Efficient one-pot synthesis of benzoxazole derivatives catalyzed by nickel supported silica

Article abstract of DOI:10.4067/S0717-97072012000200008

A simple and efficient method has been developed for the synthesis of benzoxazoles from 2-aminophenol and substituted aldehydes in the presence of a catalytic amount of nickel supported silica at room temperature.

Full text of DOI:10.4067/S0717-97072012000200008

J. Chil. Chem. Soc., 57, Nº 2 (2012)
EFFICIENT ONE-POT SYNTHESIS OF BENZOXAZOLE DERIVATIVES CATALYZED BY
NICKEL SUPPORTED SILICA
SURESH MADDILA*, SREEKANTH. B JONNALAGADDA
School of Chemistry, University of KwaZulu-Natal, West Ville Campus, Chilten Hills, Private Bag 54001,
Durban-4000, South Africa
(Received: May 27, 2011 - Accepted: March 29, 2012)
ABSTRACT
A simple and efficient method has been developed for the synthesis of benzoxazoles from 2-aminophenol and substituted aldehydes in the presence of a
catalytic amount of nickel supported silica at room temperature.
Keywords: Nickel suppoted silica, Benzoxazoles, One-pot two-component synthesis, 2-Aminophenol, Substituted aldehydes.
physical data was identified by 1H NMR, 13C NMR and LCMS spectrometers.
INTRODUCTION
RESULTS AND DISCUSSION
The benzoxazole moiety is the key structure feature of a large number
of biologically active natural products and pharmaceutical compounds1.
Two protocols for the synthesis of benzoxazoles have been developed. One
is the copper-catalyzed intramolecular o-arylations or intermolecular domino
annulations of o-arylhalides2-4 and the other is the direct condensation of
2-aminophenol with carboxylic acid or aldehyde under harsh conditions,
2-aminophenol and substituted aldehydes were selected as the model
reaction to examine catalytic activity of Ni supported SiO2 at ambient
temperature. To indicate the need of Ni supported SiO for this condensation.
We observed that the model reaction did not proceed 2in the absence of SiO2
even after 24 h (Table 1, entry 1). When using catalytic amount of 10 mol% Ni–
SiO2, the reaction gave benzoxazoles with 70% yield in 1.5 h in EtOH (Table
1, entry 3), and further lowering the catalyst loading up to 5 mol% led to lower
yield of 55% in 1.5 h (Table 1, entry 2). In the presence of 20 mol% catalyst
the reaction affords the corresponding synthesis of benzoxazoles in 98% yield
within 1.5 h (Table 1, entry 4), and Ni–SiO2 (25 mol%) also gives 98% yield
in 1.5 h (Table 1, entry 5). The solvents examined were trichloromethane,
acetonitrile and ethanol, among which ethanol is shown to be the best (Table
1). Accordingly, 20 mol% Ni-SiO2 catalysts loading in EtOH is considered
optimal for the synthesis of benzoxazoles.
such as in the presence of strong acid, high temperature5 or strong oxidants6-9
Catalytic aerobic oxidation using oxygen as terminal oxidant has received
much attention10,11 and been used in the synthesis of benzoxazoles12,13
.
.
Nickel supported silica as an environmental friendly and economical
catalyst has been attracting increasing research interest from chemists14.
Although kinds of Ni supported SiO2 catalyzed organic transformations have
been developed, the Ni-SiO2 to form carbon-carbon and carbon-heteroatom
bond has remained largely undeveloped15. Herein, we report an efficient and
environmentally friendly method for the synthesis of benzoxazoles catalyzed
by nickel supported silica at room temperature (Scheme 1).
We studied the possibility to synthesis of benzoxazoles by the reaction of
2-aminophenol and substituted aldehyde using Ni-SiO2 as the catalyst (Scheme
1). Here, an efficient and simple method for the synthesis of target compounds
is described and the synthesis of some compounds has been reported in our
previous studies.
Table 1: Two-component synthesis of benzoxazoles under various
conditionsa.
