Catalyst-free microwave-promoted one pot synthesis of 2-aryl benzoxazoles using MnO2 nanoparticles as a convenient oxidant under mild condition

Article abstract of DOI:10.1007/s11164-017-2909-4

Abstract: An efficient and facile protocol for one pot synthesis of a series of 2-aryl benzoxazoles through coupling of o-aminophenol with aromatic aldehydes under microwave irradiation in the presence of MnO₂ nanoparticles as oxidant reagent was demonstrated. The MnO₂ nanoparticles were prepared via a solid-state chemical reaction technique. The structure of oxidant was assigned by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The target molecules were obtained in good to high yields, high purity and short reaction times. The pure products were identified and characterized by physical and spectral data such as; melting point, IR, ¹H NMR and ¹³C NMR. Graphical Abstract: An efficient and facil protocol for one pot synthesis of a series of 2-aryl benzoxazoles through coupling of o-aminophenol with aromatic aldehydes under microwave irradiation in the precense of MnO₂ nanoparticles as oxidant reagent was demonstrated.

Full text of DOI:10.1007/s11164-017-2909-4

Res Chem Intermed
DOI 10.1007/s11164-017-2909-4
Catalyst-free microwave-promoted one pot synthesis
of 2-aryl benzoxazoles using MnO2 nanoparticles
as a convenient oxidant under mild condition
Hossein Naeimi1 Zahra Rouzegar1
•
•
Soraya Rahmatinejad1
Received: 7 December 2016 / Accepted: 11 February 2017
Ó Springer Science+Business Media Dordrecht 2017
Abstract An efficient and facile protocol for one pot synthesis of a series of 2-aryl
benzoxazoles through coupling of o-aminophenol with aromatic aldehydes under
microwave irradiation in the presence of MnO2 nanoparticles as oxidant reagent was
demonstrated. The MnO2 nanoparticles were prepared via a solid-state chemical reaction
technique. The structure of oxidant was assigned by Fourier transform infrared spec-
troscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM).
The target molecules were obtained in good to high yields, high purity and short reaction
times. The pure products were identified and characterized by physical and spectral data
1
such as; melting point, IR, H NMR and 13C NMR.
Graphical Abstract An efficient and facil protocol for one pot synthesis of a series of
2-aryl benzoxazoles through coupling of o-aminophenol with aromatic aldehydes under
microwave irradiation in the precense of MnO2 nanoparticles as oxidant reagent was
demonstrated.
Electronic supplementary material The online version of this article (doi:10.1007/s11164-017-2909-4)
contains supplementary material, which is available to authorized users.
&
Hossein Naeimi
naeimi@kashanu.ac.ir
1
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan,
87317-51167 Kashan, Iran
123

H. Naeimi et al.
O
N
H
O
R
O
OH
R
Or
Or
NH2
Microwave irradiation
N
O
H
R=Cl, OMe, Me, OH, NO2
Keywords Oxidant Á 2-Aryl benzoxazole Á Microwave irradiation Á MnO2
nanoparticles
Introduction
The benzoxazole scaffold appears in natural products and synthetic pharmaceutical
molecules. So, it has received specific attention in chemistry and biochemistry
[1, 2]. These five-membered heterocyclic rings, have notable biological and
therapeutic activities like anti-helmintic [3], anti-neoplastic [4], anti-parkinson [5],
anti-bacterial [6], anti-fungal [7], anti-hyperglycemic potentiating [6], analgesics
[8], anti-inflammatory [9], estrogen receptor-b agonists [10], anti-platelet [11], anti-
convulsants [12] and anti-tuberculosis agents [13] activities (Fig. 1).
Furthermore, substitution and extension of conjugation at the 2-position of the
benzoxazoles can be resulted in luminescent properties. Therefore, these compo-
nents have been used in the structure of fluorescent whitening agents [14]. Also,
benzoxazoles find applications in laser dyes, sensors for metals or organic light
emitting diodes (OLEDs) [14, 15], as ligands in asymmetric synthesis [16] and
polymer synthesis [17].
