α-ZrP/Uracil/Cu2+ nanoparticles as an efficient catalyst in the Morita-Baylis-Hillman reaction

Article abstract of DOI:10.1002/aoc.4487

A facile synthesis of uracil-Cu²⁺ nanoparticles immobilized on alpha-zirconium hydrogen phosphate (α-ZrP), abbreviated as α-ZrP/Uracil/Cu²⁺, was presented. This compound was synthesized by the thermal method and used as a reusable ca

Full text of DOI:10.1002/aoc.4487

Received: 7 March 2018
DOI: 10.1002/aoc.4487
Revised: 5 May 2018
Accepted: 26 May 2018
F U L L P A P E R
2
+
α‐ZrP/Uracil/Cu nanoparticles as an efficient catalyst in
the Morita‐Baylis‐Hillman reaction
Abdol R. Hajipour
| Saedeh Zakery
Pharmaceutical Research Laboratory,
Department of Chemistry, Isfahan
University of Technology, Isfahan
2
+
A facile synthesis of uracil‐Cu nanoparticles immobilized on alpha‐zirco-
2+
nium hydrogen phosphate (α‐ZrP), abbreviated as α‐ZrP/Uracil/Cu , was pre-
sented. This compound was synthesized by the thermal method and used as a
reusable catalyst for the Morita‐Baylis‐Hillman reaction without any additives.
First, (3‐ iodopropyl) trimethoxysilane as a linker is reacted with α‐ZrP support
to give the α‐ZrP/IPTMOS. Addition of uracil and then the addition of copper
(II) acetate to α‐ZrP/IPTMOS results in the production of selected catalyst. The
84156‐83111, Iran
Correspondence
Abdol R. Hajipour, Pharmaceutical
Research Laboratory, Department of
Chemistry, Isfahan University of
Technology, 84156‐83111, Isfahan, Iran.
Email: haji@cc.iut.ac.ir
2+
Morita‐Baylis‐Hillman reaction catalyzed by α‐ZrP/Uracil/Cu demonstrated
high product yield, short reaction time and a straightforward work‐up. The
catalyst with enough outside surface was easily recovered using centrifugation
and reused five times without a significant reduction in its activity.
KEYWORDS
Morita‐Baylis‐Hillman reaction, nanocatalyst, uracil, zirconium hydrogen phosphate support
[
14]
1
| INTRODUCTION
vinyl system and electrophile
can improve the reaction
conditions. Many additives were also used as co‐catalyst
to accelerate this reaction, such as La (OTf) ,
[
15]
The Morita Baylis‐Hillman reaction (MBH) has been used
in the various synthetic methodologies for making the
carbon–carbon bonds.
bonding in an activated vinyl system to electrophilic
carbon (sp ) in carbonyl compounds, catalyzed by the
nucleophilic catalyst such as tertiary amines and
phosphines (Scheme 1).
MBH reaction, allylic alcohols, are used as the building
block for the synthesis of natural compounds and
lithium
One of
3
[
16]
[17]
[18]
perchlorate,
urea
and BrØnsted acid.
[1–4]
It includes the α‐carbon
the most challenges in the MBH reaction is to design a
suitable and renewable catalyst to improve the reaction
rate. The focus and main goal of this research are to the
preparation of a new nanocatalyst without any additives
to reduce the MBH reaction time and increase its effi-
ciency. {Uracil‐Cu}‐propyltrimethoxysilane immobilized
on alpha‐zirconium hydrogen phosphate used in this
reaction. ZrP is an important class of crystalline layered
2
[5,6]
Multifunctional products of
[7,8]
drugs.
properties.
Most of these compounds have biological
[8,9]
[19]
Also, these products can play the role of
multi‐functional materials with well‐ordered structure
which has been synthesized by various methods.
[20,21]
starting material or intermediate on total synthesis in
organic chemistry.
A brief survey in the old published articles displays
that, the MBH reactions suffered from a low reaction
rate.
drawn to the design of different methods to increase the
MBH reaction rate and yield. Based on previous
researches,
In
[6,10,11]
the layered structure of this material, the Zr (IV) ions
are located on the top and bottom of each layer. By
connecting each Zr cations to the three oxygen atoms
of the phosphate groups, the hydroxyl group of the
phosphate groups points to the interlayer space and
interacts chemically with water molecules located
4+
[12]
Therefore, the attention of scientists has been
[
4,5]
the
use
of
high
pressures,
between the layers. In the presence of these hydrogens,
[
12]
[13]
[21]
organocatalysis,
type of ligands
and the activated
ZrP will be a Brønsted acid.
