Magnetically recoverable and reusable CuFe2O4 nanoparticle-catalyzed synthesis of benzoxazoles, benzothiazoles and benzimidazoles using dioxygen as oxidant

Article abstract of DOI:10.1039/c4ra00559g

A green and efficient strategy for the synthesis of benzoxazoles, benzothiazoles and benzimidazoles has been developed by using inexpensive, readily available, dioxygen-stable and recyclable CuFe₂O₄ as the nanocatalyst, and o-substituted aminobenzene and various aldehydes as the starting materials. The CuFe₂O₄ nanoparticles are dioxygen insensitive and easily recoverable with an external magnet from the reaction medium. The catalyst can be reused ten times without significant loss of catalytic activity. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra00559g

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Magnetically recoverable and reusable CuFe2O4
nanoparticle-catalyzed synthesis of benzoxazoles,
benzothiazoles and benzimidazoles using dioxygen
as oxidant†
Cite this: RSC Adv., 2014, 4, 17832
Daoshan Yang,a Xiao Zhu,a Wei Wei,a Nana Sun,a Li Yuan,a Min Jiang,b Jinmao Youac
a
*
and Hua Wang
A green and efficient strategy for the synthesis of benzoxazoles, benzothiazoles and benzimidazoles has
been developed by using inexpensive, readily available, dioxygen-stable and recyclable CuFe2O4 as the
nanocatalyst, and o-substituted aminobenzene and various aldehydes as the starting materials. The
CuFe2O4 nanoparticles are dioxygen insensitive and easily recoverable with an external magnet from the
reaction medium. The catalyst can be reused ten times without significant loss of catalytic activity.
Received 22nd January 2014
Accepted 1st April 2014
DOI: 10.1039/c4ra00559g
www.rsc.org/advances
Aldehydes are important and common building blocks, and
they are easily prepared from readily available materials. Using
Introduction
o-substituted aminoaromatics and aldehyde as the starting
materials to construct these heterocycles have caught consid-
erable attention (Scheme 1c). In this regard, several examples of
aerobic oxidation pathways have been reported with various
transition metal salts or oxidants, such as ZrOCl2$8H2O,12
Pd(OAc)2/O2,13 CuCl2,14 Sc(OTf)3,15 Yb(OTf)3,16 FeCl3$6H2O,17
HAuCl4$4H2O/O2,18 DDQ,19 PhI(OAc)2,20 H2O2–HCl,21 TEMPO,22
activated carbon23 and cyanide.24 However, in some cases, most
of these methods might suffer from some drawbacks such as
undesirable stoichiometric oxidants, noble transition metal
catalyst, long reaction times, toxic reaction reagents, and
residual metal catalysts in the end products, which should still
impede their applications for the heterocycle synthesis on a
large scale.
In recent years, heterogeneous catalysts have attracted much
attention in organic transformations due to their interesting
reactivity as well as for economic and environmental reasons. A
large number of recyclable supported catalytic systems have
been developed (Scheme 1c).25–27 For example, Satyanarayana's
group reported an efficient method for the synthesis of ben-
zoxazoles using silica-supported sodium hydrogen sulphate.25
Recently, Kidwai and co-workers reported an efficient CuO
nanoparticles catalyzed coupling aromatic or heteroaromatic
aldehydes with 2-aminophenol to construct benzoxazoles in the
presence of K2CO3 in MeOH.26 Gracefully excellent as these
works could be, the small size of catalyst particles might oen
make their separation and recyclization difficult, especially the
catalysis efficiency of the recovered catalysts might be some-
what reduced through a ltration step.
N-Heterocycles widely occur in natural products, biologically
active molecules and organic materials, and they play an
important role in the design and discovery of new drugs.
Therefore, the development of novel, efficient and practical
methods for heterocycle synthesis is an important goal in
modern organic synthesis. Benzoxazoles, benzothiazoles and
benzimidazoles are now known to have a wide range of useful
biological and medicinal properties, such as polymers,1 enzyme
inhibitors,2 antibacterial,3 anticancer agents,4 antimicrobial,5
anti-inammatory,6 antiparkinson,7 antioxidants,8 and anti-
allergy activities,9 so their synthesis is attracting much attention.
Consequently, a lot of signicant methods for the synthesis of
these important building blocks have been developed. The
conventional methods for the synthesis of these important
compounds typically involve two approaches. One is the metal-
catalyzed intramolecular condensation of o-haloanilides or their
analogues (Scheme 1a).10 The second approach mainly involves
the coupling of o-substituted aminoaromatics with carboxylic
acids or acyl halides (Scheme 1b).11 Despite these methods have
made various successes, the uneasily available precursors and
undesired by-products limit their wide applications. Therefore,
a more effective process is needed.
aShandong Province Key Laboratory of Life-Organic Analysis, School of Chemistry and
Chemical Engineering, Qufu Normal University, Qufu 273165, P. R. China. E-mail:
huawang_qfnu@126.com; Fax: +86-5374458306; Tel: +86-5374458306
bBeijing Key Laboratory for Analytical Methods and Instrumentation, Department of
Chemistry, Tsinghua University, Beijing 100084, P. R. China
cKey Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of
Plateau Biology, Chinese Academy of Science, Xining 810008, P. R. China
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra00559g
Recently, magnetic nanoparticles (MNPs) have been exten-
sively used in organic transformations owing to their easy
17832 | RSC Adv., 2014, 4, 17832–17839
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an increasing demand for the use of dioxygen as an oxidant for
many oxidation reactions, because water is the only waste when
dioxygen is used as oxidant. Inspired by the utilization of
magnetically separable CuFe2O4 nanoparticles as a powerful
and excellent catalyst for many organic transformations.30
Herein, we report a simple, practical and efficient method for
the synthesis of substituted benzoxazoles, benzothiazoles and
benzimidazoles by using the cheap, dioxygen-stable CuFe2O4
nanoparticles as a magnetically recoverable catalyst and O2 as a
green oxidant (Table 1).
Scheme 1 Strategies for the synthesis of benzoxazoles, benzothia-
zoles and benzimidazoles.
Results and discussion
The CuFe2O4 nanoparticles were synthesis by reaction of Cu2+
ions and Fe3+ in alkaline condition according to the literature
procedure31 and characterized by X-ray diffraction (Fig. 1), TEM
spectrum (Fig. 2) and EDX spectrum (Fig. 1, ESI†). The
diffraction patterns of all the peaks are in agreement with the
standard XRD pattern (JCPDS34-0425). The XRD pattern of the
CuFe2O4 nanoparticles before reaction (Fig. 1a) and aer
reaction in the 3th cycle (Fig. 1b) showed that the Cu remains
in the +2 oxidation state. Additionally, the TEM and SEM
images analysis of the recovered nano CuFe2O4 particles
revealed that the morphology of the catalyst remains
unchanged, even aer three cycles under dioxygen atmosphere
(Fig. 2 and 3).
