Accepted: 10 May 2016
© Iranian Chemical Society 2016
Abstract P4VPy–CuO nanoparticles were synthesized
using ultrasound irradiations. Relevant properties of the
synthesized nanoparticles were investigated by X-ray dif-
fraction, scanning electron microscopy, transmission elec-
tron microscopy and Fourier transform infrared spectros-
copy. After identification, the prepared reagent was used
for the promotion of different types of protection reactions
of alcohols, phenols and amines. Easy workup, short reac-
tion times, excellent yields, relatively low cost and reusa-
bility of the catalyst are the striking features of the reported
methods.
and the side chain of some of the amino acids. During oxi-
dation, acylation, halogenation and/or dehydration of these
types compounds, this moiety must be protected [3].
Amines protection continues to attach a great deal of
attention in a wide range of chemical fields, such as pep-
tide, nucleoside, polymer and catalyst ligand synthesis.
Moreover, in recent years, a number of nitrogen-protected
groups have been used as chiral auxiliaries. Thus, the
design of new, mild and effective methods for nitrogen pro-
tection is an active topic in synthetic chemistry [2].
Although various catalysts and methods are available for
the above-mentioned purposes, most of them have one or
more drawbacks, including long reaction times, harsh con-
ditions, harmful organic solvents, and tedious workup pro-
cedures [4–12]. Green chemistry has been defined as a set
of principles that reduce or eliminate the use or generation
of hazardous substances [13]. Therefore, it is important
to find more efficient catalysts and methods which can be
used in several number of protection reactions.
Keywords P4VPy–CuO nanoparticles · Heterogeneous
catalyst · Ultrasound · Protection reactions · Hydroxyl
groups · Amino groups
Introduction
It is well known that functional group transformation is the
basic part of organic synthetic reactions. Depending on the
nature of the functional group, different reagents could be
examined which their use may obviate some difficulties [1].
Protection of alcohols, phenols and amines has received
attention in recent years not only because of their funda-
mental importance, but also for their role in multistep
synthesis [2]. Hydroxyl groups are present in a number of
compounds of biological and synthetic interest, including
nucleoside, carbohydrates, steroids, macrolides, polyethers
Nanotechnology and nanoscience have attracted scien-
tist’s attention over recent years due to their vast number
of technological applications. Nanotechnology is defined
as the synthesis of materials by controlling their size and
shape at a nanometer scale, where the physical and chemi-
cal properties considerably differ from those of the bulk
substances. During the past decade, the synthesis of metal
oxide nanoparticles such as those of titanium, zinc, iron and
magnesium has caught the interest of researchers. Among
these metal oxides, CuO nanoparticles have been investi-
gated quite considerably. Cupric oxide (CuO) is a transi-
tion metal oxide, p-type semiconducting material with a
monoclinic crystal structure and an indirect bandgap, e.g.,
of 1.0–2.08 eV [14, 15]. This oxide is used as antimicro-
bial [16] and photothermal and photoconductive agent [17],
in chemical and biological sensing [18, 19], as a promoter
* Farhad Shirini
shirini@guilan.ac.ir
1
Department of Chemistry, Faculty of Science, University
of Guilan, Rasht 41335, Islamic Republic of Iran
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J IRAN CHEM SOC
in catalytic reactions [20], in lithium-ion batteries [21] and
solar cells [22].
carried out with PHILIPS CM10. The compositions of the
products were characterized by the FT-IR spectroscopy
with a Bruker ALPHA. Elf (with a frequency of 50 Hz and
a nominal power 200 W) ultrasonic bath was used for ultra-
sonic irradiation.
Throughout the past decade, different routes have been
suggested to fabricate the CuO nanoparticles, including
electrochemical method [23], wet chemical reaction [24],
hydrothermal method [25], thermal oxidation [26], micro-
wave irradiation [27] and quick precipitation [28]. Some of
these methods have limitations due to the requirement of
high temperatures, expensive instruments and special catal-
ysis. For cost-effectiveness and simplicity of operation,
ultrasonic irradiations are used. On the other hand in recent
years, ultrasound irradiation has been established as a sig-
nificant technique in synthetic organic chemistry. Shorter
reaction times, simple experimental procedure, high yields,
improved selectivity and clean reaction conditions are the
main benefits of ultrasound-assisted reactions [29–32].
In the synthesis of metal oxide nanoparticles, polymers
are used to stabilize the aggregation of metal oxides [33].
One of the most common polymers which is used in the
preparation of the metal oxides NPs is polyvinylpyridine
(PVP) due to its distinct shape, dissolved metal salts and
transport facility.
