Application of Pd-2A3HP-MCM-41 to the Suzuki, Heck and Stille coupling reactions and synthesis of 5-substituted 1H-tetrazoles

Article abstract of DOI:10.1002/aoc.3494

An ecofriendly heterogeneous catalyst has been synthesized by anchoring palladium onto the surface of organically modified mesoporous silica. The prepared catalyst was characterized using X-ray diffraction, Fourier transform infrared and energy-dispersive X-ray spectroscopies, transmission and scanning electron microscopies, inductively coupled plasma and thermogravimetric techniques. The catalyst shows high activity in the Suzuki, Heck and Stille cross-coupling reactions and the synthesis of 5-substituted 1H-tetrazoles from sodium azide (NaN₃). These methods have the advantages of high yields, green reaction conditions, simple methodology and easy separation and workup.

Full text of DOI:10.1002/aoc.3494

Full paper
Received: 17 February 2016
Revised: 13 March 2016
Accepted: 27 March 2016
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.3494
Application of Pd-2A3HP-MCM-41 to the Suzuki,
Heck and Stille coupling reactions and synthesis
of 5-substituted 1H-tetrazoles
Mohsen Nikoorazm*, Arash Ghorbani-Choghamarani
and Maryam Khanmoradi
An ecofriendly heterogeneous catalyst has been synthesized by anchoring palladium onto the surface of organically modified
mesoporous silica. The prepared catalyst was characterized using X-ray diffraction, Fourier transform infrared and energy-
dispersive X-ray spectroscopies, transmission and scanning electron microscopies, inductively coupled plasma and thermogravi-
metric techniques. The catalyst shows high activity in the Suzuki, Heck and Stille cross-coupling reactions and the synthesis of
5-substituted 1H-tetrazoles from sodium azide (NaN3). These methods have the advantages of high yields, green reaction
conditions, simple methodology and easy separation and workup. Copyright © 2016 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: Suzuki; Heck; Stille; 5-substituted 1H-tetrazoles; cross-coupling reactions; mesoporous silica; palladium
require the use of microwaves, homogeneous or non-reusable
and difficult synthetic procedure.
Therefore, in order to overcome some of these drawbacks, herein
Introduction
The Heck,[1] Stille,[2] Kumada,[3] Negishi,[3] Hiyama[4] and Suzuki[5]
reactions are efficient and well-established methods for the con-
struction of new carbon–carbon bonds. Tetrazoles are heterocyclic
compounds having a five-membered ring containing one carbon
and four nitrogen atoms and are unnatural. Recently, tetrazoles
have received considerable attention because they have a wide
range of applications in pharmaceutical science.[6,7] Tetrazoles are
used as plant growth regulators, herbicides and fungicides.[8] They
possess anti-allergic, antihypertensive and antibiotic activities.[9,10]
Amino-substituted tetrazoles have anti-inflammatory[11] receptor
modulator and antiviral[12,13] activities. These reactions are usually
promoted by a Pd-based catalyst, Pd being a precious metal. In this
regard heterogeneous catalysis seems particularly well suited, since
palladium catalysts immobilized on supports such as organic
polymers,[14–19] silica,[20,21] MCM-41,[22] carbon nanotubes,[23–25]
activated carbon,[26,27] clays[28,29] and molecular sieves[30] could
be easily separated from products and recycled without any loss
of metal residues. Among the supports mentioned above, mesopo-
rous silica materials with nano-sized pores and controllable porous
structure and pore volume, a huge specific surface area and excel-
lent stability (chemical and thermal), and the fact that organic
groups can be robustly anchored to the surface to provide catalytic
centres,[31] are some of the most suitable catalyst supports, because
they provide high dispersion of metal nanoparticles and facilitate
the access of substrates to active sites.[32] The majority of novel het-
erogeneous catalysts are immobilized on silica supports.[33] In the
last few years, several procedures including various catalysts have
been reported for C&bond;C coupling reactions and synthesis of
5-substituted 1H-tetrazoles such as: Pd-SH-SBA-15,[34] Pd(II)–MCM-
41,[35] Pd[N-MorphC(S)NP(O)(OiPr)2-O,S]2,[36] Pd(0)-MCM-41,[37]
PEG-Q-PPh2,[38] Pd@MOF-5,[39] Pd@polymer,[40] Pd-dtz-Fe3O4,[41]
Pd@UiO-66[42] and SiO2@Fe3O4–Pd.[43] However, most of them
have some drawbacks such as toxicity, instability, expensive,
we report the use of modified MCM-41 as a catalyst vehicle to sup-
port palladium nanoparticles and the application of the system in
Suzuki–Miyaura, Mizoroki–Heck and Stille coupling reactions and in
the synthesis of 5-substituted 1H-tetrazoles from sodium azide
(NaN3). This catalytic system can be well dispersed in the reaction
medium, conveniently separated from the reaction mixture and
reused several times without significant loss of its activity (Scheme 1).