At rst, 2-aminophenol (1a) and 4-methylbenzaldehyde
(2b) were chosen as the model substrates to optimize reaction
conditions including the amount of catalysts, solvents and
reaction temperatures under oxygen atmosphere. First, ve
solvents were tested in the presence of 0.2 equiv. of CuFe2O4
nanoparticles, and toluene gave the highest yield (94%),
interestingly, without solvent, also afforded the target product
(3a) in 45% yield (entries 1–6). Furthermore, when the
amount of the catalyst was changed from 20 mol% to 1 mol
%, the reaction yield decreased, providing only 30% yield
(entries 5, 8–10). Control experiments conrmed that the
product was not formed in the absence of the catalyst (entries
8). We attempted different temperature (compare entries 5
and 11–14), and 110 ꢀC was optimal. The reaction under air
also gave a good yield (76%) (entry 15). Therefore, the stan-
dard reaction condition for the CuFe2O4-catalyzed synthesis
preparation, large surface area ratio, low toxicity, high disper-
sion property in organic solvents, facile separation by using an
external magnetic force and without the need for ltration
step.28 Very recently, Brahmachari et al. reported an elegant
work for the synthesis of 2-substituted benzimidazoles and
quinoxalines using MnFe2O4 as a heterogeneous catalyst.29
However, challenges still remain, magnetic-nanoparticles cata-
lyzed direct coupling of 2-aminophenol or 2-aminobenzenethiol
with aldehyde has not been reported to date. Additionally, we
couldn't get benzoxazoles and benzothiazoles under the stan-
dard conditions reported by lit.28 We therefore set out to look for
an improved catalyst system for this transformation and to
demonstrate the generality with which it can be employed.
Recently, for economical and environmental reasons, there is
Table
1 Magnetic CuFe2O4-catalyzed condensation of 2-amino-
phenol (1a) with 4-methylbenzaldehyde (2b) leading to 2-p-tolylbenzo
[d]oxazole (3b): optimization of conditionsa
Entry
Solvent
Temp. [ꢀC]
Yieldb [%]
1
2
H2O
EtOH
100
80
0
0
3
4
CH3CN
THF
80
80
0
0
5
6
7
8
Toluene
—
110
110
110
110
110
110
25
60
90
100
110
94
45
Tracec
30d
45e
65f
0
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
9
10
11
12
13
14
15
0
58
78
76g
a
Reaction conditions: 2-aminophenol (1a) (0.75 mmol), benzaldehyde
(2b) (0.5 mmol), catalyst (0.1 mmol), solvent (0.5 mL) under oxygen
b
c
d
atmosphere. Isolated yield. Without catalyst. In the presence of
e
f
Fig. 1 (a) XRD spectrum of native CuFe2O4 catalyst. (b) XRD spectrum
catalyst (0.005 mmol). In the presence of catalyst (0.0125 mmol). In
the presence of catalyst (0.05 mmol). g Under air conditions.
of reused CuFe2O4 catalyst after 3th cycle.
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Table
2
Magnetic CuFe2O4-catalyzed synthesis of benzoxazoles,
benzothiazoles and benzimidazolesa
Fig. 2 TEM image of the fresh CuFe2O4 nanoparticles (a). TEM image
of the CuFe2O4 nanoparticles after 3th cycle (b).
Fig. 3 SEM images of CuFe2O4 nanoparticles before (a) and after (b)
3th cycle.
of benzoxazole derivatives is as follows: 20 mol% of CuFe2O4
as the catalyst and toluene as the solvent under oxygen
atmosphere.
We then investigated the scope of CuFe2O4-catalyzed reac-
tions of substituted 2-aminophenol (1) with benzaldehyde (2)
under the optimized catalytic conditions determined above. As
shown in Table 2, most of the examined substrates provided
good to excellent yields. For the substituted 2-aminophenol
and benzaldehyde the electronic effect of the substituted
groups including electron-rich, -neutral, and -decient
substituents did not display evident difference in reactivity as
shown in Table 2. For the substituted benzaldehyde, the
substrates containing nitro groups gave moderate yields.
Under a similar condition, the methodology was extended to
the synthesis of various benzothiazoles and benzimidazoles
from other building blocks like o-aminothiophenol and
o-phenyldiamine. The results are also summarized in Table 2.
The CuFe2O4-catalyzed domino reactions could tolerate some
functional groups such as alkyl group, C–F bonds, C–Cl bonds,
C–Br bonds, and nitro groups. Although aromatic aldehyde
showed high reactivity, unfortunately, aliphatic ones were poor
substrates, they are suitable for 2-aminobenzenethiol but
unactive for o-aminophenols or o-phenylenediamines. In order
to explain this, two control experiments were performed under
the standard conditions as shown in Scheme 2. Treatment of
a
Reaction conditions: o-substituted aminobenzene (1) (0.75 mmol),
benzaldehyde (2) (0.5 mmol), catalyst (0.1 mmol), solvent (0.5 mL)
under oxygen atmosphere. Isolated yield.
b
Scheme 2 Control experiments.
We also studied the recyclability of the catalyst. For this, we
(E)-2-(butylideneamino)phenol and (E)-2-(butylideneamino) investigated the CuFe2O4-catalyzed cyclization of 2-amino-
benzenethiol under the standard conditions provided 2-pro- phenol (1a) with benzaldehyde (2a) under the optimized
pylbenzo[d]thiazole (3x) in 97% yield and no 2-propylbenzo[d]- conditions. Aer completion of the reaction, the reaction
oxazole was observed. This result indicate an weaker nucleo- mixture was cooled to room temperature, and the catalyst was
philicity of the hydroxyl group under the CuFe2O4 catalyzed magnetically separated from the reaction mixture, washed with
ꢀ
conditions.
ethanol and dried at 100 C for 2 h and then used directly for
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General procedure for CuFe2O4-catalyzed synthesis of
benzoxazoles, benzimidazoles and benzothiazoles: (3)
A 25 mL Schlenk tube equipped with a magnetic stirring bar was
charged with CuFe2O4 nanoparticles (0.05 mmol, 12 mg),
substituted o-substituted aminobenzene (1) (0.5 mmol). The
tube was evacuated twice and backlled with oxygen, and
toluene (0.5 mL) was added to the tube under oxygen atmo-
sphere. The tube was sealed with a balloon and then the mixture
was allowed to stir under oxygen atmosphere at 110 ꢀC for 24 h.