Poly(4-vinylpyridine) (P4VPy)-supported reagents are
active in various organic transformations including oxida-
tion, reduction and halogenation reactions. Simple recovery
from the reaction mixtures, reusability, physical stability,
compatibility with a wide range of solvents and their toler-
ation of a great number of reaction conditions are the main
advantages of these methods. It bodes well for the future of
P4VPy reagents in which their properties can be fine-tuned
in organic reactions [34].
Preparation of P4VPy–CuO nanoparticles (PC–NPs)
A mixture of poly(4-vinylpyrridine) (100 mg) [poly(4-
vinylpyridine) cross-linked with 2 % DVB ~60 mesh, MW:
60,000] and bulk copper(II) oxide (25 mg, 0.31 mmol) in
(10 mL) ethanol was irradiated by ultrasound for 2 h. Then,
the black solid powder was separated by centrifugation and
washed three times with ethanol (3 × 2 mL) and dried at
60 °C (115 mg).
General procedure for the acetyl protection reactions
A mixture of the substrate (1 mmol), acetic anhydride
(1 mmol) and PC–NPs (12 mg) was stirred at room temper-
ature. After completion of the reaction (monitored by TLC
using a 1:1 mixture of EtOAc/n-hexane), EtOAc (15 mL)
was added and the catalyst was filtered. The organic layer
was washed with saturated solution of NaHCO3 and water
(3 × 15 mL), and dried over anhydrous MgSO4. Evapo-
ration of the solvent under reduced pressure gave the
requested acetates in high purity.
General procedure for the methoxymethyl protection
reactions
A mixture of the substrate (1 mmol), dimethoxymethane
(DMM) (4 mmol) and PC–NPs (12 mg) was stirred at room
temperature for the appropriate time. The progress of the
reaction was monitored by TLC (EtOAc: n-hexane; 1:1).
After completion of the reaction, the mixture was filtered,
and the solid residue was washed with Et2O (5 mL). The
filtrate was washed with a saturated solution of NaHCO3
and H2O and dried over MgSO4. Evaporation of the solvent
afforded the requested methoxymethyl (MOM) ether in
high purity.
Experiment
General
All chemicals were purchased from Merck or Fluka Chem-
ical Companies. All yields refer to the isolated products.
Products were characterized by their physical constants,
comparison with authentic samples and IR spectroscopy.
The purity determination of the substrates and reaction
monitoring were accompanied by TLC using silica gel SIL
G/UV 254 plates.
General procedure for the tetrahydropyranyl
protection reactions
Instrumentation
A mixture of the substrate (1 mmol), 3,4-dihydro-2H-pyran
(1 mmol) and PC–NPs (12 mg) in CH2Cl2 (3 drops) was
stirred at room temperature. The progress of the reaction
was monitored by TLC (EtOAc: n-hexane; 1:1). After com-
pletion of the reaction, the mixture was filtered to separate
the solid catalyst. Then, the solution was filtered through a
silica gel pad and washed with CH2Cl2 (2 × 5 mL). Evapo-
ration of the solvent gave the desired product in high yields.
X-ray diffraction (XRD) measurements were taken at
room temperature on a D8-Bruker Advanced X-ray pow-
der diffractometer, using Ni filter and Cu-Ka radiation
(k = 1.542 A °). Scanning electron microscopy (SEM) and
energy-dispersive X-ray spectroscopy (EDX) studies were
carried out with SEM HITCHI S4160. TEM studies were
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J IRAN CHEM SOC
General procedure for the trimethylsilyl protection
reactions
Results and discussion
Catalyst characterization
A mixture of the substrate (1 mmol), HMDS (1 mmol)
and PC–NPs (20 mg), in acetonitrile (3 mL), was refluxed
at 75 °C. After completion of the reaction (monitored by
TLC using a 1:1 mixture of EtOAc/n-hexane), the mixture
was filtered and the residue was washed with acetonitrile
(5 mL). Evaporation of the solvent gave almost the pure
product(s). Further purification was proceeded by bulb-to-
bulb distillation under reduced pressure or recrystallization
to afford the pure silyl ether.
In order to understand the chemical and structural nature of
the synthesized P4VPy–CuO–NPs, FT-IR analysis was car-
ried out. In Fig. 1a, which shows the FT-IR of P4VPy, the
absorption bands at 1600, 1556, 1498, and 1414 cm−1 are
assigned to the characteristic vibrations of the pyridine ring.
The absorption bands at 1069 and 995 cm−1 are assigned to
the in-plane and out-of-plane bending of the C–H bonds of
the ring, respectively [35]. Metal oxides commonly show
absorption bands below 1000 cm−1 [36]. In this Fig. 1b, the
absorption bands which are observed at 604 and 504 cm−1
are related to bare Cu–O. Fig 1c shows the FT-IR spectrum
of the prepared catalyst. In this Fig., the bands related to
the pyridine ring are appeared at 1603, 1558, 1499 and
1415 cm−1, while their intensities are decreased. The two
characteristic bands of CuO were also observed at 608 and
511 cm−1 [37].
