Copper(II)-diaminosarcophagine-functionalized SBA-15: A heterogeneous nanocatalyst for the synthesis of benzimidazole, benzoxazole and benzothiazole derivatives under solvent-free conditions

Article abstract of DOI:10.1002/aoc.3400

Solvent-free organic reactions were studied over periodic mesoporous silica (SBA-15) containing a Cu(II) organometallic complex. This heterogeneous catalyst was achieved by coordination of Cu(II) ions with the diaminosarcophagine ligand and then its grafting onto the surface of SBA-15. This catalyst displayed ordered mesoporous channels, which implies an extremely high dispersion of the Cu(II) complex and the convenient diffusion of reactant molecules into the pore channels. Therefore, this catalyst can offer high activity and also facile separation or recycling when compared with its homogeneous counterparts.

Full text of DOI:10.1002/aoc.3400

Full paper
Received: 21 September 2015
Revised: 3 October 2015
Accepted: 6 October 2015
Published online in Wiley Online Library: 6 November 2015
(wileyonlinelibrary.com) DOI 10.1002/aoc.3400
Copper(II)–diaminosarcophagine-
functionalized SBA-15: a heterogeneous
nanocatalyst for the synthesis of
benzimidazole, benzoxazole and benzothiazole
derivatives under solvent-free conditions
Ghasem Rezanejade Bardajeea*, Marzieh Mohammadib
and Nahale Kakavanda
Solvent-free organic reactions were studied over periodic mesoporous silica (SBA-15) containing a Cu(II) organometallic complex.
This heterogeneous catalyst was achieved by coordination of Cu(II) ions with the diaminosarcophagine ligand and then its
grafting onto the surface of SBA-15. This catalyst displayed ordered mesoporous channels, which implies an extremely high dis-
persion of the Cu(II) complex and the convenient diffusion of reactant molecules into the pore channels. Therefore, this catalyst
can offer high activity and also facile separation or recycling when compared with its homogeneous counterparts. Copyright ©
2015 John Wiley & Sons, Ltd.
Keywords: heterogeneous catalysis; Cu(II)–DiAmSar complex; benzimidazole; benzoxazole; benzothiazole
positron emission tomography imaging.[24–29] Molecular imaging
Introduction
is a developing technology that helps visualize interactions among
molecular excavators and biological targets.[30–35]
Mesoporous materials, such as M41s and SBA families, were ini-
Leaching of the metal ions from metal ion-based catalysts into
the reaction solution is, however, a central problem in heteroge-
neous catalysis. Metal leaching to the supernatant reduces the per-
formance of a catalyst, in terms of either catalyst replacement or
additional purification and recovery processes. In drug synthesis,
there are strict limits on residual metals in active pharmaceutical in-
gredients. DiAmSar is useful in this regard because the six nitrogen
donor atoms of the macrobicyclic cages bind very strongly to many
metal ions; for example, this ligand coordinates the metal ion Cu2+
within the multiple macrocyclic rings comprising the sarcophagine
cage structure, yielding extraordinarily stable complexes that are in-
ert to dissociation of the metal ion (<6% in 18 h at ca 25 °C).[36–39]
In this paper, in continuation of our earlier work,[40,41] we report
the application of Cu(II)–DiAmSar (as an organometallic complex)
covalently bonded to SBA-15 (Cu(II)-DiAmSar/SBA-15), as a non-
leaching and heterogeneous organometallic catalyst for the
tially studied at the beginning of the 1990s. They have received
considerable attention in catalysis due to their large pore sizes
(2.0–50.0 nm), high surface areas (up to 1200 m2 gÀ1) and organic
solvent tolerance. Furthermore, pore sizes and surface areas facil-
itate the covalent anchoring of bulky organic species to their
walls, and these surface-functionalized mesoporous materials
have been applied as heterogeneous catalysts in organocatalysis,
metallic catalysis and organometallic catalysis.[1–6] Heterogeneous
catalysts are rather effective from environmental and economic
viewpoints,[7] since they have the benefits of easy recovery and re-
use after the completion of the reactions.