Due to the presence of
Appl Organometal Chem. 2018;e4487.
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https://doi.org/10.1002/aoc.4487

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HAJIPOUR AND ZAKERY
TPD‐NH3 with a Quantachrome ChemBET 3000 was
used for the measuring the total acidity of α‐ZrP. FT‐IR
spectroscopy (JASCO FT‐IR 680‐Plus spectrophotometer)
was employed for characterization of the α‐ZrP/Uracil/
2
+
Cu
catalyst. Also Inductive coupled plasma Perkin
1
Elmer Optima 7300 DV was used. H NMR spectra was
recorded with a Bruker (300 MHz) Avance DRX in the
[4]
SCHEME 1 The MBH reaction
pure DMSO‐d solvent with tetramethylsilane as internal
6
2+
standard. TGA of the α‐ZrP/Uracil/Cu catalyst was
conducted using a lab‐made TGA instrument.
the hooked P‐OH groups on the surface of ZrP, it will be
used as a suitable support for immobilization various
materials such as drugs, enzymes (enzyme‐controlled
2
.1 | α‐ZrP preparation
[20,22,23]
drug delivery) and catalysts.
Immobilized catalysts
[
24]
can be prepared by a linker with long alkyl chain
to
A
20% solution of Polyvinylpyrrolidone (PVP)
connect a homogeneous catalyst to a solid support.
Hence, this material has been used as a heterogeneous
solid acid catalyst in many organic synthesis reac-
(Mw = 40,000) was prepared by dissolving the polymer
in deionized hot water under stirring at 90 °C. Then the
pH value was adjusted by adding HCl to below 2.
Zirconyl chloride octahydrate (ZrOCl ·8H O) was used
[25,26]
tions.
The layered structure of these compounds
2
2
results in the interlayer intercalation of many compounds
as a zirconium source in this experiment. 30 ml of the
1 M solution of ZrOCl ·8H O was added dropwise to the
[27,28]
into ZrP, especially type of drugs.
Previous
2
2
researches have shown the potential for conversion of
PVP solution and heated at 80 °C for 12 hr using
magnetic stirrer. By adding a drop by drop of 10 ml
concentrated phosphoric acid to the previous homoge-
neous solution, zirconium phosphate begins to produce.
After 3 hours, the stirring was stopped and the mixture
was kept at ambient temperature for 10 hr. After this
step, the resulting precipitate was filtered and washed
with ethanol and distilled water. The obtained white
powder was finally dried in an oven at 70 °C overnight.
In order to decompose the polymer chains, white
powder was calcined at 600 °C for 3 hours. The final
product is α‐ZrP nanoparticles.
[29–31]
[21,32]
ZrP to nanoparticles,
composites.
nanoplates
There are some new polymers such as
polyvinylpyrrolidone polymers (PVP) based precursor
and nano-
[33,34]
[34–36]
methods to prepare nanoparticles.
These polymers,
as the dispersing agents, can play an important role in
[37,38]
the production of nano‐sized particles.
The best type
of crystalline ZrP is α‐phase. Its composition has been
[39–41]
defined as Zr (HPO ) .H O.
In previous studies,
4
2
2
the interlayer spacing of 7.4–7.6°A for the planes of this
compound is revealed by X‐ray powder diffraction
[31,42,43]
(XRPD).
According to the latest literature, there is no report to
use ZrP‐based nanocatalysts for MBH reaction. Accord-
ingly, in continuation of our research, to design an effi-
cient catalyst, we have investigated MBH reaction over
α‐ZrP/Uracil/Cu nanoparticles under different condi-
tions. The reaction conditions such as solvent, the
amount of catalyst and temperature were tested in details.
2+
2.2 | α‐ZrP/Uracil/Cu preparation
2 g of α‐ZrP in 40 ml of dry toluene was dispersed for
1 hour, then 3.5 mmol of IPTMOS was added to the pre-
vious mixture and refluxed to 100 °C for 48 hr. After that
time, the resulting precipitate was filtrated, washed with
dichloromethane and dried at room temperature. In a
round‐bottomed flask, 2 g of dried powder, 15 ml of
DMF, 2 mmol of uracil (0.22 g) and 3 mmol of cesium
carbonate (0.96 g) were added. This mixture was heated
at 80 °C for 24 hours under argon. After this step, the
white precipitate was collected and washed with ethanol
several times. The powder drying was carried out in a
vacuum oven at 50 °C overnight. In order to add a cata-
lyst metal section, 1 g of the modified support is dispersed
in 30 ml of ethanol. Then 0.2 g of copper (II) acetate
monohydrate was dissolved in 10 ml of ethanol and was
added to the dispersed mixture over two hours. The
resulting mixture stirred for 1 hr at room temperature
and then was sonicated for 15 min. The precipitate was
2+
2
| EXPERIMENTAL
All chemical reagents were purchased from Aldrich and
Merck Chemical Company and were used without
further purification. X‐ray diffraction (XRD) powder
patterns were obtained using a Philips X'pert X‐ray
diffractometer, with Cu Kα radiation (40 kV, 30 mA).