(a)
(b)
(c)
P4VPy-CuO
The P4VPy and P4VPy–CuO–NPs samples were also
analyzed by powder X-ray diffraction (XRD) (Fig. 2). All
of the peaks in the diffraction diagram could be assigned
to the CuO. The peaks at 2θ values of 32.86, 35.89, 39.09,
46.37, 49.04, 54.15, 58.63, 61.88, 66.62, 68.46, 72.58 and
75.34 correspond to the crystal planes of copper oxide 110,
002, 111, 112, 202, 020, 202, 113, 311, 113, 311 and 004,
respectively, which are in good agreement with the recent
observations [37]. No other peak is observed belonging to
the impurities, indicating the high purity of as-obtained
samples. These values are consistent with the respective
Joint Committee on Powder Diffraction Standard Card No.
45-0937.
CuO
P4VPy
4000
3500
3000
2500
2000
1500
1000
500
Wavenumber cm-1
Scanning electron microscopy (SEM) is used to deter-
mine the size of the CuO particles (Fig. 3). This method
Fig. 1 FT-IR spectra of a P4VPy, b CuO and P4VPy–CuO–NPs (c)
Fig. 2 XRD patterns of a
P4VPy and b P4VPy–CuO–NPs
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J IRAN CHEM SOC
Fig. 3 SEM images of a P4VPy and b, c P4VPy–CuO–NPs and EDX of P4VPy–CuO–NPs (d)
clarified that these particles are in nanosize. On the basis of
the obtained results, it can be concluded that because of the
reduction in the size of the CuO particles which increases
its surface area the activity of the prepared reagent in the
requested reactions became higher (as described in the next
sections).
formation mechanism for the CuO nanorod made by CuO
nanospheres can be described based on cementing process
or an orientated attachment. In this process, a large crystal
structure is formed from small ones by direct jointing of
the suitable crystal planes [38].
Typical transmission electron microscopy (TEM) dis-
plays the morphologies of the prepared sample. In Fig. 4,
nanorod and nanosphere structures can be observed for
the prepared reagent. The existence of nanospheres proved
that the nanorods were composed of them. A possible
Catalytic activity
Nowadays, the development of heterogeneous catalysts
became a major area of research in synthetic organic chem-
istry. Some potential advantages of these materials over
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J IRAN CHEM SOC
Fig. 4 TEM images of P4VPy–CuO–NPs
Table 1 Comparison of different loading amounts of CuO on the cat-
alytic activity of PC–NPs on the acetylation of 4-chlorobenzyl alco-
hol
homogeneous systems are simplified recovery, reusability,
enhanced selectivity and reactivity, easy product isolation
and incorporation in continuous reactors and microreactors
[39].
Entry Loading amounts of CuO
(mg) on 100 mg of P4VPya
Time (min) Conversion (%)b
As we have mentioned previously, CuO is one of the
most prominent catalysts and is extensively used in envi-
ronmental catalysis. CuO nanoparticles typically have
higher catalytic activity than their bulk or microcoun-
terparts caused by their large surface area [40]. In addi-
tion, CuO on various supporters have also been exten-
sively investigated and is known to be highly active [20].
Although these methods are useful, but most of them need
difficult conditions such as high temperature and basic
media.
In the present study and after preparation and identifica-
tion of P4VPy–CuO–NPs and in order to solve the above-
mentioned drawbacks, we were interested to investigate the
applicability of this reagent in the promotion of different
types of protection methods used for alcohols, phenols and
amines.
The acetyl protection was selected as the first reaction
for this purpose. In this study and for obtaining the opti-
mum reaction conditions, the influence of the following
factors on the protection of 4-chlorobenzyl alcohol with
acetic anhydride was studied as a model reaction: (1) the
amounts of PC–NPs, (2) solvents and (3) temperature.
The results showed that the best results can be obtained
using 12 mg of the catalyst (prepared from the addition of
25 mg CuO on 100 mg P4VPy) (Table 1, entry 2) in the
absence of solvent (Table 2, entry 6) at room temperature
(Scheme 1).