Entry
Catalyst (%)
Time (hour)
24 h
Yieldb (%)
1
2
3
4
5
6
7
No catalyst
0
5
1.5 h
55
70
98
98
86c
90d
10
20
25
20
20
1.5 h
1.5 h
1.5 h
2 h
Scheme 1
2.5 h
a
EXPERIMENTAL SECTION
Ni-SiO2 was added to a mixture of 1.5 mmol of 2-aminophenol and 1
mmol of aromatic aldehydes.
b Isolated yield.
All reagents and solvents were purchased and used without further
purification. Crude products were purified by column chromatography on silica
gel of 60–120 mesh. 1H and 13C NMR spectra were recorded on the 400 MHz
instruments, and spectral data are reported in ppm relative to tetramethylsilane
(TMS) as internal standard. LCMS Mass spectra were recorded on a MASPEC
low resolution mass spectrometer operating at 70 eV.
To conclude, we have shown that the Ni supported silica is a highly
active catalyst for the synthesis of benzoxazoles. General procedure for the
preparation of benzoxazoles: A mixture of 2-aminophenol (1.5 mmol) and
substituted aldehydes (1 mmol) with Ni supported SiO (20mol%) in EtOH
(10 mL) was stirred at ambient temperature for an appro2priate time (Table 1).
After completion of the reaction as indicated by TLC, the Ni-SiO was filtered
and washed with 50% EtOH (2×10 mL). The crude product was2 purified by
recrystallization from diethyl ether (solid products) or by chromatography
using silica gel and mixtures of hexane/ethyl acetate of increasing polarity. The
c In the presence of CHCl3.
d In the presence of CH3CN.
To word, we prepared a range of benzoxazoles under the optimized
conditions (Table 2). 2-Aminophenol, different aldehydes were coupled with
under these reaction conditions. The reactions are clean and highly selective
affording exclusively benzoxazoles in high yields in a short reaction time. The
reaction of 2-aminophenol coupled with 3,4-dimethyl, 4-methyl and 4-methoxy
is completed within 1.5 h with 98%, 96% and 94% yield, respectively (Table
2, entries 3a-3c). Similar reaction of 2-aminophenol coupled with simple
benzaldehyde produces the corresponding products in excellent yield of 93%
in 1.5 h, respectively (Table 2, entry 3d). This method is equally effective with
electron-withdrawing 4-fluoro, 4-trifluoromethyl and 4-chloro benzaldehydes
produces the corresponding products in 89%, 86% and 88% yield in ‘longer’
e-mail address: sureshmskt@gmail.com
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J. Chil. Chem. Soc., 57, Nº 2 (2012)
reaction time 2.5, 3 and 2.5 h in respectively (Table 2, entries 3e-3g). The
reaction of 2-aminophenol coupled with 3-thienyl, 4-pyridyl and 1-naphthyl
benzaldehyde produces the corresponding products in 91%, 93% and 90% yield
in 1.5 h, respectively (Table 2, entries 3h-3j). The reaction of 2-aminophenol
coupled with ethyl, butylaldehyde produces the corresponding products in
94%, and 94% yield in 1.5 h, respectively (Table 2, entries 3k-3l).
Hz, 1H, Ar–H), 7.58 (t, J = 7.4 Hz, 1H, Ar–H), 7.44 (s, 1H, Ar–H), 7.37–7.32
(m, 2H, Ar–H); 13C NMR (CDCl , 100 MHz, ppm): δ 159.7, 150.3, 141.9,
129.2, 128.0, 126.9, 126.6, 124.9,3124.5, 119.9, 110.4; MS (70 eV, EI): m/z
(%): 201 (M+).
2-(Pyridine-4-yl)benzoxazole (3i): 1H NMR (CDCl3, 400 MHz, ppm): δ
8.79 (d, J = 7.9 Hz, 2H), 8.05 (d, J = 8.1 Hz, 2H, Ar–H), 7.81 (t, J = 7.5 Hz,
1H, Ar–H), 7.62 (t, J = 7.3 Hz, 1H, Ar–H), 7.42–7.35 (m, 2H); 13C NMR
(CDCl , 100 MHz, ppm): δ 160.5, 150.7, 150.6, 141.6, 134.2, 126.2, 125.0,
120.9, 3120.6, 110.8; MS (70 eV, EI): m/z (%): 197 (M+1).
