Microwave Assisted Synthesis of Two-Substituted Benzoxazoles in the Presence of Potassium Cyanide under Mild Conditions

Article abstract of DOI:10.1080/15533174.2014.988794

Various two-substituted benzoxazoles were prepared using microwave-assisted reaction of 2-aminophenol with aromatic aldehydes in the presence of one equivalent of potassium cyanide as an equimolecular catalyst. Aldehydes having either electron-donating or withdrawing groups afforded the target products. The important features of this method were high yields, short reaction times and easy work up. The structure of synthesized products was characterized by nuclear magnetic resonance (NMR) and infrared (IR).

Full text of DOI:10.1080/15533174.2014.988794

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Microwave Assisted Synthesis of 2-Substituted
Benzoxazoles in the Presence of Potassium Cyanide
Under Mild Conditions
a
a
Hossein Naeimi & Soraya Rahmatinejad
a
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan,
7317–51167, I.R. Iran
8
Accepted author version posted online: 30 Jul 2015.
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To cite this article: Hossein Naeimi & Soraya Rahmatinejad (2015): Microwave Assisted Synthesis of 2-Substituted
Benzoxazoles in the Presence of Potassium Cyanide Under Mild Conditions, Synthesis and Reactivity in Inorganic, Metal-
Organic, and Nano-Metal Chemistry, DOI: 10.1080/15533174.2014.988794
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Microwave Assisted Synthesis of 2-Substituted Benzoxazoles in the Presence of Potassium
Cyanide Under Mild Conditions
Hossein Naeimi* and Soraya Rahmatinejad
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan,
87317–51167, I.R. Iran
*Corresponding author. Email: naeimi@kashanu.ac.ir
ABSTRACT
Various 2-substituted benzoxazoles were prepared using microwave assisted reaction of
-aminophenol with aromatic aldehydes in the presence of one equivalent of potassium cyanide
2
as an equimolecular catalyst. Aldehydes having either electron-donating or withdrawing groups
afforded the target products. The important features of this method were high yields, short
reaction times and easy work up. The structure of synthesized products was characterized by
nuclear magnetic resonance (NMR) and infrared (IR).
Keywords: Benzoxazoles; Potassium cyanide; 2-aminophenol; Microwave, Synthesis.
1
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INTRODUCTION
Benzoxazoles and their derivatives have received considerable attention due to their
[1]
[2]
[3]
biological and therapeutic activities such as anti-inflammatory, antiulcer, hypoglycemic,
[4]
[5]
[6]
[7]
antimicrobial, antitumor, antihistaminic and anticancer properties. They have also been
[8]
[9]
[8]
[10]
used as fluorescent-whitening agent dyes, dye lasers, herbicides, sensors for metals,
[11]
[12,13]
electronic devices, and intermediates for organic syntheses.
The common methods used
for the synthesis of benzoxazoles include the condensation of 2-aminophenol with aldehydes in
[14]
[15]
[16]
[17]
the presence of oxidants such as; NaCN,
NiO
2
,
DDQ,
Cu-nanoparticle,
heteropoly
[
18]
[19]
[20]
acids, ThClO4, o-iodoxybenzoic acid (IBX) and the condensation of o-substituted amino
[
21-24]
[25]
[26]
[27,28]
aromatics with carboxylic acids,
nitriles,
orthoesters,
acyl chlorides
and
[29]
amides. Some other methods have been reported for the synthesis of benzoxazoles, including
[
30]
the reaction between 1,1-dibromoethenes with 2-aminophenol,
the reaction of 2-hydroxy
[31]
[32,33]
ketones with acetohydroxamic acid, condensation of alcohols with 2-aminophenoles,
the
[34]
reaction of 1,2-dihaloarenes with carboxamides,
the reaction of α-keto acides with 2-
[35]
[36]
aminophenol and reaction of 2-(aryloxy)-anilines.
Recently, the synthesis of 2-arylbenzoxazoles from the reaction of 2-aminophenols and
aromatic aldehydes in the presence of potassium cyanide at room temperature has been
[37]
reported. These methods suffer from one or suffer from one or more drawbacks such as; long
reaction times, the usage of excess catalysts, harsh reaction conditions or low yields of the
desired products. Hence, there is a scope for the development of an efficient, simple, economical
and eco-friendly synthetic strategy for the preparation of 2-arylbenzoxazoles.