Various protocols for the synthesis of benzoxazoles have been reported in past
years including coupling of amino aromatics with carboxylic acids [18], orthoesters
[19], nitriles [20], primary alcohol [21], amines [22] acyl halides [23], cyclization of
Schiff’s bases derived from the condensation of o-aminophenols and aldehydes in
the presence of oxidants [24], cyclization of o-halobenzanilides [25] or o-
hydroxyanilides [26] and reaction of bromoaniline with acyl halides [27].
Time saving is one of the important factors in organic chemistry. Microwave
dielectric heating has been applied in order to reduce reaction times [28]. In the
conventional form of heating (oil bath, hot plate or isomantle), the heat needs to
pass through the walls of vessels to reach the solvent and reactants. Therefore, this
mediate heat transfer could result in slow activation of reactants. By contrast, direct
interactions of microwave energy with chemicals leads to a quick temperature rise
123

Catalyst-free microwave-promoted one pot synthesis of 2…
R1
O
O
N
N
H2
C
O
N
R2
N
R
R
R
3
2
1
O
N
N
C
H
F
4
Fig. 1 Some examples of bioactive benzoxazoles
[29]. Microwave irradiation removes or reduces the side reactions. So, microwave
irradiation as an efficient technology enhances the purity of products. Compared to
the conventional reactions, microwave assisted reactions are cleaner and have easier
work up procedures. Other advantages of microwave assisted reactions are, high
yields, reproducibility, mild reaction conditions, low chemical wastes and solvent
consumption, fast reaction optimization, synthesis of difficult compounds and
saving of energy [30, 31].
Due to the importance of the described compounds, and in continuation of our
previous study on synthesis of compounds under microwave irradiation [32–35],
herein, we report the in situ preparation of 2-substituted benzoxazoles by the
condensation of o-aminophenol with corresponding aldehydes using nano MnO2 as
a mild oxidant under microwave irradiation.
Experimental section
Materials
All commercially available reagents were used without further purification and
purchased from Merck and Aldrich Company in high purity. The used solvents were
purified by standard procedure.
Apparatus
FT-IR spectra were obtained with KBr pellets in the range 400–4000 cm-1 with a
1
Perkin Elmer 550 spectrometer. H NMR and 13C NMR were recorded in CDCl3
solvent on a Bruker DRX-400 spectrometer with tetramethylsilane as the internal
reference. X-ray diffraction patterns of samples were taken by using CuKa radiation
(k = 1.5406A) on a Rigaku D-Max CIII diffractometer. Scanning electron
microscope (SEM) of nano MnO2 was performed on a XL30 Philips SEM
instrument. The Microwave conditions were carried out in microwave oven
specially designed for organic synthesis (Milestone LAVIS Basic Microwave).
123

H. Naeimi et al.
Melting points obtained with a Yanagimoto micro melting point apparatus and were
uncorrected. Determination of the substrates purity and the reaction monitoring
were accomplished by TLC on silica-gel polygram SILG/UV 254 plates (from
Merck Company).
A procedure for preparation of MnO2 nanoparticles
Briefly, a mixture of MnSO4ÁH2O (1 mmol, 0.169 g) and (NH4)2C2O4ÁH2O
(1.2 mmol, 0.17 g) was mixed and ground in a mortar at room temperature for
40 min. For drying the wet mixture, it was placed in a water bath of 80 °C for
several hours. The obtained dry mixture was washed with distilled water to remove
the unreacted substances and dried at 110 °C for 10 h. Then, the resulted white solid
was calcined to produce manganese oxide in atmosphere at 400 °C for 10 h.
Afterwards, the resulted MnO2 was added to a 2 M H2SO4 solution and stirred at
80 °C for 2 h in order to increase its degree of oxidation. The product was filtered
and washed with distilled water and finally dried at 105 °C to obtain the target
MnO2 nanoparticles.
General procedure for the preparation of 2-substiuted benzoxazoles
A mixture of 2-aminophenol (1.1 mmol, 0.12 g), aromatic aldehyde (1 mmol), and
MnO2 nanoparticles (1 mmol, 0.086 g) in acetonitrile (4 mL) as solvent in an open
tall beaker was irradiated inside microwave oven at 400 W for the appropriate time
indicated in Table 4. After completion of the reaction as indicated by thin-layer
chromatography (petroleum ether/ethyl acetate, 6/2), the reaction mixture was
cooled to room temperature. The minerals were separated by simple filtration. Then
filtrate solution was poured onto ice. The solid crude product was filtered, washed
with ice-water and recrystallized from ethanol/H2O (1:1) to give the pure product.