1
2
3
15
25
35
10
2
85
100
100
2
The reaction was performed in the absence of solvent at room tem-
perature
a
12 mg of the prepared catalyst was used
b
GC
Table 2 Effect of different solvents on the acetylation of 4-chlo-
robenzyl alcohol
Entry
Solvent
Time (min)
Yield (%)a
1
2
3
4
5
6
Ethanol
30
30
30
30
30
2
–
Methanol
–
Chloroform
Dichloromethane
n-Hexane
50
20
20
95
Solvent-free
a
Isolated yield
efficiently acetylated with acetic anhydride under the opti-
mized conditions (Table 3, entries 1–14). Phenol and sub-
stituted phenols were also acetylated under the same condi-
tions (Table 3, entries 15–17). This method was also found
to be useful for the acetylation of amines and substituted
amines (Table 3, entries 18–20). As shown in Table 3, thi-
ols are resistant to this catalyst and remain intact in the
reaction mixture (Table 3, entries 21, 22). Therefore, this
After the above-mentioned initial studies, a wide range
of ring-substituted benzyl alcohols with electron-donating
and electron-withdrawing groups and also primary, sec-
ondary and sterically hindered tertiary aliphatic ones were
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Scheme 1 Acylation of 4-chlorobenzyl alcohol catalyzed by P4VPy–CuO–NPs
Table 3 Acylation of alcohols,
phenols and amines catalyzed
Entry Substrate
Product
Time (min) Yield (%)a
by PC–NPs
1
4-ClC6H4CH2OH
4-NO2C6H4CH2OH
2-MeC6H4CH2OH
2-BrC6H4CH2OH
4-MeOC6H4CH2OH
4-(CH3)3CC6H4CH2OH
PhCH2OH
4-ClC6H4CH2OAc
4-NO2C6H4CH2OAc
2-MeC6H4CH2OAc
2-BrC6H4CH2OAc
4-MeOC6H4CH2OAc
4-(CH3)3CC6H4CH2OAc
PhCH2OAc
2
2
95
90
95
92
90
80
95
92
90
90b
90
92
2
3
2
4
2
5
2
6
5
7
5
8
C6H5CH(CH3)OH
Ph2CHOH
C6H5CH(CH3)OAc
Ph2CHOAc
1
9
2
10
11
12
PhCHOHCH2OH
C6H5CH(CH3)CH2OH
PhCHOAcCH2OAc
C6H5CH(CH3)CH2OAc
14
1
2
13
14
3
2
95
92
15
16
17
18
19
20
21
22
23
24
25
PhOH
PhOAc
2
2
92
2-ClC6H4OH
4-CH3C6H4OH
C6H5NH2
2-ClC6H4OAc
4-CH3C6H4OAc
C6H5NHAc
95
5
90
8
90
4-ClC6H4NH2
4-CH3C6H4NH2
4-CH3C6H4SH
4-BrC6H4SH
4-ClC6H4NHAc
4-CH3C6H4NHAc
4-CH3C6H4SAc
4-BrC6H4SAc
10
10
30
30
2
90
90
0c
0c
100 + 0d
100 + 0d
100 + 0d
2-BrC6H4CH2OH + CH3C6H4SH 2-BrC6H4CH2OAc + CH3C6H4SAc
PhOH + CH3C6H4SH
C6H5NH2 + BrC6H4SH
PhOAc + CH3C6H4SAc
C6H5NHAc + BrC6H4SAc
4
10
Products were characterized by their physical constants, comparison with authentic samples and IR and
1H NMR spectroscopy
a
Isolated yields
b
2 mmol of Ac2O and 24 mg of P4VPy–CuO–NPs were used
c
The starting material was recovered unchanged
d
Selective acetylation of 2-bromobenzyl alcohol, phenol and aniline in the presence of thiols; conversion
methodology shows selectivity and is suitable for the selec-
tive acetylation of alcohols, phenols and amines in the pres-
ence of thiols (Table 3, entries 23–25).
To illustrate the efficiency of the proposed method,
Table 4 compares our result obtained from the acetylation
of 4-chlorobenzyl alcohol with some of those reported in
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Table 4 Comparison of the results obtained from the acetyl protection of 4-chlorobenzyl alcohol in the presence of various catalysts
Entry
Catalyst
Conditions
Substrate/reagent (molar ratio)
Time (min)
Yield (%)
References
1
2
3
4
5
P4VPy–CuO–NPs
Melamine trisulfonic acid
Nano-CdO
Solvent-free, r.t.
CH2Cl2, r.t.
1:1
2
8
95
90
97
90
92
This work
[41]
1:1
Solvent-free, MW
Solvent-free,)))))
Solvent-free, 80 °C
1:1.2
1:2
10
5
[6]
Natural ferrous chamosite
Rice husk
[5]
1:3
90
[42]
Scheme 2 Methoxymethylation
of alcohols, phenols and amines
catalyzed by P4VPy–CuO–NPs
the literature, which demonstrates the significant superior-
ity of PC–NPs in the compared reactions.