2
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Preparation of organic compounds could be accelerated by microwave (MW) irradiation
with higher yields and purity, lower quantities of by-products, easier work up and purification
[
38,39]
compared to other more conventional techniques.
Moreover, some reactions that do not
occur by conventional thermal heating techniques or produce products in poor yields can be
[
40]
accomplished in high yields under microwave irradiation.
By keeping this point in mind,
herein we report the synthesis of 2-substituted benzoxazoles by a non-conventional technique.
RESULTS AND DISCUSSION
In this research, an efficient, convenient microwave-assisted method was applied to the
reaction of aromatic aldehydes and 2-aminophenol under mild conditions (Scheme 1).
Fortunately, microwave irradiation as a facile and general method afforded the corresponding
products within a few minutes in excellent yields.
An important factor in performing reactions under microwave irradiation is choosing an
appropriate solvent. Polar and ionic species interact with microwaves more efficiently. The
different solvents, due to variation in polarities, have different behaviors under microwave
irradiation. The ability of a specific substance (solvent or reagent) to convert electromagnetic
[
41]
radiation into heat is determined by the so-called loss factor (tan δ). A reaction medium with a
high tan δ absorbs most of the microwave energy and converts it into heat. So firstly, the solvent
effect on the reaction of 2-aminophenol with benzaldehyde in the presence of KCN as a model
reaction was investigated. The results are presented in Table 1.
As can be seen from Table 1, the solvents play an important role in the reaction. It was
found that the best solvent for this reaction was N,N-dimethylformamide (DMF) and the reaction
3
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in this solvent afforded the desired product in 95% yield, while the performance of acetonitrile,
and ethanol as solvents led to lower yields (Table 1, entries 1-3). The reaction in
dichloromethane did not produce benzoxazoles at all (Table 1, entry 4).
Also, we carried out the reaction of 1.1 mmol 2-aminophenol with 2.2 mmol
benzaldehyde in the presence of various amounts of KCN under 450 Watt microwave irradiation.
The corresponding results can be seen in Table 2. As shown, the desired product was obtained
with high yield in a short reaction time and in the presence of 1.1 mmol KCN (Table 2, entry 4).
In continuation of this work, in order to optimize the microwave power, the reaction of 2-
aminophenol with benzaldehyde in the presence of KCN was carried out under different powers
of microwave irradiation. It was observed that the reaction in the presence of microwave
irradiation with the power of 450 watt led to the best result, which was the obtained product with
95 % isolated yield after 3 min (Table 3, entry 3).
To ascertain the scope and limitation of the present work, the microwave-assisted
reaction of 2-aminophenol with several aromatic aldehydes was carried out according to the
general experimental procedure. The corresponding results are shown in Table 4. As shown, the
products were prepared in high yields and short reaction times, thereby confirming the generality
and scope of this efficient method for one-pot synthesis of 2-substituted benzoxazoles under
microwave irradiation. The feature of this method was that, aromatic aldehydes with electron
withdrawing groups (Entries 4-6) as well as electron-donating groups (Entries 2, 7 and 9) gave
the excellent yields except a strong electron-withdrawing group at position 4 of benzaldehyd e
that did not yield the product (Entry 15). Furthermore, heterocyclic aldehydes could also be used
for the facile synthesis of several 2-heterocyclic substituted benzoxazoles (Entries 12 and 13).
4
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[
28,30,42-44]
Comparing the results of microwave irradiation with conventional conditions
indicates that the synthesis of benzoxazoles from the reaction of 2-aminophenol with aromatic
aldehydes can be accelerated by microwave irradiation. In this study, the products were
obtained in the excellent yields after a short reaction time (about min), while in the previously
reported works the products were obtained in good to high yields after long reaction times
[45]
(
about hour). For example, in the previous report,
the reaction of 2-aminophenol with 4-
o
methoxybenzaldehyde or 4-chlorobenzaldehyde catalyzed by FeCl
3
at 110 C after 24 h
afforded 2-(4-methoxyphenyl) benzoxazole and 2-(4-chlorophenyl) benzoxazole in 76% and
6% yields respectively (Table 4, entries 16 and 17 ). Whereas the present procedure needs
6
only 4 min to result 2-(4-methoxyphenyl) benzoxazole in 92% yield (Table 4, entry 8) and 5.50
min to result 2-(4-chlorophenyl) benzoxazole in 93% yield (Table 4, entry 5).
