Metal-free one-pot domino reaction: Chemoselective synthesis of polyarylated oxazoles

Article abstract of DOI:10.1016/j.tet.2015.03.119

A convenient method has been established for the chemoselective synthesis of polyarylated oxazoles from aromatic aldehydes and 2-cyano heteroarenes. The protocol presents a novel one-pot methodology for the synthesis of oxazole derivatives without any metal catalysts or extra oxidants. Photophysical test showed that the polyarylated oxazoles may serve as potential fluorescent materials with blue light-emitting properties.

Full text of DOI:10.1016/j.tet.2015.03.119

Accepted Manuscript
Metal-free One-pot Domino Reaction: Chemoselective Synthesis of Polyarylated
Oxazoles
Hua Meng, You Zi, Xiao-Ping Xu, Shun-Jun Ji
PII:
S0040-4020(15)00459-7
10.1016/j.tet.2015.03.119
TET 26601
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 7 February 2015
Revised Date: 19 March 2015
Accepted Date: 30 March 2015
Please cite this article as: Meng H, Zi Y, Xu X-P, Ji S-J, Metal-free One-pot Domino Reaction:
Chemoselective Synthesis of Polyarylated Oxazoles, Tetrahedron (2015), doi: 10.1016/j.tet.2015.03.119.
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Metal-free One-pot Domino Reaction:
Chemoselective Synthesis of
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Polyarylated Oxazoles
Hua Meng, You Zi, Xiao-Ping Xu,* and Shun-Jun Ji*
College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of
Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, P.R.China

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Tetrahedron
journal homepage: www.elsevier.com
Metal-free One-pot Domino Reaction: Chemoselective Synthesis of Polyarylated
Oxazoles
Hua Meng, You Zi, Xiao-Ping Xu,* and Shun-Jun Ji*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation
Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People’s Republic of China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A convenient method has been established for the chemoselective synthesis of
polyarylated oxazoles from aromatic aldehydes and 2-cyano heteroarenes. The
protocol presents a novel one-pot methodology for the synthesis of oxazole
derivatives without any metal catalysts or extra oxidants. Photophysical test showed
that the polyarylated oxazoles may serve as potential fluorescent materials with blue
light-emitting properties.
Available online
Keywords:
Metal-free
©
2015 Elsevier Ltd. All rights reserved.
Chemoselective
Triarylated oxazoles
1
. Introduction
© 2015 Elsevier Ltd. All rights reserved.
Oxazoles are one of the most important heterocyclic
compounds, which ubiquitously exist in natural and non-natural
The extensive application of oxazoles and its derivatives have
driven an ever increasing number of scientists into this field.
There are several ways to construct oxazole framework,
1
products. It has been proved that the derivatives of oxazole
2
possessed excellent biological activities. For example,
6
Leucamide A (Figure 1) and its analogues, containing several
including direct cross-coupling arylation, cyclization of acyclic
3
7
8
oxazole moieties, can function as anticancer reagents. Besides,
precursors and oxidation of oxazolines . Cyclization is much
more effective due to the diversity of substrates. Recently,
various methods have been exploited to synthesize polyarylated
4
oxazole derivatives also have a place in functional materials,
such as 4,5-bis(4-methoxyphenyl)-2-(naphthalen-1-yl)oxazole
9
(NAPOXA) (Figure 1), which plays a role as blue light-emitting
oxazoles. For instance, Saito and co-works developed a metal-
species in organic light-emitting device (OLED) showing
free procedure for [2 + 2 + 1] annulations of alkynes, nitriles and
4a
10
excellent properties. Furthermore, functional oxazoles are
PhIO (Figure 2, eq 1). Jiang’s group reported a novel one-pot
4d
useful metal ligand in coordination chemistry. They could
function as building blocks in constructing complex functional
process involving a TBHP/I -mediated oxidative cyclization for
2
11a
the synthesis of oxazoles (Figure 2, eq 2). Shortly afterwards,
they also developed an efficient copper catalyzed oxidative
transformation of nitriles, internal alkynes and water to oxazoles
5
molecules, which means a lot to methodology.