Experimental
Materials
Tetraethylorthosilicate (TEOS; 98%), cationic surfactant cetyltri-
methylammonium bromide (CTAB; 98%), solvents and other
reagents were purchased from Merck, Aldrich or Fluka and were
used as received without further purification.
Preparation of Pd-2A3HP-MCM-41
Silica MCM-41 was synthesized by adding 1 g of CTAB to a solution
containing 3.5 ml of NaOH solution (2 M) and deionized water
(480 ml) which was stirred at 80 °C. Then, 5 ml of TEOS was slowly
added into the solution. The resulting mixture was refluxed for
2 h at the same temperature. The collected product was washed
with deionized water and calcined at 823 K for 5 h at a rate of
*
Correspondence to: Mohsen Nikoorazm, Department of Chemistry, Faculty of
Science, Ilam University, PO Box 69315516, Ilam, Iran. E-mail: e_nikoorazm@yahoo.
com
Department of Chemistry, Faculty of Science, Ilam University, PO Box 69315516,
Ilam, Iran
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.

M. NIKOORAZM, A. GHORBANI-CHOGHAMARANI AND M. KHANMORADI
2A3HP-MCM-41) was characterized using X-ray diffraction (XRD),
Fourier transform infrared (FT-IR) spectroscopy, energy-dispersive
X-ray spectroscopy (EDS), transmission electron microscopy (TEM),
scanning electron microscopy (SEM), inductively coupled plasma
(ICP) and thermogravimetric analysis (TGA) techniques. The ob-
tained results indicate that Pd-2A3HP was successfully immobilized
onto the modified MCM-41.
General procedure for synthesis of biphenyl derivatives
A mixture of arylhalide (1 mmol), PhB(OH)2 (1 mmol) or Ph3SnCl
(0.5 mmol), base (K2CO3, 3 mmol) and Pd-2A3HP-MCM-41 (4 mg,
0.89 mol%) as catalyst in PEG-400 solvent was stirred at 80 °C for
an appropriate time. The progress of the reaction was monitored
by TLC (eluent: n-hexane–acetone, 8:2). The catalyst was separated
by filtration. After completion of the reaction, the products were ex-
tracted with diethyl ether and water. The solvent was evaporated
and the products were obtained.
General procedure for synthesis of butyl cinnamate derivatives
Scheme 1. Palladium-catalysed C&bond;C bond formation and synthesis
of 5-substituted 1-H-tetrazole.
A mixture of aryl halide (1.0 mmol), n-butyl acrylate (1.2 mmol), base
(K2CO3, 3 mmol), Pd-2A3HP-MCM-41 (4 mg, 0.89 mol%) and 2 ml of
dimethylformamide (DMF) as solvent was stirred at 120 °C for an
appropriate time. The progress of the reaction was monitored by
TLC (eluent: n-hexane–acetone, 8:2). After completion of the reac-
tion, the catalyst was separated by filtration and the products were
extracted with diethyl ether. The solvent was evaporated and the
products were obtained in good to excellent yields.
2 °C minÀ1 to remove the residual surfactant and afford MCM-41.
Post-synthesis organic modification of mesoporous materials was
performed by stirring 4.8 g of MCM-41 with 4.8 g of 3-
chloropropyltriethoxysilane and refluxing in n-hexane (96 ml) for
24 h. The resulting white solid (nPrCl-MCM-41) was filtered, washed
with n-hexane and dried at 70 °C, and then this solid (0.5 g) was
refluxed with trimethylamine (2 mmol, 0.202 g) and 2-amino-3-
hydroxypyridine (2A3HP; 1 mmol, 0.110 g) in toluene for 24 h. The
resulting solid was washed with ethanol, and dried in vacuum. Fi-
nally Pd-2A3HP-MCM-41 was prepared by stirring 2A3HP-MCM-41
(0.25 g) with palladium acetate (0.57 mmol, 0.128 g) in ethanol
(25 ml). The mixture was refluxed at 80 °C for 18 h. Afterward, the
resulting mixture containing palladium(II) was reduced with NaBH4
(0.057 mmol, 0.022 g) under the same conditions for another 2 h.