Recently, we have reported the synthesis of metal complexes of
Schiff-base supported SBA-15 as organometallic catalysts and used
them for the synthesis of quinoxaline heterocycles; attachment of
catalytic centers to SBA-15 by covalent linkages is a practical way
to produce heterogeneous catalysts and avoids leaching of catalyst
centers to the reaction mixture.[8–10]
Diaminosarcophagine (DiAmSar) as a new class of chelator based
on sarcophagine has good properties for encapsulation of a variety
of metal ions, the resulting complex cations being extraordinarily
stable and kinetically inert against leaching of metal ions.[11–15] This
multifunctional chelator also has diverse kinds of biological sites.
DiAmSar can conjugate to peptides, sugars, antibodies and biolog-
ically compatible polymers via its end group, and the products can
be radiolabeled with radioisotopes such as 64Cu.[16–23] These prop-
erties lead to some important usages, especially in diagnostic
*
Correspondence to: Ghasem Rezanejade Bardajee, Department of Chemistry,
Payame Noor University (PNU), PO Box 19395-3697, Tehran, Iran. E-mail:
rezanejad@pnu.ac.ir
a Department of Chemistry, Payame Noor University (PNU), PO Box 19395-3697,
Tehran, Iran
b Department of Chemistry, Faculty of Science, Urmia University, 57159, Urmia, Iran
Appl. Organometal. Chem. 2016, 30, 51–58
Copyright © 2015 John Wiley & Sons, Ltd.

G. R. Bardajee et al.
synthesis of benzimidazole, benzothiazole and benzoxazole hetero-
cyclic compounds under solvent-free conditions.
analytical grade and were used as received. Silica gel (Merck, grade
9385, 230–400 mesh, 60 Å) for column chromatography was used as
received. All other reagents were purchased from Merck and used
as received unless otherwise noted. The course of the synthesis of
heterocycles was followed using TLC with silica gel plates (Merck,
silica gel 60 F254, ready to use), using n-hexane–ethyl acetate (4:1)
as eluent. The eluent for column chromatography was the same
as that for TLC.
Molecules with benzimidazole, benzoxazole and benzothiazole
moieties are of great interests in synthesis, as they show various
and significant biological and pharmacological attributes such as
Gram-positive antibacterial, antibiotic, anti-parasitic, anti-
inflammatory, elastase inhibitory, anti-stress, ulcer, anticancer and
antiviral attributes.[42] There are also plenty of commercial drugs
for which these cores are used in their structures (Fig. 1). For exam-
ple, mebendazole (1) exhibits potent antitumor properties and sig-
nificantly inhibits cancer cell growth.[43] Thiabendazole (2) is a
useful therapeutic agent for treatment of many helminthic infec-
tions in animals and humans.[44] Riluzole (3) has clinical use in mood
and anxiety disorders and it has been shown to have antidepres-
sant properties in the treatment of refractory depression.[45]
Albendazole (4) has a broad range of anthelmintic activity, effective
against roundworms, tapeworms and flukes of domestic animals
and humans.[46] Flunoxaprofen (5) significantly improves symp-
toms of osteoarthritis and rheumatoid arthritis.[47]
Due to the importance of these heterocycles, various procedures
have been reported in the literature for their synthesis,[48–56] includ-
ing condensation of 1,2-phenylenediamine, 2-aminophenol and 2-
aminobenzenethiol with acyl chlorides or aldehydes under strongly
acidic conditions. Most of the customary processes suffer from one
or more difficulties, such as strong acidic conditions, pollution, high
cost, low yields of products, long reaction times, high reaction tem-
peratures, need for additional quantities of reagents and use of toxic
catalysts and/or solvents. Consequently, the development of a sim-
ple, convenient and eco-friendly method would be interesting.
