Synthesis of benzoxazoles catalyzed by MCM-41, a green and reusable catalyst

Article abstract of DOI:10.1080/00397910802585910

Benzoxazoles can be rapidly and efficiently synthesized from acyl chloride with 2-aminophenols in one simple step, which provided a practical and efficient method for high-throughput synthesis of this important class of heterocyclic compounds. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802585910

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Synthesis of Benzoxazoles
Catalyzed by MCM-41, a Green
and Reusable Catalyst
Rahim Hekmat Shoar a , Maryam Heidary a , Maryam
Farzaneh a & Reihaneh Malakouti b
a Department of Chemistry, School of Sciences,
Azzahra University, Vanak, Tehran, Iran
b Department of Chemistry, University of Birjand,
Birjand, South Khorasan, Iran
Published online: 15 Apr 2009.
To cite this article: Rahim Hekmat Shoar , Maryam Heidary , Maryam Farzaneh &
Reihaneh Malakouti (2009) Synthesis of Benzoxazoles Catalyzed by MCM-41, a Green
and Reusable Catalyst, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 39:10, 1742-1751
To link to this article: http://dx.doi.org/10.1080/00397910802585910
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Synthetic Communications1, 39: 1742–1751, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802585910
Synthesis of Benzoxazoles Catalyzed by
MCM-41, a Green and Reusable Catalyst
Rahim Hekmat Shoar,1 Maryam Heidary,1 Maryam Farzaneh,1
and Reihaneh Malakouti2
1Department of Chemistry, School of Sciences, Azzahra University,
Vanak, Tehran, Iran
2Department of Chemistry, University of Birjand, Birjand,
South Khorasan, Iran
Abstract: Benzoxazoles can be rapidly and efficiently synthesized from acyl
chloride with 2-aminophenols in one simple step, which provided a practical
and efficient method for high-throughput synthesis of this important class of
heterocyclic compounds.
Keywords: Benzoxazoles, catalyst, MCM-41, reusable
The benzoxazole scaffold is a useful structural motif for the development
of molecules of pharmaceutical or biological interest. Appropriately sub-
stituted benzoxazole derivatives have found diverse therapeutic activities
including antibiotic,[1] antimicrobial,[2–5] antiviral,[6] topoisomerase I and
II inhibitory,[7] and antitumor activities.[8] Hence, the synthesis of benz-
oxazole derivatives is currently of much importance. Common synthetic
routes to benzoxazoles have typically involved coupling of carboxylic
acids or their derivatives with 2-aminophenols in the presence of acids
at high temperatures.[9] However, some of these methods suffer from
one or more of the following drawbacks such as strong acidic conditions,
long reaction times, low yields of the products, tedious workup, need for
Received October 12, 2008.
Address correspondence to Rahim Hekmat Shoar, Department of Chemistry,
School of Sciences, Azzahra University, Vanak, Tehran, Iran. E-mail: rhekmatus
@yahoo.com
1742

