Iron-promoted practical one-pot synthesis of 2,5-disubstituted oxazoles

Article abstract of DOI:10.1002/cjoc.201100683

A practical one-pot protocol for the synthesis of 2,5-disubstituted oxazoles from 1-aryl-2-nitroethanones was reported. In the presence of iron/AcOH in acetonitrile, the reaction of 1-aryl-2-nitroethanones with trimethyl orthoacetate or trimethyl orthobenzoate delivered the corresponding 2,5-disubstituted oxazoles in moderate to good yields. Copyright

Full text of DOI:10.1002/cjoc.201100683

FULL PAPER
DOI: 10.1002/cjoc.201100683
Iron-Promoted Practical One-Pot Synthesis of
2,5-Disubstituted Oxazoles
Chen, Songhuia,†(陈松辉)
Bai, Donghua,†(白东虎)
Shi, Fenga(时锋)
Li, Jiana(李健)
Li, Chunjua(李春举)
Jia, Xueshun*,a,b(贾学顺)
a Department of Chemistry, Shanghai University, Shanghai 200444, China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China
A practical one-pot protocol for the synthesis of 2,5-disubstituted oxazoles from 1-aryl-2-nitroethanones was
reported. In the presence of iron/AcOH in acetonitrile, the reaction of 1-aryl-2-nitroethanones with trimethyl
orthoacetate or trimethyl orthobenzoate delivered the corresponding 2,5-disubstituted oxazoles in moderate to good
yields.
Keywords oxazole, iron, one pot synthesis
Introduction
Results and Discussion
In an effort to develop a better reaction system, our
initial experiment was carried out by using 1-phenyl-
2-nitroethanone and trimethyl orthoacetate as model
substrate (Eq. 1). Firstly, we investigated the direct
transformation of 1-phenyl-2-nitroethanone and trimeth-
yl orthoacetate with metallic samarium in the absence of
any additive in acetonitrile as a solvent. No reaction
occurred when 1-phenyl-2-nitroethanone and trimethyl
orthoacetate were mixed with samarium powder in ace-
tonitrile (Table, Entries 1). Fortunately, 10% yield of
2-methyl-5-phenyloxazole was isolated when the reac-
tion was carried out in the presence of acetic acid (Table
1, Entry 2). Subsequently, a few molecular iodines or
titanium(IV) chloride were then added to activate the
metallic samarium powder to afford lower yields of
product (Table 1, Entries 3, 4). Similar results were ob-
served under the same reaction conditions when zinc
was used as a reducing agent (Table 1, Entries 5—7).
To our delight, applying iron powder to this system
brought great improvement. As can be seen from Table
1, in the presence of iron powder and acetic acid,
2-methyl-5-phenyloxazole was obtained in 50% yield
(Table 1, Entry 8). While the titanium(IV) chloride or
iodine was employed, 2-methyl-5-phenyloxazole was
obtained in 40% and 21% yields, respectively (Table 1,
Entries 9, 10). Moreover, the increase or reduction of
acetic acid dosage also resulted in low yields (Table 1,
Entries 11, 12). Then we investigated the effect of dif-
ferent solvents on this reaction. The experimental results
indicated that when 1,4-dioxane, THF, toluene, or DCM
Oxazoles occur widely in numerous natural products,
and are an important class of heterocycle that exhibit
various biological activities such as antihypertensive,
anticancer, antiulcer, anti-inflammatory agents, fungi-
cides, and adrenergic antagonists.[1] Many compounds
containing an oxazole structural unit are also used as
versatile synthetic intermediates in organic synthesis.[2]
Thus, much attention[3] has been devoted to the devel-
opment of new and efficient methods for the synthesis
of oxazole derivatives. The cyclodehydration of the
α-acylamino ketones (Robinson-Gabriel reaction)[4] and
the oxidation of oxazolines represent direct approaches
in literature precedents.[5,3b]
Recently, an indium-mediated one-pot synthesis of
2,5-disubstituted oxazoles from the reaction of 1-aryl-2-
nitroethanones and trimethyl orthobenzoate or trimethyl
orthoacetate has been reported.[6] However, this method
was not economical and practical as indium metal is
expensive. In addition, only an example was explored
on the reactivity of trimethyl orthoacetate to result in the
poor yield of 2-methyl-5-phenyloxazole. As a continua-
tion on the syntheses of carbocycles and potentially
bioactive heterocycles as well as the organic synthetic
reactions mediated by metal,[7] we wish to report here a
practical and economic one-pot synthesis of 2,5-disub-
stituted oxazoles from the reaction of 1-aryl-2-nitro-
ethanones with trimethyl orthoacetate, or trimethyl or-
thobenzoate using cheap iron powder as promoter.
