Direct transition-metal-free intramolecular C-O bond formation: Synthesis of benzoxazole derivatives

Article abstract of DOI:10.1039/c0ob00454e

A direct base-mediated intramolecular carbon-oxygen bond formation has been developed without a transition-metal catalyst. In the presence of 2.0 equiv of K₂CO₃ in DMSO at 140 °C, the intramolecular cyclization of o-haloanilides affords benzoxazoles in high yields. A mechanism via an initial formation of a benzyne intermediate followed by nucleophilic addition to form the C-O bond has been proposed.

Full text of DOI:10.1039/c0ob00454e

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PAPER
Direct transition-metal-free intramolecular C–O bond formation: synthesis of
benzoxazole derivatives†
Jinsong Peng,* Cuijuan Zong, Min Ye, Tonghui Chen, Dewei Gao, Yufeng Wang and Chunxia Chen*
Received 19th July 2010, Accepted 3rd November 2010
DOI: 10.1039/c0ob00454e
A direct base-mediated intramolecular carbon-oxygen bond formation has been developed without a
transition-metal catalyst. In the presence of 2.0 equiv of K2CO3 in DMSO at 140 ◦C, the intramolecular
cyclization of o-haloanilides affords benzoxazoles in high yields. A mechanism via an initial formation
of a benzyne intermediate followed by nucleophilic addition to form the C–O bond has been proposed.
or n-BuLi in hexane), inconvenience in handling and workup,
Introduction
moderate yields, or a relatively narrow scope of substrates.12
Benzoxazoles are frequently found in a diverse array of com-
Herein, we report metal-free weak base-mediated intramolecular
carbon-oxygen bond formation reaction of ortho-haloanilides to
afford synthetically valuable benzoxazole derivatives under mild
pounds, including biologically and therapeutically active agents,1
a wide range of natural products,2 and functional materials.3
Therefore, the construction of these heterocycles has received
conditions.
much attention. The conventional method for the synthesis
of 2-substituted benzoxazoles is via condensation of ortho-
aminophenols and aldehydes or carboxylic acid derivatives under
oxidative conditions.4 Although these transformations are widely
Results and discussion
N-(2-Iodo-4-methylphenyl)benzamide (1a) derived from benzoy-
lation of 2-iodo-4-methylbenzenamine, was selected as a model
substrate for the metal-free intramolecular O-arylation reaction.
To optimize the reaction conditions, we examined different
bases, solvents and temperature. Some results from that study
are summarized in Table 1. At first, the intramolecular C–
O coupling reaction of 1a was examined by using potassium
carbonate (K2CO3, 2.0 equiv) as the base in DMSO at 100 ◦C
for 48 h. To our delight, the desired product benzoxazole 2a
was smoothly obtained in 94% yield (entry 1, Table 1). To
explore the possibility of metal impurities in the commercially
available potassium carbonate that would potentially induce this
transformation,14 we analyzed K2CO3 using inductively coupled
plasma atomic emission spectroscopy (ICP-AES). 1–3 ppm of
Fe, Co and Mg were detected in the base. However, the reaction
efficiency was reduced when 10 mol% CoBr2 or FeCl3 was added
to the reaction mixture. On the other hand, different sources of
K2CO3 and purified K2CO3 were used with new glassware, almost
the same results were obtained. Based on the above experiments,
we concluded that the presence of trace metal impurities were
not involved in this carbon-oxygen bond formation reaction. We
then carried out a set of experiments to reveal the crucial role
of the reaction temperature (entries 1–3, Table 1). At a higher
temperature, the reaction time was significantly shortened (8 h
vs. 48 h, entries 3 and 1, Table 1) giving comparable yield to the
reaction at 100 ◦C. A brief survey of reaction medium showed that
use of polar solvent such as DMF, water, or a co-solvent of DMSO
and water gave no products (entries 4, 5 and 7, Table 1). The
reaction carried out in the nonpolar solvent toluene didn’t proceed
used in the preparation of benzoxazoles, there remain many
drawbacks to overcome such as the use of highly toxic reagents,
strong acids and, in some cases, harsh reaction conditions.4,5
To develop more milder, novel and sustainable processes for
the assembly of the benzoxazole ring system, much effort has
been devoted to the survey of the transition metal-catalyzed
intramolecular O-arylation of ortho-haloanilides. Among the
different catalysts, inexpensive and nontoxic copper6 and iron7
provide the efficient and straightforward means for this carbon-
heteroatom cross-coupling reaction.