Characterization
Transmission electron microscopy (TEM) observation was per-
formed with a Hitachi H-700 CTEM. Fourier transform infrared
(FT-IR) spectra were recorded with KBr pellets using a Jasco
4200 FT-IR spectrophotometer. X-ray diffraction (XRD; Bruker
D8 ADVANCE with Ni-filtered Cu Kα radiation at 1.5406 Å) pat-
terns were recorded with a speed of 2° minÀ1 and a step of
0.05°. 1H NMR and 13C NMR spectra were recorded at room tem-
perature with Bruker AC 300, 400 and 500 MHz spectrometers
1
using CDCl3 or dimethylsulfoxide-d6 as solvents. H NMR spectra
were referenced to tetramethylsilane (0.00 ppm) and 13C NMR
spectra to the solvent central peak (e.g. 77.23 ppm for CDCl3).
Chemical shifts are given in ppm. Nitrogen adsorption–desorption
isotherms were obtained at 77.35 K with a Quantachrome Autosorb-1
apparatus. Before measurements, the samples were outgassed at
120 °C for 12 h. The specific surface areas and pore size distributions
were obtained from the desorption branch of the isotherms, respec-
tively, using the Brunauer–Emmett–Teller (BET) method and
Barrett–Joyner–Halenda (BJH) analyses. A Shimadzu AA-6300 flame
atomic absorption spectrometer was used to obtain the concen-
tration of metal ions. For this purpose, 0.1 g of the catalyst was
digested with HNO3 by stirring at room temperature for a week.
Then the mixture was filtered to afford a colorless solution for metal
measurements. Thermogravimetric analysis (TGA) was carried out
with a Shimadzu-50 TGA/DTA instrument equipped with a platinum
pan. The samples were heated in air from 25 to 1000 °C with a
heating rate of 10 °CminÀ1. The weight losses as a function of
temperature were recorded. Melting points were recorded using a
Buchi B540 melting point apparatus and were uncorrected.
Experimental
Materials
Double-distilled water was used when necessary. Acetonitrile, etha-
nol, formaldehyde, sodium hydroxide, hydrochloric acid, methanol,
stannous chloride dihydrate, cobalt(II) chloride hexahydrate, sodium
cyanide, nitromethane, ethylenediamine, commercial-grade 1,2-
phenylenediamine, 2-aminophenol, 2-aminobenzenethiol, carbonyl
compounds, poly(ethylene oxide)-block-poly(propylene oxide)-block-
poly(ethylene oxide) triblock copolymer (P123), (3-chloropropyl)
trimethoxysilane, copper(II) acetate monohydrate, tetraethyl
orthosilicate and HNO3 were purchased from Sigma-Aldrich, Merck
and Acros chemical companies. All materials were used without fur-
ther purification. The solvents used for the syntheses were of
Preparation of SBA-15
SBA-15 was prepared using a previously reported procedure.[57] In
summary, P123 (2 g) was first dissolved in a solution of deionized
water (15 g) and HCl (60 g, 2 M) under vigorous stirring. Then,
tetraethyl orthosilicate (4.25 g) was added into the solution with
stirring at 40 °C for 24 h. After that, the solution was heated at
100 °C for another 24 h. The product was filtered off, washed and
dried at room temperature, then calcined at 600 °C for 8 h to re-
move the surfactant molecules. For activation of the SBA-15 surface,
which results in better dissolution of the material and increased
pore radius, SBA-15 was suspended in HCl (6M) at 100 °C for 6 h.
The product was then filtered and washed with deionized water
and methanol two times; then it was dried. After drying, the SBA-
15 was placed in a vacuum oven at 80 °C for 8 h.
Preparation of DiAmSar (Scheme 1)[58,59]
Synthesis of tri(ethylenediamine)cobalt(III) chloride (6)
Ethylenediamine (61ml, 30%) was added to HCl (17 ml, 6 N), and
then a solution of cobalt chloride hexahydrate (24 g) in water
Figure 1. Drug products that contain benzimidazole, benzothiazole and
benzoxazole moieties.