The resulting black solid impregnated with the metal complex
was filtered and washed with ethanol to afford the grey palla-
dium(0) complex. The grimy solid was filtered, washed with ethanol
and dried under vacuum (Scheme 2). The prepared catalyst (Pd-
General procedure for synthesis of 5-substituted 1 h-tetrazoles
Pd-2A3HP-MCM-41 (30 mg, 6.69 mol %) was added to benzonitrile
(1 mmol), sodium azide (0.08 g, 1.2 mmol) and PEG-400 (2 ml). The
mixture was stirred at 120 °C for 3 h. After completion of the reac-
tion as indicated by TLC (eluent: n-hexane–acetone, 8:2), the cata-
lyst was separated by filtration and the filtrate was treated with
ethyl acetate and 0.1 N HCl (5 ml). The resultant organic layer was
separated and the aqueous layer was extracted with ethyl acetate
(20 ml).
Results and discussion
Figure 1 illustrates the low-angle powder XRD patterns of MCM-41
and Pd-2A3HP-MCM-41 samples. The XRD pattern of MCM-41
shows the presence of three reflection peaks corresponding to
d100, d110 and d200 planes at 2θ = 2.41°, 3.87° and 4.33°, respectively,
Scheme 2. Synthesis of Pd-2A3HP-MCM-41 nanostructure.
Figure 1. XRD patterns of MCM-41 and Pd-2A3HP-MCM-41.
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Appl. Organometal. Chem. (2016)

Organic reactions catalyzed by Pd-2A3HP-MCM-41
typically confirming the presence of ordered hexagonal mesopo-
rous structure of MCM-41. However, upon post-synthetic grafting,
the d110 and d200 reflections are no longer observed and an overall
decrease in intensity of d100 is observed. This is probably due to the
difference in scattering contrast of the pores and the walls, and to
the irregular immobilization of Pd(0) complex on nano-channels.
The pattern at higher diffraction angles of Pd-2A3HP-MCM-41 is
shown in Fig. 2. In this wide-angle powder XRD pattern of the cata-
lyst there are reflection peaks at 2θ = 39.84°, 46.17° and 67.75° cor-
responding to d111, d200 and d220 planes, respectively, that relate to
Pd nanoparticles (Fig. 2). These observations and the absence of im-
purity peaks indicate the high purity and good dispersion of the Pd
(0) complex on the inner pore channels of MCM-41.[44]
The Pd-2A3HP-MCM-41 catalyst was characterized using FTIR
spectroscopy and the corresponding spectra are depicted in Fig. 3.
The FTIR spectrum of the MCM-41 sample displays characteristic
absorption peaks at 1059, 963 and 451 cmÀ1 corresponding to
Si&bond;O&bond;Si asymmetric stretching, Si&bond;O&bond;Si
symmetric stretching and Si&bond;O&bond;Si bending vibrations,
respectively (Fig. 3(a)). The FTIR spectrum of the chloro-
functionalized MCM-41 indicates the stretching band around
2900 cmÀ1 related to the aliphatic C&bond;H group, which shows
that 3-chloropropyltriethoxysilane (nPrCl) is successfully anchored
on MCM-41 (Fig. 3(b)). Bands at 1479 cmÀ1 (C&dbond;C bond) and
1627 cmÀ1 (C&dbond;N bond) confirm the presence of 2-amino-3-
hydroxypyridine (2A3HP) ring (Fig. 3(c)). The free ligand exhibits a
stretching band at 1528 cmÀ1 while in the Pd-2A3HP-MCM-41
spectrum this band is shifted to higher frequency and appears at
1540 cmÀ1 indicating the formation of Pd–ligand bond (Fig. 3(d)).
Figure 4 shows SEM micrographs of MCM-41 and Pd-2A3HP-
MCM-41, which confirms the presence of uniform nanometric par-
ticles with spherical shape for the catalyst. Moreover, the Pd con-
tent in the complex anchored on MCM-41 was determined using
EDS in combination with TEM. The EDS data (Fig. 5) indicate the
presence of Pd as well as nitrogen and carbon in the complex. Also,
to extend the scope of catalyst characterization, we determined the
loading of Pd on MCM-41 using the ICP atomic emission spectros-
copy technique. The amount of Pd of the catalyst immobilized on
MCM-41 is found to be 2.10 × 10À3 mol gÀ1
.