The intramolecular addition reaction of a benzyne by side-
chain nucleophiles to generate benzo-fused heterocycles is another
useful synthetic strategy introduced independently by Huisgen8
and Bunnett9 in the 1950s. This methodology has potential
advantages over the transition metal-catalyzed cross-coupling
reactions, avoiding the generation of the waste and hazards
associated with metal.10 Despite this protocol being successfully
employed in the synthesis of various heterocycles by using
aryne-tethered nitrogen,11 oxygen,11b,12 or sulfur nucleophiles13 in
common laboratory practice, it is recognized that this procedure
is especially problematic for large-scale operations with some
disadvantages: rather low reaction temperatures, the use of
excess strong base (generally potassium amide in liquid ammonia
Department of Chemistry and Chemical Engineering, College of Science,
Northeast Forestry University, Harbin 150040, P. R. China. E-mail:
jspeng1998@163.com, ccx1759@163.com
† Electronic supplementary information (ESI) available: NMR data. See
DOI: 10.1039/c0ob00454e
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Table 2 Direct base-mediated synthesis of benzoxazole derivativesa
Table 1 Optimization of base-mediated intramolecular C–O bond for-
mation of amide 1aa
temp (◦C) time (h) yieldb (%)
entry
X
benzoxazole
yield (%)b
entry base
solvent
1
2
I
92 (86)c
61
1
2
3
4
5
K2CO3
DMSO
DMSO
DMSO
DMF
H2O
Toluene
100
120
140
120
120
120
48
24
8
94
88
92
0
0
0
Br
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
Et3N
48
48
48
48
36
36
36
36
3
I
97
6
7c
8
DMSO/H2O 120
0
DMSO
DMSO
DMSO
140
140
140
140
40
82
0
4
5
I
Br
96
58
9
10
11
K3PO4·3H2O DMSO
74
6
7
I
I
92
86
a Conditions: 1.0 equiv of o-haloanilide, 2.0 equiv of base, solvent (0.2 M).
b Yield of isolated product after chromatography. c A mixture solvent of
DMSO and H2O (v/v = 1) was used.
(entry 6, Table 1). DMSO as the stronger polar solvent proved to be
the most effective for this coupling (entries 1–3, Table 1). Finally,
other bases such as Na2CO3, Cs2CO3, Et3N and K3PO4·3H2O were
examined, K2CO3 provided better results (entries 8–11, Table 1).
Noteworthy was the fact that this reaction was insensitive to air
and moisture, hence, there was no need for an inert atmosphere.
With the optimized reaction conditions in hand, we prepared a
large range of benzoxazole derivatives to explore the generality
of the present reaction (Table 2). As shown in Table 2, this
method is efficient for the synthesis of a number of benzoxazoles
2 in good to excellent yields. The nature of the substituent R1
directly linked to the carbonyl moiety was very important to
the reaction outcome. Although o-iodoanilide substrates bearing
various different aromatic substituents can smoothly be converted
to the desired products in moderate to excellent yields (entries
1, 3, 4, 6–8, 10–14 and 16–18, Table 2), the electronic nature of
the aromatic motifs had a great effect on the yields. In general,
a variety of electron neutral, rich aromatic and heteroaromatic
substrates were efficiently transformed into the corresponding
benzoxazoles in excellent yields (entries 1, 3, 4, 6–8, 17 and 18,
Table 2). The presence of relatively electron withdrawing o- and
p-chlorophenyl substituents did not have much effect and led to
similar results (entries 10 and 11, Table 2), whereas, for substrates
with stronger electron-withdrawing functional groups on aromatic
rings (with the exception of -CN, entry 14), the yield decreased
significantly (entries 12, 13 and 16, Table 2). Haloanilide with
an (E)-styryl substituent R1 gave the corresponding product in
78% yield (entry 19, Table 2). In contrast to aromatic and styryl
substituents, halobenzamides with vinyl or aliphatic functional
groups R1 provided a trace amount of the products (entries 20 and
21, Table 2), the most of the starting materials were unchanged and
recovered from the reaction mixture. Interestingly, steric hindrance
seemed not to hamper the reaction, the benzoxazoles can be
obtained in excellent yields (entries 4, 7 and 11, Table 2).
