An efficient procedure for the synthesis of benzoxazole and benzothiazole derivatives using a H2O2/SiO2-FeCl3 system

Article abstract of DOI:10.1080/10426501003598630

A series of benzoxazole and benzothiazoles was readily prepared from the reaction of ortho-aminophenol/ortho-aminothiophenol and aldehydes using solid silica supported ferric chloride (SiO₂-FeCl₃) as catalyst followed by oxidation with H₂O₂ under ambient conditions. Some of advantages of this method are a simple and convenient procedure, easy purification, and shorter reaction times. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426501003598630

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An Efficient Procedure for the Synthesis
of Benzoxazole and Benzothiazole
Derivatives Using a H O /SiO -FeCl
2
2
2
3
System
a
a
Mohammad Hossein Mosslemin & Abbas Fazlinia
a
Department of Chemistry , Islamic Azad University–Yazd Branch ,
Yazd, Iran
Published online: 24 Sep 2010.
To cite this article: Mohammad Hossein Mosslemin & Abbas Fazlinia (2010) An Efficient
Procedure for the Synthesis of Benzoxazole and Benzothiazole Derivatives Using a H O /SiO -
2
2
2
FeCl System, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:10, 2165-2170, DOI:
3
10.1080/10426501003598630
To link to this article: http://dx.doi.org/10.1080/10426501003598630
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Phosphorus, Sulfur, and Silicon, 185:2165–2170, 2010
Copyright ꢀ
Taylor & Francis Group, LLC
C
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003598630
AN EFFICIENT PROCEDURE FOR THE SYNTHESIS OF
BENZOXAZOLE AND BENZOTHIAZOLE DERIVATIVES
USING A H O /SiO -FeCl SYSTEM
2
2
2
3
Mohammad Hossein Mosslemin and Abbas Fazlinia
Department of Chemistry, Islamic Azad University–Yazd Branch, Yazd, Iran
A series of benzoxazole and benzothiazoles was readily prepared from the reaction of ortho-
aminophenol/ortho-aminothiophenol and aldehydes using solid silica supported ferric chlo-
ride (SiO2-FeCl3) as catalyst followed by oxidation with H2O2 under ambient conditions.
Some of advantages of this method are a simple and convenient procedure, easy purification,
and shorter reaction times.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Aldehydes; benzothiazoles; benzoxazoles; SiO2-FeCl3, H2O2
INTRODUCTION
Heterocycles containing a nitrogen atom are an important class of heterocyclic com-
pounds, since many of these heterocyclic systems exhibit building blocks and biological
1
activities. A wide spectrum of these properties is displayed by 2-substituted benzoxazoles
and benzothiazole skeletons. These find applications in material sciences as melatonin
receptor agonist, cyclooxygenase inhibitory, anticancer, antimycobacterial, and antago-
2
nist activities. The widespread interest in these structures has prompted extensive studies
for their synthesis. Numerous synthetic methods are available for the preparation of 2-
arylbenzothiazoles and 2-arylbenzoxazoles. The most important ones include the reaction
of o-aminophenols and o-aminothiophenols with aromatic aldyhydes in a wide set of con-
3
ditions. But some of these procedures have certain limitations such as tedious process,
long reaction times, harsh reaction conditions, and low yields.
In our program, we introduced a simple and convenient method for the synthesis of
2-substituted benzoxazoles and benzothiazoles via one-pot cyclocondensation-oxidation of
ortho-aminophenol or ortho-aminothiophenol and aldehydes using silica supported ferric
4
chloride (SiO2-FeCl3) as catalyst under ambient conditions (Scheme 1). Among several
Received 2 November 2009; accepted 4 January 2010.
We are thankful to the Islamic Azad University of Yazd Research Council for the partial support of this
research.
Address correspondence to Abbas Fazlinia, Department of Chemistry, Islamic Azad University–Yazd
Branch, Yazd 89168-71967, Iran. E-mail: fazlinia@gmail.com
2
165