The Brunauer–Emmett‐.
Teller (BET) method on a Quantachrome ChemBET
3
000 instrument was used for N adsorption–desorption
2
isotherm. TEM (Philips CM10 microscope) and SEM
MIRA3 TESCAN) were used to characterize the catalyst.
(

HAJIPOUR AND ZAKERY
3 of 12
collected and washed with acetone and ethanol. After
drying in a vacuum oven at 50 °C, the desired catalyst
was obtained as a blue solid.
F. 2‐(hydroxy (phenyl)methyl)cyclopent‐2‐en‐1‐one
1
Brown solid, mp: 162–163 °C; H NMR (300 MHz,
DMSO‐d6): δ 2.30 (t, J = 8 Hz, 2H), 2.56 (m, 2H), 3.64
(
s, 1H), 5.32 (s, 1H), 5.64 (t, J = 8 Hz, 1H), 7.31
2
.3 | MBH reaction catalyzed by α‐ZrP/
2+
(m, 5H).
Uracil/Cu
To a solution of methyl acrylate (1.2 mmol) and aldehyde
1 mmol) in 3 ml DMF, 20 mg of catalyst was added and
G. 2‐(hydroxy (4‐methoxyphenyl)methyl)acrylamide
(
1
stirred at room temperature for 12 hours. The progress of
the reaction was monitored by TLC. After consumption
of aldehyde, the reaction mixture was cooled and then
the catalyst was separated by centrifugation. After
extraction the remaining solution with ethyl acetate
Brown solid, mp: 148–149 °C; H NMR (300 MHz,
DMSO‐d6): δ 2.72 (s, 1H), 3.74 (s, 3H), 4.49 (s, 1H), 4.91
(s, 1H), 5.48 (s, 1H), 6.35 (dd, J = 10 Hz, 2H), 7.25 (dd,
J = 10 Hz, 2H), 7.70 (t, J = 2 Hz, 2H).
(
3 × 10 ml), the organic phase was dried by CaCl . The
2
product was purified by column chromatography (n‐hex-
ane/ethyl acetate, 3:1). The physical and spectroscopic
data for selected compounds are listed below and the
original spectra for these molecules could be found in
the supporting information file.
3
| RESULTS AND DISCUSSION
.1 | Support material
3
Initially, α‐ZrP nanoparticles as support with an average
particle size of 65 nm have been prepared. By adding
4
+
A. Methyl 2‐(hydroxy (pyridin‐3‐yl)methyl)acrylate
phosphate ions to the PVP/Zr solutions, a white solid
product, namely α‐ZrP, was quickly formed. Polymeric
chains of PVP, like a capsule around Zr (IV) ions, pre-
vent them from sticking together. Also, this organic
1
White solid, mp: 170–172 °C; H NMR (300 MHz,
DMSO‐d6): δ 3.71 (s, 3H), 4.85 (s, 1H), 5.61 (s, 1H), 6.01
s, 1H), 6.40 (s, 1H), 7.27 (dd, J = 12 Hz, 1H), 7.74 (d,
[26]
(
matrix can act as the dispersing agent of particles.
J = 6.0 Hz, 1H), 8.45 (d, J = 15.0 Hz, 2H).
H‐bond interactions between the polar sites of polymer
chains, water molecules around the Zr (IV) ions and
the P‐OH groups of α‐ZrP have an effective role in the
better distribution of α‐ZrP particles. After calcination
of PVP/ZrP at 600 °C for 3 hr and decomposition of
the polymer chains, pure α‐ZrP nanoparticles were
obtained. A brief synthetic route for the preparation of
these nanoparticles is depicted in Scheme 2. FT‐IR
Spectroscopy was used to confirm the structure of α‐ZrP
B. Methyl 2‐(hydroxy (naphthalen‐2‐yl)methyl)acrylate
1
White solid, mp: 132–134 °C; H NMR (300 MHz,
DMSO‐d6): δ 3.23 (s, 1H), 3.60 (s, 3H), 5.63 (s, 1H), 5.79
(s, 1H), 6.29 (s, 1H), 7.38 (m, 3H), 7.72 (m, 4H).