Table 2: Preparation of various benzoxazoles in the presence of Ni-SiO2
in EtOH at room temperaturea.
2-(Naphthalene-1-yl)benzoxazole (3j): 1H NMR (CDCl , 400 MHz,
ppm): δ 9.54 (d, J = 8.4 Hz, 1H), 8.46 (d, J = 8.2 Hz, 1H, Ar–H), 83.03 (d, J = 8.4
Hz, 1H, Ar–H), 7.97 (t, J = 7.7 Hz, 2H, Ar–H), 7.76 (t, J = 7.2 Hz, 1H, Ar–H),
7.69–7.58 (m, 3H, Ar–H), 7.45–7.44 (m, 2H, Ar–H); 13C NMR (CDCl3, 100
MHz, ppm): δ 162.7, 150.1, 142.3, 133.9, 132.2, 130.6, 129.2, 128.6, 127.8,
126.4, 126.3, 125.2, 124.8, 124.4, 123.5, 120.2, 110.4; MS (70 eV, EI): m/z
(%): 246 (M+1).
Entry
3a
3b
3c
R
Time (hour)
Yield (%)
3,4-MeC6H3
4-MeC6H4
4-MeOC6H4
H
1.5
1.5
1.5
1.5
2.5
3.0
2.5
1.5
1.5
98
96
94
93
89
86
88
91
93
2-Ethylbenzoxazole (3k): 1H NMR (CDCl3, 400 MHz, ppm): δ 7.60 (d, J
= 7.6 Hz, 1H, Ar–H), 7.42 (d, J = 7.2 Hz, 1H, Ar–H), 7.23 (t, J = 8.3 Hz, 2H,
Ar–H), 2.93–2.85 (q, J = 7.3 Hz, 2H, CH2), 1.40–1.19 (t, J = 7.63 Hz, 3H, CH3);
13C NMR (CDCl , 100 MHz, ppm): δ 167.4, 150.9, 141.5, 124.6, 124.2, 119.7,
110.4, 22.4, 11.13; MS (70 eV, EI): m/z (%): 148 (M+1).
3d
3e
4-FC6H4
4-CF3C6H4
4-ClC6H4
3-thienyl
4-pyridyl
3f
3g
3h
3i
2-Butylbenzoxazole (3l): 1H NMR (CDCl3, 400 MHz, ppm): δ 7.67 (d, J
= 7.8 Hz, 1H, Ar–H), 7.47 (d, J = 7.5 Hz, 1H, Ar–H), 7.29 (t, J = 8.3 Hz, 2H,
Ar–H), 2.93 (t, J = 7.6 Hz, 2H, CH2) 1.89–1.81 (m, 2H, CH2), 1.46–1.40 (m,
2H, CH2), 0.97 (t, J = 7.6 Hz, 3H, CH3); 13C NMR (CDCl , 100 MHz): δ 167.6,
150.9, 141.6, 124.6, 124.2, 119.7, 110.5, 29.0, 28.6, 223.5, 13.9; MS (70 eV,
EI): m/z (%): 176 (M+1).
3j
3k
3l
1-naphthyl
ethyl
butyl
1.5
1.5
1.5
90
94
94
CONCLUSION
a Reaction conditions: 2-aminophenol (1.5 mmol), substituted aldehyde (1
mmol), Ni-SiO2 (20 mol%), room temperature, EtOH.
In conclusion, we have developed a novel and highly efficient method for
the synthesis of benzoxazoles by treatment of 2-aminophenol and substituted
aldehyde in the presence of Ni supported silica as an effective Lewis acid.
The significant advantages of this methodology are good yields, short reaction
times, a simple workup procedure, and easy preparation and handling of the
catalyst. This methodology may find widespread uses in organic synthesis for
preparation of the benzoxazoles.
1
2-(3,4-Dimethylphenyl)benzoxazole (3a): H NMR (CDCl3, 400 MHz,
ppm): δ 8.10 (d, J = 8.1 Hz, 2H, Ar–H), 7.75 (t, J = 7.6 Hz, 1H, Ar–H), 7.57 (t,
J = 7.5 Hz, 1H, Ar–H), 7.36–7.24 (m, 3H, Ar–H), 2.40 (s, 6H, CH ); 13C NMR
(CDCl , 100 MHz, ppm): δ 163.0, 150.2, 141.6, 140.9, 132.5, 1330.9, 128.4,
125.7, 3124.4, 124.6, 121.6, 119.6, 110.4, 20.1, 18.9; MS (70 eV, EI): m/z (%):
224 (M+1).