Figure 2. XRD pattern of Pd-2A3HP-MCM-41 for high diffraction angles.
Figure 4. SEM images: (a) MCM-41; (b) Pd-2A3HP-MCM-41.
Figure 3. FT-IR spectra: (a) pure MCM-41; (b) nPrCl-MCM-41; (c) 2A3HP-
MCM-41; (d) Pd-2A3HP-MCM-41.
Figure 5. EDS spectrum of Pd-2A3HP-MCM-41.
Appl. Organometal. Chem. (2016)
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M. NIKOORAZM, A. GHORBANI-CHOGHAMARANI AND M. KHANMORADI
The TEM image of Pd-2A3HP-MCM-41 shows clearly highly
ordered hexagonal mesostructure (Fig. 6). It is clear that MCM-41
still retains its mesostructure after grafting of the 3-chloro-
propyltriethoxysilane and the organic moiety (2A3HP). The size of
particles is around 50 nm.[45]
TGA was used to determine the presence of chemisorbed or-
ganic functional groups on mesoporous MCM-41. The TGA mea-
surements were conducted in nitrogen and oxygen. The TGA data
fir MCM-41 and Pd-2A3HP-MCM-41 catalyst are shown in Fig. 7.
The TGA trace of the synthesized MCM-41 shows a one-step weight
loss of approximately 4% below 100 °C, which is due to desorption
of physically absorbed water and organic solvent.[46] The TGA trace
of 2A3HP-MCM-4 indicates three weight losses. The first weight loss
(2%) below 200 °C is the result of loss of physically adsorbed water
and other solvents, the second (12%) at 200–400 °C is related to the
decomposition of organic moieties and the third (2%) at 650 to ca
670 °C is likely attributed to decomposition of silanol groups.
The catalytic activity of Pd-2A3HP-MCM-41 was first tested in the
Suzuki cross-coupling reaction between iodobenzene as model
substrate and phenylboronic acid. Solvent and base have a marked
influence on the activity of the catalyst in the Suzuki cross-coupling
reaction. Reaction time was 30 min. The coupling reaction does not
occur in the absence of the catalyst (Table 1, entry 16). Keeping
K2CO3 as the base, it is found that notable activity of the catalyst
can be achieved when PEG-400 is used as solvent. However, the
yield of product is zero when the reaction is carried out in 1,4-
dioxane. Other bases do not give satisfactory results (Table 1,
entries 6–9). In the case of KOH, negligible amount of product is
obtained (Table 1, entry 7). Optimization of temperature shows that
80 °C is the best temperature. Furthermore the amount of catalyst
was evaluated. An amount of 4 mg (0.89 mol%) of catalyst is found
to be the optimal amount. When the amount of catalyst is
decreased, lower yield is achieved (Table 1, entry 15). The results
are summarized in Table 1.
A series of biphenyl derivatives were prepared successfully with
excellent yields. The results are summarized in Table 2.
Application of Pd-2A3HP-MCM-41 complex in organic
reactions
The activity of the prepared catalyst was investigated in the Heck
coupling reaction. In order to determine the optimum reaction
conditions, the influence of n-butyl acrylate and styrene was inves-
tigated. The results show that the stereoselectivity and conversion
for styrene are lower than for n-butyl acrylate (Table 3, entries
1–4). Therefore, 1.2 mmol of n-butyl acrylate, 1 mmol of iodo-
benzene and 3 mmol of base in the presence of Pd-2A3HP-MCM-
41 were selected for model reaction, which was studied with
various solvents, temperatures, catalyst concentrations and bases.
The reactions are sensitive to temperature and therefore we
investigated the effect of temperature on the outcome of reaction.
It is obvious that higher temperatures (more than 100 °C) strongly
improve the selectivity and conversion and shorten the reaction time
(Table 3, entries 8, 10, 11). Further studies reveal stereoselectivity for
the Heck reaction at 120 °C (Table 3, entry 8). We employed PEG-400
as solvent, but only low conversion of the aryl halides is achieved.
The use of more polar solvents such as DMF produces a clear in-
In our study of the application of the Pd-2A3HP-MCM-41 catalyst in
organic synthesis, we investigated the applicability of the catalyst for
the synthesis of biaryl derivatives using aryl halide (1 mmol), PhB
(OH)2 (1 mmol) and base (3 mmol) in the presence of Pd-2A3HP-
MCM-41 with short reaction times in good to excellent yields.