C. Methyl 4‐(1‐hydroxy‐2‐(methoxycarbonyl)allyl)benzoate
(
Figure 1). As can be observed, there are several main
1
−1
White solid, mp: 140–142 °C; H NMR (300 MHz,
DMSO‐d6): δ 3.68 (s, 3H), 3.87 (s, 4H), 5.57 (s, 1H), 5.88
(
absorption bands in 3435, 1630, 1070 and 605 cm .
The broad band at 3435 cm and the sharp band at
1630 cm ascribed to the asymmetric O‐H stretching
and bending of the O‐H bonds, respectively. The strong
sharp and broad band at 1070 cm corresponded to
the P‐O symmetrical stretching vibration of PO4
groups. Also, Zr‐O bond stretching vibrations located at
605 cm (Figure 1).
−
1
−
1
s, 1H), 6.33 (s, 1H), 7.43 (d, J = 12 Hz, 2H), 7.96 (d,
J = 12 Hz, 2H).
−
1
3
−
D. Methyl 2‐(hydroxy (3‐methoxyphenyl)methyl)acrylate
1
−1
[44,45]
Yellow solid, mp: 151–153 °C; H NMR (300 MHz,
DMSO‐d6): δ 3.19 (s, 1H), 3.63 (s, 3H), 3.73 (s, 3H), 5.44
The nitrogen adsorption–desorption isotherm (the
BET method) was used to investigate the α‐ZrP specific
surface area. Before each analysis, in order to remove
any adsorbent on the surface, the sample was degassed
at 400 °C for 3 hr. Three adsorption stages are recogniz-
able from the isotherm. The first stage is in P/Po < 0.38,
the next stage is in 0.38 < P/Po < 0.86 and the third stage
in higher partial pressure (P/Po > 0.86). The total surface
(s, 1H), 5.76 (s, 1H), 6.25 (s, 1H), 6.73 (dd, J = 9 Hz,
1
H), 6.85 (m, 2H), 7.17 (m, 1H).
E. Methyl 2‐(hydroxy (3‐nitrophenyl)methyl)acrylate
White solid, mp: 133–135 °C; δ 3.63 (s, 3H), 5.60 (s, 1H),
6
.10 (s, 1H), 6.14 (s, 1H), 6.29 (s, 1H), 7.63 (t, J = 15 Hz,
2
−1
1
H), 7.78 (d, J = 9 Hz, 1H), 8.14 (m, 2H).
area of 120.1 m g was obtained. As shown in Figure 2,

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HAJIPOUR AND ZAKERY
3 4 2
SCHEME 2 Preparation of α‐ZrP nanoparticles: (a) 12 M H PO , H O, reflux, 6 h; (b) Calcination at 600 °C, 3 hr
FIGURE 3 TPD ammonia curve over α‐ZrP
FIGURE 1 FT‐IR spectra of α‐ZrP
the weak acidic sites. The NH desorption temperature
3
peak at 250‐450 °C belongs to the moderate acidic sites.
Finally, the desorption peak at 450‐650 °C shows the
[
46–48]
strong acidic sites on the surface of α‐ZrP.
This
indicates that the acidity of the α‐ZrP is in the moderate
−
1
range (1.65 mmol NH g ) which is attributed to the
3
presence of P‐OH groups on the surface of α‐ZrP.
3
.2 | Surface modification of α‐ZrP with
immobilization of the linker
Linker 1 (IPTMOS) has been immobilized on the α‐ZrP
surface to form 1a using the reported method for
[
49–53]
FIGURE 2 Nitrogen adsorption–desorption isotherms of α‐ZrP
immobilization on oxide supports (Scheme 3).
The
compound 1a was prepared by heating a mixture of 1
and α‐ZrP in dry toluene to 100 °C for 48 hr. The
increase in absorption at a higher relative pressure (P/Po)
indicates a large surface area in the α‐ZrP structure.