2-P-tolylbenzoxazole (3b): 1H NMR (CDCl3, 400 MHz, ppm): δ 8.15 (d,
J = 8 Hz, 2H, Ar–H), 7.79 (t, J = 7.7 Hz, 1H, Ar–H), 7.57 (t, J = 7.6 Hz, 1H,
Ar–H), 7.36–7.30 (m, 4H, Ar–H), 2.42 (s, 3H, CH3); 13C NMR (CDCl3, 100
MHz, ppm): δ 163.2, 150.6, 142.1, 141.9, 129.5, 127.5, 124.8, 124.4, 124.3,
119.8, 110.4, 21.5; MS (70 eV, EI): m/z (%): 209 (M+).
ACKNOWLEDGEMENTS
The authors are thankful to the authorities of School of Chemistry,
University of KwaZulu-Natal, Westville campus, Durban, South Africa for the
facilities and encouragement.
2-(4-Methoxyphenyl)benzoxazole (3c): 1H NMR (CDCl3, 400 MHz,
ppm): δ 8.20 (d, J = 9.2 Hz, 2H, Ar–H), 7.76 (t, J = 7.8 Hz, 1H, Ar–H), 7.56
(t, J = 7.5 Hz, 1H, Ar–H), 7.36–7.29 (m, 2H, Ar–H), 7.03 (d, J = 8.8 Hz, 2H,
Ar–H), 3.88 (s, 3H, OCH3); 13C NMR (CDCl , 100 MHz, ppm): δ 163.1, 162.3,
150.6, 142.2, 129.3, 124.6, 124.4, 119.7, 119.36, 114.3, 110.3, 55.4; MS (70 eV,
EI): m/z (%): 226 (M+1).
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7.38–7.34 (m, 2H, Ar–H); 13C NMR (CDCl , 100 MHz, ppm): δ 162.9, 150.7,
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2-(4-Fluorophenyl)benzoxazole (3e): 1H NMR (CDCl3, 400 MHz, ppm):
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Hz, 1H, Ar–H), 7.36 (d, J = 8.1 Hz, 2H, Ar–H), 7.21 (d, J = 7.9 Hz, 2H, Ar–H);
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(M+1).
1
2-(4-(Trifluoromethyl)phenyl)benzoxazole (3f): H NMR (CDCl3, 400
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H), 7.83 (t, J = 7.8 Hz, 2H, Ar–H), 7.69–7.59 (m, 2H, Ar–H), 7.44–7.37 (m,
2H, Ar–H); 13C NMR (CDCl3, 100 MHz, ppm): δ 161.5, 150.8, 141.9, 131.8,
130.6, 129.5, 128.0, 127.9, 125.7, 124.9, 124.5 (J = 4 Hz), 120.3, 110.7; MS
(70 eV, EI): m/z (%): 263 (M+1).
2-(4-(Chlorophenyl)benzoxazole (3g): 1H NMR (CDCl3, 400 MHz,
ppm): δ 8.17 (d, J = 8.1 Hz, 2H, Ar–H), 7.79 (t, J = 7.5 Hz, 1H, Ar–H), 7.54 (t,
J = 7.2 Hz, 1H, Ar–H), 7.49 (d, J =7.3 Hz, 2H, Ar–H), 7.37 (d, J = 7.4 Hz, 2H,
Ar–H); 13C NMR (CDCl3, 100 MHz, ppm). δ 161.9, 150.7, 141.9, 137.6, 129.2,
128.7, 125.6, 125.2, 124.6, 120.0, 110.5; MS (70 eV, EI): m/z (%): 230 (M+1).
1
2-(Thiophen-3-yl)benzoxazole (3h): H NMR (CDCl3, 400 MHz, ppm):
δ 8.20 (dd, J = 2.8, 1.0 Hz, 1H), 7.80 (dd, J = 4.8, 1.0 Hz, 1H), 7.78 (t, J = 7.8
1100