In continue, the P4VPy–CuO–NPs catalyst was used
for the promotion of the protection of alcohols, phenols
and amines as their corresponding tetrahydropyranylated
products under similar reaction conditions. First of all tet-
rahydropyranyl protection of 4-chlorobenzyl alcohol was
studied as a probe reaction. However, the reaction was not
as efficient as the acetylation and methoxymethylation of
the same alcohol under the predescribed conditions. There-
fore, the reaction was performed in the presence of little
amounts of CH2Cl2 at room temperature using 12 mg of
P4VPy–CuO–NPs. Under the new conditions, 4-chloroben-
zyl alcohol was protected in 1 min to furnish the requested
product in high isolated yields (96 %) (Scheme 3).
Then, the protocol was followed using a series of alco-
hols, phenols and amines for generalization, and the
results are shown in Table 7. Regardless of the nature of
the substituent attached to them, all the substrates pro-
duced excellent yields in short reaction times. Under the
selected conditions, tetrahydropyranyl protection of thiols
was not successful and the starting material was recovered
unchanged (Table 7, entries 21, 22). Therefore, the chem-
oselectivity of this method was also investigated and the
results are reported in Table 7 (entries 23–25). The obtained
results clearly showed that this method could be efficiently
used for the chemoselective protection of different types of
alcohols, phenols and amines in the presence of thiols.
In order to show the suitability of this method, Table 8
compares the results obtained from the tetrahydropyranyl
protection of 4-chlorobenzyl alcohol in the presence of
P4VPy–CuO–NPs with some of those reported in the litera-
tures. It is noteworthy that some of the previously reported
methods require longer reaction times and some of them
need more amounts of the solvent (Table 8, entries 3, 5).
After the above-mentioned reactions, we also decided
to study the trimethylsilylation reactions in the pres-
ence of PC–NPs. For this purpose, the silyl protection of
4-chlorobenzyl alcohol was selected as a model reaction.
In continuation of the above-mentioned studies, we have
tried to extend the applicability of PC–NPs in the other
organic transformations by studying the role of this cata-
lyst in the promotion of the methoxtmethylation reactions.
Our investigations clarified that P4VPy–CuO–NPs is also
efficiently able to catalyze the methoxymethyl protection
of alcohols, phenols and amines with dimethoxymethane.
Optimization of the reaction conditions showed that all
reactions can be performed under mild reaction conditions
as shown in Scheme 2.
Using this method, different types of benzylic (includ-
ing a variety of substitutes) and primary, secondary and
tertiary aliphatic alcohols and phenols were converted
to their corresponding methoxymethylated products in
quantitative yields (Table 5, entries 1–16). This method is
also very useful for the effective methoxymethylation of
amines (Table 5, entries 17–19). Under the selected condi-
tions, no elimination and rearrangement by-products were
observed at all. Furthermore, our examinations showed that
this method is not applicable for the protection of thiols
(Table 5, entry 20, 21). On the basis of these results, we
have also studied the chemoselectivity of this method in the
methoxymethyl protection of alcohols, phenols and amines
in the presence of thiols. The obtained results are tabulated
in Table 5 (entries 22–24).
In order to show the merit of this method, Table 6 com-
pares our results obtained from the methoxymethylation of
4-cholorobenzyl alcohol with DMM catalyzed by P4VPy–
CuO–NPs with some of the other results reported in the lit-
erature. This comparison shows that all the catalysts require
more reaction times than PC–NPs. In addition, the reaction
using some of these catalysts (sulfonic acid-functionalized
ordered nanoporous Na+- montmorillonite, SnIV(Br8TPP)
(OTf)2 and SnIV(TPP)(OTf)2) need higher amounts of
DMM (Table 6, entries 3–5).