[
26]
Thermodesorption curves for ammonia (NH ‐TPD)
3
has been used to measure the surface acidity of the α‐ZrP
(Figure 3). The absorption of ammonia by α‐ZrP is carried
out at a temperature between 150 to 650 °C, which corre-
sponds to the number of medium and the strong acidic
sites. The desorption peak below 250 °C demonstrates
SCHEME 3 Surface modification of α‐ZrP

HAJIPOUR AND ZAKERY
5 of 12
prepared material 1a is separated from the reaction media
by filtration and washed with dry toluene. Finally, after
drying, a white powder is obtained. This material was
analyzed by XRD, FT‐IR and ICP‐OES. The powder
XRD patterns of the α‐ZrP and 1a are shown in
Figure 4a and b. Similar reflections are observed in the
X‐ray diffractogram of two compounds in the 2θ range
o
of 5‐40 . It is observed that the peaks are broadened after
o
immobilization. According to the peak at 2θ = 12 the
[
31,54]
basal spacing of the (002) plane in α‐ZrP is 7.5 Å.
Above all, 1a is not entered between the α‐ZrP layers
during the immobilization process because the same
interlayer spacing is exactly observed in 1a (Figure 4b).
The FT‐IR spectra of 1 and 1a are shown in Figure 5a
and b. The Specific bands of 1 appearing at 2943 and
−
1
3
2
841 cm correspond to the sp C‐H stretching of methy-
lene groups. The observation of this absorption band at
−
1
2
924 and 2854 cm and also the main characteristic bands
−
1
of α‐ZrP at 3422, 1637, 1061 and 607 cm in the FT‐IR
spectra of 1a is a proof of immobilization of the linker 1.
ICP‐OES analysis was used to determine the Zr and Si
contents of the 1a. These analytical results are Zr (11.20),
Si (1.46), P (19.1) and O (61.23) wt. %.
FIGURE 5 FT‐IR spectra of 1 (a) and 1a (b)
3.3 | Immobilization of the catalyst
The immobilized catalyst 1b has been obtained from 1a
by iodine exchange with uracil and addition of Cu
(
OAc) at 110 °C (Scheme 4).
2
The important point is uracil does not intercalate
between the α‐ZrP layers (Figure 6). Also, copper has
not been replaced by the hydrogen atoms of P‐OH
SCHEME 4 Formation of the immobilized catalyst 1b
[55]
groups.
This is investigated by the XRD pattern of
1
b, which indicates that the peak corresponding to the
FIGURE 6 XRD pattern of 1b
layer spacing of 7.5 Å in analogy to the display in
Figure 4.
In the FT‐IR spectrum of uracil, the main characteris-
tic vibrational band appears in 3112, 1710, 1630, 1507,
FIGURE 4 XRD pattern of α‐ZrP (a) and 1a (b)

6
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HAJIPOUR AND ZAKERY
−
1 [56]
1
451, 1414 and 1387 cm .
The observation of the
main absorption bands of 1a and uracil with variations
in the frequency in the FT‐IR spectrum of 1b is a reason
[
57–59]
for iodine substitution with uracil (Figure 7).
The presence of C, O, N, Zr and Cu in the structure of
1b as the catalyst were confirmed by EDS analysis
(
Figure 8). The CHNS analysis also showed the exact con-
tents of these elements; C: 15.09%, H: 1.53% and N: 4.60%.
The quantitative of the Zr, Si and Cu contents, as
determined by ICP‐OES were obtained to be 10.67, 0.95
and 1.07%, respectively.
SEM microscopy was used for nanocatalyst surface
analysis. As shown in Figure 9a, the SEM micrograph a
series of uniform particles with a smooth surface and a
large dispersion. The TEM image confirms good
monodispersity of nanoparticles (Figure 9b). Using the
Dynamic light scattering (DLS) method, the average
particle size of the catalyst was calculated to be 62 nm
FIGURE 7 FT‐IR spectra of 1b
(
Figure 9c).
Thermogravimetric analysis (TGA) was used to
measure the thermal stability of catalyst (Figure 10). As
shown in the curve, approximately 7% of the weight was
lost from room temperature to 120 °C is related to the loss
FIGURE 8 EDS spectrum of 1b as catalyst
FIGURE 9 SEM photograph of nanocatalyst (a), TEM image of nanocatalyst (b) The histogram of the particle size distribution (c)

HAJIPOUR AND ZAKERY
7 of 12
TABLE 1 The effect of catalyst amount for the reaction of methyl
a
acrylate with 4‐methoxybenzaldehyde
The % conversion of
The catalyst
amount (mg)
methyl acrylate/
4‐methoxybenzaldehyde
b
Entry
1
2
3
4
5
6
7
8
5
7
45
47
60
71
80
89
96
78
10
12
15
17
20
22
FIGURE 10 TGA curve of catalyst
of water molecules. The second weight loss (16%) in the
range of 140 to 440 °C is attributed to the condensation
of P‐OH groups. After this temperature, no weight loss
[60]
a
was observed at 700 °C.