Aer completion of the reaction, the resulting solution was
cooled to room temperature, and the solvent was removed with
the aid of a rotary evaporator. The residue was puried by
column chromatography on silica gel using petroleum ether–
ethyl acetate as eluent to provide the desired product (3).
2-Phenylbenzo[d]oxazole (3a).32 Eluent petroleum ethꢀer–
Scheme 3 Reactions of o-aminophenol with benzaldehyde in the
presence of TEMPO under the optimized reaction condition.
ethyl acetate (30 : 1). White solid. mp 94–95 C (lit.32 94–96 C)
ꢀ
(petroleum ether–ethyl acetate ¼ 40 : 1, Rf ¼ 0.3). 1H NMR
(CDCl3, 400 MHz, ppm) d 8.29 (d, 2H, J ¼ 7.6 Hz), 7.81 (d, 1H, J ¼
3.3 Hz), 7.61 (d, 1H, J ¼ 3.4 Hz), 7.62–7.54 (m, 3H), 7.38 (d, 2H,
J ¼ 6.0 Hz) 13C NMR (CDCl3, 200 MHz, ppm) d 163.1, 150.8,
142.1, 131.5, 128.9, 127.6, 127.2, 125.1, 124.6, 120.0, 110.6. ESI-
MS [M + H]+ m/z 196.4.
Scheme 4 Possible mechanism for CuFe2O4-catalyzed synthesis of
benzoxazoles, benzimidazoles and benzothiazoles.
further catalytic reactions. The catalyst could be reused ten
times without signicant loss in catalytic activity (average yields
in 90%).
2-p-Tolylbenzo[d]oxazole (3b).33 Eluent petroleum ether–
ethyl acetate (30 : 1). White solid. mp 116–117 ꢀC (lit.33 118–119
Finally, we investigated the formation mechanism of ben-
zoxazole derivatives. As shown in Scheme 3, when one equiva-
lent of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy, a well
known radical-capturing species) was added to the reaction
system, no signicant difference was observed in the yield,
ruling out the presence of radicals during the reaction.
On the basis of these results above, a possible mechanism is
thus proposed as illustrated in Scheme 4. Initially, CuFe2O4
nanoparticles could act as a Lewis acid which activates the
aldehyde and promote the imine (A) formation. The resulting
imine could further undergo the ring closure by the intra-
molecular attack of hydroxyl, sulydryl and amino group on the
C]N double bond to give intermediate (B) that subsequently
could proceed the aromatization by aerial oxidation under the
reaction conditions so as to afford the desired products (3).
1
ꢀC) (petroleum ether–ethyl acetate ¼ 40 : 1, Rf ¼ 0.3). H NMR
(CDCl3, 400 MHz, ppm) d 8.15 (d, 2H, J ¼ 8.0 Hz), 7.78 (d, 1H, J ¼
4.8 Hz), 7.59 (d, 1H, J ¼ 5.2 Hz), 7.37–7.34 (m, 4H), 2.46(s, 3H)
13C NMR (CDCl3, 200 MHz, ppm) d 163.3, 150.7, 142.2, 142.1,
129.7, 127.6, 124.9, 124.5, 124.4, 119.9, 110.5, 21.7. ESI-MS [M +
H]+ m/z 210.4.
2-(4-Chlorophenyl)benzo[d]oxazole (3c).34 Eluent petroleum
ether–ethyl acetate (30 : 1). White solid. mp 157–159 ꢀC (lit.34
ꢀ
155–156 C) (petroleum ether–ethyl acetate ¼ 30 : 1, Rf ¼ 0.4).
1H NMR (CDCl3, 400 MHz, ppm) d 8.21 (d, 2H, J ¼ 4.0 Hz), 7.79
(d, 1H, J ¼ 6.4 Hz), 7.60 (d, 1H, J ¼ 4.0 Hz), 7.57–7.41 (m, 2H),
7.36–7.36 (m, 2H). 13C NMR (CDCl3, 200 MHz, ppm) d 162.1,
150.8, 142.0, 137.8, 129.3, 128.9, 125.7, 124.7, 120.1, 124.8,
110.6. ESI-MS [M + H]+ m/z 230.5.
2-(4-Bromophenyl)benzo[d]oxazole (3d).35 Eluent petroleum
ether–ethyl acetate (15 : 1). White solid. mp 158–160 ꢀC (lit.35
ꢀ
Experimental section
General
156–158 C) (petroleum ether–ethyl acetate ¼ 30 : 1, Rf ¼ 0.3).
1H NMR (CDCl3, 400 MHz, ppm) d 8.14 (d, 2H, J ¼ 8.8 Hz), 7.79
(d, 1H, J ¼ 3.2 Hz), 7.69 (d, 2H, J ¼ 8.8 Hz), 7.60 (d, 1H, J ¼ 5.6
Hz), 7.42–7.37 (m, 2H). 13C NMR (CDCl3, 200 MHz, ppm) d
162.2, 150.8, 142.0, 132.3, 129.0, 126.3, 125.4, 124.8, 120.1,
110.7. ESI-MS [M + H]+ m/z 273.5, 275.4.
All reagents and solvents were obtained from commercial
suppliers and used without further purication. All reagents
were weighed and handled in air at room temperature. Flash
chromatography was performed on silica gel (200–300 mesh).
1H and 13C NMR data were recorded at 400 and 100 MHz on a
BRUKER 400 spectrometer. Chemical shis (d) are expressed in
parts per million (ppm) coupling constants (J) are in Hz. Proton
and carbon magnetic resonance spectra (1H NMR and 13C NMR)
were recorded using tetramethylsilane (TMS) in the solvent of
CDCl3 as the internal standard (1H NMR: TMS at 0.00 ppm,
CDCl3 at 7.24 ppm; 13C NMR: CDCl3 at 77.0 ppm) or were
recorded using tetramethylsilane (TMS) in the solvent of DMSO-
D6 as the internal standard (1H NMR: TMS at 0.00 ppm, DMSO
at 2.50 ppm; 13C NMR: DMSO at 40.0 ppm).
5-Methyl-2-p-tolylbenzo[d]oxazole (3e).36 Eluent petroleum
ether–ethyl acetate (30 : 1). White solid. mp 104–105 ꢀC (lit.36
ꢀ
103–104 C) (petroleum ether–ethyl acetate ¼ 20 : 1, Rf ¼ 0.4).