Table 1. Optimization of solvent, base, temperature and concentration
of catalyst for the synthesis of biphenyl in 30 min
Entry Temperature
(°C)
Solvent
Base
Catalyst Time Yield
(eq.) (mg, mol%) (min) (%)a
1
80
80
80
80
80
80
80
80
80
25
50
60
70
80
80
80
DMSO
K2CO3
K2CO3
K2CO3
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
5, 1.11
3, 0.22
0
30
30
30
30
30
30
45
75
2
H2O
Figure 6. TEM micrograph of Pd-2A3HP-MCM-41.
3
EtOH
30
b
4
1,4-Dioxane K2CO3
—
5
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
K2CO3
Et3N
96
93
6
7
KOH
30 Trace
8
Na2CO3
NaHCO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
30
30
93
90
9
10
11
12
13
14
15
16
30 Trace
30
30
45
75
84
96
30
30
30
83
b
24 h
—
aIsolated yield.
bNo reaction.
Figure 7. TGA thermograms of (red curve) MCM-41 and (green curve) Pd-
2A3HP-MCM-41.
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Appl. Organometal. Chem. (2016)

Organic reactions catalyzed by Pd-2A3HP-MCM-41
Table 2. Suzuki coupling of aryl halides with phenylboronic acid in the
(Table 3, entries 13 and 14). Hence, the optimized amount of cata-
lyst is 0.89 mol% (4 mg). The results are summarized in Table 3.
Under the optimized reaction conditions, various aryl halides are
rapidly converted to corresponding products in excellent yields.
The results are given in Table 4. The results clearly demonstrate that
the Pd-2A3HP-MCM-41 catalyst is effective for the Heck reaction.
The reaction between 4-iodotoluene (1 mmol) and Ph3SnCl
(0.5 mmol) was selected as a model Stille reaction and the influence
of various reaction parameters such as base, solvent, temperature
and catalyst loading was studied (Table 5). Several solvent systems
presence of Pd-2A3HP-MCM-41 (4 mg, 0.89 mol%) as catalysta
Entry
X
R
Time
(min)
Yield
(%)b
Melting
TOF
(hÀ1
point (°C)
)
1
I
H
30
20
45
40
40
55
45
80
25
50
20
50
35
25
45
96
96
93
91
97
86
90
93
92
98
93
90
91
93
94
64–66[47]
45–46[47]
106–108[48]
83–86[47]
62–65[47]
82[48]
56–57[41]
160–164[47]
112–114[49]
50–53[50]
126–127[50]
60–62[51]
Oil[52]
215.25
322.87
139.01
153.03
163.12
105.18
134.53
78.19
2
I
p-CH3
2-CO2H
p-OCH3
H
Table 4. Heck reaction of aryl halides with olefin using heterogeneous
3
I
Pd-2A3HP-MCM-41 (4 mg, 0.89 mol%) catalysta
4
I
5
Br
6
Br p-CN
7
Br p-CHO
Br p-OH
Br p-NO2
Br p-NH2
Br p-CO2H
Br 2-CH2OH
Br 3-CHO
Br p-CH3
Br p-Cl
8
9
247.53
131.84
312.78
121.08
174.89
250.22
140.51
Entry
X
R
Time (min)
Yield (%)b
TOF (hÀ1
)
10
11
12
13
14
15
1
2
3
4
5
6
7
8
9
10
I
H
30
30
35
40
35
50
35
45
50
35
94[53]
96[53]
93[53]
95[53]
91[54]
90[53]
90[55]
85[53]
82[53]
87[53]
210.76
215.25
178.73
159.75
174.89
121.08
172.97
127.25
110.31
167.20
I
p-CH3
p-OCH3
2-OCH3
2-CH3
H
43–46[47]
70–73[47]
I
I
I
aReaction conditions: aryl halide (1 mmol), PhB (OH)2 (1 mmol), K2CO3
(3 mmol), Pd-2A3HP-MCM-41 (4 mg, 0.89 mol%), PEG-400 (2 ml).
bIsolated yield.