*
E-mail: xsjia@mail.shu.edu.cn; Tel.: 0086-021-66132408; Fax: 0086-021-66132408
Received December 9, 2011; accepted February 2, 2012; published online XXXX, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201100683 or from the author.
† With equal contribution to this work.
Chin. J. Chem. 2012, XX, 1—X
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1

Chen et al.
FULL PAPER
was used as solvent respectively, low yields of the
product were afforded (Table 1, Entries 13—16). On the
other hand, the product conversion was susceptible to
temperature change. The decrease of reaction tempera-
ture to 25 ℃ led to long reaction time and low yield
(Table 1, Entry 17). Therefore, the best result was ob-
tained when the reaction of 1-phenyl-2-nitroethanones
(0.5 mmol) with trimethyl orthoacetate (2.0 mmol) was
carried out in the presence of iron powder (2.0 mmol),
AcOH (5.0 mmol) using acetonitrile as solvent at reflux
(Table 1, Entry 8).
bromo, chloro, fluoro, methoxy and methyl group sub-
stitution on the aromatic ring were all tolerated, which
were potentially useful for further functionalization.
O
MeO
Fe, AcOH
OMe
NO2
+
Me
OMe
CH3CN
R
O
Me
(2)
N
R
1a 1j
Table 2 Synthesis of various 2-methyl-5-aryloxazoles a
Yield b/%
50 (1a)
52 (1b)
70 (1c)
65 (1d)
65 (1e)
75 (1f)
47 (1g)
63 (1h)
59 (1i)
49 (1j)
O
MeO
Entry
R
Time/h
OMe
OMe
M, Additive
solvent
NO2
+
Me
1
2
3
4
5
6
7
8
9
H
4
o-CH3
m-CH3
p-CH3
o-OCH3
m-OCH3
o-Cl
6
8
O
N
(1)
Me
13
11
8
Table 1 Optimization of reaction conditiona
M Solvent
Additive Time/h Yield b/%
10
5
Entry
1
p-Cl
Sm CH3CN
Sm CH3CN
Sm CH3CN
Sm CH3CN
Zn CH3CN
Zn CH3CN
Zn CH3CN
Fe CH3CN
Fe CH3CN
Fe CH3CN
Fe CH3CN
Fe CH3CN
Fe 1,4-dioxane
Fe THF
—
4
0
p-F
9
2
AcOH
Iodine
TiCl4
AcOH
Iodine
TiCl4
AcOH
I2
4
10
3
10
m-Br
4.5
3
4
a
Reaction conditions: 1-aryl-2-nitroethanone (0.5 mmol),
trimethyl orthoacetate (2 mmol), acetonitrile (15 mL), reflux.
b Isolated yields.