11b
O
(
Figure 2, eq 3). Another copper mediated domino process by
O
N
Wang’s group leading to polyarylated oxazoles was also
attractive, but a minor limitation was that the protocol cannot be
applied in the construction of 2-pyridyl substituted oxazoless
O
H
N
N
O
N
HN
S
O
12
O
(Figure 2, eq 4). It is obvious that extra oxidants or heavy
NH
metals were necessary to promote the reactions in the above
mentioned reactions. The reason why it is worthy to synthesize
oxazoles with an effective means is that tedious synthetic
procedures and purification are obstacles of the application of
oxazoles.
Leucamide A
Figure 1. Representative structures of the derivatives of oxazoles.
____________
[
a] Corresding auother. Tel: +86-512-65880307; Fax: (+) 86-512-65880307;
E-mail: xuxp@suda.edu.cn (X.-P. Xu); shunjun@suda.edu.cn (S.-J. Ji.)
1

a
Our keen interest has been focused on constructing
Entry
Ar
Product
Yield (%)
ACCEPTED MANUSCRIPT
heterocyclic compounds efficiently, conveniently and
b
1
3a
60 (68 )
13
environmentally friendly for years. Recently, we found that the
domino reaction of aromatic aldehydes and 2-cyano N-
heteroarenes in acetic acid could lead to the facile formation of
polyarylated oxazoles without the involvement of heavy metals
or extra oxidants in the reactions (Figure 2, eq 5).
(
1a)
2
3b
45
(
1b)
3
4
3c
62
64
Br
(1c)
3d
(1d)
5
6
7
8
3e
3f
63
45
55
52
(
1e)
(
1f)
3g
3h
(
1g)
(1h)
b
9
3i
3j
32 (45 )
(
1i)
1
0
40
52
Figure 2. Recent progress on synthesising polyarylated oxazoles.
(1j)
1
1
1
2
3k
3l
2
. Results and discussion
(1k)
b
21
In our initial study, 3-bromobenzaldehyde (1a) and 2-
(1l)
cyanopyridine (2a) were selected as model substrates to optimize
the reaction conditions (Table S1). To get a better outcome,
parameters of the reaction such as temperature (Table S1, entries
b
13
3m
23
1
(
1
-3), reaction time (Table S1, entries 3-7), ratio of substrates
Table S1, entries 8-11) and kind of acids (Table S1, entries 12-
6) were screened. Eventually, the optimized condition was
(
1m)
1
1
1
4
5
6
3n
3o
3p
21
(
1n)
obtained as follows: the yield was 60% when the reaction was
performed in 3.0 mL HOAc for 10 h at 170 C with molar ratio
of 1:2.5 for 3-bromobenzaldehyde and 2-cyanopyridine. The
structure of product was confirmed by H, C NMR, HRMS as
well as X-ray single crystal diffraction (Figure S1).
b
o
39
(1o)
1
13
68
With the optimal conditions established, we subsequently
investigated the scope of aldehydes. As shown in Table 1, the
halogen-substituted aldehydes worked well in the reactions
regardless of the position on the benzene ring (Table 1, entries 1-
(1p)
a
b
Yield calculated from precipitation.
Products were purified by silica gel column chromatography.
8
).
Aldehydes
bearing
electron-withdrawing
groups
demonstrated higher efficiency than those bearing electron-
donating groups when they reacted with 2-cyanopyridine (Table
In addition, the scope of 2-cyano N-heteroarene was examined
as well (Table 2). Among the arbitrary combination of aromatic
aldehydes and 2-cyano N-heteroarenes, only the use of pyrazine-
1
, entries 9-16). However, aliphatic aldehydes almost cannot
react with 2-cyanopyridine under the standard conditions.
2
-carbonitrile (2b) showed less reactivity, all other reactions
could proceed well to give the desired products in moderate to
good yields (Table 2, entries 2-10). It was fortunate to find that
heteroaromatic aldehyde (1q) could also react with 2e to afford
the product in 32% yield.