Reaction conditions: methyl acrylate (1.2 mmol), 4‐methoxybenzaldehyde
1.0 mmol), r. t., time (12 hr) and DMF (3.0 ml).
(
b
isolated yield.
3.4 | Catalytic activity
After preparation and characterization of the catalyst, the
catalytic activity was tested in MBH reaction, using
methyl acrylate and 4‐methoxybenzaldehyde as the
model substrates by changing the reaction parameters
such as the amount of catalyst, reaction temperature,
the molar ratio of reactants, type of aldehyde and solvent.
3.4.1 | The effect of catalyst amount
The reaction was carried out under the following condi-
tions in the presence of 5–50 mg of catalyst:
room temperature, reaction time 12 hr and methyl
acrylate/4‐methoxybenzaldehyde mole ratio 1:1.
The results of the % conversion of methyl acrylate/4‐
methoxybenzaldehyde to the reaction product are shown
in Table 1. By increasing the mass of catalyst from 5 to
SCHEME 5 The proposed mechanism for MBH reaction
2
4
0 mg, the conversion of two substances increases from
5 to 96%, which is due to the increase in the number
methyl acrylate and aldehyde with copper as a catalyst
metal section leads to the activation of the carbonyl
of catalyst active sites but the mass of more than 20 mg
reduces the reaction efficiency. The proposed mechanism
is presented in Scheme 5. Step 1 involves a Michael‐type
addition of the catalyst from nitrogen (*) to the beta‐car-
[
13,61]
groups (Scheme 6).
As a result, the Michael‐type
addition in step 1 and the nucleophilic attack in step 2
are better done.
[57,58]
bon of the alkene.
The resulting zwitterionic
compound (A) is formed. In step 2 (as the rate‐determin-
ing step (RDS)), by the nucleophilic attack of (A) on the
aldehyde, intermediate B is formed. Finally, the product
C is produced by transferring, removing hydrogen, and
exiting the catalyst.
It is guessed that increasing the catalyst content by
more than 20 mg can prevent the effective interactions
between substance molecules in step 2. For this reason,
the percentage of conversion is reduced. As noted in
Section 1, a metal can accelerate the catalysis of the
SCHEME 6 Metal can accelerate the catalysis of the MBH
reactions
[13]
MBH reactions.
The interaction of carbonyl groups in

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HAJIPOUR AND ZAKERY
TABLE 3 The effect of molar ratio of reactants for the reaction of
methyl acrylate with 4‐methoxybenzaldehyde
3
.4.2 | The effect of reaction temperature
a
and solvent
The mole ratio of
methyl acrylate/
The
MBH
reaction
of
methyl
acrylate/4‐
methoxybenzaldehyde was carried out from room tem-
perature (25 °C) to 40 °C. As is clear from results, the
increase in temperature did not affect the reaction effi-
ciency. So the ambient temperature was chosen as the
optimum temperature for the reaction (Table 2, Entry 1).
The solvent effect for the MBH reaction was also
surveyed. The best result was obtained in the presence
of DMF as solvent (Table 2, Entry 1).
b
Entry
4‐methoxybenzaldehyde
Yield
1
2
3
4
5
6
7
1:1
85
96
91
80
76
95
90
1.2:1
1.4:1
1.6:1
1.8:1
1.2:1.1
1.2: 1.3
a
3
.4.3 | The effect of molar ratio of
Reaction conditions: time (12 hr), amount of catalyst (20 mg), r. t. and DMF
3.0 ml).
(
b
reactants and type of aldehyde
isolated yield.
Several tests were performed to establish the effect of
reactant ratio on % conversion by changing the mole ratio
of the methyl acrylate/4‐methoxybenzaldehyde from 1:2
to 2:1, in the same conditions (Table 3). It was observed
that when the mole ratio of methyl acrylate/4‐
methoxybenzaldehyde was changed from 1:1 to 1.2:1, the
percentage of conversion increased (From 85% to 96%).