4
4
8
5
4
30
18
15
50
21
40
30
28
27
26
35
19
30e
6
4
7
4
MeO
Ph
O
O
R1
Fe, AcOH
CH3CN
OMe
OMe
Ph
(3)
+
NO2
8
4
R1
N
2a 2m
9
4
10
11
12
13
14
15
16
TiCl4
AcOHc
AcOHd
AcOH
AcOH
AcOH
AcOH
AcOH
4
Finally, the reaction of 1-aryl-2-nitroethanones with
10
10
6
trimethyl orthobenzoate was tested using the same reac-
tion condition (Scheme 3) and the results were summa-
rized in Table 3. In all cases, 1-aryl-2-nitroethanones
5
Table 3 Synthesis of various 2,5-diaryloxazolesa
R1
Fe toluene
5
Entry
1
Time/h
3.5
6
Yieldb/%
72 (2a)
50 (2b)
77 (2c)
80 (2d)
54 (2e)
62 (2f)
46 (2g)
62 (2h)
65 (2i)
68 (2j)
60 (2k)
61 (2l)
50 (2m)
F
DCM
5
C6H5
17
a
Fe CH3CN
24
2
o-CH3C6H4
m-CH3C6H4
p-CH3C6H4
o-CH3OC6H4
m-CH3OC6H4
p-CH3OC6H4
o-ClC6H4
m-ClC6H4
p-ClC6H4
p-FC6H4
Reaction conditions: 1-phenyl-2-nitroethanone (0.5 mmol),
trimethyl orthoacetate (2 mmol), solvent (15 mL), M (2 mmol),
3
5
additive (5 mmol) reflux. b Isolated yields. AcOH (8 mmol).
c
4
18
9
d AcOH (3 mmol). e Room temperature.
5
6
11
We then focused on our attention to substrate gener-
ality using the optimized reaction conditions. The reac-
tion of various 1-aryl-2-nitroethanones with trimethyl
orthoacetate was examined (Eq. 2) and the results were
summarized in Table 2. As can be seen from Table 2,
the reaction of various 1-aryl-2-nitroethanones having
electron-neutral, electron-deficient, and electron-rich
substituent groups on the aromatic ring with trimethyl
orthoacetate was performed well to provide the corre-
sponding 2-methyl-5-aryloxazoles in moderate to good
yields (Table 2), and no obvious sterical hindrance ef-
fect was observed in all cases (Table 2). In addition,
7
3.5
3.75
14
5
8
9
10
11
12
13
11.5
5
m-BrC6H4
furan-2-yl
13
a
Reaction conditions: 1-aryl-2-nitroethanone (0.5 mmol),
b
trimethyl orthobenzoate (2 mmol), acetonitrile (15 mL), reflux.
Isolated yields.
2
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Chin. J. Chem. 2012, XX, 1—X

Iron-Promoted Practical One-Pot Synthesis of 2,5-Disubstituted Oxazoles
bearing both electron-withdrawing and electron-donat-
ing groups on aromatic rings underwent smooth trans-
formation to the corresponding 2,5-diaryloxazoles in
moderate to good yields (Table 3).
solvent and TMS as internal reference. Coupling con-
stants (J) are reported in Hz. High-resolution mass
spectra (HRMS) were recorded on an IonSpec 4.7 Tesla
FTMS instrument.
A possible mechanism is proposed in Eq. 4. By the
consequent electron transfers and proton transfers, the
nitro group could first transform into a nitroso interme-
diate. The nitroso intermediate may be converted into
the amine species by electron transfer and proton trans-
fer processes as well as the change of ketone to enol,
and then it can react further to the imidate intermediate.
Next, an acid-assisted attack by the hydroxyl group to-
ward the neighboring imidate group followed by the
loss of MeOH and proton would produce oxazoles.
General procedure
The suspension of iron powder (2 mmol), 1-aryl-2-
nitroethanones (0.5 mmol) and acetic acid (5 mmol) in
CH3CN (5 mL) was stirred for 5 min at room tempera-
ture under a nitrogen atmosphere. And then trimethyl
orthoacetate, or trimethyl orthobenzoate in acetonitrile
(10 mL) was added. The reaction mixture was allowed
to react at reflux. The progress of the reaction was
monitored by TLC. After completion of the reaction, the
mixture was filtered and the solid was washed with di-
chloromethane. The solvent was removed under reduced
pressure. The residue was purified by column chroma-
tography on silica gel eluting with petroleum ether/ethyl
acetate to afford the corresponding 2,5-disubstituted
oxazoles in moderate to good yields. All the compounds
reported were identified by melting points, 1H NMR and
13C NMR spectra. The new compounds were identified
by HRMS.
