Facile and efficient one-pot protocol for the synthesis of benzoxazole and benzothiazole derivatives using molecular iodine as catalyst

Article abstract of DOI:10.1080/00397910600781448

Rapid and efficient condensation reactions of 2-aminothiophenol and 2-aminophenol with various aldehydes were carried out using I₂ in solvent-free conditions with or without microwave irradiation to afford the corresponding 2-substituted benzothiazole and benzoxazole derivatives in good to excellent yields. Copyright Taylor & Francis Group, LLC.

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Facile and Efficient One‐Pot Protocol for the
Synthesis of Benzoxazole and Benzothiazole
Derivatives using Molecular Iodine as Catalyst
a
a
Firouz Matloubi Moghaddam , Ghasem Rezanejade Bardajee , Hossein
a
a
Ismaili & Seyedeh Maryam Dokht Taimoory
a
Department of Chemistry, Sharif University of Technology, Tehran, Iran
Available online: 27 Oct 2006
To cite this article: Firouz Matloubi Moghaddam, Ghasem Rezanejade Bardajee, Hossein Ismaili & Seyedeh
Maryam Dokht Taimoory (2006): Facile and Efficient One‐Pot Protocol for the Synthesis of Benzoxazole and
Benzothiazole Derivatives using Molecular Iodine as Catalyst, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 36:17, 2543-2548
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Synthetic Communications , 36: 2543–2548, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600781448
Facile and Efficient One-Pot Protocol for the
Synthesis of Benzoxazole and Benzothiazole
Derivatives using Molecular Iodine
as Catalyst
Firouz Matloubi Moghaddam, Ghasem Rezanejade Bardajee,
Hossein Ismaili, and Seyedeh Maryam Dokht Taimoory
Department of Chemistry, Sharif University of Technology, Tehran, Iran
Abstract: Rapid and efficient condensation reactions of 2-aminothiophenol and
2
2-aminophenol with various aldehydes were carried out using I in solvent-free con-
ditions with or without microwave irradiation to afford the corresponding 2-substituted
benzothiazole and benzoxazole derivatives in good to excellent yields.
Keywords: Aldehydes, benzothiazole, benzoxazole, iodine, microwave, solvent free
Benzothiazoles and benzoxazoles are very important group of heterocyclic
compounds that have many applications in both pharmaceutical and industrial
research. They are widely found in bioorganic and medicinal chemistry with
applications in drug discovery such as antitumour, anticonvulsant, and
[
1–3]
antiviral applications.
antioxidants, vulcanization accelerators, and as a dopant in a light-emitting
They have also found applications in industry as
[
4,5]
organic electroluminescent device.
synthesis of title compounds. The important ones include the reaction of
There are a few methods for the
2
or its derivatives in presence of polyphosphoric acid,
-aminothiophenol or 2-aminophenol with the substituted carboxylic acids
polyphosphate
[
6]
[7]
[8]
ester, a mixture of methanesulfonic acid and phosphorous pentoxide, or
[9]
an ionic liquid; palladium-catalyzed direct coupling of benzothiazoles or
Received in Poland December 16, 2005
Address correspondence to Firouz Matloubi Moghaddam, Department of
Chemistry, Sharif University of Technology, PO Box 11365-9516, Tehran, Iran.
E-mail: matloubi@sharif.edu
2
543