Benzoxazoles Synthesis Catalyzed by MCM-41
1743
excess amounts of reagent, and the use of toxic reagents, catalysts, and=or
solvents. Therefore, there is a strong demand for a highly efficient and
environmentally benign method for the synthesis of these heterocycles.
Solvent-free reactions obviously reduce pollution and bring down
handling costs because of the simplification of experimental procedure
and workup technique. These would be especially important during
industrial production, and also heterogeneous catalysts make synthetic
processes clean, safe, high-yielding, and inexpensive.
Porous materials have been intensively studied with regard to technical
applications as catalysts and catalyst supports. According to the Interna-
tional Union of Pure and Applied Chemistry (IUPAC) definition, porous
materials are divided into three classes: microporous (pore size <2 nm),
mesoporous (2–50 nm), and macroporous (>50 nm) materials.[10] Among
the family of microporous materials, the best-known members are zeolites,
which have a narrow and uniform micropore size distribution due to their
crystallographically defined pore system. In recent years, environmental
and economic considerations have raised strong interest in redesigning
commercially important processes so that the use of harmful substances
and the generation of toxic waste could be avoided. In this respect, there is
no doubt that heterogeneous catalysis can play a key role in the development
of environmentally benign processes in petroleum chemistry and in the pro-
duction of chemicals, for instance, by substitution of liquid acid catalysts by
solid materials. Zeolites especially have attracted strong attention as such
acids but also as base and redox catalysts. However, zeolites present severe
limitations when large reactant molecules are involved, especially in liquid-
phase systems, as is frequently the case in the synthesis of fine chemicals,
because mass transfer limitations are very severe for microporous solids.
Attempts to improve the diffusion of reactants to the catalytic sites have so
far focused on increasing the zeolite pore sizes,[11] decreasing zeolite crystal
size,[12] and providing an additional mesopore system within the micropor-
ous crystals.[13,14] An important line of research has focused on the enlarge-
ment of the pore sizes into the mesopore range, allowing larger molecules to
enter the pore system, be processed there, and leave the pore system again.
The first synthesis of an ordered mesoporous material was described in the
patent literature in 1969. However, because of a lack of analysis, the remark-
able features of this product were not recognized.[15] In 1992, a similar
material (M41S family) was obtained by scientists in Mobil Oil Corporation,
who discovered the remarkable features of this novel type of silica and
opened up a whole field of research.[16] The M41S family has been classified
into four main groups, as depicted in Fig. 1. The first one refers to disordered
rods, and the three others are well-defined mesostructures: (i) MCM-41,
with a hexagonal array of unidirectional and noninterconnecting pores;
(ii) MCM-48, with a three-dimensional cubic pore structure; and (iii)

1744
R. H. Shoar et al.
Figure 1. The M41S family structures.
MCM-50, with an unstable lamellar structure. MCM-41 could be viewed as
the ultimate model for mesoporous adsorbent material for investigating fun-
damental features of adsorption, such as the effects of pore size and hyster-
esis, because of its relatively uniform cylindrical=hexagonal pore
channels.[17] MCM-41 was recently reported to be an efficient agent to some
reactions such as hydrodesulfurization, hydrodenitrogenation, and mild
hydrocracking (MHC)[18] and as an acid catalyst for Friedel–Crafts alkyla-
tion of 2,4-di-tert-butylphenol (bulky aromatic) with cinnamyl alcohol and
for the tetrahydropyranylation of alcohol and phenol.[19,20]
Herein, we report an efficient, convenient, and facile method for the
condensation of 2-aminophenols with benzoyl chlorides using MCM-41
as catalyst to obtain the corresponding benzoxazoles (Scheme 1).
RESULTS AND DISCUSSION
At first we studied the synthesis of benzoxazoles from the condensation
of 2-aminophenol and benzoyl chloride to optimize the reaction condi-
tions (Table 1).
The optimum yield of the product was obtained when 0.02 g of
MCM-41 was used. Among the solvents tested for this reaction
(i.e., EtOH, AcOH, CH3CN, and water), it was found that the best result
(short reaction time and maximum yield of the product) was obtained
under solvent-free condition, which is also economically and environ-
mentally favorable.
Scheme 1. The condensation reaction of 2-aminophenols with benzoyl chlorides
using MCM-41 as catalyst.