2166
M. H. MOSSLEMIN AND A. FAZLINIA
NH2
+
N
X
CHO SiO -FeCl (Cat)
2
3
Y
H O ; r.t.; EtOH
2
2
Y
XH
X = O, S
Scheme 1
reusable and heterogeneous catalysts designed and used in organic reactions, silica sup-
ported ferric chloride (SiO2-FeCl3) is one of the useful examples of them that has performed
as an inexpensive catalyst that can be easily separated and reused, and is not contaminated
4
by the products. Also, this catalyst is an active catalyst, nontoxic, safe, easy to handle, and
environmentally benign with fewer disposal problems.
RESULTS AND DISCUSSION
In order to estimate the catalytic efficiency of SiO2-FeCl3 and to determine the most
appropriate reaction conditions, at first we carried out the cyclocondensation-oxidation
reaction of ortho-aminophenol with benzaldehyde as a model reaction under different
reaction conditions (Table I).
Among the various tested solvents regarding the amount of the catalyst and temper-
ature, 0.02 g of catalyst in ethanol at room temperature was the best reaction condition for
cyclocondensation-oxidation of ortho-aminophenol with benzaldehyde (Table I). In order
to improve the yields, we performed reaction using different quantities of reagents. The
best results were obtained with 1:1.1 molar ratios of ortho-aminophenol and aryl aldehyde,
respectively. The results are summarized in Table I.
Table I Optimization of the reaction conditions
◦
Yield (%)a
Entry
Catalyst (g)
Temp. ( C)
Solvent
Time (min)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.05
0.1
150
125
100
80
50
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
—
—
—
—
—
23
28
30
48
70
135
50
22
135
135
42
78
76
69
58
42
—
40
89
—
—
38
59
63
61
83
88
H2O
H2O/EtOH (50:50)
EtOH
CH2Cl2
n-Hexane
EtOAc
EtOH
EtOH
EtOH
EtOH
1
1
1
1
1
1
1
15
10
19
13
0.025
0.075
0.02
EtOH
15
aIsolated yields.

H2O2/SiO2-FeCl3–CATALYZED SYNTHESIS OF BENZOTHIAZOLES
2167
Using these optimized reaction conditions, the scope and efficiency of these proce-
dures were explored for the synthesis of corresponding 2-arylbenzoxazoles (Scheme 2).
NH2
OH
N CHPh
-
H O
2
PhCHO +
A
OH
FeCl3
H O
2
2
N
FeCl (OOH)
3
-
H O
2
Ph
O
FeCl OH
3
H
N
FeOCl3
Ph
O
H
N
O
B
Ph
Scheme 2
Generally, the cyclocondensation-oxidation reaction between ortho-aminophenol and
aryl aldehydes proceeded well and afforded the desired products (Table II, entries 1–9) in
good to high yields. As shown in Table II, the reaction was carried out successfully with a
variety of aryl aldehydes having electron-donating and electron-withdrawing substituents.
We further investigated the one-pot synthesis of benzothiazole derivatives from the
reaction of ortho-aminothiophenol and aryl aldehydes (Scheme 3). We applied the above
optimal reaction conditions (Table I) for this reaction. As shown in Table II, a variety of
aldehydes was investigated. The reaction of ortho-aminothiophenol with aromatic aldehy-
des containing both electron-donating and electron-withdrawing groups was compatible
successfully in good yields (Table II, entries 10–17).
FeCl + H O
FeCl
3
(OOH)
FeOCl
3
FeCl OH
3
3
2
2
Scheme 3
The work-up procedure is very easy; that is, the products were isolated and purified by
simple filtration and crystallization from ethanol. An efficient conversion of benzoxazole
and benzothiazole derivatives has been achieved in high yield by the use of ambient
temperature during the reaction process, making it superior to the previous methods.
The suggested mechanism of the SiO2-FeCl3 catalyzed transformation is shown in
Scheme S1 (Supplemental Materials, available online).