Table 1. Scope study of aldehydes for the synthesis of 2,4,5-
trisubstituted oxazoles
Table 2. Substrate scope for the synthesis of 2,4,5-trisubstituted
oxazoles
2

2
5b
5c
25
38
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(
2a)
2a)
(
1p)
(1e)
(1j)
Entry
Ar
R
Product
4a
Yield
3
4
a
(%)
b
1
2
11
(
(
1p)
(2b)
(
1a)
1a)
5d
37
4b
56
(
(1j)
(2e)
(1p)
(2c)
5
6
5e
5f
42
44
3
4
5
6
7
8
9
4c
4d
4e
4f
41
72
34
65
84
(
1j)
(2d)
(
1j)
1j)
(
1p)
(2e)
(2e)
(1a)
(2e)
(2e)
(2e)
(2e)
(
(
1l)
(
1e)
a
b
The structure was determined by HMBC analysis.
Products were purified by silica gel column chromatography.
(1g)
4g
4h
4i
(1c)
b
32
(
1q)
(
2e)
2e)
80
(
(
1p)
1
0
4j
35
(
1j)
Yield calculated from precipitation.
Products were purified by silica gel column chromatography.
(2e)
a
b
Based on above results, different aromatic aldehydes were
Figure 3. The practical ratio of the theoretical products.
expected to react in the domino reaction to generate cross-
condensation products, thereby providing structurally diverse of
products. Interestingly, it was found that 2-cyano N-heteroarenes
could also react with two different aldehydes simultaneously to
furnish the chemoselective products (Table 3). The structure was
determined by HMBC spectroscope (take product 5e as example,
see Figure S2). We also performed the careful separation of final
products from the reaction of 1l, 1j and 2e. As shown in Figure 3,
a ratio of about 8: 4: 0: 88 was observed between the homo- and
cross-condensation products a, b, c and d, which indicated the
good chemoselectivity of the reaction.
Subsequently, control experiments were carried out to get
more insight into the reaction mechanism. As seen from Figure 4,
the use of 3-cyanopyridine, 4-cyanopyridine and benzonitrile
could not lead to the desired product, which means that the
cyano group should be located at 2-position of N-heteroarenes.
We supposed that the N-atom neighboring to the cyano group
might involve in the reaction process.
Table 3. Substrate scope for the synthesis of 2,4,5-trisubstituted
oxazoles
1
2
a
Entry
1
Ar
Ar
R
Product
Yield
b
(%)
5a
23
Figure 4. Control experiment: the effect of N-atom in the
aromatic ring.
(2a)
(1p)
(1m)
3

It should be noticed that in some reactions using 2-
ACCEPTED MANUSCRIPT
cyanopyridine as substrate, the hydrolysis of cyano group was
observed. Thus, further controlled reaction of the hydrolyzed
product with 3-bromobenzaldehyde was carried out under the
standard reaction condition (Figure 5). It was pleased to find that
the desired product could also be obtained in 59% yield. It
implies that 2-pyridyl formamide might serve as an important
intermediate in the reaction.
Figure 7. Taking the intermediates F as starting material under the
standard condition.
The previous report had shown that the O-atom in oxazole
15
came from the amide framework. Thus, another control
18
experiment was carried out. When 0.5 mL of H2
O was added
into the reaction, we did observe the existence of oxazole
18
bearing O atom via LC-MS analysis. The result indicated that
the O-atom in oxazole come from the in situ generated amide
group instead of the aldehyde (Figure 8).
Figure 5. Control experiment: using picolinamide as substrate.
14-16
Based on these control experiments and literature reports,
a plausible mechanism was proposed (take the formation of 3j as
an example, see Figure 6). Firstly, 2-cyanopyridine was
hydrolyzed to generate 2-pyridyl formamide (A) in HOAc at 170
o
18
C, which reacted further with aldehyde to afford intermediate B.
Figure 8. H O was added into the system.
2
With the nucleophilic addition of nitrogen atom from pyridine to
another aldehyde, C was thus formed. Subsequently, a hydrogen
transfer procedure occurred, leading to the formation of D. Next,
an intramolecular nucleophilic addition took place which
resulted in the generation of E. With the cleavage of C-N bond
and elimination of H , F was produced. After going through a
Robinson-Gabriel reaction, F was further converted into 3j, and
intermediate G was supposed to be a critical intermediate
It is known that oxazoles are widely used in functional
1
7
materials because of the fluorescence properties.