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Appl. Organometal. Chem. 2016, 30, 51–58

The application of Cu(II)-DiAmSar/SBA-15 in organic synthesis
Synthesis of DiAmSar (9)
Sodium hydroxide (2.11 eq., 77mg) was dissolved in deoxygenated
water (7ml) and the solution was placed under nitrogen to elimi-
nate oxygen. The bubbling was continued for 30 min. Then, com-
plex 8 (1 eq., 500 mg) and cobalt(II) chloride hexahydrate (1.01eq.,
118 mg) were dissolved in the basic solution. After homogenization
of the solution, sodium cyanide (17.7 eq., 783mg) was added under
vigorous stirring. The mixture was heated to 70 °C, being vigorously
stirred under nitrogen until the solution turned yellow (7h). The fi-
nal solution was taken to dryness under air flow, and the residue
was extracted with boiling acetonitrile. The total extract was re-
duced under vacuum, and cooled to À10 °C to precipitate white
crystals of the product. The product was recovered by filtration
and dried. Compound 9 was obtained in 56% yield. White solid.
FT-IR (KBr; ν, cmÀ1): 3400, 3048, 3012, 2810, 2720. 1H NMR
(400MHz, D2O; δ, ppm): 2.69 (s, 12H), 2.76 (s, 12H). 13C NMR
(400MHz, D2O; δ, ppm): 48.15, 51.78, 57.40. GC-MS (EI): 315.3
(M+ H)+.
Preparation of Cu(II)–DiAmSar complex anchored onto SBA-15
(Cu(II)-DiAmSar/SBA-15)
Compound 9 (0.0318 mmol, 0.01 g) was first dissolved in methanol
(20 ml) and the solution stirred at room temperature for 1 h; then,
(3-chloropropyl)trimethoxysilane (0.0318mmol, 0.006 g) was added
to the solution and stirred at room temperature for 24 h. After that,
copper(II) acetate monohydrate (0.0318mmol, 0.006g) was added
and the solution heated at 80 °C for a further 6 h. Finally, activated
SBA-15 (2g) was added and heated for 24 h. The solvent was evap-
orated using a rotary evaporator and the resulting a blue solid dried
at 80 °C overnight. The product was washed with methanol and
deionized water until the filtrate became colorless. Further drying
was carried out in an oven at 80 °C for 8 h.
Scheme 1. Preparation of DiAmSar.
(75 ml) was added to the partially neutralized ethylenediamine. The
cobalt was oxidized by bubbling violently a stream of air through
the solution for 3 h. The solution was first evaporated to a volume
of 15 ml; then HCl (37%, 15 ml) and ethanol (30ml) were added.
The residue was cooled in an ice bath, filtered, washed with ethanol
and dried (89% yield).
General procedure for preparation of 2-substituted benzimid-
azole, benzoxazole and benzothiazole heterocycles in water
Synthesis of [Co(1,8-dinitro)sarcophagine]Cl3 complex (7)
Complex 6 (1 eq., 2 g) was first dissolved in a solution of water (3 ml)
and aqueous formaldehyde (37%, 10.4 eq., 4.5 ml), followed by the
addition of nitromethane (1.06 ml). The reaction mixture was
cooled to 4 °C in an ice–water bath. Then, a solution of aqueous so-
dium hydroxide (4 M, 3.45 eq., 5 ml) was cooled to 4 °C and added
to the resulting solution. It was stirred in the ice–water bath until
the initial orange color changed to deep violet-brown, then the
reaction temperature was raised to 35 °C. After 15 min, when the
temperature decreased to 20°C, concentrated HCl (60mmol, 5 ml)
was added to the solution. Finally, the solution was cooled in an
ice bath and after 1 h the orange residue was filtered, washed with
methanol and dried to afford the desired product in 70% yield.