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J IRAN CHEM SOC
Yield (%)a
Table 5 Methoxymethylation of alcohols, phenols and amines catalyzed by PC–NPs
Entry
Substrate
Product
Time (min)
1
4-ClC6H4CH2OH
2-NO2C6H4CH2OH
3,4-Cl2C6H4CH2OH
2-BrC6H4CH2OH
3-MeOC6H4CH2OH
PhCH2OH
4-ClC6H4CH2OMOM
2-NO2C6H4CH2OMOM
3,4-Cl2C6H4CH2OMOM
2-BrC6H4CH2OMOM
3-MeOC6H4CH2OMOM
PhCH2OMOM
1
2
95
89
92
90
95
94
92
92
95
95
92
2
3
2
4
1
5
1
6
2
7
C6H5CH(CH3)CH2OH
4-(CH3)3CC6H4CH2OH
C6H5CH(CH3)OH
Ph2CHOH
C6H5CH(CH3)CH2OMOM
4-(CH3)3CC6H4CH2OMOM
C6H5CH(CH3)OMOM
Ph2CHOMOM
8
8
15
15
1
9
10
11
15
12
13
5
93
92
15
14
15
16
17
18
19
20
21
22
23
24
PhOH
PhOMOM
10
10
5
90
4-ClC6H4OH
4-ClC6H4OMOM
95
4-CH3C6H4OH
C6H5NH2
4-CH3C6H4OMOM
90
C6H5NHMOM
15
15
10
30
30
2
90
4-ClC6H4NH2
4-ClC6H4NHMOM
93
4-CH3C6H4NH2
4-CH3C6H4SH
4-CH3C6H4NHMOM
4-CH3C6H4SMOM
87
0b
0b
100 + 0c
100 + 0c
100 + 0c
4-BrC6H4SH
4-BrC6H4SMOM
4-ClC6H4CH2OH + CH3C6H4SH
PhOH + CH3C6H4SH
C6H5NH2 + BrC6H4SH
4-ClC6H4CH2OMOM + CH3C6H4SMOM
PhOMOM + CH3C6H4SMOM
C6H5NHMOM + BrC6H4SMOM
13
20
Products were characterized by their physical constants, comparison with authentic samples and IR and 1H NMR spectroscopy
a
Isolated yields
b
The starting material was recovered unchanged
c
Selective methoxymethylation of 4-chlorobenzyl alcohol, phenol and aniline in the presence of thiols; conversion
The reaction was performed in the presence of 20 mg of
the P4VPy–CuO–NPs sample in refluxing acetonitrile
(Scheme 4). Using this method, various alcohols were
silylated efficiently to provide the corresponding trimethyl-
silyl ethers in good to excellent yields (Table 9, entries
1–11). Under the selected conditions, phenols were also
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J IRAN CHEM SOC
Table 6 Comparison of the results obtained from the methoxymethyl protection of 4-chlorobenzyl alcohol in the presence of various catalysts
Entry Catalyst
Conditions
Substrate/reagent (molar ratio) Time (min) Yield (%) References
1
2
3
P4VPy–CuO–NPs
Solvent-free, r.t. 1:4
1
25
90
95
95
95
This work
[43]
Melamine trisulfonic acid
CHCl3, reflux
CHCl3, reflux
1:4
1:6
Sulfonic acid-functionalized ordered
nanoporous Na+- montmorillonite
[44]
4
5
SnIV(Br8TPP)(OTf)2
SnIV(TPP)(OTf)2
Solvent-free, r.t. 1:7
Solvent-free, r.t. 1:7
10
15
96
97
[9]
[45]
Scheme 3 Tetrahydropyranylation of alcohols, phenols and amines catalyzed by P4VPy–CuO–NPs
readily transformed into their corresponding silyl ethers in
high yields (Table 9, entries 12–14). Amines and thiols did
not protected using this method (Table 9, entries 15–18).
Furthermore, our examination showed that this method
is efficient for the chemoselective protection of alcohols
and phenols in the presence of amines and thiols (Table 9,
entries 19–22).
The advantages of P4VPy–CuO–NPs over reported cata-
lysts for the trimethylsilylation of 4-cholorobenzyl alcohol
are shown in Table 10. It is noteworthy that some of the
previously reported methods require longer reaction times.
During a separate investigation and in order to evalu-
ate the ability of the method used for the preparation of
the catalyst, the reagent was also synthesized via two other
methods. In first method, P4VPy–CuO nanoparticles were
synthesized by quick precipitation route. For this purpose,
Cu(NO3)2.3H2O was added to the suspension of P4VPy in
deionized water and stirred for 15 min. Then, a solution of
NaOH 1 M was added to the mixture at 60 °C to form black
nanoparticles [33]. In the second method, P4VPy–CuO
nanoparticles were prepared from the reaction of CuO and
P4VPy in ethanol at reflux temperature under ambient con-
ditions according to the method reported by Albadi et al.
[34].
After preparation, the catalytic activity of these catalysts
was examined in acetylation, methoxymethylation, tetrahy-
dropyranylation and trimethylsilylation of 4-chloroben-
zylalcohol. The results showed that the catalytic activity
was not affected by the preparation method of the reagent,
while the ultrasound irradiation assisted the preparation of
the catalyst in shorter reaction times and lower temperature.
In the other study and in order to examine the potential
ability of the catalyst, the catalytic activity of P4VPy and
bare CuO was also studied in model reactions. The results
showed that in the presence of P4VPy–CuO–NPs, the reac-
tions were done at higher conversion in shorter reaction
times (Table 11).
It should be noted that using bare CuO as the catalyst,
phenol and its substituted derivatives were decomposed
under the same conditions and CuO reduced to Cu, while
in the presence of P4VPy–CuO–NPs, they can be protected
successfully, which is the one of the most important advan-
tages of this new efficient reagent.