8
9
I
Br
96
93
10
11
I
I
83
94
12
13
I
I
43
41
14
15
I
Br
96
66
16
17
18
19
I
I
I
I
29
84
82
78
Regarding the aryl halide moiety, it is obvious that o-
bromoanilides afforded inferior results to their iodo analogues
(entries 2, 5, 9, 15, 22 and 24–26, Table 2), despite the fact that
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Table 2 (Contd.)
entry
20d
X
I
benzoxazole
yield (%)b
trace
21d
I
<10
Scheme 1 Proposed mechanism for the base-mediated intramolecular
O-arylation of o-haloanilides.
22
23
Br
Cl
55 (46)e
18
addition11–13,18 of amide to 3 afforded carbanion18 intermediate
4, followed by subsequent protonation by DMSO to give the final
products 2. To prove the benzyne-type mechanism,12b the substrate
m-iodoanilide 5 was used to conduct this transformation under the
optimized reaction condition, benzoxazole 2r was obtained in 71%
yield (eqn (1)).
24
25
26
Br
Br
Br
93
64
42
(1)
27
I
I
92
0
Conclusions
28f
In summary, we have established an efficient and practical
method for direct base-promoted intramolecular O-arylation of o-
haloanilides to afford benzoxazoles in good to excellent yields. Par-
ticular valuably, without the addition of any exogenous transition
metal catalysts, this easy-to-handle and environmentally benign
chemical process is suitable for large-scale synthesis, providing a
valuable synthetic protocol for industrial applications.
a Conditions: 1.0 equiv of o-haloanilide (0.3 mmol), 2.0 equiv of K2CO3,
DMSO (0.2 M), 140 ◦C for 8–48 h. b Yield of isolated product after chro-
matography. c 2.0 mmol of o-haloanilide was used. d Most of the starting
materials were unchanged and recovered from the reaction mixture. e The
value in the parenthesis is an isolated yield of the corresponding product
with t-BuOK as a base. f Most of the starting materials were unchanged
and recovered from the reaction mixture.
Experimental
in some cases the yield was comparable (entries 8 and 9, 6
and 24, Table 2). o-Chloroanilide showed the poorest tendency
to undergo this transformation, giving only 18% isolated yield
(entry 23, Table 2). In addition, R2 substituents on the haloarene
were essential to the reaction. For instance, aromatic amides
bearing H, Me or Cl substituents furnished the corresponding
products in good yields (entries 1, 22 and 27, Table 2), whereas for
the substrate with strong electron-withdrawing functional groups
(-NO2), no product was obtained (entry 28, Table 2).
A proposed reaction mechanism for base-mediated intramolec-
ular C–O coupling of o-haloanilides to benzoxazole derivatives
is shown in Scheme 1. In nucleophilic aromatic substitution,
the formation of the addition intermediate is usually the rate-
determining step, so the ease of C–X bond breaking does not
affect the rate and the order of reactivity is often Cl > Br >
I.15 Obviously an aromatic nucleophilic substitution process is
inconsistent with our experimental results (entries 1, 22 and 23,
Table 2). This reaction presumably occurred by an initial formation
of a benzyne intermediate 3 in the presence of a base,11c,16 which
was trapped by furan through [2+4] cycloaddition reaction17
in an additional experiment. An intramolecular nucleophilic
Chemicals and solvents were all purchased from commercial
suppliers and used without further purification. All reactions were
carried out under an air atmosphere in dried glassware. 1H NMR
spectra were recorded on a Bruker-300 or 400 MHz spectrometer,
13C NMR spectra were recorded at 75 or 100 MHz. Chemical
shifts (d) are given in parts per million (ppm) downfield relative to
CDCl3. Coupling constants are given in hertz (Hz). Unless other-
wise stated deuterochloroform was used as solvent. In assignment
of the 1H NMR spectra, multiplicities and abbreviations used are
as follows: Ar = aromatic, Ph = phenyl, d = doublet, dd = doublet
of doublets, m = multiplet, q = quartet, s = singlet, t = triplet. High-
resolution mass spectra were recorded on a Bruker BIO TOF Q
mass spectrometer.