The change in the mole ratio of 4‐methoxybenzaldehyde/
methyl acrylate from 1:1 to 2:1 did not affect the conver-
sion. Thus, the optimum mole ratio was found to be 1.2:1
for methyl acrylate/4‐methoxybenzaldehyde (Table 3,
Entry 2). According to the proposed mechanism in ‘The
effect of catalyst amount’ section, with an increase in the
concentration of methyl acrylate, the contact surface of
this material with the catalyst active sites as the starting
point of the MBH reaction increases. Therefore, better
conditions for the absorption of aldehyde molecules are
provided. But increasing the mole ratio of tow materials
to more than 1.2:1, increases the steric hindrance around
the catalyst surface. Therefore, aldehyde molecules
cannot approach the catalytic effective surface (Table 3,
Entry 4–7). This problem reduces the conversion of raw
materials to the reaction product.
Finally, the effect of the selected aldehydes on the
reaction efficiency has been studied (Table 4). The
results showed that the MBH reaction in the presence
of an activated vinyl system with aldehydes carrying
electron‐withdrawing substituents has a higher efficiency
TABLE 4 The MBH reaction of various aldehyde with methyl
a
acrylate
b
Entry
Aldehyde
Time (h)
Yield (%)
1
Benzaldehyde
12
10
12
10
8.5
12
12
10
12
11
11
11
76
95
90
95
100
92
87
98
93
90
92
90
TABLE 2 The effect of temperature and solvent for the reaction
2
3‐Nitrobenzaldehyde
3‐Methoxybenzaldehyde
Methyl 4‐formylbenzoate
3‐Pyridinecarboxaldehyde
4‐Bromobenzaldehyde
4‐Methoxybenzaldehyde
2‐Naphthaldehyde
a
of methyl acrylate with 4‐methoxybenzaldehyde
3
b
Entry
T (°C)
solvent
Yield
4
1
2
3
4
5
6
7
8
25
30
35
40
25
25
25
25
DMF
DMF
DMF
DMF
DMSO
96
95
95
96
92
80
86
75
5
6
7
8
9
4‐Chlorobenzaldehyde
2‐Bromobenzaldehyde
Salicylaldehyde
CH
3
CN
10
11
12
THF
EtOH
5‐Bromosalicylaldehyde
a
a
Reaction conditions: methyl acrylate (1.2 mmol), 4‐methoxybenzaldehyde
1.0 mmol), time (12 hr), amount of catalyst (20 mg) and DMF (3.0 ml).
Reaction conditions: aldehyde (1.0 mmol), methyl acrylate (1.2 mmol),
(
DMF (3 ml), catalyst (20 mg), r. t.,
b
b
isolated yield.
isolated yield.

HAJIPOUR AND ZAKERY
9 of 12
and shorter time than other aldehydes carrying electron‐
releasing substituents. Compared with other aldehydes,
3‐pyridinecarboxaldehyde acts as a very active substance
and the reaction is performed in its presence with
excellent efficiency and low time (Table 4, Entry 5).
In Table 5, instead of methyl acrylate, 2‐
cyclopentenone and acrylamide were used as acceptor.
The results of the aldehyde type in section ‘The effect of
molar ratio of reactants and type of aldehyde’ are also
observed in this section. In addition, methyl acrylate is
more effective than the other active vinyl systems used
in this MBH reaction.
FIGURE 11 Recyclability of the catalyst
thoroughly with ethyl acetate. The catalyst was dried at
0 °C and reused for the next run. The recycling test
5
3
.4.4 | Recyclability characteristic of
showed that the catalyst was used up to 5 times without
significantly reducing the reaction efficiency. The catalyst
activity and the conversion of reactants to the product
were reduced after the 5th runs. This observation was
supported by XRD and TEM analysis of the recycled
catalyst. The XRD patterns of the new and recovered
catalyst are similar but the peaks are broadened in the
XRD pattern of the recovered catalyst after being sub-
jected to 5 runs (Figure 12).
catalyst
The ability to recycle the catalyst determines its
sustainability. The regenerated catalyst and its recycling
characteristic have been studied. This is represented in
Figure 11. In order to investigate this property, the
MBH reaction between methyl acrylate and 4‐
methoxybenzaldehyde was performed in the presence of
2+
α‐ZrP/Uracil/Cu
as the model reaction under the
optimum conditions. At the end of the reaction, the
catalyst was separated by centrifugation and washed
As shown in Figure 13, the TEM images of the
recycled catalyst and the fresh catalyst are very similar
a
TABLE 5 The MBH reaction of various aldehyde with activated vinyl
b
Entry
Aldehyde
activated vinyl
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
Benzaldehyde
2‐cyclopentenone
2‐cyclopentenone
2‐cyclopentenone
2‐cyclopentenone
2‐cyclopentenone
acrylamide
15
13
15
15
12
15
13
15
13
12
74
90
83
90
92
70
80
77
85
85
3‐Nitrobenzaldehyde
4‐Methoxybenzaldehyde
2‐Naphthaldehyde
3‐Pyridinecarboxaldehyde
Benzaldehyde
3‐Nitrobenzaldehyde
4‐Methoxybenzaldehyde
2‐Naphthaldehyde
acrylamide
acrylamide
acrylamide
1
0
3‐Pyridinecarboxaldehyde
acrylamide
a
Reaction conditions: aldehyde (1.0 mmol), activated vinyl (1.2 mmol), DMF (3 ml), catalyst (20 mg), r. t.,
b
isolated yield.