2168
M. H. MOSSLEMIN AND A. FAZLINIA
Table II Synthesis of benzoxazole and benzothiazole derivatives using SiO2-FeCl3 as catalyst
Entry
Y
X = O, S
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
H
O
O
O
O
O
O
O
O
O
S
S
S
S
S
S
S
S
15
9
8
8
8
8
8
9
9
8
7
8
8
8
8
9
9
88
77
86
89
87
90
89
73
70
76
82
89
83
88
86
71
69
2-Nitro
4-N,N-Dimethylamino
2-Bromo
4-Bromo
2-Chloro
4-Chloro
3-Nitro
4-Nitro
2-Nitro
4-N,N-Dimethylamino
2-Bromo
4-Bromo
2-Chloro
4-Chloro
1
1
1
1
1
1
1
1
3-Nitro
4-Nitro
a
Isolated yields. All known products have been reported previously in the literature and were characterized by
3
comparison of IR and NMR spectra with authentic samples.
Upon investigating the reaction mechanism, and in accordance with the reported
procedures, the formation of benzimidazoles causes a connection with the formation of
intermediate Schiff base A, which is equilibrated with the hydrobenzimidazole B that is
produced by intramolecular participation of the o-hydroxyl group (Scheme S1, Supplemen-
tal Materials).4
The mechanisms of the catalytic decomposition of H2O2 by Fe(III) in homogeneous
aqueous solution have been the subject of numerous studies. The mechanisms involved
may be quite complex and are not clearly established. According to previous reports,
different reactive species are supposed to be formed: free- and bound-hydroxyl radicals,
5
and hypervalent iron species [Fe(IV), Fe(V)] (Scheme 3).
The route of SiO2-FeCl3 can be shown as SiO2-FeCl3(OOH), SiO2-FeCl3O, and
SiO2-FeCl3(OH). Finally, the oxidative dehydrogenation of adduct B in the presence of the
SiO2-FeCl3O complex affords the desired 2-arylbenzimidazoles (Scheme S1, Supplemental
Materials).
Table III Comparison results of SiO2-FeCl3 with some catalytic systems reported in the literaturea
Entry
Conditions
Time
Yield (%)Ref
◦
3c
1
2
3
4
5
6
Fe(NO3)3; H2O2; solvent-free, 50 C
DDQ, MeCN, r.t.
Me2S BrBr , MeCN, r.t.
2 min
6 h
5 h
3 h
4 h
98
90
85
3d
+
−
3e
◦
◦
903f
Cu-nanoparticles; MeOH, K2CO3,O2; 80–100 C
Activated carbon(Darco KB); O2, xylene, 120 C
3g
78
SiO2-FeCl3; EtOH, r.t.; H2O2
15 min
88
aBased on the preparation of 2-phenylbenzoxazole.

H2O2/SiO2-FeCl3–CATALYZED SYNTHESIS OF BENZOTHIAZOLES
2169
Recyclability of the Catalyst
To test its recyclability, the SiO2-FeCl3 catalyst was studied with respect to the
preparation of 2-phenyl benzoxazole. After each cycle, the used catalyst was filtered and
◦
activated at 100 C before being used for the next cycle. There was no significant change in
the activity and selectivity, even after three cycles (Figure S1, Supplemental Materials).
To show the merit of the present work in comparison with reported results in the
literature, we compared results of SiO2-FeCl3 with some catalytic systems reported in the
literature used in the synthesis of 2-phenyl benzoxazole (Table III). As shown in Table III,
SiO2-FeCl3 is an effective catalyst with respect to reaction times, yields, and the obtained
products.
CONCLUSION
In conclusion, we have demonstrated that SiO2-FeCl3 is an efficient and heteroge-
neous catalyst for synthesis of a variety of benzoxazole and benzothiazole derivatives using
aryl aldehydes and ortho-aminophenol/ortho-aminothiophenol under ambient conditions.
The reactions were carried out at room temperature with short reaction time and produced
the corresponding product in good to high yields.
EXPERIMENTAL
All reagents were purchased from Merck and Aldrich and were used without further
purification. All yields refer to isolated products after purification. SiO2-FeCl3 was prepared
4
according to the reported procedure. Products were characterized by spectroscopic data
(IR, NMR spectra), and melting points were compared with authentic samples. The NMR
spectra were recorded on a Bruker Avance DEX 300 MHz instrument. The spectra were
measured in DMSO-d6 relative to TMS (0.00 ppm). IR spectra were recorded on a Jasco
FT-IR 460plus spectrophotometer. All of the compounds are solids, and solid state IR
spectra were recorded using the KBr disk technique. Melting points were determined in
open capillaries with a Buchi 510 melting point apparatus. TLC was performed on silica
gel polygram SIL G/UV 254 plates.
General Procedure
To a mixture of ortho-aminophenol/ortho-aminothiophenol (1 mmol), aryl aldehydes
(1.1 mmol), and aq. 30% H2O2 (7 mmol) in ethanol (5 mL), SiO2-FeCl3 (0.02 g) was
added, and the mixture was stirred at room temperature for the appropriate time shown in
Table II. The progress of the reaction was monitored by TLC (eluent: n-hexane:EtOAc,
7:3). When the starting materials had completely disappeared, the mixture was dissolved
in CH2Cl2 (10 mL). The catalyst was separated, and the organic layer was washed with
water (2 × 10 mL). Then the combined extracts were dried under MgSO4. The filtrate was
evaporated, and the corresponding benzoxazoles/benzothiazoles were obtained as the only
product after recrystallization in ethanol (Table I).
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