General procedures for direct metal-free intramolecular C–O bond
formation of o-haloanilides (Tables 1 and 2)
A two-necked dried round-bottomed flask was charged with o-
haloanilide substrates (0.3 mmol, 1.0 equiv) and K2CO3 (82.8 mg,
0.6 mmol, 2.0 equiv). The flask was then equipped with a
thermometer and water-cooled reflux condenser, and 1.5 mL
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DMSO (5 mL mmol-1 o-haloanilide substrate) was added via
syringe. The mixture was then heated to 140 ◦C with stirring under
an air atmosphere until the starting material had been consumed
as judged by TLC. The reaction mixture was cooled to room
temperature, quenched with water (5 mL), and diluted with ethyl
acetate (5 mL). The layers were separated and the aqueous layer
was extracted with (2 ¥ 5 mL) ethyl acetate. The combined organic
extracts were dried over anhydrous sodium sulfate, filtered, and
concentrated in vacuo. The crude product was then purified by
flash chromatography on silica gel (H), eluting with 2–5% ethyl
acetate/petroleum ether.
56.1, 21.8. HRMS-ESI (m/z): [M + Na]+ calcd for C15H13NNaO2
262.0844; found 262.0851.
2-(4-Methoxyphenyl)-6-methylbenzo[d]oxazole (2f)19. Mp 90–
91 ◦C; IR (KBr): n (cm-1) 3060, 3022, 2990, 2971, 2913, 2834, 1618,
1604, 1580, 1557, 1503, 1434, 1420, 1335, 1321, 1305, 1287, 1258,
1241, 1185, 1176, 1120, 1059, 1024; 1H NMR (CDCl3, 300 MHz)
d 8.29 (d, 2H, J = 8.0 Hz), 7.68 (d, 1H, J = 8.0 Hz), 7.39 (t, 1H,
J = 0.6 Hz), 7.21 (m, 1H), 7.12 (d, 2H, J = 8.0 Hz), 3.98 (s, 3H),
2.51 (s, 3H). 13C NMR (CDCl3, 75 MHz) d 163.2, 162.3, 150.7,
142.1, 135.2, 129.4, 127.6, 119.8, 119.6, 116.3, 110.4, 55.5, 21.6.
HRMS-ESI (m/z): [M + Na]+ calcd for C15H13NNaO2 262.0844;
found 262.0847.
◦
6-Methyl-2-phenylbenzo[d]oxazole (2a)6c,6e
.
Mp 93–94 C; IR
(KBr): n (cm-1) 3053, 2955, 2915, 2846, 1614, 1552, 1479, 1446,
1335, 1246, 1175, 1125, 1096, 1052, 1020; 1H NMR (CDCl3, 300
MHz) d 8.31–8.24 (m, 2H), 7.68 (d, 1H, J = 8.2 Hz), 7.58–7.51
(m, 3H), 7.41 (t, 1H, J = 0.6 Hz), 7.20 (ddd, 1H, J = 8.1, 1.5,
0.6 Hz), 2.53 (s, 3H). 13C NMR (CDCl3, 75 MHz) d 162.6, 151.1,
140.0, 135.6, 131.3, 128.9, 127.5, 127.4, 125.8, 119.4, 110.8, 21.8.
HRMS-ESI (m/z): [M + Na]+ calcd for C14H11NNaO 232.0738;
found 232.0736.
2-(4-Chlorophenyl)-6-methylbenzo[d]oxazole (2g)6e. Mp 151–
◦
152 C; IR (KBr): n (cm-1) 3076, 3021, 2920, 1612, 1590, 1547,
1480, 1456, 1400, 1329, 1279, 1244, 1159, 1125, 1108, 1087, 1051,
1
1007; H NMR (CDCl3, 300 MHz) d 8.22 (d, 2H, J = 7.8 Hz),
7.71 (d, 1H, J = 8.0 Hz), 7.52 (d, 2H, J = 7.8 Hz), 7.41 (t, 1H,
J = 0.6 Hz), 7.19 (m, 1H), 2.52 (s, 3H). 13C NMR (CDCl3, 75
MHz) d 162.1, 150.8, 142.0, 137.8, 135.7, 129.3, 128.9, 127.7,
124.8, 119.8, 116.2, 21.8. HRMS-ESI (m/z): [M + Na]+ calcd for
C14H10ClNNaO 266.0349; found 266.0353.