2
544
F. M. Moghaddam et al.
[
10]
benzoxazoles with aryl bromides;
[
reaction of copper(I) thiobenzoat and
11]
2
-iodoanilines;
-aminothiophenol or 2-aminophenol followed by dehydrative cyclization;
palladium-catalyzed condensation of aryl halides whti
[12]
2
palladium-catalyzed cyclization of 2-bromophenylthioformamides;
[13]
and
oxidative cyclization of phenolic Schiff bases using various oxidants such as
þ
2
4
[14a–d]
PhI(OAc) , Mn(OAc) , Th ClO , and Pb(OAc) Microwave-assisted
reactions in solvent or solvent-free conditions have gained popularity
2
3
4.
[15]
because of rapid reaction rate, cleaner reactions, and ease of manipulation.
Recently, some methods use microwave heating for the synthesis of 2-
substituted benzothiazoles or benzoxazoles, such as condensation of
[16]
aromatic or aliphatic aldehydes with 2-aminothiophenol on SiO2,
aromatic aldehydes with 2-aminothiophenol in the presence of nitroben-
[17]
[18]
zene/SiO or nitrobenzene/montmorillonite K10,
carboxylic acids,
or
2
[
19]
acid chlorides
with 2-aminophenol.
Molecular iodine has received considerable attention in organic synthesis
as an inexpensive and easily available catalyst for effecting various organic
[
20a,b]
transformations.
We now report the synthesis of 2-substituted-benzothiazoles and benzox-
azoles by condensation of 2-aminothiophenol and 2-aminophenol respectively
with various aromatic aldehydes using molecular iodine as an efficient catalyst
under solvent-free conditions with or without microwave irradiation in rela-
tively short time, (Scheme 1 and Table 1).
Our investigations showed that 2-aminothiophenol reacts smoothly with
aromatic aldehydes in the presence of molecular iodine as a catalyst at
room temperature and in solvent-free conditions at relatively short times,
whereas the reaction of 2-aminophenol with aromatic aldehydes requires
more vigorous conditions and is efficiently promoted with solvent-free
microwave irradiation processes. The corresponding 2-substituted-benzothia-
zoles and benzoxazoles were obtained in high to excellent yields (Table 1).
At first we focused on the reaction of 2-aminothiophenol and aromatic
aldehydes. In a typical procedure, 2-aminothiophenol (1 mmol) with benz-
aldehyde (1 mmol) in the presence of a catalytic amount of molecular iodine
(
0.5 mmol) at room temperature afforded the desired 2-phenyl-benzothiazole
in 92% yield (Entry 9, Table 1). The reaction then was applied to a variety
of aromatic aldehydes (Scheme 1 and Table 1). Most of these reactions
proceeded in relatively short times, and pure products were obtained by
recrystallization or preparative thin layer chromatography (PTLC).
Scheme 1.