The
fluorescence emitting properties of the synthesized polyarylated
oxazoles were also examined. It was found that the range of the
fluorescence emitting wavelength varied from 375 nm to 435 nm.
It might serve as a potential materials or intermediates for the
preparation of OLEDs.
+
O
O
O
H
3. Conclusion
CN
N
NH2
N
N
N
In summary, we developed a convenient one-pot method for
the chemoselective synthesis of triarylated oxazoles from the
readily available starting material under metal-free condition.
Further study showed that the products may serve as potential
blue emitting material in OLEDs, which is under way in our
laboratory.
B
2a
A
O
H
O
O
O
NH
N
N
N
H+
N
N
HO
HO
O
4
4
. Experimental Section
.1 General
E
D
C
H+
Unless otherwise stated, all reagents were purchased from
-
commercial suppliers and used without further purification. All
reactions were carried out in air and using undistilled solvent,
without any precautions to exclude air and moisture unless
otherwise noted. Melting points were recorded on an
Electrothermal digital melting point apparatus. IR spectra were
OH
O
-H2O
O
O
N
N
N
N
N
N
H
O
1
13
F
G
3j
recorded on a FT-IR spectrophotometer using KBr optics. H, C
Figure 6. Proposed mechanism for the synthesis of polyarylated
NMR and HMBC spectra were recorded in CDCl or DMSO-d
3
6
oxazoles
on 400 MHz or 600 MHz spectometers. Tetramethylsilane
1
(
TMS) served as internal standard for H NMR and CDCl or
3
16
13
involved in the transformation. In order to confirm the
possibility of the conversion from F to 3j, we tried our isolate
the intermediate F. It was gratifying to find that the desired
product could also be synthesized under the optimized condition
by employing F as starting material (Figure 7), which indicates
the reasonability of our proposed mechanism.
DMSO-d was used as internal standard for C NMR. High
6
resolution mass spectra were obtained using a commercial
apparatus (ESI Source).
General procedure for the preparation of 2,4,5-trisubstituted
oxazoles 3a-4j.
2
-Cyanopyridine (10.0 mmol) and aldehydes (4.0 mmol) were
o
added to 3 mL acetic acid, the mixture was heated at 170 C for
4

-
1
1
1
0 h in a Teflon-lined stainless steel autoclave (25 mL of the
1500, 1451,1438, 794, 758, 693 cm ; H NMR (400 MHz,
ACCEPTED MANUSCRIPT
DMSO-d ): δ = 8.80 (d, J= 4.1 Hz, 1H), 8.25 (d, J= 7.8 Hz, 1H),
.05 (t, J= 7.4 Hz, 1H), 7.82 (t, J= 7.1 Hz, 1H), 7.73 (t, J= 7.1
Hz, 1H), 7.65–7.47 (m, 3H), 7.41–7.32 (m, 3H), 7.32–7.24 (m,
H) ppm; C NMR (100 MHz, DMSO-d ): δ = 160.5, 160.0,
59.8, 158.0, 157.5, 150.1, 144.9, 143.0, 137.6, 133.1, 131.8,
31.7, 130.8, 130.7, 130.6, 130.6, 129., 125.6, 124.8, 124.8,
124.6, 124.5, 122.4, 119.7, 119.6, 116.4, 116.3, 116.2, 116.0,
volume). Then, the mixture was poured into a glass beaker, and
acetic acid was evaporated at ambient temperature. For those
products ready to precipitate, filtration and washing operation
were performed to get the pure products. As to which have good
solubility in acetic acid, the pure products were purified by
column chromatography (silica gel, ethyl acetate/petroleum
ether).
6
8
13
1
1
1
6
+
115.8, 115.6 ppm; HRMS(ESI) calcd for C20H F N O [M+H]
12 2 2
3
35.0996, found 335.0992.