A round-bottomed flask equipped with a magnetic stirrer and
condenser was charged with 1,2-phenylenediamine or ortho-
aminophenol or ortho-aminothiophenol (1.0mmol), substituted
benzaldehyde (1.0mmol) and catalyst Cu(II)-DiAmSar/SBA-15
(0.00008 mmol). The resulting mixture was stirred and heated at
100 °C for the appropriate times under solvent-free conditions. Af-
ter completion of the reaction (monitored using TLC), the reaction
mass was cooled to room temperature and washed with hot etha-
nol to separate the catalyst. Finally, the crude mixture was purified
by column chromatography or recrystallized from toluene to obtain
the desired products. Spectral and physical data for the heterocyclic
products are reported in the supporting information.[60–73]
Synthesis of [Co(1,8-diammonium)sarcophagine]Cl5 complex (8)
Results and discussion
Stannous chloride dihydrate (13 eq., 3 g) was dissolved in a solution
of concentrated hydrochloric acid (145 eq., 12 ml) and ethanol
(6ml). The solution was stirred magnetically and heated to 70 °C
until it became clear. Then, complex 7 (1eq., 600 mg) was added
to the solution under vigorous stirring. The reaction mixture was
heated at 70 °C for 4 h while the color of the solution turned green
from orange/brown. After the addition of 6 ml of water to the solu-
tion, it was cooled at room temperature for 15 min. Then the flask
was immersed in an ice–water bath and the orange product was
filtered and dried. Complex 8 was obtained in 60% yield.
Characterization of Cu(II)-DiAmSar/SBA-15
Cu(II)-DiAmSar/SBA-15 was prepared according to Scheme 2. First,
(3-chloropropyl)trimethoxysilane reacted with DiAmSar containing
amine functional groups. This moiety after complexation with cop-
per(II) salt, attached onto the SBA-15 silica surface through silylation
reaction.
Confirmation of the successful grafting of the Cu(II)–DiAmSar
complex onto SBA-15 and characterization of the catalyst were
Appl. Organometal. Chem. 2016, 30, 51–58
Copyright © 2015 John Wiley & Sons, Ltd.
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G. R. Bardajee et al.
angles suggests the development of a unit cell due to the connec-
tion of Cu(II)–DiAmSar within the pores of SBA-15.[75]
The general structural arrangement of the mesoporous materials
can be directly observed using TEM. Fig. 3 shows TEM images in the
direction of the pore axis and in the direction of the perpendicular
to the pore axis of Cu(II)-DiAmSar/SBA-15. As can be seen, the TEM
images of Cu(II)-DiAmSar/SBA-15 show the retention of hexagonal
arrays of uniform channels with a typical honeycomb appearance
during the grafting of he complex.
TGA measures weight changes in a material as a function of tem-
perature (or time) under a controlled atmosphere. It can measure
the thermal stability of a material, filler content in polymers, mois-
ture and solvent content, and the percentage composition of com-
ponents in a compound. TGA is performed by gradually raising the
temperature of a sample in a furnace as its weight is measured
using an analytical balance that remains outside the furnace. In
TGA, mass loss is observed if a thermal event involves the loss of
a volatile component. Here, TGA was used to investigate the ther-
mal stability of the catalyst (Fig. 4). Pure siliceous SBA-15 shows a
mass loss below 100 °C attributed to the loss of physically adsorbed
water. The thermogram of Cu(II)-DiAmSar/SBA-15 shows not only a
mass loss due to dehydration, but also a greater mass loss between
200 and 700 °C (Fig. 4) which can be attributed to loss of anchored
DiAmSar ligand and organic spacer.