6-Methyl-2-m-tolylbenzo[d]oxazole (2b). Mp 96–97 ◦C; IR
(KBr): n (cm-1) 3050, 3018, 2916, 2849, 1614, 1552, 1479, 1446,
2◦-(2-Chlorophenyl)-6-methylbenzo[d]oxazole (2h)6e. Mp 78–
79 C; IR (KBr): n (cm-1) 3049, 2916, 2853, 1617, 1605, 1565,
1531, 1483, 1456, 1432, 1417, 1331, 1307, 1272, 1253, 1159, 1124,
1
1425, 1335, 1288, 1272, 1245, 1170, 1124, 1051, 1020; H NMR
(CDCl3, 300 MHz) d 7.71 (s, 1H), 7.63 (m, 2H), 7.38 (t, 1H, J = 0.6
Hz), 7.32–7.26 (m, 1H), 7.19 (d, 1H, J = 7.5 Hz), 7.14 (d, 1H, J =
8.0 Hz), 2.51 (s, 3H), 2.46 (s, 3H). 13C NMR (CDCl3, 75 MHz) d
162.7, 150.3, 139.8, 138.7, 135.5, 130.7, 129.3, 129.1, 127.1, 126.2,
124.4, 119.1, 111.2, 22.1, 21.9. HRMS-ESI (m/z): [M + Na]+ calcd
for C15H13NNaO 246.0895; found 246.0891.
1
1084, 1041, 1022; H NMR (CDCl3, 300 MHz) d 8.14–8.11 (m,
1H), 7.71 (d, 1H, J = 8.0 Hz), 7.57–7.53 (m, 1H), 7.46–7.36 (m,
3H), 7.21–7.17 (m, 1H), 2.51 (s, 3H). 13C NMR (CDCl3, 75 MHz) d
160.6, 151.1, 139.8, 136.3, 133.6, 131.9, 131.6, 127.7, 127.1, 126.6,
126.1, 120.1, 111.1, 22.1. HRMS-ESI (m/z): [M + Na]+ calcd for
C14H10ClNNaO 266.0349; found 266.0351.
6-Methyl-2-o-tolylbenzo[d]oxazole (2c). Mp 94–95 ◦C; IR
(KBr): n (cm-1) 3014, 2955, 2919, 2853, 1609, 1545, 1485, 1453,
1378, 1328, 1269, 1166, 1120, 1027; 1H NMR (CDCl3, 400 MHz)
d 8.13–8.08 (m, 1H), 7.62 (d, 1H, J = 8.0 Hz), 7.54–7.50 (m,
1H), 7.38–7.26 (m, 3H), 7.15 (d, 1H, J = 8.0 Hz), 2.75 (s, 3H),
2.50 (s, 3H). 13C NMR (CDCl3, 100 MHz) d 163.0, 149.3, 141.8,
138.9, 134.4, 131.8, 130.9, 129.9, 127.3, 126.6, 126.1, 119.9, 109.8,
22.2, 21.6. HRMS-ESI (m/z): [M + Na]+ calcd for C15H13NNaO
246.0895; found 246.0897.
2◦-(2,4-Dichlorophenyl)-6-methylbenzo[d]oxazole (2i). Mp 97–
98 C; IR (KBr): n (cm-1) 3064, 2916, 2849, 1604, 1585, 1562,
1
1485, 1459, 1384, 1329, 1252, 1126, 1104, 1089, 1031; H NMR
(CDCl3, 300 MHz) d 8.15–8.12 (d, 1H, J = 8.5 Hz), 7.71–7.62 (m,
3H), 7.41 (t, 1H, J = 0.6 Hz), 7.16 (m, 1H), 2.51 (s, 3H). 13C NMR
(CDCl3, 75 MHz) d 161.7, 152.1, 140.1, 136.3, 135.7, 134.3, 133.4,
132.1, 131.7, 128.3, 127.3, 121.1, 110.8, 22.3. HRMS-ESI (m/z):
[M + Na]+ calcd for C14H9Cl2NNaO 299.9959; found 299.9963.