Benzoxazoles Synthesis Catalyzed by MCM-41
1745
Table 1. Optimization of the reaction conditions (30 min)
Entry
Catalyst (g)
Solvent
Yield (%)a
1
2
3
4
5
6
7
MCM-41 (0.01)
MCM-41 (0.02)
MCM-41 (0.03)
MCM-41 (0.02)
MCM-41 (0.02)
MCM-41 (0.02)
MCM-41 (0.02)
—
—
—
45
94
94
45
50
55
—
CH3CN
EtOH
AcOH
Watet
aYields refer to the isolated pure products.
In a typical general experimental procedure, a mixture of 2-amino-
phenol and benzoyl chloride were heated together in solvent-free condi-
tion in the presence of a catalytic amount of MCM-41. To study the
generality of this procedure, a series of benzoxazoles were synthesized
with similar operation. The results are listed in Table 2.
It is noteworthy that the catalyst is recyclable and could be reused
without significant loss of activity. MCM-41 was recovered and reused
in the model reaction four times (Table 3).
In conclusion, we developed the use of MCM-41, a mesopore-type
catalyst, as an inexpensive, reusable, easy-to-handle, noncorrosive, and
environmentally benign catalyst for the synthesis of benzoxazoles from
2-aminophenoles and benzoyl chlorides.
EXPERIMENTAL
Melting points were determined using a 9200-Barnstead Electrothermal
apparatus, the accuracy of which was checked using standard compounds
of known melting points. Infrared (IR) spectra were recorded on a Four-
ier transform (FT)–IR Tensor 27 spectrophotometer. Gas chromatogra-
phy (GC) and GC-Mass spectra were recorded on Aglient apparatus.
1H NMR spectra were recorded in CDCl3 solvent on a Bruker instrument
at 500 MHz.
Preparation of Benzoxazoles in the Presence of MCM-41:
General Procedure
MCM-41 (0.02 g) was added to a mixture of 2-aminophenol (1 mmol) and
benzoyl chloride (1 mmol). The mixture was heated and stirred under
solvent-free conditions, and the reaction was monitored by thin-layer

1746
R. H. Shoar et al.
Table 2. Synthesis of benzoxazoles catalyzed by MCM-41 in solvent-free
condition
Time
(min) Yielda
Entry Compound
X
H
Y
H
Product
1
a
30
94
2
3
4
b
c
H
H
CH3
Cl
30
25
35
94
93
90
d
CH3
H
5
6
e
f
Cl
H
30
30
90
88
CH3 Cl
7
8
g
Cl CH3
35
35
89
90
h
CH3 CH3
9
i
Cl
Cl
25
94
aYields refer to the isolated pure products.
chromatography (TLC) using EtOAc–hexane (4:1) as eluent. After com-
pletion of the reaction, the MCM-41 was separated by simple filtration
by diluting it with ethyl acetate. The recovered MCM-41 was reused in

Benzoxazoles Synthesis Catalyzed by MCM-41
1747
Table 3. Reusability of catalyst in the model reaction (30 min)
Entry
Number of uses
Yield (%)a
1
2
3
4
Fresh
94
94
90
87
1
2
3
aYields refer to the isolated pure products.
subsequent reactions. The filterate was concentrated, and the residue was
purified by column chromatography over silica gel using EtOAc–hexane
(4:1) as eluent to obtain pure benzoxazole derivatives. To establish the
generality of the present reaction, several structurally diverse 2-amino-
phenpols and benzoyl chlorides (Table 2) were subjected to condensation
with each other under the catalytic influence of MCM-41 in solvent-free
conditions, and benzoxazoles were obtained in high yields. All products
were identified by comparison of their physical and spectroscopic data
with those reported for authentic samples.
Recycling of the Catalyst
The catalyst could be recycled by evaporating the of solvent from the resi-
due, washing it with diethyl ether, drying it at 130ꢀC for 1 h, and reusing
it in another reaction. The recycled catalyst was used for four reactions
without appreciable loss in its catalytic activities in the case of the model
reaction.
Spectroscopic Data and Melting Points for Compounds in Table 1
2-Phenyl-benzoxazole
Mp 102ꢀC, FT-IR (KBr) nmax: 3060, 2926, 1612 cmꢁ1; 1H NMR (CDCl3,
500 MHz): 8.29, 8.30 (d, 2H), 7.28, 7.39 (m, 4H), 7.56, 7.81 (m, 3H) ppm;
MS m=z (relative intensity): 195 (Mþ).
2-(4-Methyl-phenyl)-benzoxazole
1
Mp 112–114ꢀC; FT-IR (KBr) nmax: 3055, 2918, 1620 cmꢁ1; H NMR
(CDCl3, 500 MHz): 8.09, 8.07 (d, 2H), 7.77 (t, 2H), 7.42, 7.38 (m, 4H),
2.40 (s, 3H) ppm; MS m=z (relative intensity): 209 (Mþ).