Br
Br
Br
Br
Br
p-NO2
p-OCH3
p-CH3
p-Cl
crease in conversion and selectivity. To investigate the effect of the
base, systematic studies were carried out in the presence of differ-
ent bases (Table 3, entries 8–10). The best yield is found in the pres-
ence of K2CO3 as base. Finally, the amount of catalyst was evaluated
aReaction mixture consisted of aryl halide (1.0 mmol), n-butyl acrylate
(1.2 mmol), base (3 mmol), catalyst (4 mg, 0.89 mol%), and 2 ml of
DMF at 120 °C.
bIsolated yield.
Table 3. Catalytic results for the Heck reactiona
Entry
Temperature (°C)
Solvent
Base
(eq.)
Alkene
Catalyst
(mg, mol%)
Time
(min)
Yield
(%)b
c
120
120
120
120
120
120
120
120
120
120
110
100
120
120
120
EtOH
H2O
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
Styrene
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
5, 1.11
3, 0.22
0
20
20
—
c
2
Styrene
—
3
PEG-400
DMF
Styrene
20
52
67
4
Styrene
20
c
5
H2O
n-Butyl acrylate
n-Butyl acrylate
n-Butyl acrylate
n-Butyl acrylate
n-Butyl acrylate
n-Butyl acrylate
n-Butyl acrylate
n-Butyl acrylate
n-Butyl acrylate
n-Butyl acrylate
n-Butyl acrylate
20
—
c
6
EtOH
PEG-400
DMF
20
—
7
20
75
94
92
75
87
62
94
88
8
20
9
DMF
20
10
11
12
13
14
15
DMF
NaHCO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
20
DMF
20
DMF
20
DMF
20
DMF
20
c
DMF
1440
—
aReaction mixture consisted of aryl halide (1.0 mmol), n-butyl acrylate or styrene (1.2 mmol), base (3 mmol), catalyst and 2 ml of solvent. Reaction time
was 20 min.
bIsolated yield.
cNo reaction.
Appl. Organometal. Chem. (2016)
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M. NIKOORAZM, A. GHORBANI-CHOGHAMARANI AND M. KHANMORADI
Table 5. Catalytic results for the Stille reactiona
Table 7. Catalytic results for the synthesis of 5-substituted 1H-
tetrazolesa
Entry Temperature
(°C)
Solvent
Base
Catalyst Time Yield
(eq.) (mg, mol%) (min) (%)b
Entry Temperature
(°C)
Solvent
Catalyst
(mg, mol%)
Time (h) Yield (%)b
1
80
80
80
80
80
80
80
80
80
25
50
60
70
80
80
80
80
DMSO
K2CO3
K2CO3
K2CO3
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
4, 0.89
5, 1.11
3, 0.22
0
130
130
30
70
1
110
110
110
110
110
100
120
110
110
110
110
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
DMF
5, 1.11
10, 2.23
15, 3.34
20, 4.46
25, 5.57
20, 4.46
20, 4.46
20, 4.46
20, 4.46
20, 4.46
20, 4.46
3
3
3
3
3
3
3
3
3
3
3
Trace
58
2
H2O
2
3
EtOH
130 Trace
c
3
78
4
1,4-Dioxane K2CO3
130
130
130
—
90
90
4
96
5
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
K2CO3
Et3N
5
96
6
6
87
7
KOH
130 Trace
7
96
8
Na2CO3
NaHCO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
130
130
130
130
130
130
130
130
130
24 h
93
90
8
93
9
c
9
DMSO
90
10
11
12
13
14
15
16
17
—
30
54
78
94
94
80
c
10
11
EtOH
—
Water
30
aReaction mixture consisted of nitrile (1.0 mmol), sodium azide
(1.2 mmol), catalyst and 2 ml of solvent. Reaction time was 3 h.
bIsolated yield.
cNo reaction.
c
—
aReaction mixture consisted of aryl halide (1.0 mmol), Ph3SnCl
(0.5 mmol), base (3 mmol), catalyst and 2 ml of solvent. Reaction
time was 130 min.
bIsolated yield.
cNo reaction.
Table 8. Synthesis of 5-substituted 1H-tetrazoles with sodium azide in
the presence of Pd-2A3HP-MCM-41 catalyst (20 mg, 4.46 mol%)
were tested (Table 5, entries 1–5). In addition K2CO3, KOH, Na2CO3,
NaHCO3 and Et3N were employed as bases (Table 5, entries 5–9).