6-Methyl-2-p-tolylbenzo[d]oxazole (2d). Mp 103–104 ◦C; IR
(KBr): n (cm-1) 3052, 3022, 2916, 2853, 1619, 1556, 1499, 1480,
1409, 1334, 1287, 1249, 1179, 1115, 1052, 1015; 1H NMR (CDCl3,
400 MHz) d 8.13–8.11 (m, 2H), 7.62 (d, 1H, J = 8.0 Hz), 7.37 (s,
1H), 7.33–7.31 (m, 2H), 7.15 (d, 1H, J = 8.0 Hz), 2.50 (s, 3H),
2.44 (s, 3H). 13C NMR (CDCl3, 100 MHz) d 162.7, 150.9, 141.7,
139.9, 135.2, 129.5, 127.4, 125.6, 124.6, 119.6, 110.6, 21.7, 21.5.
HRMS-ESI (m/z): [M + Na]+ calcd for C15H13NNaO 246.0895;
found 246.0893.
6-Methyl-2-(3-nitrophenyl)benzo[d]oxazole (2j)20. Mp 140–
◦
142 C; IR (KBr): n (cm-1) 3095, 3037, 2915, 2853, 1607, 1551,
1523, 1473, 1349, 1240, 1132, 1102, 1050; 1H NMR (CDCl3, 300
MHz) d 8.37 (s, 1H), 8.16 (m, 1H), 7.76–7.63 (m, 3H), 7.39 (t,
1H, J = 0.6 Hz), 7.16 (m, 1H), 2.50 (s, 3H). 13C NMR (CDCl3,
75 MHz) d 161.7, 152.1, 148.9, 140.1, 134.2, 133.4, 130.5, 128.3,
127.1, 122.1, 121.7, 121.1, 110.8, 22.3. HRMS-ESI (m/z): [M +
Na]+ calcd for C14H10N2NaO3 277.0589; found 277.0592.
4-(6-Methylbenzo[d]oxazol-2-yl)benzonitrile (2k)6b. Mp 203–
◦
2◦-(2-Methoxyphenyl)-6-methylbenzo[d]oxazole (2e)6e. Mp 74–
75 C; IR (KBr): n (cm-1) 3018, 2963, 2936, 2919, 2837, 1605,
1596, 1579, 1532, 1479, 1447, 1432, 1421, 1333, 1300, 1268, 1253,
1186, 1157, 1119, 1063, 1033, 1021; 1H NMR (CDCl3, 300 MHz)
d 8.11 (dd, 1H, J = 8.0, 2.0 Hz), 7.68 (d, 1H, J = 8.0 Hz), 7.49–7.43
(m, 1H), 7.37 (t, 1H, J = 0.6 Hz), 7.16–7.04 (m, 3H), 3.98 (s, 3H),
2.48 (s, 3H). 13C NMR (CDCl3, 75 MHz) d 160.8, 158.3, 150.5,
139.9, 135.2, 132.4, 131.0, 125.4, 120.6, 119.5, 116.3, 111.9, 110.5,
204 C; IR (KBr): n (cm-1) 3022, 2917, 2223, 1617, 1598, 1544,
1483, 1407, 1333, 1283, 1246, 1055, 1011; 1H NMR (CDCl3, 400
MHz) d 8.34 (d, 2H, J = 8.0 Hz), 7.81 (d, 2H, J = 8.0 Hz), 7.68
(d, 1H, J = 8.0 Hz), 7.42 (s, 1H), 7.23 (d, 1H, J = 8.0 Hz), 2.55 (s,
3H). 13C NMR (CDCl3, 100 MHz) d 160.4, 151.2, 139.7, 136.8,
132.6, 131.3, 127.7, 126.4, 119.8, 118.2, 114.4, 110.9, 21.9. HRMS-
ESI (m/z): [M + Na]+ calcd for C15H10N2NaO 257.0691; found
257.0695.