1H NMR (CDCl3, 400 MHz, ppm) d 8.15 (d, 2H, J ¼ 8.4 Hz), 7.56
(d, 1H, J ¼ 0.8 Hz), 7.45 (d, 1H, J ¼ 8.4 Hz), 7.35–7.33 (m, 2H),
7.16 (m, 1H), 2.52 (s, 1H), 2.46(s, 1H). 13C NMR (CDCl3, 200
MHz, ppm) d 163.4, 148.9, 142.4, 142.9, 127.5, 126.0, 109.9, 21.7,
21.6. ESI-MS [M + H]+ m/z 223.6.
6-Methyl-2-p-tolylbenzo[d]oxazole (3f).37 Eluent petroleum
ether–ethyl acetate (30 : 1). White solid. mp 90–92 ꢀC (lit.37
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89–91 ꢀC) (petroleum ether–ethyl acetate ¼ 20 : 1, Rf ¼ 0.4). 1H
NMR (CDCl3, 400 MHz, ppm) d 8.14 (d, 2H, J ¼ 8.4 Hz), 7.64 (d,
1H, J ¼ 8.4 Hz), 7.39–7.33 (m, 3H), 7.17 (d, 1H, J ¼ 8.4 Hz), 2.52
(s, 1H), 2.46(s, 1H). 13C NMR (CDCl3, 200 MHz, ppm) d 162.8,
151.0, 141.8, 140.0, 135.3, 129.6, 127.4, 125.7, 124.6, 119.2,
110.7, 21.8, 21.6. ESI-MS [M + H]+ m/z 223.7.
2-(4-Bromophenyl)-6-methylbenzo[d]oxazole (3m). Eluent
petroleum ether–ethyl acetate (30 : 1). White solid. mp 171–
173 ꢀC (petroleum ether–ethyl acetate ¼ 20 : 1, Rf ¼ 0.5).1H
NMR (CDCl3, 400 MHz, ppm) d 8.10 (d, 2H, J ¼ 8.4 Hz), 7.68–
7.64 (m, 3H), 7.39 (s, 1H), 7.19 (d, 1H, J ¼ 8.0 Hz), 2.53 (s, 3H).
13C NMR (CDCl3, 200 MHz, ppm) d 161.6, 151.0, 139.8, 135.9,
132.2, 128.9, 126.3, 126.0, 125.9, 119.4, 110.8, 21.9. ESI-MS [M +
H]+ m/z 288.2, 290.4. HR-MS: m/z calcd for C14H11BrON:
2-(4-Bromophenyl)-5-methylbenzo[d]oxazole (3g). Eluent
petroleum ether–ethyl acetate (20 : 1). White solid. mp 190–
191 ꢀC (petroleum ether–ethyl acetate ¼ 20 : 1, Rf ¼ 0.5). 1H
NMR (CDCl3, 400 MHz, ppm) d 8.12 (d, 2H, J ¼ 8.4 Hz), 7.66 (d,
1H, J ¼ 8.4 Hz), 7.57 (s, 1H), 7.46 (d, 1H, J ¼ 8.4 Hz), 7.18 (d, 1H, J
¼ 8.4 Hz), 2.50 (s, 3H). 13C NMR (CDCl3, 200 MHz, ppm) d 162.2,
149.0, 128.9, 126.5, 126.3, 126.1, 120.0, 110.0, 21.6. ESI-MS [M +
H]+ m/z 287.2, 289.1. HR-MS: m/z calcd for C14H11BrON:
288.0024; found: 288.0026, 290.0010. IR: max(thin lm) (cmꢁ1
)
¼ 3086, 2920, 1612, 1588, 1548, 1480, 1397, 1068, 835, 813, 726.
2-(4-Chlorophenyl)-5-methylbenzo[d]oxazole (3n).35 Eluent
petroleum ether–ethyl acetate (20 : 1). White solid. mp 149–
151 ꢀC (lit.35 150–151 ꢀC) (petroleum ether–ethyl acetate ¼
20 : 1, Rf ¼ 0.4). 1H NMR (CDCl3, 400 MHz, ppm) d 8.15 (d, 2H,
J ¼ 8.4 Hz), 7.55(s, 1H), 7.49 (d, 2H, J ¼ 8.4 Hz), 7.44 (d, 1H, J ¼
8.4 Hz), 7.16 (d, 1H, J ¼ 8.2 Hz), 2.50 (s, 3H). 13C NMR (CDCl3,
200 MHz, ppm) d 162.1, 149.0, 142.1, 137.6, 134.6, 129.2, 128.8,
126.5, 125.8, 120.0, 109.9, 21.5. ESI-MS [M + H]+ m/z 243.7.
6-Chloro-2-phenylbenzo[d]oxazole (3o).41 Eluent petroleum
ether–ethyl acetate (20 : 1). White solid. mp 108–110 ꢀC (lit.41
288.0024; found: 288.0027, 290.0006. IR: max(thin lm) (cmꢁ1
¼ 3078, 2919, 1592, 1548, 1455, 1398, 1068, 838, 796, 7283.
)
(R)-2-(3-Nitrophenyl)benzo[d]oxazole (3h).38 Eluent petro-
leum ether–ethyl acetate (20 : 1). White solid. mp 210–212 ꢀC
(lit.38 210 ꢀC) (petroleum ether–ethyl acetate ¼ 30 : 1, Rf ¼
0.4).1H NMR (CDCl3, 400 MHz, ppm) d 9.10 (s, 1H), 8.59 (d, 1H,
J ¼ 7.6 Hz), 8.40 (d, 1H, J ¼ 7.6 Hz), 7.83 (d, 1H, J ¼ 8.4 Hz), 7.77–
7.64 (m, 2H), 7.43 (d, 2H, J ¼ 8.4). 13C NMR (CDCl3, 200 MHz,
ppm) d 160.6, 150.9, 148.7, 141.8, 133.0, 130.1, 129.5, 128.6,
126.1, 125.1, 122.5, 120.5, 110.9. ESI-MS [M + H]+ m/z 240.6.
6-Methyl-2-phenylbenzo[d]oxazole (3i).39 Eluent petroleum
ether–ethyl acetate (20 : 1). White solid. mp 100–101 ꢀC (lit.39
99–102 ꢀC) (petroleum ether–ethyl acetate ¼ 20 : 1, Rf ¼ 0.4). 1H
NMR (CDCl3, 400 MHz, ppm) d 8.26 (d, 2H, J ¼ 5.6 Hz), 7.58–
7.52 (m, 4H), 7.47 (d, 1H, J ¼ 8.4 Hz), 7.17 (d, 1H, J ¼ 8.4 Hz), 2.5
(s, 1H). 13C NMR (CDCl3, 200 MHz, ppm) d 163.1, 149.0, 142.3,
134.4, 131.4, 128.9, 127.6, 127.3, 126.2, 119.9, 109.9, 21.6. ESI-
MS [M + H]+ m/z 209.6.
ꢀ
107–108 C) (petroleum ether–ethyl acetate ¼ 20 : 1, Rf ¼ 0.4).