Benzoxazole and Benzothiazole Derivatives
2545
Table 1. Synthesis of 2-substitued-benzoxazole and benzothiazoles catalyzed by
molecular iodine under solvent-free condition with or without microwave irradiation
a
Entry
Ar
T (min)
Yield (%)
Mp/(lit.) (8C)
b
[14a]
1
2
3
4
5
6
7
8
9
C
6
H
5
3
92
65
82
93
85
95
71
91
92
73
80
93
84
92
76
89
102–104 (102)
[14a]
103–105 (101)
b
4-CH OC
2-HOC H
3
6
H
4
4
b
[21]
[22]
3
119–121 (120–121)
156–157 (154–155)
[23]
128–129 (125.5)
6
4
b
4-BrC H
3
6
4
4
4
b
2-ClC
4-ClC
6
H
3
b
3
[14a]
6
H
147–149 (147)
115–116 (113–114)
—
b
[14a]
4-CH C H
6 4
3
3
d
C
C
6
H
H
5
5
4
10
c
6
112–113 (113) [16]
124–125 (119–121)
128–130 (127–128)
c
[16]
[16]
1
1
1
1
1
1
1
0
1
2
3
4
5
6
4-CH OC H
3
20
6
4
c
2-HOC
6
H
4
15
c
[24]
4-BrC
6
H
4
4
4
10
132 (132–133)
82–83 (84–85)
c
[16]
2-ClC H
6
15
c
[16]
4-ClC
4-CH
6
H
10
120–122 (119–121)
[16]
87–88 (85)
c
3
C
6
H
4
20
c
C
6
H
5
10
—
a
All yields refer to isolated products, and the products were characterized by mp, IR,
1
and H NMR, and their physical data were similar to those reported in the literature.
b
The reaction was carried out using 2-aminophenol under microwave irradiation.
The reaction was carried out using 2-aminothiophenol at room temperature.
c
d
[18,19]
The reaction could also proceed without catalyst.
Electron-donating substituents on the aromatic ring of aldehyde decrease
the yield and increase the time of the reaction (Entries 10 and 15, Table 1). The
substituents on the ortho position act in the same manner as electron-donating
substituents (Entry 13, Table 1), whereas electron-donating ortho-substituents
increase the yield (Entry 11, Table 1). We also prepared 2-substituted
benzoxazoles under microwave-assisted, solvent-free conditions by the
reaction of 2-aminophenol and aromatic aldehydes. The behavior of these
reactions is similar to the reactions of 2-aminothiophenol and aldehydes
(Entries 1–8, Table 1). Also, the reaction of benzoic anhydride with 2-ami-
nothiophenol or 2-aminophenol was investigated. 2-aminothiophenol reacts
very efficiently with benzoic anhydride in the presence of molecular iodine
at room temperature. The reactivity of 2-aminophenol is less than 2-ami-
nothiophenol, and its reaction with benzoic anhydride promoted efficiently
in microwave-assisted, solvent-free condition with I as a catalyst (Entries 8
2
and 16, Table 1).
In conclusion, molecular iodine was found to be a mild and effective
catalyst for the one-pot reactions of 2-aminothiophenol and 2-aminophenol
with aromatic aldehydes to afford 2-substitued benzothiazole and benzoxazole
derivatives in excellent yields. The use of this inexpensive and easily available

2
546
F. M. Moghaddam et al.
catalyst under essentially neutral reaction and workup conditions and the
cleaner reaction make this protocol practical and economically attractive. With
regards to lower reactivity of 2-aminophenol relative to 2-aminothiophenol,
the use of microwave irradiation introduced a new method for the synthesis of
2-substitued-benzoxazoles with a very safe, efficient, and cheap catalyst.
EXPERIMENTAL
The compounds all gave satisfactory spectroscopic data. IR spectra were taken
as thin films for liquid compounds and as KBr pellets for solids on a Nicolet
spectrometer (Magna 550). A Bruker (DRX-500 Avance) NMR was used to
1
record the H NMR spectra. All NMR spectra were determined in CDCl at
3
ambient temperature. The microwave oven used for this work was ETHOS-
MR (800 W, 1308C) at 2450 MHz. Melting points were determined on a
Buchi B540 apparatus.
General Procedure for the Synthesis of 2-Substitued Benzothiazole
Compounds in Solvent-free Condition
A mixture of 2-aminothiophenol (1 mmol), aromatic aldehyde (1 mmol), and a
catalytic amount of molecular iodine (0.5 mmol) was stirred at room tempera-
ture for an appropriate time (see Table 1) as required for completion of the
reaction, which was monitored by thin layer chromatography (TLC). The
mixture was chromatographed over silica gel or PTLC using petroleum
ether–ethyl acetate (4:1) to afford the pure product.
General Procedure for the Synthesis of 2-Substitued Benzoxazole
Compounds in Microwave-Assisted, Solvent-Free Condition
A mixture of 2-aminophenol (1 mmol), aromatic aldehyde (1 mmol), and
w
catalytic amount of molecular iodine (0.5 mmol) was placed in a Teflon
flask (ꢀ20 mL) and subjected to microwave irradiation for appropriate time
(see Table 1). The reaction mixture was chromatographed over silica gel or
PTLC using petroleum ether–ethyl acetate (4:1) to afford the pure product.
ACKNOWLEDGMENT
We acknowledge the Islamic Development Bank (IDB) for granting the loan
in 1993 for purchasing a 500-MHz Bruker NMR spectrometer.

Benzoxazole and Benzothiazole Derivatives
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