1228 | Org. Biomol. Chem., 2011, 9, 1225–1230
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1-(4-(Benzo[d]oxazol-2-yl)phenyl)ethanone (2l). Mp 112–
(m, 1H), 7.65–7.57 (m, 1H), 7.52 (d, 2H, J = 7.8 Hz), 7.44–7.36
(m, 2H). 13C NMR (CDCl3, 75 MHz) d 162.1, 150.8, 142.0, 137.8,
129.3, 128.9, 125.7, 125.4, 124.8, 120.1, 110.6. HRMS-ESI (m/z):
[M + Na]+ calcd for C13H8ClNNaO 252.0192; found 252.0195.
◦
114 C; IR (KBr): n (cm-1) 3054, 2954, 2918, 2849, 1721, 1611,
1560, 1548, 1453, 1411, 1376, 1344, 1277, 1245, 1109, 1059, 1012;
1H NMR (CDCl3, 400 MHz) d 8.34 (d, 2H, J = 8.0 Hz), 8.19 (d,
2H, J = 8.0 Hz), 7.83–7.79 (m, 1H), 7.64–7.60 (m, 1H), 7.54–7.41
(m, 2H), 3.97 (s, 3H). 13C NMR (CDCl3, 100 MHz) d 166.3,
161.9, 150.8, 142.0, 132.5, 131.0, 130.1, 127.5, 125.7, 124.9, 120.4,
110.8, 29.7. HRMS-ESI (m/z): [M + Na]+ calcd for C15H11NNaO2
260.0687; found 260.0691.
2-(2-Methoxyphenyl)benzo[d]oxazole (2u)6e. Mp 53–55 ◦C; IR
(KBr): n (cm-1) 3045, 2978, 2841, 1644, 1616, 1603, 1580, 1503,
1
1452, 1420, 1344, 1319, 1303, 1254, 1242, 1187, 1059, 1019; H
NMR (CDCl3, 300 MHz) d 8.18 (dd, 1H, J = 7.7, 1.8 Hz), 7.90–
7.83 (m, 1H), 7.66–7.60 (m, 1H), 7.58–7.52 (m, 1H), 7.42–7.35 (m,
2H), 7.17–7.11 (m, 2H), 4.06 (s, 3H). 13C NMR (CDCl3, 75 MHz) d
161.6, 158.5, 150.4, 142.2, 132.8, 131.3, 124.9, 124.3, 120.7, 120.3,
116.2, 112.1, 110.5, 56.2. HRMS-ESI (m/z): [M + Na]+ calcd for
C14H11NNaO2 248.0687; found 248.0689.
6◦-Methyl-2-(thiophen-2-yl)benzo[d]oxazole (2m)6c,6e
. Mp 74–
76 C; IR (KBr): n (cm-1) 3072, 3057, 2916, 2857, 1613, 1589,
1507, 1490, 1476, 1415, 1368, 1329, 1270, 1248, 1227, 1206, 1124,
1
1090, 1044, 1004; H NMR (CDCl3, 300 MHz) d 7.86 (dd, 1H,
J = 4.0, 1.0 Hz), 7.58 (d, 1H, J = 8.0 Hz), 7.51 (dd, 1H, J = 5.0,
1.0 Hz), 7.33–7.31 (m, 1H), 7.17–7.12 (m, 2H), 2.47 (s, 3H). 13C
NMR (CDCl3, 75 MHz) d 158.5, 150.7, 139.7, 135.5, 129.8, 129.7,
129.5, 128.1, 125.9, 119.1, 110.5, 21.7. HRMS-ESI (m/z): [M +
Na]+ calcd for C12H9NNaOS 238.0303; found 238.0308.
6-Chloro-2-phenylbenzo[d]oxazole (2v)6b. Mp 107–108 ◦C; IR
(KBr): n (cm-1) 3089, 3060, 3006, 1616, 1552, 1460, 1448, 1425,
1331, 1284, 1262, 1229, 1048, 1021; 1H NMR (CDCl3, 300 MHz)
d 8.23–8.16 (m, 2H), 7.64 (d, 1H, J = 8.5 Hz), 7.55 (d, 1H, J = 1.9
Hz), 7.57–7.45 (m, 3H), 7.30 (dd, 1H, J = 8.5, 1.9 Hz). 13C NMR
(CDCl3, 75 MHz) d 163.7, 151.0, 140.9, 131.8, 130.7, 129.0, 127.7,
126.8, 125.3, 120.5, 111.2. HRMS-ESI (m/z): [M + Na]+ calcd for
C13H8ClNNaO 252.0192; found 252.0197.