1H NMR (CDCl3, 400 MHz, ppm) d 8.25 (d, 2H, J ¼ 5.6 Hz), 7.69
(d, 1H, J ¼ 8.4 Hz), 7.62 (s, 1H), 7.61–7.53 (m, 3H), 7.34 (d, 1H,
J ¼ 5.6 Hz). 13C NMR (CDCl3, 200 MHz, ppm) d 163.7, 150.9,
140.9, 131.8, 130.7, 129.0, 127.7, 126.7, 125.3, 120.5, 111.3. ESI-
MS [M + H]+ m/z 229.5.
6-Chloro-2-(4-uorophenyl)benzo[d]oxazole (3p).42 Eluent
petroleum ether–ethyl acetate (20 : 1). White solid. mp 130–
131 ꢀC (lit.42 132–133 ꢀC) (petroleum ether–ethyl acetate ¼
1
20 : 1, Rf ¼ 0.5). H NMR (CDCl3, 400 MHz, ppm) d 8.26–8.21
(m, 2H), 7.67 (d, 1H, J ¼ 8.4 Hz), 7.59 (s, 1H), 7.36 (d, 1H, J ¼ 8.4
Hz), 7.33–7.20 (m, 2H). 13C NMR (CDCl3, 200 MHz, ppm) d
166.2, 163.7, 162.8, 150.9, 140.8, 130.7, 130.0, 129.9, 125.4,
123.1, 123.0, 120.4, 116.4, 116.2, 111.2. ESI-MS [M + H]+ m/z
247.7.
5-Methyl-2-phenylbenzo[d]oxazole (3j).39 Eluent petroleum
ether–ethyl acetate (20 : 1). White solid. mp 112–114 ꢀC (lit.39
ꢀ
112–114 C) (petroleum ether–ethyl acetate ¼ 30 : 1, Rf ¼ 0.4).
1H NMR (CDCl3, 400 MHz, ppm) d 8.29–8.26 (m, 2H), 7.58 (s,
1H), 7.56–7.53 (m, 3H), 7.62–7.55 (m, 3H), 7.19(d, 1H, J ¼ 7.6
Hz), 7.17 (d, 1H, J ¼ 6.0 Hz), 2.51 (s, 1H). 13C NMR (CDCl3, 200
MHz, ppm) d 163.1, 149.0, 142.3, 134.4, 131.4, 128.9, 127.6,
127.3, 126.2, 119.9, 109.9, 21.6. ESI-MS [M + H]+ m/z 210.2.
2-(4-Fluorophenyl)-6-methylbenzo[d]oxazole (3k).40 Eluent
petroleum ether–ethyl acetate (20 : 1). White solid. mp 112–113
ꢀC (lit.40 113–116 ꢀC) (petroleum ether–ethyl acetate ¼ 20 : 1, Rf
6-Chloro-2-(4-chlorophenyl)benzo[d]oxazole (3q).41 Eluent
petroleum ether–ethyl acetate (20 : 1). White solid. mp 149–150
ꢀC (lit.41 148–149 ꢀC) (petroleum ether–ethyl acetate ¼ 20 : 1, Rf
1
¼ 0.5). H NMR (CDCl3, 400 MHz, ppm) d 8.18–8.15 (m, 2H),
7.68 (d, 1H, J ¼ 8.4 Hz), 7.60 (s, 1H), 7.54–7.50 (m, 2H), 7.36 (d,
1H, J ¼ 8.4 Hz). 13C NMR (CDCl3, 200 MHz, ppm) d 162.7, 150.9,
140.8, 138.1, 131.0, 129.4, 128.9, 125.5, 125.2, 120.6, 111.3. ESI-
MS [M + H]+ m/z 263.4.
1
2-(4-Bromophenyl)-6-chlorobenzo[d]oxazole (3r).42 Eluent
petroleum ether–ethyl acetate (20 : 1). White solid. mp 168–
170 ꢀC (lit.42 168–170 ꢀC) (petroleum ether–ethyl acetate ¼
30 : 1, Rf ¼ 0.4). 1H NMR (CDCl3, 400 MHz, ppm) d 8.09 (d, 2H,
J ¼ 8.4 Hz), 7.69–7.66 (m, 3H), 7.59 (s, 1H), 7.36 (d, 2H, J ¼
8.4 Hz). 13C NMR (CDCl3, 200 MHz, ppm) d 162.8, 151.0, 140.8,
132.3, 131.0, 129.0, 126.6, 125.6, 125.5, 120.6, 111.3. ESI-MS [M
+ H]+ m/z 308.4, 310.3.
¼ 0.5). H NMR (CDCl3, 400 MHz, ppm) d 8.27–8.24 (m, 2H),
7.56 (s, 1H), 7.45 (d, 1H, J ¼ 8.4 Hz), 7.24–7.17 (m, 3H), 2.5 (s,
3H). 13C NMR (CDCl3, 200 MHz, ppm) d 160.0, 163.5, 162.2,
149.0, 142.3, 134.5, 129.8, 129.7, 126.3, 123.7, 123.6, 119.9,
116.3, 116.0, 109.9, 21.5. ESI-MS [M + H]+ m/z 227.7.
2-(4-Chlorophenyl)-6-methylbenzo[d]oxazole (3l).36 Eluent
petroleum ether–ethyl acetate (20 : 1). White solid. mp 149–152
ꢀC (lit.36 151–152 ꢀC) (petroleum ether–ethyl acetate ¼ 20 : 1, Rf
¼ 0.4).1H NMR (CDCl3, 400 MHz, ppm) d 8.17 (d, 1H, J ¼ 8.4 Hz),
7.55 (s, 1H), 7.51–7.44 (m, 3H), 7.17 (s, 1H, J ¼ 8.0 Hz), 2.50 (s,
3H). 13C NMR (CDCl3, 200 MHz, ppm) d 162.1, 148.9, 142.2,
137.6, 134.6, 129.2, 128.8, 120.0, 110.0, 21.5. ESI-MS [M + H]+
m/z 243.6.
6-Chloro-2-p-tolylbenzo[d]oxazole (3s).43 Eluent petroleum
ether–ethyl acetate (20 : 1). White solid. mp 126–128 ꢀC (lit.43
ꢀ
126–127 C) (petroleum ether–ethyl acetate ¼ 30 : 1, Rf ¼ 0.4).
1H NMR (CDCl3, 400 MHz, ppm) d 8.12 (d, 2H, J ¼ 8.0 Hz), 7.67
(d, 2H, J ¼ 8.4 Hz), 7.58 (s, 1H), 7.34–7.33 (m, 3H), 2.46 (s, 3H).