Scheme 4
O
N
O
O
O
Fe/AcOH
Fe/AcOH
MeO
NH2
NO2
R
R
R
H+
OMe
OMe
R'
O
R'
O
+
O
R
O
H
N
HN
R
R
2-Methyl-5-phenyloxazole (1a) White solid, m.p.
-MeOH
-H+
55—57 ℃ (lit.[9] 57—58 ℃); H NMR (CDCl3, 500
1
+
O
O
H
N
H
+
MHz) δ: 7.61—7.28 (m, 5H), 7.19 (s, 1H), 2.52 (s, 3H);
13C NMR (CDCl3, 125 MHz) δ: 161.1, 151.2, 128.9,
128.3, 128.2, 124.0, 121.9, 14.2.
2-Methyl-5-(o-tolyl)oxazole (1b) Colorless liquid;
1H NMR (CDCl3, 500 MHz) δ: 7.66 (d, J＝7.0 Hz, 1H),
7.28—7.22 (m, 3H), 7.10 (s, 1H), 2.53 (s, 3H), 2.45 (s,
3H); 13C NMR (CDCl3, 125 MHz) δ: 160.8, 150.5,
134.7, 131.2, 128.2, 127.5, 126.6, 126.2, 124.8, 21.9,
14.1; HRMS calcd for C11H11NO [M＋H]＋ 174.0913,
found 174.0919.
O
R
O
O
R
R'
R
H
NH
proton transfer
H
O
OH
O
H+
R'
R
N
R
R
NH
Imidate
Conclusions
2-Methyl-5-(m-tolyl)oxazole (1c) Colorless liq-
uid;[10] 1H NMR (CDCl3, 500 MHz) δ: 7.41—7.25 (m,
3H), 7.18 (s, 1H), 7.10 (d, J＝7.5 Hz, 1H), 2.51 (s, 3H),
2.37 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ: 167.4,
151.3, 138.5, 128.9, 128.8, 128.7, 128.1, 124.5, 121.7,
121.1, 21.4, 14.1.
In conclusion, we have developed a facile, practical
and economic one-pot method for the synthesis of
2,5-disubstituted oxazoles from 1-aryl-2-nitroethanones.
In the presence of iron/AcOH, the reaction of 1-aryl-2-
nitroethanones with trimethyl orthoacetate, or trimethyl
orthobenzoate gave the corresponding 2,5-disubstituted
oxazoles in moderate to good yields. The great attrac-
tiveness of the current method lies in simple experi-
mental procedure, use of cheap iron powder, especially,
the development of reaction of 1-aryl-2-nitroethanones
with trimethyl orthoacetate to 2-methyl-5-aryloxazoles.
These features make this methodology economical, fac-
ile and practical for use in medicinal and synthetic
chemistry.
2-Methyl-5-(p-tolyl)oxazole (1d)
Light yellow
1
solid, m.p. 55—56.8 ℃ (lit.[10] 56—57 ℃); H NMR
(CDCl3, 500 MHz) δ: 7.49 (d, J＝8.5 Hz, 2H), 7.20 (d,
J＝8.5 Hz, 2H), 7.16 (s, 1H), 2.53 (s, 3H), 2.37 (s, 3H);
13C NMR (CDCl3, 125 MHz) δ: 161.0, 151.5, 138.3,
129.6, 129.4, 128.4, 125.4, 124.1, 121.1, 21.4, 14.2.
2-Methyl-5-(o-methoxyphenyl)oxazole (1e) Light
1
yellow solid, m.p. 57.8—60.2 ℃; H NMR (CDCl3,
500 MHz) δ: 7.73 (dd, J＝9.5, 1.5 Hz, 1H), 7.28 (s, 1H),
7.27—6.94 (m, 3H), 3.93 (s, 3H), 2.52 (s, 3H); 13C
NMR (CDCl3, 125 MHz) δ: 155.4, 128.7, 126.1, 125.6,
120.8, 117.4, 110.8, 55.4, 14.1. HRMS calcd for
C11H11NO2 [M＋Na]＋ 212.0682, found 212.0687.