◦
2-(Furan-2-yl)-6-methylbenzo[d]oxazole (2n)6e. Mp 52–53 C;
IR (KBr): n (cm-1) 3060, 2919, 2849, 1681, 1626, 1592, 1524, 1484,
1457, 1309, 1249, 1156, 1087, 1060, 1005; 1H NMR (CDCl3, 300
MHz) d 7.64 (dd, 1H, J = 2.0, 0.5 Hz), 7.61 (d, 1H, J = 8.0 Hz),
7.34–7.33 (m, 1H), 7.22 (dd, 1H, J = 3.5, 0.5 Hz), 7.17–7.13 (m,
1H), 6.59 (dd, 1H, J = 3.5, 2.0 Hz), 2.48 (s, 3H). 13C NMR (CDCl3,
75 MHz) d 154.8, 150.4, 145.4, 142.7, 139.4, 135.7, 126.0, 119.4,
113.7, 112.1, 110.6, 21.7. HRMS-ESI (m/z): [M + Na]+ calcd for
C12H9NNaO2 222.0531; found 222.0538.
Acknowledgements
We are grateful to the funds supported by the Fundamen-
tal Research Funds for the Central Universities (DL09BB34,
DL10BB07).
6-Methyl-2-styrylbenzo[d]oxazole (2o)6e. Mp 70–71 ◦C; IR
(KBr): n (cm-1) 3056, 3037, 3018, 2916, 2849, 2360, 1643, 1575,
Notes and references
1
1531, 1482, 1445, 1337, 1242, 1189, 1156, 1117, 1071; H NMR
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(CDCl3, 300 MHz) d 7.73 (d, 1H, J = 16.5 Hz), 7.59–7.56 (m, 3H),
7.43–7.31 (m, 4H), 7.12 (dd, 1H, J = 8.0, 1.0 Hz), 7.04 (d, 1H, J =
16.5 Hz), 2.48 (s, 3H). 13C NMR (CDCl3, 75 MHz) d 150.7, 140.4,
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2-Phenylbenzo[d]oxazole (2r)6c,12b
.
Mp 101–102 ◦C; IR (KBr):
n (cm-1)3057, 2952, 2917, 2845, 1615, 1551, 1470, 1445, 1342, 1316,
1288, 1240, 1196, 1144, 1052, 1021, 1002; 1H NMR (CDCl3, 300
MHz) d 8.32 (dd, 2H, J = 5.6, 2.1 Hz), 7.86–7.79 (m, 1H), 7.67–7.53
(m, 4H), 7.44–7.36 (m, 2H). 13C NMR (CDCl3, 75 MHz) d 163.1,
150.8, 142.2, 131.4, 128.9, 127.6, 127.2, 125.1, 124.6, 120.1, 110.6.
HRMS-ESI (m/z): [M + Na]+ calcd for C13H9NNaO 218.0582;
found 218.0585.
2-p-Tolylbenzo[d]oxazole (2s)21. Mp 116–117 ◦C; IR (KBr): n
(cm-1) 3052, 3021, 2914, 2849, 1620, 1555, 1500, 1470, 1449, 1408,
1
1344, 1311, 1286, 1241, 1197, 1176, 1139, 1115, 1053, 1016; H
NMR (CDCl3, 300 MHz) d 8.49 (d, 2H, J = 8.2 Hz), 7.76–7.73
(m, 1H), 7.55–7.52 (m, 1H), 7.33–7.28 (m, 4H), 2.40 (s, 3H). 13C
NMR (CDCl3, 75 MHz) d 163.7, 151.1, 142.6, 142.4, 130.0, 128.0,
125.3, 125.2, 124.9, 120.3, 110.8, 22.0. HRMS-ESI (m/z): [M +
Na]+ calcd for C14H11NNaO 232.0738; found 232.0742.
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1
1342, 1293, 1273, 1243, 1196, 1174, 1106, 1090, 1055, 1011; H
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1230 | Org. Biomol. Chem., 2011, 9, 1225–1230
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