All of the 2-substituted benzoxazole products were identified by physical and
spectroscopic data as follows.
2-Phenyl-1,3-benzoxazole (3a)
Light brown solid; m.p. = 95–97 °C (m.p. = 96–97 °C [36]); IR (KBr)/m (cm-1):
3059 (C–H, sp2 stretch), 1615 (C=N), 1551, 1448 (C=C, Ar), 1242 (C–O–C), 746,
1
692 (C–H, sp2 OOP); H NMR (CDCl3, 400 MHz)/d (ppm): 8.29–8.26 (m, 2H),
7.80–7.77 (m, 1H), 7.62–7.58 (m, 1H), 7.56–7.53 (m, 3H), 7.39–7.35 (m, 2H).
2-(2-Chlorophenyl)-1,3-benzoxazole (3b)
Light yellow solid; m.p. = 63–65 °C (m.p. = 61–64 °C [37]); IR (KBr)/m (cm-1
)
3050 (C–H, sp2), 1606 (C=N, stretch), 1537, 1452 (C=C, Ar), 1244 (C–O–C), 743
(C–H sp2 OOP); 1H NMR (CDCl3, 400 MHz)/d (ppm): 8.18–8.15 (m, 1H),
7.88–7.86 (m, 1H), 7.65–7.63 (m, 1H), 7.60–7.58 (m, 1H), 7.49–7.38 (m, 4H).
123

Catalyst-free microwave-promoted one pot synthesis of 2…
2-(4-Chlorophenyl)-1,3-benzoxazole (3c)
Light brown solid; m.p. = 144–146 °C (m.p. = 144–145 °C [38]); IR (KBr)/m
(cm-1) 3056 (C–H, sp2), 1614 (C=N), 1550, 1482 (C=C, Ar), 1243 (C–O–C), 1091
(C–Cl), 832, 738 (C–H sp2 OOP); 1H NMR (CDCl3, 400 MHz)/d (ppm): 8.22–8.21
(m, 2H), 7.79–7.76 (m, 1H), 7.61–7.58 (m, 1H), 7.53–7.51 (m, 2H), 7.39–7.36 (m,
2H).
2-(2,4-Dichlorophenyl)-1,3-benzoxazole (3d)
Light brown solid; m.p. = 122–124 °C (m.p. = 123–124 °C [39]); IR (KBr)/m
(cm-1): 3074 (C–H, sp2 stretch), 1662 (C=N), 1588, 1466 (C=C, Ar), 1241 (C–O–
1
C), 823, 742 (C–H sp2 OOP); H NMR (CDCl3, 400 MHz) d (ppm): 8.13 (d,
J = 8.4 Hz, 1H), 7.86–7.84 (m, 1H), 7.64–7.60 (m, 2H), 7.43–7.38 (m, 3H); 13C
NMR (CDCl3, 100 MHz) d (ppm): 160.0, 150.5, 141.5, 137.5, 134.2, 132.5, 131.3,
127.4, 125.8, 124.8, 124.7, 120.5, 110.7.
2-(2,6-Dichlorophenyl)-1,3-benzoxazole (3e)
Yellow solid; m.p. = 172–175 °C; IR (KBr)/m (cm-1): 3066 (C–H, sp2 stretch),
1
1621 (C=N), 1561, 1452 (C=C, Ar), 1261 (C–O–C), 798, 744 (C–H, sp2 OOP); H
NMR (CDCl3, 400 MHz) d (ppm): 7.89–7.88 (m, 1H), 7.66–7.65 (m, 1H),
7.46–7.45 (m, 5H).