Also, in this study, 2-aminophenol:KCN were used as 1:1 mol ratio and 2-phenyl
benzoxazole as desired product was obtained in excellent yield (95 %) after short reaction time
(
3 min) (Table 4, entry 1). While, in the previously reported work, 2-aminophenol:KCN has
been used as 1:2 mol ratio and the corresponding product has been obtained in 85 % yield after
[
37]
5
hours
(Table 4, entry 18). This method offered several advantages including excellent
yields, high purity, simple reaction conditions, high reaction rates and the easy work up
procedures. These results demonstrated that the microwave irradiation is an efficient method
for the one-pot synthesis of 2-substituted benzoxazoles. The structures of products were
completely characterized by spectroscopic and physical data and they were found to be in a
[
19,42,43 ,46-48]
good agreement with earlier reports.
5
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The Proposed Reaction Mechanism
The proposed mechanism for the formation of 2-substituted benzoxazoles is presented in
Scheme 2. As can be seen, the reaction likely proceeds according to the benzoin condensation,
which involves formation of the benzoin (2). Intermediate (3) is formed by the reaction of 2-
aminophenol with benzoin. Then, nucleophilic attack of hydroxyl group affords the
corresponding product (4). To prove the correctness of this mechanism, the reaction of 2-
aminophenol (1 mmol) with benzoin (1mmol) in DMF as solvent was carried out in a microwave
oven at power of 450 W and the desired product was obtained. This result was confirmed that the
mechanism of reaction proceedes according the benzoin condensation (Scheme 3). As mentioned
before, by considering the proposed mechanism through the formation of benzoin, the 4-
nitrobenzaldehyde could not be active in this reaction because of the very low nucleophilicity of
cyanohydrin anion intermediate (1). This was due to the delocalization of minus charge via
[
49]
resonance of NO group in para situation of the benzaldehyde.
2
EXPERIMENTAL
Chemicals and Instruments
All materials were of commercial reagent grade. The aromatic aldehydes and o-
aminophenol were purified by standard procedures and purity was determined by thin layer
chromatography (TLC). IR spectra were recorded as KBr pellets on a Perkin-Elmer 781
spectrophotometer or an Impact 400 Nicolet fourier transform infrared spectrophotometer
1
13
(
FTIR). H NMR and C NMR were recorded in CDCl solvent on a Bruker DRX-400
3
spectrometer with tetramethylsilane as internal reference. Melting points obtained with a
6
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Yanagimoto micro melting point apparatus are uncorrected. The purity determination of the
substrates and reaction monitoring were accomplished by TLC on silica-gel polygram SILG/UV
254 plates (from Merck Company). Microwave irradiations were carried out in microwave oven
specially designed for the organic synthesis (Milestone LAVIS 1000 Basic Microwave).
Typical Procedure for the Synthesis of Benzoxazoles from Arylaldehydes
A mixture of 2-aminophenol (0.13 gr, 1.1 mmol), substituted benzaldehydes (2.2 mmol)
and potassium cyanide (1.1 mmol) in 4 ml N,N-dimethylformamide was irradiated in a
microwave oven at 450 W. The progress of the reaction was monitored using thin-layer
chromatography (petroleum ether/ethyl acetate, 6/2). After the completion of the reaction, the
mixture was cooled and extracted with ethyl acetate (3 × 10 ml) and the organic layer was
concentrated under reduced pressure. Then, recrystallization of the crude product was carried
out in a boiling mixture of ethanol/water (1:1) to give the pure product.
[
42]
2
-Phenyl-1,3-benzoxazole: Light brown solid; m.p= 98-100 °C (Lit . 102-103 °C); IR (KBr)/ ν
-1
1
(
cm ) 1615 (C=N), 1551, 1448 (C=C, Ar), 1242 (C-O-C); H NMR (CDCl
3
, 400 MHz)/ δ
(ppm): 8.29-8.26 (2H, m, Ar), 7.80-7.78 (1H, m, Ar), 7.62-7.59 (1H, m, Ar), 7.56-7.54 (3H, m,
Ar), 7.38-7.36 (2H, m, Ar).
-(2-Hydroxyphenyl)-1,3-benzoxazole: White solid; m.p= 123-124 °C (Lit . 125-126 °C); IR
[
43]
2
-
1
1
(
(
(
KBr)/ ν (cm ) 3143 (OH), 1630 (C=N), 1544, 1485 (C=C, Ar), 1248 (C-O-C); H NMR
CDCl , 400 MHz)/ δ (ppm): 11.50 (1H, s, OH), 8.05-8.03 (1H, dd, J= 7.6, 1.4 Hz, Ar), 7.75
3
1H, m, Ar), 7.63 (1H, m, Ar), 7.47-7.40 (3H, m, Ar), 7.14-7.12 (1H, m, Ar), 7.04-7.00 (1H, m,
7
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1
3
Ar); C NMR (CDCl
3
, 100 MHz)/ δ (ppm) 162.90, 158.70, 149.13, 140.00, 133.56, 127.10,
125.30, 125.00, 119.56, 119.25, 117.40, 110.66.