Based on the above observation, K2CO3 as base and PEG-400 as sol-
vent is the best combination in terms of yield and reaction time for
the Stille reaction. The effect of temperature on the reaction was
examined at 25–80 °C (Table 5, entries 10–14). With increasing tem-
perature the yield of product also increases and it is found that the
optimal reaction temperature is 80 °C. To investigate the role of the
Pd-2A3HP-MCM-41 catalyst in the Stille reaction, various amounts
Entry
R
Time (h) Yield (%)a
Melting
TOF (hÀ1
)
point (°C)
1
2
3
4
5
6
7
8
H
3
94
90
96
95
94
91
96
93
213–215[57]
218–220[57]
254–257[57]
265–266[57]
223–225[58]
175–177[59]
128–130[58]
260–263[57]
7.03
8.07
7.17
8.52
6.02
8.16
7.17
8.34
p-NO2
p-CN
p-Br
2.5
3
2.5
3.5
2.5
3
2-OH
p-COCH3
3-Cl
Table 6. Stille reaction of aryl halides with Ph3SnCl using heteroge-
neous Pd-2A3HP-MCM-41 catalyst (4 mg, 0.89 mol%)
p-Cl
2.5
aIsolated yield.
Entry
X
R
Time
(min)
Yield
(%)a
Melting
TOF (hÀ1
)
point (°C)
1
I
H
20
120
70
96
94
93
50
92
60
40
60
98
90
90
90
66[47]
44–46[47]
Oil[47]
87–89[47]
62–65[47]
82[48]
322.87
52.69
2
I
p-CH3
2-CH3
p-OCH3
H
3
I
89.36
4
I
30
112.11
247.53
161.43
67.26
5
Br
25
6
Br p-CN
Br p-OH
Br p-NO2
Br p-NH2
Br p-CH3
Br 3-CF3
Br p-Cl
25
7
40
161–164[47]
112[49]
8
30
134.53
329.60
67.26
9
20
50–53[50]
44–47[47]
Oil[56]
10
11
12
90
35
172.97
37.87
160
70–73[47]
aIsolated yield.
Figure 8. Reusability of Pd-2A3HP-MCM-41 in the reaction of phenyl iodide
with phenylboronic acid in Suzuki reaction.
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2016)

Organic reactions catalyzed by Pd-2A3HP-MCM-41
Table 9. Catalytic activity of Pd-2A3HP-MCM-41 compared with other catalysts used for Suzuki coupling reaction
Entry
Substrate
Catalyst
Time (min)
Conditions
Yield (%)a
1
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
I-C6H5
Pd(II)-MCM-41
Pd(0)-MCM-41
120
20
H2O/EtOH, 60 °C
99[35]
93[61]
2
H2O/EtOH, 80 °C
3
MCM-41-2 N-Pd(II)
SDPP/Pd(0)
240
180
180
30
Xylene, 90 °C
93[62]
4
EtOH, 80 °C
99[63]
85[64]
5
NHC–Pd(II)
DMA, 120 °C
6
Pd-2A3HP-MCM-41
3Pd-(MCM-41)
PEG-400, 80 °C
96 (this work)
55[31]
7
1440
1440
1440
1440
60
Ethylene glycol/toluene, 140 °C
Ethylene glycol/toluene, 140 °C
Ethylene glycol/toluene, 140 °C
Ethylene glycol/toluene, 140 °C
Solvent- free, 130 °C
100 °C
8
3Pd-(MCM-41) (Si/Al_15)
4Pd-(MCM-41)
40[31]
9
58[31]
10
11
12
13
14
5Pd-(MCM-41)
64[31]
Pd(0)/SDPP
99[63]
Pd(OAc)2/[HQ-PEG-4001000-DIL] [BF4]
NHC–Pd(II)
120
360
30
93[65]
160 °C, DMA
99[64]
Pd-2A3HP-MCM-41
120 °C, DMF
94 (this work)
aIsolated yield.
of catalyst were examined (Table 5, entries 15 and 16). As evident
from Table 5, increasing the amount of Pd-2A3HP-MCM-41 catalyst
to 1.11 mol% (5 mg) does not improve the result to an appreciable
extent. Hence 0.89 mol% (4 mg) of catalyst was chosen. The results
are summarized in Table 5.
The optimized reactions of various aryl halides with Ph3SnCl,
using K2CO3 as base and PEG-400 as solvent in the presence of
0.89 mol% (4 mg) of Pd-2A3PH-MCM-41, were carried out. The re-
sults show that coupling of aryl halides with Ph3SnCl proceeded
smoothly to afford good to excellent yields of the corresponding
coupled products (Table 6).