1748
R. H. Shoar et al.
2-(4-Chloro-phenyl)-benzoxazole
1
Mp 148–151ꢀC; FT-IR (KBr) nmax: 3056, 2924, 1615 cmꢁ1; H NMR
(CDCl3, 500 MHz): 8.23, 8.25 (d, 2H), 7.54, 7.56 (d, 2H), 7.81, 7.82
(m, 1H), 7.62, 7.64 (m, 1H), 7.40, 7.42 (m, 2H) ppm; MS m=z (relative
intensity): 229 (Mþ).
2-Phenyl-5-methyl-benzoxazole
1
Mp 103–105ꢀC, FT-IR (KBr) nmax: 3055, 2918, 1600 cmꢁ1; H NMR
(CDCl3, 500 MHz): 8.28, 8.30 (d, 2H), 7.60 (s, 1H), 7.55, 7.57 (m, 3H),
7.49, 7.50 (d, 1H), 2.58 (s, 3H) ppm; MS m=z (relative intensity):
209 (Mþ).
2-Phenyl-5-chloro-benzoxazole
1
Mp 110–113ꢀC, FT-IR (KBr) nmax: 3055, 2918, 1604 cmꢁ1; H NMR
(CDCl3, 500 MHz): 8.30, 8.32 (d, 2H), 7.62 (s, 1H), 7.55, 7.57 (m, 3H),
7.49, 7.50 (d, 1H), 7.20, 7.21 (d, 1H) ppm; MS m=z (relative intensity):
229 (Mþ).
2-(4-Chloro-phenyl)-5-methylbenzoxazole
1
Mp 148–150ꢀC; FT-IR (KBr) nmax: 3075, 2919, 1618 cmꢁ1; H NMR
(CDCl3, 500 MHz): 8.21, 8.23 (d, 2H), 7.59 (s, 1H), 7.53, 7.55 (d, 2H),
7.48, 7.50 (d, 1H), 7.21, 7.22 (d, 1H), 2.53 (s, 3H) ppm; MS m=z (relative
intensity): 243 (Mþ).
2-(4-Methyl-phenyl)-5-chlorobenzoxazole
1
Mp 132–135ꢀC, FT-IR (KBr) nmax: 3050, 2924, 1614 cmꢁ1; H NMR
(CDCl3, 500 MHz): 8.16, 8.18 (d, 2H), 7.77 (d, 1H), 7.52 (d, 1H), 7.36,
7.39 (d, 2H), 7.34 (d, 1H), 2.49 (s, 3H) ppm; MS m=z (relative intensity):
243 (Mþ).
2-(4-Methyl-phenyl)-5-methylbenzoxazole
1
Mp 138–141ꢀC; FT-IR (KBr) nmax: 3024, 2916, 1614 cmꢁ1; H NMR
(CDCl3, 500 MHz): 8.16, 8.18 (d, 2H), 7.58 (d, 1H), 7.47, 7.48 (m, 3H),

Benzoxazoles Synthesis Catalyzed by MCM-41
1749
7.36, 7.37 (d, 1H), 7.17, 7.19 (d, 1H), 2.52 (s, 3H), 2.48 (s, 3H) ppm; MS
m=z (relative intensity): 223 (Mþ).
2-(4-Chloro-phenyl)-5-chlorobenzoxazole
1
Mp 195–197ꢀC; FT-IR (KBr) nmax: 3061, 2924, 1657 cmꢁ1; H NMR
(CDCl3, 500 MHz): 8.21, 8.23 (d, 2H), 7.78, 7.79 (d, 1H), 7.55, 7.57
(m, 3H), 7.30 (d, 1H), 7.39, 7.54 (d, 1H) ppm; MS m=z (relative intensity):
263 (Mþ).
ACKNOWLEDGMENT
The authors are thankful to Azzahra Research Council for the partial
financial support.
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