FT-IR spectroscopy was employed to confirm the structural integ-
rity of the silica surface. Fig. 5 shows the FT-IR spectra of SBA-15 and
Cu(II)-DiAmSar/SBA-15. The FT-IR spectra of SBA-15 and the
immobilized complex are affected by the silicate surface. The con-
stitution of the immobilized complex is demonstrated by peaks be-
tween 1000 and 1200 cmÀ1 which are due to stretching vibrations
of (Si–O–Si) bonds and peaks at 3406 and 1648 cmÀ1 which are due
Scheme 2. Preparation of Cu(II)-DiAmSar/SBA-15.
carried out using XRD, TEM, TGA, FT-IR spectroscopy and nitrogen
adsorption–desorption (BET) techniques.
The quality and structural ordering of Cu(II)-DiAmSar/SBA-15
were measured using XRD. Fig. 2 shows the XRD patterns of SBA-
15 and Cu(II)-DiAmSar/SBA-15. The XRD patterns of both show
reflections of (100), (110) and (200), which are characteristic of
mesoporous materials with a two-dimensional hexagonal structure.
They indicate that the ordered mesoporous structure of SBA-15 re-
mains intact after anchoring of Cu(II)–DiAmSar complex. XRD peaks
of Cu(II)-DiAmSar/SBA-15 are of lower intensities and at slightly
lower angles than those of SBA-15. Lower intensities are due to
the reduction of local order because of the incorporation of Cu(II)
complex inside the pore channels of SBA-15. Furthermore, the in-
teraction between the Cu(II)–DiAmSar complex and SBA-15 reduces
the diameter of the pores.[74] The slight shift of peaks to lower
Figure 3. TEM images (a) in the direction of the pore axis and (b) in the
Figure 2. XRD patterns of SBA-15 and Cu(II)-DiAmSar/SBA-15.
direction perpendicular to the pore axis.
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The application of Cu(II)-DiAmSar/SBA-15 in organic synthesis
Figure 4. TGA results for SBA-15, Cu(II)-DiAmSar/SBA-15 and DiAmSar.
Figure 6. Nitrogen adsorption–desorption isotherms and (inset) corresponding
pore size distributions.
Table 1. Textural properties of SBA-15 and Cu(II)-DiAmSar/SBA-15a
Material
SBET (m2 gÀ1
)
VBJH (cm3 gÀ1
)
DBJH (nm)
SBA-15
532
317
0.6004
0.5601
6.24
7.1
Cu(II)-DiAmSar/SBA-15
aSBET, specific surface area; VBJH, pore volume; DBJH, pore diameter
(calculated from the adsorption branch).
examined. In a first attempt, we examined the reaction at room
temperature without catalyst: it gives no yield of products. Al-
though using toluene and ethanol as solvent gives reasonable
yields (Table 2, entries 8 and 9), the best yield is obtained under
solvent-free conditions at 100 °C and in the presence of 8 × 10À5
Figure 5. FT-IR spectra of (a) SBA-15 and (b) Cu(II)-DiAmSar/SBA-15.
to amine NH (also O–H) stretching and NH bending, respectively.
The spectrum also shows a peak at 2940 cmÀ1 due to aliphatic
CH2 stretching. The band at 1400–1500 cmÀ1 in the spectrum of
the catalyst is due to absorption of C–N groups in DiAmSar. These
results suggest that the Cu(II)–DiAmSar complex is grafted success-
fully onto the surface of the silica.
Table 2. Screening of reaction conditions for reaction of 1,2-
phenylenediamine and benzaldehydea
Nitrogen adsorption–desorption isotherms (BET) can be used to
explain the physical adsorption of gas molecules on a solid surface
and serve as an important analysis technique for the measurement
of the specific surface area of a material. Nitrogen adsorption–
desorption isotherms of SBA-15 and Cu(II)-DiAmSar/SBA-15 are
plotted in Fig. 6. As can be seen, SBA-15 has a regular pore diameter
of 6.24 nm, a specific surface area of 532 m2 gÀ1 and a pore volume
of 0.6004 cm3 gÀ1, while Cu(II)-DiAmSar/SBA-15 has a regular pore
diameter of 7.1nm, a specific surface area of 317 m2 gÀ1 and a pore
volume of 0.5601 cm3 gÀ1. The presence of Cu(II)–DiAmSar an-
chored on the SBA-15 surface induces a marked reduction of the
surface area and a decrease in mesopore volume. Textural proper-
ties of SBA-15 and Cu(II)-DiAmSar/SBA-15 are given in Table 1.