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13C NMR (CDCl3, 200 MHz, ppm) d 164.0, 150.9, 142.5, 141.0,
130.4, 129.7, 127.6, 125.2, 123.9, 120.3, 111.2, 21.7. ESI-MS [M +
H]+ m/z 243.7.
2-(4-Fluorophenyl)benzo[d]thiazole (3z).47 Eluent petroleum
ether–ethyl acetate (10 : 1). White solid. mp 98–99 ꢀC (lit.47 100–
1
102 ꢀC) (petroleum ether–ethyl acetate ¼ 20 : 1, Rf ¼ 0.4). H
2-Phenylbenzo[d]thiazole (3t).43 Eluent petroleum ether–ethyl
acetate (10 : 1). White solid. mp 113–115 ꢀC (lit.43 112–114 ꢀC)
(petroleum ether–ethyl acetate ¼ 30 : 1, Rf ¼ 0.4). 1H NMR
(CDCl3, 400 MHz, ppm) d 8.14–8.11 (m, 3H), 7.93 (d, 2H, J ¼
8.0 Hz), 7.55–7.51 (m, 4H), 7.42 (t, 1H, J ¼ 8.0 Hz). 13C NMR
(CDCl3, 200 MHz, ppm) d 168.1, 154.2, 135.1, 133.6, 131.0, 129.1,
127.6, 126.3, 125.2, 123.3, 121.7. ESI-MS [M + H]+ m/z 211.7.
2-p-Tolylbenzo[d]thiazole (3u).44 Eluent petroleum ether–
NMR (CDCl3, 400 MHz, ppm) d 8.16–8.07 (m, 3H), 8.05 (d, 2H,
J ¼ 8.0 Hz), 7.57 (t, 1H, J ¼ 7.2 Hz), 7.55–7.38 (m, 3H). 13C NMR
(CDCl3, 200 MHz, ppm) d 172.4, 153.3, 135.1, 125.9, 124.6,
122.5, 121.5, 34.1, 31.8, 22.3, 13.8. ESI-MS [M + H]+ m/z 229.5.
(R)-2-(2-Bromo-5-methoxyphenyl)benzo[d]thiazole
(3a0).
Eluent petroleum ether–ethyl acetate (10 : 1). White solid. mp
252–254 ꢀC (petroleum ether–ethyl acetate ¼ 20 : 1, Rf ¼ 0.3).1H
NMR (DMSO-D6, 400 MHz, ppm) d 8.16 (d, 2H, J ¼ 8.4 Hz), 7.97
(d, 2H, J ¼ 7.6 Hz), 7.64–7.54 (m, 3H), 7.47 (t, 1H, J ¼ 8.0 Hz),
7.47 (d, 1H, J ¼ 8.4 Hz), 3.90 (s, 3H). 13C NMR (DMSO-D6, 200
MHz, ppm) d 165.6, 158.9, 152.6, 136.2, 135.1, 134.8, 126.3,
125.5, 123.6, 121.5, 118.2, 116.6, 112.5, 55.7. ESI-MS [M + H]+ m/
z 319.5, 321.4. HR-MS: m/z calcd for C14H11BrNOS: 319.9745;
found: 319.9745, 321.9725. IR: max(thin lm) (cmꢁ1) ¼ 3064,
3005, 2939, 2834, 1593, 1564, 1484, 1380, 1316, 853, 759, 603.
(R)-2-(2-Bromo-4-uorophenyl)benzo[d]thiazole (3b0). Eluent
petroleum ether–ethyl acetate (10 : 1). White solid. mp 246–
248 ꢀC (petroleum ether–ethyl acetate ¼ 5 : 1, Rf ¼ 0.4). 1H NMR
(DMSO-D6, 400 MHz, ppm) d 8.15 (d, 2H, J ¼ 8.0 Hz), 8.06 (t, 1H,
J ¼ 8.8 Hz), 7.97 (d, 2H, J ¼ 8.0 Hz), 7.58–7.45 (m, 3H), 7.20 (t,
1H, J ¼ 8.8 Hz). 13C NMR (DMSO-D6, 200 MHz, ppm) d 164.6,
164.3, 161.8, 152.7, 136.1, 133.6, 133.5, 131.0, 130.9, 126.4,
125.6, 123.6, 122.6, 122.5, 121.4, 121.2, 115.2, 115.0. ESI-MS [M
+ H]+ m/z 307.5, 309.4. HR-MS: m/z calcd for C13H8BrFNS:
ethyl acetate (30 : 1). White solid. mp 83–85 C (lit.44 85–86 C)
(petroleum ether–ethyl acetate ¼ 30 : 1, Rf ¼ 0.3). 1H NMR
(CDCl3, 400 MHz, ppm) d 8.09 (d, 1H, J ¼ 8.0 Hz), 8.01 (d, 2H, J ¼
8.0 Hz), 7.92 (d, 2H, J ¼ 8.0 Hz), 7.51 (m, 1H), 7.41 (t, 1H, J ¼
8.0 Hz), 7.37–7.31 (m, 2H), 2.45 (s, 3H). 13C NMR (CDCl3, 200
MHz, ppm) d 168.2, 154.2, 141.4, 135.0, 131.0, 129.7, 127.5,
126.2, 125.0, 123.1, 121.6, 21.5. ESI-MS [M + H]+ m/z 225.6.
2-(4-Bromophenyl)benzo[d]thiazole (3v).45 Eluent petroleum
ether–ethyl acetate (10 : 1). White solid. mp 130–131 ꢀC (lit.45
ꢀ
ꢀ
ꢀ
132–133 C) (petroleum ether–ethyl acetate ¼ 30 : 1, Rf ¼ 0.4).
1H NMR (CDCl3, 400 MHz, ppm) d 8.10 (d, 1H, J ¼ 8.0 Hz), 7.97
(d, 2H, J ¼ 8.0 Hz), 7.92 (d, 2H, J ¼ 8.0 Hz), 7.51 (m, 1H), 7.65
(t, 2H, J ¼ 8.0 Hz), 7.54 (t, 1H, J ¼ 8.0 Hz), 7.43 (t, 1H, J ¼ 8.0 Hz).
13C NMR (CDCl3, 200 MHz, ppm) d 166.7, 154.1, 135.1, 132.6,
132.2, 128.9, 126.5, 125.5, 125.4, 123.3, 121.7. ESI-MS [M + H]+
m/z 290.4, 291.3.
307.9545; found: 307.9557, 308.9547. IR: max(thin lm) (cmꢁ1
¼ 3084, 2971, 2900, 1614, 1490, 1464, 1241, 1042, 857, 750.