Also, it is noteworthy that the mentioned protecting
system allowed the homoselective protection of 1,4-dihy-
droxy benzene and 1,4- diamino benzene to their monop-
protected derivatives (Table 12).
At the end step of this study, the reusability of the cata-
lyst was tested in the acetylation, methoxymethylation,
tetrahydropyranylation and trimethylsilylation of 4-chlo-
robenzyl alcohol. After completion of the reaction, the
The obtained catalysts were characterized by FT-IR, and
the same FT-IRs clarified that the prepared samples are the
same as each other.
1 3

J IRAN CHEM SOC
Yield (%)a
Table 7 Tetrahydropyranylation of alcohols, phenols and amines catalyzed by PC–NPs
Entry
Substrate
Product
Time (min)
1
4-ClC6H4CH2OH
2-NO2C6H4CH2OH
3,4-Cl2C6H4CH2OH
2-BrC6H4CH2OH
4-MeOC6H4CH2OH
2-CH3C6H4CH2OH
4-(CH3)3CC6H4CH2OH
PhCH2OH
4-ClC6H4CH2OTHP
2-NO2C6H4CH2OTHP
3,4-Cl2C6H4CH2OTHP
2-BrC6H4CH2OTHP
4-MeOC6H4CH2OTHP
2-CH3C6H4CH2OTHP
4-(CH3)3CC6H4CH2OTHP
PhCH2OTHP
1
2
96
92
95
90
92
95
90
95
92
92
90
87
2
3
2
4
2
5
1
6
1
7
2
8
1
9
C6H5CH(CH3)CH2OH
Ph2CHOH
C6H5CH(CH3)CH2OTHP
Ph2CHOTHP
15
1
10
11
12
C6H5CH(CH3)OH
C6H5CH(CH3)OTHP
5
1
13
14
20
10
85
95
15
16
17
18
19
20
21
22
23
24
25
PhOH
PhOTHP
1
1
90
2-ClC6H4OH
2-ClC6H4OTHP
95
4-CH3C6H4OH
4-CH3C6H4OTHP
1
90
C6H5NH2
C6H5NHTHP
1
92
4-ClC6H4NH2
4-ClC6H4NHTHP
5
95
4-CH3C6H4NH2
4-CH3C6H4SH
4-CH3C6H4NHTHP
4-CH3C6H4STHP
5
92
0b
0b
100 + 0c
100 + 0c
100 + 0c
30
30
2
4-BrC6H4SH
4-BrC6H4STHP
2-BrC6H4CH2OH + 4-CH3C6H4SH
PhOH + 4-BrC6H4SH
C6H5NH2 + 4-CH3C6H4SH
2-BrC6H4CH2OTHP + 4-CH3C6H4STHP
PhOTHP + 4-BrC6H4STHP
C6H5NHTHP + 4-CH3C6H4STHP
2
2
Products were characterized by their physical constants, comparison with authentic samples and IR and 1H NMR spectroscopy
a
Isolated yields
b
The starting material was recovered unchanged
c
Selective tetrahydropyranylation of alcohol, phenol and aniline in the presence of thiols; conversion
Table 8 Comparison of the results obtained from the tetrahydropyranyl protection of 4-chlorobenzyl alcohol in the presence of various catalysts
Entry Catalyst
Condition
Substrate/reagent
(molar ratio)
Time (min) Yield (%) References
1
2
3
4
5
P4VPy–CuO–NPs
CH2Cl2, (3 drops) r.t. 1:1
1
19
8
96
93
90
94
98
This work
[46]
Vanadium(V)-substituted polyoxomolybdates Solvent-free, r.t.
1:1
Melamine trisulfonic acid
CH2Cl2 (3 mL), r.t.
Solvent-free, 60 °C
CH2Cl2, (3 mL), r.t.