Entry
Solvent
Catalyst
(mmol)
Temperature
(°C)
Time
(min)
Yield
(%)b
1
Free
0
r.t.
320
40
—
30
2
Free
0.00008
0.00016
0.000008
0.00008
0.00008
0.00008
0.00008
0.00008
0.00008
r.t.
3
Free
r.t.
40
30
4
Free
r.t.
40
30
5
Free
60
40
65
6
7
Free
H2O
100
100
Reflux
100
Reflux
40
81 (80)c
60
240
210
180
160
8
EtOH
DMF
Toluene
80
9
76
10
80
aAll reactions were run under the following conditions: 1,2-
phenylenediamine (1 mmol, 1 eq.), benzaldehyde (1.0 mmol, 1 eq.)
and catalyst (0–0.00016 mmol, 0–0.005 g) were heated for the
appropriate time in desired solvent (2 ml) or solvent-free conditions.
Synthesis of heterocyclic derivatives
Initially, 1,2-phenylenediamine and benzaldehyde were selected as
model substrates for optimization of reaction conditions. In order to
find the best efficiency of our catalyst for the synthesis of benzimid-
azole, benzoxazole and benzothiazole derivatives, some parame-
ters like solvent, amount of catalyst and temperature were
bBased on GC yields.
cOptimum conditions.
dIsolated yield in parentheses.
Appl. Organometal. Chem. 2016, 30, 51–58
Copyright © 2015 John Wiley & Sons, Ltd.
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G. R. Bardajee et al.
mol of catalyst (Table 2, entry 6). Generally, it is found that the effi-
ciency of the catalyst is mostly affected by the quantity of catalyst,
solvent and temperature used in the reaction.
Table 4. Reuse of the catalyst for the synthesis of 2-
phenylbenzimidazole (12)
Run
Yield (%)a
1
2
3
4
5
6
In order to examine the generality of this methodology, various
aldehyde derivatives were reacted with 1,2-phenylenediamine,
ortho-aminophenol and ortho-aminothiophenol. The results are
summarized in Table 3. As evident from the table, most of the ex-
amined substrates provide good to excellent yields. The first step
of our investigation of the generality of the reaction was the reac-
tion of 1,2-phenylenediamine with substituted aldehydes (Table 3,
entries 1–8). It seems that the reaction of 1,2-phenylenediamine
with substituted aldehydes bearing electron-deficient groups at
the para-position of aromatic rings gives higher yields of products
than those bearing electron-rich aromatic rings (Table 3, entries
1–8). The reason may be that strongly electron-withdrawing groups
(NO2) enhance the reaction rate due to an increase in the electro-
philicity of the carbonyl carbon of aldehydes. Yields of reactions
are also influenced by the steric hindrance of substituted alde-
hydes. For example, the more sterically hindered ortho-
chlorobenzaldehyde reacts with 1,2-phenylenediamine, and affords
the target product in lower yield than para-chlorobenzaldehyde
(Table 3, entries 2 and 7).
90
90
90
89
89
89
aIsolated yield.
Table 5. Investigation of methods for preparation of 2-
phenylbenzimidazole (12)
Entry
Catalyst
Solvent Yield (%) Time (h)
Ref.