)
2-(4-Chlorophenyl)benzo[d]thiazole (3w).46 Eluent petroleum
ether–ethyl acetate (10 : 1). White solid. mp 116–117 ꢀC (lit.46
ꢀ
2-p-Tolyl-1H-benzo[d]imidazole (3c0).48 Eluent petroleum
ether–ethyl acetate (3 : 1). White solid. mp 276–277 ꢀC (lit.48
275–276 ꢀC) (petroleum ether–ethyl acetate ¼ 5 : 1, Rf ¼ 0.3).1H
NMR (DMSO-D6, 400 MHz, ppm) d 12.83 (s, br, 1H), 8.07 (d, 2H,
J ¼ 8.4 Hz), 7.58 (m, 2H), 7.36 (d, 2H, J ¼ 8.0 Hz), 7.20 (d, 2H, J ¼
8.5 Hz). 13C NMR (DMSO-D6, 200 MHz, ppm) d 168.2, 151.8,
140.0, 130.0, 127.9, 126.9, 21.4. ESI-MS [M + H]+ m/z 209.6.
2-(4-Chlorophenyl)-1H-benzo[d]imidazole (3d0).49 Eluent
petroleum ether–ethyl acetate (3 : 1). White solid. mp 300–
301 ꢀC (lit.49 303 ꢀC) (petroleum ether–ethyl acetate ¼ 5 : 1, Rf ¼
0.4).1H NMR (DMSO-D6, 400 MHz, ppm) d 13.00 (s, br, 1H), 8.20
(d, 2H, J ¼ 8.8 Hz), 7.69–7.54 (m, 4H), 7.23 (t, 2H, J ¼ 8.0 Hz),
7.20 (d, 2H, J ¼ 8.5 Hz). 13C NMR (DMSO-D6, 200 MHz, ppm) d
150.6, 144.2, 135.5, 134.9, 129.5, 128.6, 123.2, 122.3, 119.4,
111.9. ESI-MS [M + H]+ m/z 228.7.
115–116 C) (petroleum ether–ethyl acetate ¼ 30 : 1, Rf ¼ 0.4).
1H NMR (CDCl3, 400 MHz, ppm) d 8.08 (d, 1H, J ¼ 8.0 Hz), 8.01
(d, 2H, J ¼ 8.0 Hz), 7.92 (d, 1H, J ¼ 7.6 Hz), 7.52 (t, 1H, J ¼ 7.6
Hz), 7.45 (t, 2H, J ¼ 8.4 Hz), 7.39 (t, 1H, J ¼ 7.6 Hz). 13C NMR
(CDCl3, 200 MHz, ppm) d 166.6, 154.1, 137.0, 135.1, 132.1,
129.3, 128.7, 126.5, 125.4, 123.3, 121.7. ESI-MS [M + H]+ m/z
245.5.
2-Propylbenzo[d]thiazole (3x). Eluent petroleum ether–ethyl
acetate (10 : 1). Yellow oil (petroleum ether–ethyl acetate ¼
30 : 1, Rf ¼ 0.2). 1H NMR (CDCl3, 400 MHz, ppm) d 7.98 (d, 1H,
J ¼ 8.4 Hz), 7.83 (d, 2H, J ¼ 8.4 Hz), 7.43 (t, 1H, J ¼ 8.0 Hz), 7.31
(t, 1H, J ¼ 8.0 Hz), 3.09 (t, 2H, J ¼ 7.6 Hz), 1.91 (dt, 2H, J ¼ 7.2
Hz), 1.05 (t, 2H, J ¼ 7.2 Hz). 13C NMR (CDCl3, 200 MHz, ppm) d
172.1, 153.3, 135.2, 125.9, 124.6, 122.5, 121.5, 36.3, 23.1, 13.7.
ESI-MS [M + H]+ m/z 177.6. HR-MS: m/z calcd for C10H11NS:
178.0690; found: 178.0687. IR: max(thin lm) (cmꢁ1) ¼ 3414,
2968, 1617, 1560, 1518, 1455, 1405, 1381, 1068, 879, 759.
2-Butylbenzo[d]thiazole (3y). Eluent petroleum ether–ethyl
acetate (10 : 1). yellow oil (petroleum ether–ethyl acetate ¼ 30 : 1,
2-(4-Bromophenyl)-1H-benzo[d]imidazole (3e0).50 Eluent
petroleum ether–ethyl acetate (5 : 1). White solid. mp 300–
301 ꢀC (lit.50 299–300 ꢀC) (petroleum ether–ethyl acetate ¼ 5 : 1,
Rf ¼ 0.5).1H NMR (DMSO-D6, 400 MHz, ppm) d 13.00 (s, br, 1H),
8.12 (d, 2H, J ¼ 8.8 Hz), 7.77 (d, 2H, J ¼ 6.8 Hz), 7.61 (m, 2H),
7.22 (d, 2H, J ¼ 8.8 Hz). 13C NMR (DMSO-D6, 200 MHz, ppm) d
150.6, 135.5, 132.4, 129.9, 123.7, 122.3, 119.4, 111.9. ESI-MS [M
+ H]+ m/z 272.7, 274.6.
1
Rf ¼ 0.2). H NMR (CDCl3, 400 MHz, ppm) d 7.90 (d, 1H, J ¼
8.0 Hz), 7.85 (d, 2H, J ¼ 8.0 Hz), 7.47 (t, 1H, J ¼ 6.8 Hz), 7.34 (t, 1H,
J ¼ 6.8 Hz), 7.45 (t, 2H, J ¼ 8.4 Hz), 7.39 (t, 1H, J ¼ 7.6 Hz), 3.14 (t,
2H, J ¼ 7.2 Hz), 1.88 (t, 2H, J ¼ 6.8 Hz), 1.50 (t, 2H, J ¼ 7.2 Hz), 0.99
(t, 3H, J ¼ 7.2 Hz). 13C NMR (CDCl3, 200 MHz, ppm) d 172.4,
153.3, 135.1, 125.9, 124.6, 122.5, 121.5, 34.1, 31.8, 22.3, 13.8. ESI-
MS [M + H]+ m/z 191.6. HR-MS: m/z calcd for C11H15NS: 192.0847;
found: 192.0850. IR: max(thin lm) (cmꢁ1) ¼ 3436, 3306, 2957,
2871, 1630, 1561, 1520, 1456, 1436, 1381, 1127, 855, 758.
6-Bromo-2-(4-uorophenyl)-1H-benzo[d]imidazole
(3f0).