Experimental
All reagents and solvents were obtained from com-
mercial sources and used without purification, unless
indicated otherwise. Nitro ketones were prepared ac-
cording to reported method.[8] NMR spectra were re-
corded on a Bruker DRX-500 NMR spectrometer (500
2-Methyl-5-(m-methoxyphenyl)oxazole
(1f)
Colorless liquid;[10] 1H NMR (CDCl3, 500 MHz) δ: 7.31
—7.18 (m, 2H), 7.13 (s, 1H), 6.85—6.83 (m, 1H), 3.84
(s, 3H), 2.53 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ:
1
MHz for H and 125 MHz for 13C) with CDCl3 as the
Chin. J. Chem. 2012, 29, 1—6
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3

Chen et al.
FULL PAPER
159.9, 130.0, 129.4, 122.2, 120.8, 116.5, 113.9, 112.3,
109.3, 55.3, 14.1.
125.9, 120.9, 120.2, 117.3, 111.0, 55.6.
2-Phenyl-5-(m-methoxyphenyl)oxazole
(2f)
1
2-Methyl-5-(o-chlorophenyl)oxazole
(1g)
White solid, m.p. 96—98 ℃ (lit.[6] 97—98 ℃); H
NMR (CDCl3, 500 MHz) δ: 8.09 (d, J＝7.0 Hz, 2H),
7.48—7.23 (m, 7H), 6.87 (d, J＝7.5 Hz, 1H), 3.85 (s,
3H); 13C NMR (CDCl3, 125 MHz) δ: 160.0, 151.2,
130.4, 130.1, 129.3, 128.9, 127.4, 126.3, 123.8, 116.8,
109.8, 55.4.
Colorless liquid; 1H NMR (CDCl3, 500 MHz) δ: 7.77 (d,
J＝7.5 Hz, 1H), 7.64 (s, 1H), 7.45—7.27 (m, 2H), 7.22
(t, J＝7.5 Hz, 1H), 2.54 (s, 3H); 13C NMR (CDCl3, 125
MHz) δ: 161.0, 147.7, 130.7, 130.4, 128.7, 127.5, 127.1,
127.0, 126.9, 14.1; HRMS calcd for C10H8ClNO [M＋
Na]＋ 216.0186, found 216.0190.
2-Phenyl-5-(p-methoxyphenyl)oxazole
(2g)
1
2-Methyl-5-(p-chlorophenyl)oxazole (1h) White
White solid, m.p. 85—88 ℃ (lit.[6] 88—89 ℃); H
NMR (CDCl3, 500 MHz) δ: 8.10 (dt, J＝7.0, 1.5 Hz,
2H), 7.64 (t, J＝8.5 Hz, 2H), 7.49—7.42 (m, 3H), 7.32
(s, 1H), 6.96 (d, J＝9.0 Hz, 2H), 3.84 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ: 160.6, 159.9, 151.4, 130.2, 128.8,
127.6, 126.2, 125.8, 122.0, 120.9, 114.4, 55.4.
1
solid, m.p. 73—74.5 ℃ (lit.[11] 74—75.5 ℃); H
NMR (CDCl3, 500 MHz) δ: 7.51 (d, J＝8.5 Hz, 2H),
13
7.35 (d, J＝8.5 Hz, 2H), 7.18 (s, 1H), 2.51 (s, 3H); C
NMR (CDCl3, 125 MHz) δ: 161.4, 150.2, 133.9, 129.2,
126.7, 125.2, 122.4, 14.2.