-1
2
-(3-Hydroxy-phenyl)-1,3-benzoxazole: White solid; m.p=172-174 °C; IR (KBr)/ ν (cm ) 3428
1
(
OH), 1600 (C=N), 1550, 1452 (C=C, Ar), 1241 (C-O-C); H NMR (CDCl
3
, 400 MHz)/ δ (ppm):
8.91 (1H, s, OH), 7.75-7.73 (3H, m, Ar), 7.70 (1H, m, Ar), 7.42-7.41 (3H, m, Ar), 7.00 (1H, m,
Ar).
-(2-Chlorophenyl)-1,3-benzoxazole: Light yellow solid; m.p= 63-65 °C (Lit . 61-64 °C); IR
[
19]
2
-1
1
(
KBr)/ ν (cm ) 1606 (C=N), 1537, 1452 (C=C, Ar), 1244 (C-O-C); H NMR (CDCl
3
, 400 MHz)/
δ (ppm): 8.18-8.15 (1H, dd, J= 7.20, 1.6 Hz, Ar), 7.88-7.86 (1H, m, Ar), 7.65-7.63 (1H, m, Ar),
7.60-7.58 (1H, m, Ar), 7.49-7.38 (4H, m, Ar).
[
42]
2
-(4-Chlorophenyl)-1,3-benzoxazole: Light brown solid; m.p= 149-151 °C (Lit . 153-154 °C);
-
1
1
IR (KBr)/ ν (cm ) 1614 (C=N), 1482, 1550 (C=C, Ar), 1243 (C-O-C); H NMR (CDCl
MHz)/ δ (ppm): 8.20-8.19 (2H, m, Ar), 7.79-7.77 (1H, m, Ar), 7.61-7.58 (1H, m, Ar), 7.53-7.51
2H, m, Ar), 7.39-7.37 (2H, m, Ar).
3
, 400
(
[
46]
2
-(2,4-Dichlorophenyl)-1,3-benzoxazole: Light brown solid; m.p= 120-123 °C (Lit . 118-
-1
1
1
19 °C); IR (KBr)/ ν (cm ) 1662 (C=N), 1588, 1466 (C=C, Ar), 1241 (C-O-C); H NMR
(
(
CDCl
3
, 400 MHz)/ δ (ppm): 8.14-8.12 (1H, d, J= 8.40 Hz, Ar), 7.86-7.84 (1H, m, Ar), 7.64-7.60
1
3
2H, m, Ar), 7.43-7.40 (3H, m, Ar); C NMR (CDCl
3
, 100 MHz)/ δ (ppm): 160.07, 150.51,
141.58, 137.54, 134.24, 132.51, 131.30, 127.43, 125.81, 124.82, 124.71, 120.56, 110.77.
[47]
2
-(3-Methoxyphenyl)-1,3-benzoxazole: Light yellow solid; m.p= 72-74 °C (Lit . 71.3-73.8 °C);
-1
1
IR (KBr)/ ν (cm ) 1642 (C=N), 1541, 1453 (C=C, Ar), 1278 (C-O-C); H NMR (CDCl
3
, 400
8
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MHz)/ δ(ppm): 8.11 (1H, m, Ar), 7.47 (1H, m, Ar), 7.44-7.42 (2H, m, Ar), 7.26 (1H, m, Ar),
7
2
1
.18-7.14 (1H, m, Ar), 7.09-7.07 (1H, m, Ar), 6.95-6.91 (1H, m, Ar), 3.89 (3H, s, Me).
[
42]
-(4-Methoxyphenyl)-1,3-benzoxazole: Light yellow solid; m.p= 100-101 °C (Lit . 103-
-1
1
05 °C); IR (KBr)/ ν (cm ) 1613 (C=N), 1501, 1452 (C=C, Ar), 1249 (C-O-C); H NMR
(
(
(
CDCl
1H, m, Ar), 7.35-7.32 (2H, m, Ar), 7.05-7.03 (2H, d, J= 8 Hz, Ar), 3.90 (3H, s, Me); C NMR
CDCl , 100 MHz)/ δ(ppm): 163.18, 162.32, 150.68, 142.30, 129.39, 124.60, 124.42, 119.70,
19.62, 114.36, 110.39, 55.45.