Eluent petroleum ether–ethyl acetate (5 : 1). White solid. mp
320–321 ꢀC (petroleum ether–ethyl acetate ¼ 5 : 1, Rf ¼ 0.4).1H
NMR (DMSO-D6, 400 MHz, ppm)
d 13.10 (s, br, 1H),
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8.23–8.21(m, 2H), 7.86–7.49 (m, 2H), 7.43–7.34 (m, 3H). 13C
NMR (DMSO-D6, 200 MHz, ppm) d 164.9, 165.2, 134.6, 129.4,
125.5, 116.5, 114.4, 113.6. ESI-MS [M + H]+ m/z 290.4, 292.3. HR-
MS: m/z calcd for C13H9BrFN2: 290.9933; found: 290.9936,
292.9911. IR: max(thin lm) (cmꢁ1) ¼ 3445, 2965, 1628, 1600,
1464, 1430, 1383, 1233, 915, 805, 734.
4 N. J. Liverton, D. J. Armstrong, D. A. Claremon, D. C. Remy,
J. J. Baldwin, R. J. Lynch, G. Zhang and R. J. Gould, Bioorg.
Med. Chem. Lett., 1998, 8, 483.
5 P. J. Palmer, R. B. Trigg and J. V. Warrington, J. Med. Chem.,
1971, 14, 248.
6 M. L. McKee and S. M. Kerwin, Bioorg. Med. Chem., 2008, 16,
1775.
6-Bromo-2-(4-chlorophenyl)-1H-benzo[d]imidazole
(3g0).
Eluent petroleum ether–ethyl acetate (2 : 1). White solid. mp
336–337 ꢀC (petroleum ether–ethyl acetate ¼ 1 : 1, Rf ¼ 0.5). 1H
NMR (DMSO-D6, 400 MHz, ppm) d 13.17 (s, br, 1H), 8.17 (d, 2H,
J ¼ 8.8 Hz), 7.79 (m, 1H), 7.62–7.55 (m, 3H), 7.34 (d, 1H, J ¼ 8.4
Hz). 13C NMR (DMSO-D6, 200 MHz, ppm) d 152.1, 132.5, 129.4,
129.0.125.8, 125.3, 124.1, 121.8, 121.1, 114.5, 113.6. ESI-MS [M +
7 A. Benazzou, T. Boraund, P. Dubedat, J. M. Boireau and
C. Stutzmann, Eur. J. Pharmcol., 1995, 284, 299.
8 S. K. Ivanov and V. S. Yuritsyn, Neekhimiya, 1971, 11, 99.
9 H. Nakano, T. Inoue, N. Kawasaki, H. Miyataka,
H. Matsumoto, T. Taguchi, N. Inagaki, H. Nagai and
T. Satoh, Bioorg. Med. Chem., 2000, 8, 373.
H]+ m/z 306.4, 308.3. HR-MS: m/z calcd for C13H9BrClN2: 10 For selected examples, see: (a) H. Wang, L. Wang, J. Shang,
306.9638; found: 306.9634, 308.9604. IR: max(thin lm) (cmꢁ1
¼ 3271, 2900, 1629, 1507, 1393, 1241, 1015, 1233, 879, 732.
)
X. Li, H. Wang, J. Gui and A. W. Lei, Chem. Commun.,
2012, 48, 76; (b) J. Bonnamour and C. Bolm, Org. Lett.,
2008, 10, 2665–2667; (c) B. Zou, Q. Yuan and D. Ma, Angew.
Chem., Int. Ed., 2007, 46, 2598; (d) E. A. Jaseer,
D. J. C. Prasad, A. Dandapat and G. Sekar, Tetrahedron
Lett., 2010, 51, 5009; (e) G. Evindar and R. A. Batey, J. Org.
Chem., 2006, 71, 1802; (f) P. Saha, T. Ramana, N. Purkait,
M. Ali, R. Paul and T. Punniyamurthy, J. Org. Chem., 2009,
74, 8719; (g) S. Ueda and H. Nagasawa, Angew. Chem., Int.
Ed., 2008, 47, 6411; (h) D. Bernardi, L. A. Ba and G. Kirsch,
Synlett, 2007, 18, 2121; (i) C. Benedi, F. Bravo, P. Uriz,
E. Fernandez, C. Claver and S. Castillon, Tetrahedron Lett.,
2003, 44, 6073.
Conclusions
In conclusion, we have developed a simple, green and efficient
strategy for the synthesis of benzoxazoles, benzothiazoles and
benzimidazoles. The couplings were performed using readily
available starting materials (o-substituted aminobenzene and
various aldehydes), magnetically separable and reusable
CuFe2O4 nanoparticles as the catalyst and dioxygen as the green
oxidant, importantly, organic oxidizing agents, strong acids or
bases were not necessary. The present method shows eco-
friendly, economical, broad scope of substrates and practical 11 For selected examples, see: (a) L. M. Dudd, E. Venardou,
advantages over the previous methods. Further applications of
CuFe2O4 magnetic nanoparticles in the synthesis of other useful
heterocycles is underway in our laboratory.
E. Garcia-Verdugo, P. Licence, A. J. Blake, C. Wilson and
M. Poliakoff, Green Chem., 2003, 5, 187; (b) K. Takeda,
S. Yano, M. Sato and E. Yoshii, J. Org. Chem., 1987, 52, 413;
(c) V. K. Tandon and M. Kumar, Tetrahedron Lett., 2004, 45,
4185; (d) J. Charton, S. Girault-Mizzi and C. Sergheraert,
Chem. Pharm. Bull., 2005, 53, 492; (e) S.-Y. Lin, Y. Isome,
E. Stewart, J.-F. Liu, D. Yohannes and L. Yu, Tetrahedron
Lett., 2006, 47, 2883; (f) L. M. Dudd, E. Venardou,
E. Garcia-Verdugo, P. Licence, A. J. Blake, C. Wilson and
M. Poliakoff, Green Chem., 2003, 5, 187; (g)
M. B. Maradolla, S. K. Allam, A. Mandha and
G. V. P. Chandramouli, ARKIVOC, 2008, 15, 42; (h)
V. K. Tandon and M. Kumar, Tetrahedron Lett., 2004, 45,
4185; (i) X. Wen, J. E. Bakali, R. D. Poulain and B. Deprez,
Tetrahedron Lett., 2012, 53, 2440.
Acknowledgements
The authors gratefully acknowledge the nancial support from
the National Natural Science Foundation of China (no.
21302110, 21375075 and 21302109), the Taishan Scholar
Foundation of Shandong Province, the Project of Shandong
Province Higher Educational Science and Technology Program
(J13LD14), the Natural Science Foundation of Shandong Prov-
ince (ZR2013BQ017), and the Scientic Research Foundation of
Qufu Normal University (BSQD 2012021). We thank Ning Zhang
in this group for reproducing the results of 3k, 3u and 3C0.
12 I. M. Baltork, A. R. Khosropour and S. F. Hojati, Catal.
Commun., 2007, 8, 1865.
13 R. S. Varma and D. J. Kumar, Heterocycl. Chem., 1998, 35,
1539.
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