In continuation of this work on the applications of Pd-2A3HP-
MCM-41, we report the preparation of 5-substituted 1H-tetrazoles
from a wide variety of nitriles. Initially, we examined the reaction
of benzonitrile (1 mmol) and sodium azide (1.2 mmol) as a model
reaction to synthesize the corresponding tetrazoles.
The effect of various parameters such as catalyst concentration,
temperature and solvent was studied for the model reaction. Ini-
tially, the catalyst concentration was investigated and the results
show that the amount of catalyst plays a very important role in
the reaction. It is evident that a small loading of catalyst (1.11 mol
%) leads to very poor yield of final compound and a higher ratio
of catalyst (4.46 and 5.57 mol%) improves the yield of tetrazoles
(Table 7, entries 1–5). Next, in order to get the optimal temperature
we carried out the model reaction at various temperatures (Table 7,
entries 6 and 7). It is observed that the reaction is successfully com-
pleted at 110 °C in 3 h with a yield of 96% (Table 7, entry 4). With an
increase in temperature above 110 °C, no change in the yield of
product is observed (Table 7, entry 7). So, 110 °C was fixed as the
most suitable temperature. For this work we also examined the re-
actions in several solvents (Table 7, entries 8–11). PEG-400 is found
to be the most suitable solvent giving a maximum yield of 96%.
Although other solvents such as DMF and dimethylsulfoxide
(DMSO) give suitable yield, PEG-400 was selected because it is a
more desirable solvent from an environmental viewpoint. The
results are summarized in Table 7.
Reuse property of heterogeneous catalyst
The recovery of the catalyst supported on mesoporous silica was
performed using the Suzuki reaction. After completion of each
run, the catalyst was separated by centrifugation and was subjected
into another batch of the reaction. As shown in Fig. 8, the Pd-
2A3HP-MCM-41 catalyst can be reused seven times without signif-
icant loss of activity.
In order to determine whether the catalyst was behaving in a
truly heterogeneous manner or from leaching of palladium re-
leased from the solid catalyst during the reaction, a hot filtration
test was performed. In this experiment, Pd-2A3HP-MCM-41 (4 mg,
0.89 mol%), phenyl iodide (1 mmol), K2CO3 (3 mmol) and PEG-400
(2 ml(were added to a round-bottom flask and stirred at 80 °C.
The catalyst was rapidly separated by centrifugation after 15 min re-
action time (the conversion reached 48%) and the hot liquid mix-
ture allowed to react for a further 15 min under the same
conditions. There is no detectable increase in the product concen-
tration, which might be evidence for a heterogeneous mechanism
during the recycling. Also, the amount of Pd species dissolved into
solution caused by leaching of the catalyst was determined using
ICP after recovery of the catalyst (1.90 × 10À3 mol gÀ1). The ICP re-
sults show that 2% of the total amount of the original palladium
species is lost into solution during the course of the reaction. These
results illustrate that minimal leaching of palladium takes place
during the reaction and the catalyst is heterogeneous in nature.
The activity of Pd-2A3HP-MCM-41 in comparison with that of
other reported catalysts was evaluated (Table 9). The obtained re-
sults indicate the superiority of the present catalyst in terms of yield
or reaction time compared with the other catalysts reported in the
literature. On the other hand, some of the reported catalysts have
not covered the conversion of a wide range of aryl halides.[60]
Conclusions
Palladium with chloropropyltriethoxysilane and 2-amino-3-
hydroxypyridine immobilized on MCM-41 was found to be an ac-
tive and selective catalyst for the Suzuki coupling of aryl halides
with phenylboronic acid and Heck coupling of aryl halides with
n-butyl acrylate as well as Stille coupling of aryl halides with Ph3SnCl
and the synthesis of 5-substituted 1H-tetrazoles from sodium azide
To determine the scope of this synthesis, we studied the effect of
substituents on the aromatic nitriles under the optimized conditions.
The results are presented in Table 8. Aromatic nitriles having both
electron-donating and electron-withdrawing groups at any position
result in the corresponding tetrazoles in good to excellent yields.
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

M. NIKOORAZM, A. GHORBANI-CHOGHAMARANI AND M. KHANMORADI
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conditions to give the corresponding biphenyl derivatives in mod-
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yields in lower reaction times. This heterogeneous catalyst was eas-
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catalyst was able to be used in more than seven reaction cycles
without losing activity.
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version of this article at the publisher’s web site.
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