-(3-Methylphenyl)-1,3-benzoxazole: Light yellow solid; m.p= 80-81 °C (Lit . 79-80 °C); IR
3
, 400 MHz)/ δ(ppm): 8.22-8.20 (2H, d, J= 8.40 Hz, Ar), 7.75-7.74 (1H, m, Ar), 7.58-7.56
1
3
3
1
[47]
2
-1
1
(
KBr)/ ν (cm ) 1598 (C=N), 1550, 1451 (C=C, Ar), 1244 (C-O-C); H NMR (CDCl
3
, 400 MHz)/
δ (ppm): 8.08 (1H, s, Ar), 8.07-8.05 (1H, d, J= 7.60 Hz, Ar), 7.79-7.77 (1H, m, Ar), 7.60-7.58
(
1H, m, Ar), 7.45-7.41 (1H, t, J= 7.80 Hz, Ar), 7.37-7.35 (3H, m, Ar), 2.47 (3H, s, Me).
[
42]
2
-(4-Methylphenyl)-1,3-benzoxazole: Light brown solid; m.p= 114-115 °C (Lit . 115-116 °C);
-1
1
IR (KBr)/ ν (cm ) 1619 (C=N), 1500, 1451 (C=C, Ar), 1241 (C-O-C); H NMR (CDCl
3
, 400
MHz)/ δ(ppm): 8.16-8.14 (2H, d, J= 8 Hz, Ar), 7.78-7.75 (1 H, m, Ar), 7.59-7.54 (1H, m, Ar),
7.36-7.34 (4H, m, Ar), 2.45 (3H, s, Me).
[
48]
2
-(4-Isopropyl-phenyl)-1,3-benzoxazole: Light brown solid; m.p= 80-82 °C (Lit . 76-78 °C);
-
1
1
IR (KBr)/ ν (cm ) 1613 (C=N), 1553, 1451 (C=C, Ar), 1240 (C-O-C); H NMR (CDCl
MHz)/ δ(ppm): 8.20-8.18 (2H, d, J= 8 Hz, Ar), 7.78–7.76 (1H, m, Ar), 7.60–7.58 (1H, m, Ar),
.41–7.39 (2H, d, J= 8 Hz, Ar), 7.36-7.34 (2H, m, Ar), 3.00-2.99 (1H, m, CH), 1.32-1.30 (6H, d,
J= 6.80 Hz, Me).
3
, 400
7
9
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[
42]
2
-(2-Thiophen-2-yl)-1,3-benzoxazole: Brown solid; m.p= 82-84 °C (Lit . 82-83 °C); IR (KBr)/
-
1
1
ν (cm ) 1659 (C=N), 1576, 1481 (C=C, Ar), 1310 (C-O-C); H NMR (CDCl
δ(ppm): 7.93-7.92 (1H, d, J= 4 Hz, Ar), 7.76-7.74 (1H, m, Ar), 7.58-7.54 (2H, m, Ar), 7.36-7.34
2H, m, Ar), 7.22-7.19 (1H, t, J= 4.1 Hz, Ar).
-(2-Furan-2-yl)-1,3-benzoxazole: Red brown solid; m.p= 80-82 °C (Lit . 85-86 °C); IR
3
, 400 MHz)/
(
[
42]
2
-1
1
(
KBr)/ ν (cm ) 1640 (C=N), 1553, 1451 (C=C, Ar), 1246 (C-O-C); H NMR (CDCl
3
, 400 MHz)/
δ (ppm): 7.77-7.76 (1H, m, Ar), 7.68 (1H, s, Ar), 7.57-7.56 (1H, m, Ar), 7.38-7.36 (2H, m, Ar),
7.29 (1H, m, Ar), 6.63 (1H, m, Ar).
2
-(4-N,N-Dimethylaminophenyl)-1,3-benzoxazole: Light Brown solid; m.p=185-187 °C; IR
-
1
1
(
KBr)/ ν (cm ) 1613 (C=N), 1510, 1447 (C=C, Ar), 1239 (C-O-C); H NMR (CDCl
δ (ppm): 8.13-8.11 (2H, d, J= 8 Hz, Ar), 7.71-7.69 (1H, d, J= 7.20 Hz, Ar), 7.54-7.52 (1H, d, J=
.20 Hz, Ar),7.31-7.27 (2H, m, Ar), 6.79-6.77 (2H, d, J= 8 Hz, Ar), 3.08 (6H, s, Me).