2-Methyl-5-(p-fluorophenyl)oxazole (1i)
Light
2-Phenyl-5-(o-chlorophenyl)oxazole (2h) White
1
1
yellow solid, m.p. 51.5—53.4 ℃; H NMR (CDCl3,
500 MHz) δ: 7.56—7.53 (m, 2H), 7.12 (s, 1H), 7.11—
7.06 (m, 2H), 2.49 (s, 3H); 13C NMR (CDCl3, 125 MHz)
δ: 163.5, 161.5, 161.1, 150.4, 125.9, 125.8, 124.6, 124.5,
121.5, 116.1, 115.9, 14.1; HRMS calcd for C10H8FNO
[M＋Na]＋ 177.0590, found 177.0591.
solid, m.p. 78.7—80.2 ℃ (lit.[6] 79—80 ℃); H NMR
(CDCl3, 500 MHz) δ: 8.11 (dt, J＝4.0, 1.5 Hz, 2H), 7.88
—7.34 (m, 8H); 13C NMR (CDCl3, 125 MHz) δ: 161.0,
147.8, 130.8, 130.6, 128.9, 128.9, 128.5, 128.1, 127.6,
127.2, 127.1, 126.8, 126.5.
2-Phenyl-5-(m-chlorophenyl)oxazole (2i) White
1
2-Methyl-5-(m-bromophenyl)oxazole
(1j)
solid, m.p. 118—119.5 ℃ (lit.[6] 119—120 ℃); H
Colorless liquid;[10] 1H NMR (CDCl3, 500 MHz) δ: 7.75
(s, 1H), 7.74—7.22 (m, 4H), 2.53 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ: 161.7, 149.8, 131.1, 130.5, 130.1,
126.9, 123.1, 122.8, 122.5, 14.2.
NMR (CDCl3, 500 MHz) δ: 8.13 (dt, J＝3.5, 3.0 Hz,
2H), 7.71 (s, 1H), 7.61—7.32 (m, 7H); 13C NMR
(CDCl3, 125 MHz) δ: 161.7, 150.3, 135.3, 131.4, 130.5,
129.3, 129.2, 128.9, 126.8, 126.3, 124.4, 123.3, 122.5.
2-Phenyl-5-(p-chlorophenyl)oxazole (2j) White
2,5-Diphenyloxazole (2a) White solid, m.p. 74.5
1
1
—76.2 ℃ (lit.[6] 75—77 ℃); H NMR (CDCl3, 500
solid, m.p. 106—108 ℃ (lit.[6] 110—111 ℃); H
MHz) δ: 8.12 (d, J＝8.0 Hz, 2H), 7.73 (d, J＝7.5 Hz,
2H), 7.50—7.33 (m, 7H); 13C NMR (CDCl3, 125 MHz)
δ: 161.3, 151.4, 130.5, 129.1, 128.9, 128.6, 128.1, 127.6,
126.4, 124.3, 123.6.
NMR (CDCl3, 500 MHz) δ: 8.10—8.08 (m, 2H), 7.63 (d,
J＝8.5 Hz, 2H), 7.48—7.39 (m, 6H); 13C NMR (CDCl3,
125 MHz) δ: 161.3, 150.4, 134.3, 130.6, 129.3, 128.9,
127.3, 126.6, 126.4, 125.5, 123.9.
2-Phenyl-5-(o-tolyl)oxazole (2b) White solid, m.p.
2-Phenyl-5-(p-fluorophenyl)oxazole (2k) White
1
1
72—73.8 ℃ (lit.[6] 72—74 ℃); H NMR (CDCl3, 500
solid, m.p. 100—102 ℃ (lit.[6] 101—103 ℃); H
MHz) δ: 8.11—7.23 (m, 10H), 2.51 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ: 160.8, 150.8, 134.9, 131.3, 130.4,
128.9, 128.4, 127.5, 127.3, 126.8, 126.4, 126.3, 126.2,
22.0.
NMR (CDCl3, 500 MHz) δ: 8.10—7.44 (m, 7H), 7.38 (s,
1H), 7.16—7.12 (m, 2H); 13C NMR (CDCl3, 125 MHz)
δ: 163.8, 161.6, 161.2, 150.5, 130.5, 128.9, 127.4, 126.4,
126.2, 126.2, 124.5, 124.4, 123.2, 116.3, 116.1.