2-(3-Methylphenyl)-1,3-benzoxazole (3f)
°
Yellow solid; m.p. = 77–79 C (m.p. = 79–80 °C [39]); IR (KBr)/m (cm-1): 3040
(C–H, sp2 stretch), 2980 (C–H, sp3), 1598 (C=N), 1550, 1451 (C=C, Ar), 1244 (C–
1
O–C), 862, 745 (C–H, sp2 OOP); H NMR (CDCl3, 400 MHz) d (ppm): 8.11 (s,
1H), 8.05 (d, J = 7.6 Hz, 1H), 7.79–7.77 (m, 1H), 7.60–7.58 (m, 1H), 7.45–7.41
(m, 1H), 7.37–7.35 (m, 3H), 2.47 (s, 3H).
2-(4-Methylphenyl)-1,3-benzoxazole (3g)
Light brown solid; m.p. = 114–116 °C (m.p. = 113–115 °C [40]); IR (KBr)/m
(cm-1): 3056 (C–H, sp2 stretch), 2919 (C–H, sp3), 1619 (C=N), 1500, 1451 (C=C,
1
Ar), 1241 (C–O–C), 821, 748 (C–H, sp2 OOP); H NMR (CDCl3, 400 MHz) d
(ppm): 8.15 (d, J = 8.0 Hz, 2H), 7.78–7.75 (m, 1H), 7.59–7.54 (m, 1H), 7.36–7.34
(m, 4H), 2.45 (s, 3H).
2-(2-Methoxyphenyl)-1,3-benzoxazole (3h)
Yellow solid; m.p. = 51–54 °C (m.p. = 53–54 °C [41]); IR (KBr)/m (cm-1): 3069
(C–H, sp2 stretch), 2937 (C–H, sp3), 1610 (C=N), 1545, 1455 (C=C, Ar), 1247 (C–
1
O–C, stretch), 819, 750 (C–H, sp2 OOP); H NMR (CDCl3, 400 MHz) d (ppm):
8.14 (d, J = 7.6 Hz, 1H), 7.83 (dd, J = 5.6, 3.2, 1H), 7.60–7.58 (m, 1H), 7.50 (t,
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H. Naeimi et al.
7.8 Hz, 1H), 7.35–7.33 (m, 2H), 7.12–7.07 (m, 2H), 4.01 (s, 3H); 13C NMR (CDCl3,
100 MHz) d (ppm): 161.5, 158.4, 150.3, 142.1, 132.7, 131.3, 124.9, 124.2, 120.7,
120.2, 116.1, 112.0, 110.4, 56.2.
2-(4-Methoxyphenyl)-1,3-benzoxazole (3i)
Light yellow solid; m.p. = 97–99 °C (m.p. = 97–98 °C [36]); IR (KBr)/m (cm-1):
3049 (C–H, sp2 stretch), 2979 (C–H, sp3), 1613 (C=N), 1501, 1452 (C=C, Ar), 1249
(C–O–C, stretch), 832, 737 (C–H sp2 OOP); 1H NMR (CDCl3, 400 MHz) d (ppm):
8.21 (d, J = 8.4 Hz, 2H), 7.76–7.74 (m, 1H), 7.58–7.56 (m, 1H), 7.35–7.32 (m,
2H), 7.04 (d, J = 8.0 Hz, 2H), 3.90 (s, 3H); 13C NMR (CDCl3, 100 MHz) d (ppm):
163.1, 162.3, 150.6, 142.3, 129.3, 124.6, 124.4, 119.7, 119.6, 114.3, 110.3, 55.4.
2-(3,4-Dimethoxyphenyl)-1,3-benzoxazole (3j)
white solid; m.p. = 108–110 °C (m.p. = 109–111 °C [39]); IR (KBr)/m (cm-1):
3049 (C–H, sp2 stretch), 2924 (C–H, sp3), 1616 (C=N), 1504, 1455 (C=C, Ar), 1246
(C–O–C, stretch), 869, 755 (C–H sp2 OOP); 1H NMR (CDCl3, 400 MHz) d (ppm):
7.87 (dd, J = 8.4, 1.6 Hz, 1H), 7.77–7.75 (m, 2H), 7.58–7.56 (m, 1H), 7.36–7.32
(m, 2H), 7.01–6.99 (d, J = 8.4 Hz, 1H), 4.03 (s, 3H), 3.98 (s, 3H); 13C NMR
(CDCl3, 100 MHz) d (ppm): 163.1, 151.9, 150.6, 149.2, 142.2, 124.7, 124.4, 121.1,
119.7, 119.6, 111.0, 110.3, 110.0, 56.1, 56.0.