.6 4,5-bis(4-fluorophenyl)-2-(pyridin-2-yl)oxazole
White solid; m.p. 172.0–172.8 °C; IR (KBr): ν = 3055, 1587,
515, 1495, 833, 791, 693 cm ; H NMR (400 MHz, DMSO-d ):
General procedure for the chemoselective synthesis of the
trisubstituted oxazoles 5a-5f
4
(3e):
-
1 1
1
6
δ = 8.77–8.73 (m, 1H), 8.20 (d, J= 7.9 Hz, 1H), 8.04–7.98 (m,
H), 7.672–7.65 (m, 4H), 7.59–7.54 (m, 1H), 7.39–7.26 (m, 4H)
2
-Cyanopyridine (10 mmol) and two kinds of aldehydes (2 mmol,
1
respectively) were combined and heated in 3 mL acetic acid at
1
of the volume). The pure product was obtained by column
chromatography (silica gel, ethyl acetate/petroleum ether).
13
o
ppm; C NMR (100 MHz, DMSO-d
6
): δ = 163.6, 163.3, 161.1,
70 C for 10 h in a Teflon-lined stainless steel autoclave (25 mL
1
1
1
60.9, 158.7, 150.0, 145.3, 145.0, 137.5, 135.2, 129.8, 129.72,
29.2, 129.1, 128.0, 127.9, 125.4, 124.4, 124.4, 122.2, 116.4,
16.1, 115.9, 115.7 ppm; HRMS(ESI) calcd for C H F N O
2
0
12
2
2
+
[
M+H] 335.0996, found 335.0983.
General operation for the photophysical test
4
.7
4,5-bis(3-chlorophenyl)-2-(pyridin-2-yl)oxazole
(3f):
White solid; m.p. 148.9–149.7 °C; IR (KBr): ν = 3059, 1594,
0
.01 mmol product was dissolved in dichloromethane in a 10 mL
-1
1
1
482, 1441, 881, 786, 753, 707 cm ; H NMR (400 MHz,
volumetric flask. Then 0.04 mL solution was pipetted and
diluted to 4 mL with dichloromethane. The final concentration of
solution was 10 M. Fluorescence spectra were measured
DMSO-d ): δ = 8.78 (d, J= 3.8 Hz, 1H), 8.26 (d, J= 7.5 Hz, 1H),
6
8.11–8.00 (m, 1H), 7.72 (d, J= 5.4 Hz, 2H), 7.67–7.47 (m, 7H)
-
5
13
ppm; C NMR (100 MHz, DMSO-d
): δ = 159.1, 150.1, 145.3,
6
o
1
1
44.8, 137.6, 135.7, 133.8, 133.6, 133.4, 131.1, 130.8, 129.6,
29.4, 128.7, 127.4, 126.4, 126.2, 125.6, 125.4, 122.5 ppm;
using a conventional quartz cell (10 × 10 × 45 mm) at 25 C
with the excitation and emission slits of 1 nm width. The
sample solutions were excited at 330 nm to give a strong
emission, and fluorescence spectra were obtained on a Varian
Eclipse spectrofluorometer.
+
HRMS(ESI) calcd for C H Cl N O [M+H] 367.0405, found
20
12
2
2
3
67.0416.
4
.8 4,5-bis(4-chlorophenyl)-2-(pyridin-2-yl)oxazole (3g):
White solid; m.p. 152.0–153.1 °C; IR (KBr): ν = 3050, 1587,
1
-
1 1
497, 1457, 825, 789, 711 cm ; H NMR (400 MHz, DMSO-d ):
6
δ = 8.76 (d, J= 4.2 Hz, 1H), 8.20 (d, J= 7.9 Hz, 1H), 8.06–7.98
4
.2 4,5-bis(3-bromophenyl)-2-(pyridin-2-yl)oxazole (3a):
1
3
(
m, 1H), 7.70–7.63 (m, 4H), 7.60–7.51 (m, 5H) ppm; C NMR
White solid; m.p. 156.0–156.3 °C; IR (KBr): ν = 3057, 1549,
1
DMSO-d ): δ = 8.76 (s, 1H), 8.21 (d, J= 7.5 Hz, 1H), 8.01 (t, J=
-
1
1
(100 MHz, DMSO-d ): δ = 158.9, 150.0, 145.4, 144.9, 137.6,
6
457, 784, 880, 783, 727, 706 cm ; H NMR (400 MHz,
1
1
35.6, 134.0, 133.3, 130.3, 129.4, 129.3, 128.9, 128.4, 126.7,
6
+
25.5, 122.3 ppm; HRMS(ESI) calcd for C H Cl N O [M+H]
20
12
2
2
7
7
1
1
1
.1 Hz, 1H), 7.82 (d, J= 11.3 Hz, 2H), 7.62 (t, J= 19.4 Hz, 5H),
13
367.0405, found 367.0433.