[76]
[77]
[78]
[79]
[80]
[81]
1
2
3
4
5
6
7
Cu-np/SiO2
Methanol
Dioxane
CH3CN
CH3CN
DMF
93
85
88
90
87
94
80
4
16
3
—
CdCl2
Sm(OTf)3
4
Co(NO3)2/H2O2
15% PPA
0.5
0.16
0.7 This work
NMP
Cu(II)-DiAmSar/SBA-15
—
Having successfully achieved solvent-free syntheses of ben-
zoimidazoles, the use of the Cu(II)-DiAmSar/SBA-15 system was
expanded to catalyze the syntheses of benzothiazoles (Table 3,
entries 9–19) and benzoxazoles (Table 3, entries 20–23) using
ortho-aminothiophenol and ortho-aminophenol with substituted
aldehydes. In reactions of ortho-aminothiophenol with substituted
aldehydes, those containing both electron-rich and electron-poor
groups show good reactivities and afford benzothiazoles in high
yields in short times. Also, 2-(1H-indol-3-yl)benzothiazole is obtained
in high yield via the reaction of indole-3-carbaldehyde with ortho-
aminothiophenol. Reactions of ortho-aminophenol with substituted
aldehydes (Table 3, entries 20–23) are also highly selective and af-
ford benzoxazoles in good yields in appropriate reaction times.
Continuing the study, the recyclability of the catalyst was exam-
ined for a model reaction, the synthesis of 2-phenylbenzimidazole
(12). For this, we examined turnover number of the heterogeneous
catalyst under optimized conditions and a series of tests were de-
signed for the model reaction under optimized status. After accom-
plishment of the first reaction with 81% yield, the catalyst was first
filtered, then washed with hot ethanol and dried at 80 °C for 60 min.
The recovered catalyst was used in further reactions, and we find
that the turnover number of Cu(II)-DiAmSar/SBA-15 is six (Table 4).
Some earlier reported data for the synthesis of 12 (Table 3, entry
1) were compared with our results in terms of method, tempera-
ture, solvent, reaction time and percentage yields. As evident from
Table 5, development of alternative routes for the synthesis of
benzimidazole, benzoxazole and benzothiazole derivatives is an
important goal. Our results compare very well with previously re-
ported data in terms of yields and reaction times. We also offer
green techniques for this organic synthesis by use of a heteroge-
neous catalyst which is expected for possible recycling, since the
metal complex is anchored on the silica surface. Furthermore, the
elimination of solvents from the reaction mixture is an important
issue because it means a significant reduction of solvent wastes.
Table 3. Synthesis of desired heterocyclic derivatives catalyzed by Cu
(II)-DiAmSar/SBA-15a
Entry
X
R
Yield (%) m.p.found/m.p.lit (°C)[60–73]
1
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
SH
H
80
85
82
80
78
77
80
76
94
90
92
92
92
90
95
90
92
90
92
90
90
88
82
292–294/289–290
288–290/294
2
p-Cl
p-NO2
3
318–320/316
4
3,4,5-(OMe)3
p-Me
258–260/254–256
275–276/270
5
6
m-Cl
234–236/236–238
230–232/232–234
201–203/203–204
121–122/123–124
166–168/173
7
o-Cl
8
m-NO2
p-OMe
p-NMe2
o-OH
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
SH
SH
132–134/133–134
110–114/112–114
114–116/112–114
227–229/229–230
146–148/152
SH
H
SH
p-Cl
SH
p-NO2
3,4,5-(OMe)3
p-Me
SH
SH
81–84/80–84
SH
m-Cl
93–94/98–100
SH
o-Cl
80–82/80–82
SH
m-NO2
p-NO2
3,4,5-(OMe)3
p-Me
182–184/83–185
262–264/266–268
115–117/113–115
112–114/113–114
116–118/—
OH
OH
OH
OH
p-NMe2
aAll reactions were run under the following conditions: 1,2-
phenylenediamine (1 mmol, 1 eq.), benzaldehyde (1.0 mmol, 1 eq.)
and catalyst (0.00008 mmol, 0.005 g) were heated at 100 °C under
solvent-free conditions for 40 min.
Conclusions
We have developed a simple, green and efficient method for the
synthesis of benzoxazoles, benzothiazoles and benzimidazoles
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 51–58

The application of Cu(II)-DiAmSar/SBA-15 in organic synthesis
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