3
, 400 MHz)/
7
CONCLUSIONS
In summary, we have used microwave irradiation as a facile and efficient method for
preparing of 2-substituted benzoxazole derivatives. This method involved one pot synthesis of 2-
substituted benzoxazoles by the reaction of 2-aminophenol with benzaldehydes, which was
assisted by potassium cyanide under microwave irradiation. The reaction was performed to
afford the desired products in good to excellent yields and short reaction times.
SUPPLEMENTARY MATERIAL
Supplemental data for the article is available at the publisher’s website.
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Acknowledgments
The authors are grateful to University of Kashan for supporting this work by Grant No.
159148/17.
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a
Table 1 Optimizition of solvent effect on the reaction
Entry
Solvent
Time
Yield (%)
(
min)
1
2
3
4
Ethanol
N,N-Dimethylformamide
Acetonitrile
12
43
95
25
-
3
15
15
Dichloromethane
a
Reaction of benzaldehyde with o-aminophenol in the presence
of different solvents.
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a
Table 2 Optimization of the amounts of KCN
Amount of KCN
Entry
Time (min) Yield (%)
(
mmol)
1
2
3
4
5
6
0.5
10
10
5
45
78
91
95
95
95
0.8
1
1.1
1.4
1.8
3
3
3
a
Reaction conditions: 2-aminophenol 1.1 mmol (0.13 gr),
benzaldehyde 2.2 mmol, DMF as solvent (5 ml), under
50 Watt microwave irradiation.
4
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a
Table 3 Optimization of the microwave power
Entry
Power (Watt)
Time (min) Yield (%)
1
2
3
4
5
150
300
450
600
750
15
8
53
71
95
94
3
3
b
3
81
a
Reaction conditions: 2-aminophenol 1.1 mmol (0.13
gr),benzaldehyde 2.2 mmol, 1.1 mmol KCN, DMF as
solvent 5 ml, under different powers of microwave
irradiation.
b
Some side reactions were obtained under this condition.
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Table 4
The reaction of 2-aminophenol with several aromatic aldehydes under microwave irradiation
b
o
o
Yield
(%)
Mp( C)
Mp( C)
Time
a
Entry
1
Aldehyde
Product
(
min)
Found
Reported
3
95
96
98-100
102-103
2
3
1.5
1.6
123-124 125-126
96
172-174
63-65
-
4
5
6
6
5.5
5
92
93
86
61-64
CHO
149-151 153-154
120-123 118-119
Cl
7
8
9
3.75
4
89
92
94
72-74 71.3-73.8
100-101 103-105
4.3
80-81
79-80
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1
1
0
1
5
91
94
114-115 115-116
3.8
80-82
76-78
1
1
2
3
6
91
90
82-84
80-82
82-83
85-86
N
O
O
5.6
1
1
1
1
1
4
5
6
7
8
4
92
-
185-187
-
-
-
-
-
-
15
-
-
-
-
c
24h
76
66
85
d
24h
e
300
a
All compounds are known and their physical and spectroscopic data were in good agreement
with those of authentic samples.
b
Yields refer to pure isolated products
c
Reaction conditions: 2-aminophenol 1 mmol, 4-methoxybenzaldehyde 1.1 mmol, FeCl
3
(0.05
(0.05
o
mmol), toluene (1 ml), 110 C, under 1 atm O atmosphere.
d
2
Reaction conditions: 2-aminophenol 1 mmol, 4-chlorobenzaldehyde 1.1 mmol, FeCl
3
o
mmol), toluene (1 ml), 110 C, under 1 atm O atmosphere.
2
e
Reaction conditions: 2-aminophenol 1.1 mmol, benzaldehyde 2.2 mmol, KCN (2 mmol), DMF
as solvent (5 ml).
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Scheme 1. Synthesis of 2-substituted benzoxazoles in the presence of KCN
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O
O
O
OH
CN
H
H
H
NC
C N
1
O-
H
OH
H
NC
CN
OH
-
O
HO
CH
O
C N
HO
HO
2
3
NH2
OH
N
O
4
Scheme 2. Proposed mechanism for the synthesis of benzoxazoles.
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Scheme 3. Reaction of benzoin with 2-aminophenol under microwave irradiation.
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