2-Phenyl-5-(m-tolyl)oxazole (2c) White solid, m.p.
119—120.5 ℃ (lit.[6] 120—121 ℃); 1H NMR (CDCl3,
500 MHz) δ: 8.12 (dd, J＝9.5, 1.5 Hz, 2H), 7.54—7.15
(m, 8H), 2.42 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ:
161.2, 151.5, 138.8, 130.4, 129.4, 129.0, 128.9, 128.0,
127.6, 126.4, 124.9, 123.5, 121.5, 21.6.
2-Phenyl-5-(m-bromophenyl)oxazole (2l) White
1
solid, m.p. 115—116.9 ℃ (lit.[6] 116—117 ℃); H
NMR (CDCl3, 500 MHz) δ: 8.17—8.07 (m, 2H), 7.87 (s,
1H), 7.64 (d, J＝7.78 Hz, 1H), 7.51—7.44 (m, 5H),
7.31 (t, J＝7.89 Hz, 1H); 13C NMR (CDCl3, 125 MHz)
δ: 161.8, 149.8, 131.4, 130.7, 130.6, 130.0, 129.0, 127.1,
126.5, 124.5, 123.2, 122.8.
2-Phenyl-5-(p-tolyl)oxazole (2d) White solid, m.p.
1
83.8—85 ℃ (lit.[6] 85—86 ℃); H NMR (CDCl3, 500
2-Phenyl-5-(furan-2-yl)oxazole (2m) White solid,
1
MHz) δ: 8.11—8.10 (m, 2H), 7.60 (d, J＝8.0 Hz, 2H),
7.49—7.44 (m, 3H), 7.40 (s, 1H), 7.23 (d, J＝7.5 Hz,
2H), 2.38 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ: 160.8,
151.5, 138.5, 130.2, 129.6, 128.8, 127.6, 126.3, 125.3,
124.2, 122.8, 21.4.
m.p. 71.5—73.2 ℃; H NMR (CDCl3, 500 MHz) δ:
8.08—8.07 (m, 2H), 7.47—7.41 (m, 4H), 7.35 (s, 1H),
6.68 (d, J＝3.50 Hz, 1H), 6.50—6.48 (m, 1H); 13C
NMR (CDCl3, 125 MHz) δ: 160.8, 143.8, 143.7, 142.9,
133.0, 130.5, 129.6, 128.9, 128.4, 127.2, 126.4, 123.4,
111.7, 107.4; HRMS calcd for C13H9NO2 [M＋Na]＋
234.0525, found 234.0529.
2-Phenyl-5-(o-methoxyphenyl)oxazole
(2e)
White solid, m.p. 126—128 ℃ (lit.[6] 129—131 ℃);
1H NMR (CDCl3, 500 MHz) δ: 8.15—8.12 (m, 2H),
7.90 (dd, J＝7.5, 1.5 Hz, 1H), 7.65 (s, 1H), 7.53—6.96
(m, 6H), 3.98 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ:
160.1, 155.8, 147.9, 130.3, 129.2, 128.9, 127.7, 126.4,
Acknowledgement
We thank the National Natural Science Foundation
4
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—X

Iron-Promoted Practical One-Pot Synthesis of 2,5-Disubstituted Oxazoles
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of China (Nos. 20872087, 21002061, 20902057,
21142012), the State Key Laboratory of Applied Or-
ganic Chemistry, Lanzhou University, Leading Aca-
demic Discipline Project of Shanghai Municipal Educa-
tion Commission (No. J50101), and the Graduate Inno-
vation Fund of Shanghai University for financial sup-
port. We thank Dr. Hongmei Deng (Laboratory for Mi-
crostructures, Shanghai University) for NMR measure-
ments. We are indebted to Professor Ran Hong of SIOC
for enlightening discussions.
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