2-(2-Nitrophenyl)-1,3-benzoxazole (3k)
Light yellow solid; m.p. = 87–89 °C (m.p. = 99–102 °C [42]); IR (KBr)/m (cm-1):
3060 (C–H, sp2 stretch), 1610 (C=N), 1534, 1449 (C=C, Ar), 1239 (C–O–C), 747
1
(C–H sp2 OOP); H NMR (CDCl3, 400 MHz) d (ppm): 8.16–8.15 (m, 1H), 7.9 (d,
J = 8.0 Hz, 1H), 7.84–7.80 (m, 1H), 7.77–7.68 (m, 2H), 7.60–7.56 (m, 1H),
7.43–7.38 (m, 2H).
2-(2-Hydroxyphenyl)-1,3-benzoxazole (3l)
White solid; m.p. = 123–124 °C (m.p. = 125–126 °C [43]); IR (KBr)/m (cm-1):
3143 (OH), 3060 (C–H, sp2 stretch), 1630 (C=N), 1544, 1485 (C=C, Ar), 1248 (C–
1
O–C), 744, 709 (C–H sp2 OOP); H NMR (CDCl3, 400 MHz) d (ppm): 11.50 (s,
1H), 8.04 (d, J = 7.6 Hz, 1H), 7.76–7.74 (m, 1H), 7.65–7.61 (m, 1H), 7.47–7.40
(m, 3H), 7.13 (d, J = 8 Hz, 1H), 7.04–7.00 (m, 1H); 13C NMR (CDCl3, 100 MHz)
d (ppm): 162.9, 158.7, 149.1, 140.0, 133.5, 127.1, 125.38, 125.0, 119.5, 119.2,
117.4, 110.6.
2-(2-Hydroxy-naphthyl)-1,3-benzoxazole (3m)
white solid; m.p. = 75–78 °C; IR (KBr)/m (cm-1): 3431 (OH), 3060 (C–H, sp2
stretch), 1618 (C=N), 1536, 1464 (C=C, Ar), 1258 (C–O–C), 811, 749 (C–H, sp2
1
OOP); H NMR (CDCl3, 400 MHz) d (ppm): 13.54 (s, 1H), 9.14 (d, J = 8.8 Hz,
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Catalyst-free microwave-promoted one pot synthesis of 2…
1H), 7.93 (d, J = 8.8 Hz, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.81–7.61 (m, 2H), 7.69 (t,
J = 7.2 Hz, 1H), 7.47–7.43 (m, 3H), 7.35 (d, J = 8.8 Hz, 1H); 13C NMR (CDCl3,
100 MHz) d (ppm): 167.7, 161.5, 158.4, 150.31, 142.1, 132.7, 132.4, 131.2, 130.8,
128.7, 124.9, 124.2, 120.6, 120.1, 116.1, 112.0, 110.4.
Results and discussion
Preparation and characterization of nano MnO2
Nano MnO2 was prepared via grinding reaction between (NH4)2C2O4ÁH2O and
MnSO4ÁH2O with a mole ratio of 1:1.2, calcination of manganese oxalate (MnC2O4)
precursors, and acid-treatment process according to the previous reported method
[44]. The different steps of preparation of MnO2 NPs are shown in Scheme 1.
After successful preparation of MnO2 NPs, the oxidant was characterized by FT-
IR, SEM and XRD techniques.
The FT-IR spectrum of MnO2 NPs is shown in the Fig. 2. The absorption bands
in the region of 527 cm-1 is attributed to the stretching vibrations of the metal–
oxygen bond and proves the formation of the MnO2.
The scanning electron microscope (SEM) of MnO2 particles displays nanopar-
ticles with dimensions of about 35.5–46.3 nm (Fig. 3).
The X-ray diffraction (XRD) patterns of the nano MnO2 are shown in Fig. 4. The
position and relative intensities of all peaks confirm well with standard XRD pattern
of MnO2 (JCPDSNo. 14-0644) indicative of the nanocrystalline structure of the
prepared MnO2. The average crystalline size of MnO2 particles according to the
Scherrer equation was obtained 17 nm.