1:1.1
1:1.1
1:1.4
[47]
aluminum chloride hexahydrate
30
3
[48]
Sulfonic acid-functionalized ordered
nanoporous Na+- montmorillonite
[49]
1 3

J IRAN CHEM SOC
Scheme 4 Silylation of alco-
hols and phenols catalyzed by
P4VPy–CuO–NPs
Table 9 Trimethylsilylation of alcohols and phenols catalyzed by PC–NPs
Entry
Substrate
Product
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
9
10
4-ClC6H4CH2OH
4-NO2C6H4CH2OH
3,4-Cl2C6H4CH2OH
4-MeOC6H4CH2OH
2-CH3C6H4CH2OH
4-(CH3)3CC6H4CH2OH
PhCH2OH
4-ClC6H4CH2OTMS
4-NO2C6H4CH2OTMS
3,4-Cl2C6H4CH2OTMS
4-MeOC6H4CH2OTMS
2-CH3C6H4CH2OTMS
4-(CH3)3CC6H4CH2OTMS
PhCH2OTHP
2
11
2
95
90
95
93
95
92
92
92
94
92
2
3
3
5
Ph2CHOH
Ph2CHOTMS
15
20b
10
PhCHOHCH2OH
PhCHOTMSCH2OTMS
11
20
95
12
13
14
15
16
17
18
19
20
21
22
PhOH
PhOTMS
1
2
95
4-ClC6H4OH
4-ClC6H4OTMS
95
4-CH3C6H4OH
4-CH3C6H4OTMS
2
93
0c
0c
0c
4-ClC6H4NH2
4-ClC6H4NHTMS
60
60
30
30
1
4-CH3C6H4NH2
4-CH3C6H4NHTMS
4-CH3C6H4SH
4-CH3C6H4STMS
4-BrC6H4SH
4-BrC6H4STMS
0c
4-NH2C6H4OH
4-NH2C6H4OTMS
93
4-MeOC6H4CH2OH + 4-BrC6H4SH
2-BrC6H4CH2OH + 4-CH3C6H4NH
PhOH + 4-BrC6H4SH
4-MeOC6H4CH2OTMS + 4-BrC6H4STMS
2-BrC6H4CH2OTMS + 4-CH3C6H4NTMS
PhOTMS + 4-BrC6H4STMS
1
100 + 0d
100 + 0d
100 + 0d
2
2
Products were characterized by their physical constants, comparison with authentic samples and IR and 1H NMR spectroscopy
a
Isolated yields
b
2 mmol of HMDS and 40 mg of P4VPy–CuO–NPs were used
c
The starting material was recovered unchanged
d
Selective trimethylsilslstion of alcohol, phenol and aniline in the presence of amines and thiols; conversion
Table 10 Comparison of the results obtained from the trimethylsilyl protection of 4-chlorobenzyl alcohol in the presence of various catalysts
Entry
Catalyst
Condition
Substrate/reagent (molar ratio)
Time (min)
Yield (%)
References
1
2
3
4
5
P4VPy–CuO–NPs (20 mg)
Zirconyl triflate (0.5 mol %)
Fe(HSO4)3 (87 mg)
CH3CN, reflux
CH3CN, r.t.
1:1
2
1
95
100
55
This work
[11]
1:2
CH3CN, reflux
CH3CN, r.t.
1:1
120
8
[50]
Rice husk (80 mg)
1:0.7
1:0.6
93
[42]
Sulfonic acid-functionalized
ordered nanoporous
silica (3 mol %)
CH2Cl2, r.t.
75
95
[12]
1 3

J IRAN CHEM SOC
Table 11 Comparison of the results obtained from the protection
of 4-chlorobenzyl alcohol in the presence of P4VPy, bare CuO and
P4VPy–CuO–NPs
catalyst was washed well with acetone, then dried at 60 °C
prior to use and tested for its activity in subsequent run and
the fresh catalyst was not added. It was seen that the cata-
lyst displayed very good reusability (Fig. 5).
Entry
Catalyst
Time(min)
Conversion(%)a
Although the actual role of P4VPy–CuO–NPs is not
clear, but increasing the catalytic activity of P4VPy–CuO
nanoparticles in comparison with CuO and P4VPy directed
us to accept that the combination of P4VPy and CuO causes
a synergistic effect in their catalytic activity. This section of
the study is under investigation in our laboratory.
1
P4VPy
3
30
2
90b
60b
95b
95c
2
CuO
3
P4VPy–CuO
P4VPy
4
2
5
CuO
30
1
60c
6
P4VPy–CuO
P4VPy
100c
95d
50d
100d
95e
50e
100e
7
2
8
CuO
30
1
Conclusions
9
P4VPy–CuO
P4VPy
10
11
12
10
30
2
In conclusion, we have prepared, identified and used
P4VPy–CuO–NPs as a novel recyclable catalyst for the
promotion of the acetylation, methoxymethylation, tet-
rahydropyranilation and trimethylsilylation reactions. The
most important advantages of the presented procedure are
(1) simplicity of the operation and workup, (2) ease of the
preparation of the catalyst (3) very mild conditions, (4)
good reusability, (5) chemoselectivity, (6) short reaction
CuO
P4VPy–CuO
a
GC
b
Acetylation
c
d
e
Methoxymethylation
Tetrahydropyranylation
Trimethylsilylation
Table 12 Homoselective protection of 4-chlorobenzyl alcohol in the presence of P4VPy–CuO–NPs
Entry
1
Substrate
Products
Time (min)
5
Conversion (%)a
100
2
3
4
5
6
7
8
3
5
100
100
100
100
100
100
100
6
30
15
10
35
a
GC
1 3

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