10 of 12
HAJIPOUR AND ZAKERY
3
.4.5 | The importance of α‐ZrP in the role
2+
of α‐ZrP/Uracil/Cu as a catalyst in MBH
reaction
For this purpose, Non‐supported 1‐methyluracil/Cu (II)
catalyst was prepared. This way, 1‐methyluracil was
purchased from Sigma‐Aldrich. The synthesis of 1‐
methyluracil/Cu (II) was performed according to the
[
62]
reported methodology.
After preparation of 1‐
methyluracil/Cu (II), this combination as the catalyst
was tested in MBH reaction, using methyl acrylate and
4‐Methoxybenzaldehyde as the model reaction. After
th
48 hr, the reaction was carried out to 70% efficiency. In
the meantime, catalyst separation was very difficult and
its ability to recover and reuse was zero. The MBH reac-
tion with 4‐Methoxybenzaldehyde and 2‐cyclopentenone
was also carried out in the presence of 1‐methyluracil/
Cu (II) as the catalyst. After 48 hr, the reaction was car-
ried out to 55% efficiency. The presence of α‐ZrP as a
nanosupport plays a very important role in the α‐ZrP/
FIGURE 12 XRD pattern of catalyst after 5 runs
2+
Uracil/Cu function as a catalyst in the Morita‐Baylis‐
Hillman reaction.
4
| CONCLUSIONS
Briefly, we have reported the preparation of a new and
efficient heterogeneous catalyst based on α‐zirconium
phosphate (α‐ZrP) nanoparticles for the Baylis‐Hillman
reaction. α‐ZrP serves as a sustainable support for
(
3‐ iodopropyl) trimethoxysilane as a linker, uracil as a
ligand and Cu (II) as a metal section in the catalyst
structure. The linker and ligand do not intercalate into
the layers of the α‐ZrP support. These factors, in addition
to increasing the reaction efficiency, significantly reduce
the reaction time. The prepared catalyst can be easily
recycled and this catalytic system offers negligible
leaching of Cu (II) to the reaction media and high cata-
lytic activity over five successive runs. In general, this
research is the first report of applying the {uracil‐Cu}‐
propyltrimethoxysilane immobilized on α‐ZrP nanopar-
ticles as an effective catalyst in the Morita‐Baylis‐Hillman
Reaction.
th
FIGURE 13 TEM image of catalyst after 5 runs
and there is no noteworthy change in the recovered
catalyst structure. In order to prove this point that the
prepared catalyst is heterogeneous, a hot filtration test
was conducted during the reaction of methyl acrylate
and 4‐methoxybenzaldehyde. So that the heterogeneous
catalyst was separated from the hot reaction mixture by
filtration after 6 hr. The remaining solution was then
allowed to react for another 6 hr. The results showed that
in these conditions, the reactants have not been
converted. In addition, the ICP result from the resultant
supernatant showed that only 0.05 ppm of copper species
was lost into solution during the reaction. These
observations are evidence of high catalyst activity and
the catalytic system stability.
ACKNOWLEDGMENTS
The authors are thankful to research Council of Isfahan
University of Technology (IUT), and Isfahan Science
and Technology Town (ISTT) for their supports.
The results of the nitrogen adsorption–desorption
analysis of catalyst after 5 runs indicate that the
th
nanoparticles of the catalyst do not clump during the
reaction and maintain their high specific surface area
ORCID
2
−1
(110.7 m g ).
Abdol R. Hajipour http://orcid.org/0000-0002-7737-0558

HAJIPOUR AND ZAKERY
11 of 12
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How to cite this article: Hajipour AR, Zakery S.
2+
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α‐ZrP/Uracil/Cu nanoparticles as an efficient
catalyst in the Morita‐Baylis‐Hillman reaction.
Appl Organometal Chem. 2018;e4487. https://doi.
org/10.1002/aoc.4487
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.