Application of MnO2 nanoparticles as oxidant agent in synthesis of 2-
substituted benzoxazoles
In this study, the reaction of o-aminophenol with aromatic aldehydes was carried
out in the presence of MnO2 nano particles as oxidant in acetonitrile solution under
the microwave irradiation (Scheme 2).
80 oC
Grinding
r.t. , 40 min
Wet Mixture
MnSO4.H2O
(NH4)2C2O4.H2O
Dry Mixture
+
1) Washed with
distilled water
H2SO4 (2 M)
80 oC, 2 h
Calcination
400 oC, 10 h
MnC2O4
Manganese oxide
2) 110 oC, 10 h
Washed with
distilled water
Nano MnO2
105 oC
Scheme 1 Different steps of preparation of MnO2 NPs
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H. Naeimi et al.
Fig. 2 FT-IR spectra of MnO2 nanoparticles
Fig. 3 SEM of MnO2
nanoparticles
Firstly, to optimize the reaction conditions, the reaction of o-aminophenol
(1.1 mmol, 0.12 g) with 2-chlorobenzaldehyde (1 mmol) as a model reaction was
performed in the presence of different amounts of nano MnO2 as oxidant. The
results are summarized in Table 1.
As can be seen from this table, in the absence of nano MnO2 no benzoxazole
product was obtained even an extension of the reaction time up to 30 min (Table 1,
entry 1). Therefore, MnO2 nanoparticles as reactive and appropriate oxidant agents
were used in this reaction. It was shown that 1 mmol of MnO2 nanoparticles lead to
higher yield and shorter reaction time compared to other runs (Table 1, entry 4).
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Catalyst-free microwave-promoted one pot synthesis of 2…
Fig. 4 XRD pattern of MnO2 nanoparticles
O
H
N
O
R
MnO2 nano particles
CH3CN, MW
OH
R
Or
Or
O
NH2
N
O
H
R=Cl, OMe, Me, OH, NO2
Scheme 2 Synthesis of 2-substituted benzoxazoles
In continuation of this research, to investigate the effect of various powers of
microwave irradiation, the model reaction was carried out under different powers of
microwave oven (Table 2). An increase in microwave power (100–600 W)
decreased time of the reactions and enhanced yields of the products. The model
reaction, at 450 W afforded the best yield of product, with 90% isolated yield after
10 min (Table 2, entry 3).
Choosing a proper solvent has important effects on the successful microwave-
promoted organic reactions. Polar and ionic species can absorb microwave
irradiation and convert it to heat. Organic solvents due to different polarities have
different behavior under microwave irradiation [30]. Hence, the model reaction,
with 1 mmol of nano MnO2, was investigated in different solvent systems such as
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H. Naeimi et al.
Table 1 Optimization of nano MnO2 amounts for synthesis of 2-(2-chlorophenyl)-1,3-benzoxazole
Entry
Oxidant amount (mmol)
Time (min)
Yield (%)a
1
2
3
4
5
6
–
30
10
10
10
20
10
–
0.5
0.7
1
43
67
90
90
90
1
1.3
Reaction conditions: o-aminophenol (1.1 mmol), 2-chloro benzaldehyde (1 mmol), and MnO2
nanoparticles in acetonitrile solution (4 mL) under microwave irradiation (450 W)
a
Isolated yields
Table 2 Survey the effect of microwave irradiation power on the formation of 2-(2-chlorophenyl)-1,3-
benzoxazole
Entry
Power (W)
Time (min)
Yield (%)a
1
2
3
4
5
100
300
450
450
600
40
15
10
20
10
Trace
60
90
90
90
Reaction conditions: o-aminophenol (1.1 mmol), 2-chlorobenzaldehyde (1 mmol), and MnO2 nanopar-
ticles (1 mmol) in acetonitrile as solvent (4 mL) at room temperature
a
Isolated yields
Table 3 Effect of solvent on the rate of microwave-assisted reaction using nano MnO2
Entry
Solvent
Time (min)
Yield (%)a
1
2
3
4
H2O
20
10
10
15
–
DMF
CH3CN
EtOH
80
90
78
Reaction conditions: o-aminophenol (1.1 mmol), 2-chlorobenzaldehyde (1 mmol), and MnO2 nanopar-
ticles (1 mmol) in selected solvent (4 mL)
a
Isolated yields of products
H2O, DMF, CH3CN and EtOH under microwave irradiation. The results are
summarized in Table 3. It can be seen from the Table 3 that the optimal solvent for
this reaction is acetonitrile.
To show the applicability and merit of this approach, we extended the study with
o-aminophenol and several aldehydes for the synthesis of 2-substituted benzoxa-
zoles in the presence of nano MnO2 NPs in according to the general experimental
procedure. The pertinent results are presented in Table 4. The cyclocondensation-
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Catalyst-free microwave-promoted one pot synthesis of 2…
Table 4 Preparation of 2-substituted benzoxazoles under optimized conditions
O
N
H
R
O
MnO2 nano particles
OH
R
Or
CH3CN, MW
Or
O
NH2
N
O
H
R=Cl, OMe, Me, OH, NO2
3a–3m, Melting point, Time (min), Yield (%)a
Cl
N
N
N
O
Cl
O
O
3a: 95–97, 11, 89
3b: 63–65, 10, 90
3c: 144–146, 10, 90
Cl
N
Me
N
Cl
N
Cl
O
O
O
Cl
3d: 122–124, 9, 88
3e: 172–175, 7.3, 87
3f: 77–79, 13, 83
MeO
N
N
N
OMe
O
Me
O
O
3g: 114–116,13, 83
3h: 51–54, 12.4, 85
3i: 97–99, 12, 88
OMe
N
O2N
N
HO
N
OMe
O
O
O
3j: 108–110, 14, 89
3k: 102–103, 9, 75
3l: 123–124,11.5, 92
HO
N
O
3m: 75–78, 8, 94
Reaction conditions: o-aminophenol (1.1 mmol), aromatic aldehyde (1 mmol), and MnO2 nanoparticles (1
mmol) in CH3CN solvent (4 mL) under microwave irradiation (450 W) at room temperature
a
Isolated yield
oxidation reaction between o-aminophenol and aromatic aldehydes smoothly
proceeded to give the corresponding 2-aryl benzoxazoles in excellent yields and
short reaction times. The yields of the products vary in the range of 75–94% yields.
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H. Naeimi et al.
O
NH2
OH
H
R
- H2O
O
N
OH
N
R
H
(1)
O
H
R
N
H
Mn(OH)2
(2)
R
MnO2 NPs
O
Mn
O
Scheme 3 Proposed reaction mechanism for the formation of 2-substitued benzoxazoles in the presence
of nano MnO2 as an oxidant agent
The structures of products were completely characterized by spectroscopic data
1
such as; IR, H NMR, 13C NMR and melting point and these were consistent with
those of authentic samples [36–40, 45].
The proposed reaction mechanism
The mechanistic proposal for the formation of 2-substituted benzoxazoles using
aromatic aldehydes and o-aminophenol by MnO2 nano particles under microwave
irradiation is presented in Scheme 3. The procedure likely proceeds via a
cyclocondensation-oxidation reaction. First, condensation of o-aminophenol and
aromatic aldehyde and elimination of H2O afford intermediate (1). Then, species (2)
are formed from nucleophilic attack of ortho-hydroxyl group on the carbon atom of
imine (1). Radical oxidation of species (2) by nano MnO2 and elimination of
Mn(OH)2 lead to the corresponding product.
Conclusion
In conclusion, we have described the synthesis of 2-substitued benzoxazoles via the
reaction of o-aminophenol with variety of aryl aldehydes in acetonitrile solution
under microwave irradiation. For this purpose, nano MnO2 as an available and
123

Catalyst-free microwave-promoted one pot synthesis of 2…
economically acceptable oxidant was prepared and was used in this reaction. The
reaction was efficiently performed under ambient conditions, giving the corre-
sponding products in good to high isolated yields and short reaction times. The
1
products were confirmed by spectroscopic and physical data such as; IR, H NMR,
13C NMR and the melting point.
Acknowledgements The authors are grateful to the University of Kashan for supporting this work by
Grant No. 159148/69.
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