.49–7.37 (m, 2H) ppm; C NMR (100 MHz, DMSO-d ): δ =
6
59.1, 150.1, 145.1, 144.8, 137.6, 135.6, 133.6, 132.3, 131.6,
31.3, 131.0, 130.2, 129.8, 129.2, 126.5, 125.7, 125.6, 122.5,
4
.9 4,5-bis(2,4-dichlorophenyl)-2-(pyridin-2-yl)oxazole (3h):
White solid; m.p. 142.1–142.9 °C; IR (KBr): ν = 3090, 3047,
-
1 1
22.2, 122.0 ppm; HRMS (ESI) calcd. for C H Br N O
20
12
2
2
1589, 1554, 1483, 1439, 816, 797, 711, 696 cm ; H NMR (400
+
[
M+H] 454.9395, found 454.9386.
MHz, DMSO-d ): δ = 8.79–8.74 (m, 1H), 8.21 (d, J= 7.9 Hz,
6
1
H), 8.07–8.01 (m, 1H), 7.81 (t, J= 1.1 Hz, 1H), 7.73 (d, J= 2.0
4
.3 4,5-bis(2-bromophenyl)-2-(pyridin-2-yl)oxazole (3b):
13
Hz, 1H), 7.64–7.52 (m, 5H) ppm; C NMR (100 MHz, DMSO-
d6): δ = 160.3, 150.6, 145.3, 145.3, 138.2, 136.4, 136.1, 135.0,
1
1
White solid; m.p. 141.5–143.3 °C; IR (KBr) : ν = 3060, 1589,
-
1
1
1
8
1
1
517, 1458 761, 696 cm ; H NMR (400 MHz, DMSO-d ): δ =
6
33.7, 133.6, 133.5, 133.2, 130.4, 123.0, 130.0, 128.5, 128.3,
26.5, 126.2, 122.9 ppm; HRMS(ESI) calcd for C H Cl N O
.77 (d, J= 4.4 Hz, 1H), 8.21 (d, J= 7.9 Hz, 1H), 8.06–8.00 (m,
H), 7.78 (d, J= 7.6 Hz, 1H), 7.74–7.69 (m, 1H), 7.62–7.56 (m,
20
12
4
2
+
13
[M+H] 434.9625, found 434.9616.
H), 7.53–7.33 (m, 6H) ppm; C NMR (100 MHz, DMSO-d ): δ
6
=
159.1, 150.1, 146.6, 145.1, 137.8, 137.7, 133.4, 133.0, 132.3,
32.2, 132.1, 131.9, 130.8, 128.9, 127.9, 127.8, 125.5, 122.7+,
22.6, 122.3 ppm; HRMS(ESI) calcd for C H Br N O [M+H]
4
.10 4,5-diphenyl-2-(pyridin-2-yl)oxazole (3i): White solid;
1
1
4
m.p. 118.3–119.5 °C; IR (KBr): ν = 3050, 1585, 1495, 1435,
773, 690 cm ; H NMR (400 MHz, DMSO-d ): δ = 8.79–8.72
-
1
1
20
12
2
2
6
54.9395, found 454.9396.
(m, 1H), 8.24–8.18 (m, 1H), 8.04–7.99 (m, 1H), 7.70–7.63 (m,
13
4
H), 7.59–7.54 (m, 1H), 7.52–7.40 (m, 6H) ppm; C NMR (100
4
.4 4,5-bis(4-bromophenyl)-2-(pyridin-2-yl)oxazole (3c):
MHz, DMSO-d ): δ = 158.7, 145.0, 146.1, 145.2, 137.5, 136.2,
131.7, 129.3, 129.0, 128.7, 128.5, 128.0, 127.6, 126.6, 125.3.
1
6
White solid; m.p. 154.3–156.2 °C; IR (KBr): ν = 3058, 2922,
-
1
1
1
591, 1550, 1457, 881, 784, 727, 705, 686 cm . H NMR (400
+
22.2 ppm; HRMS(ESI) calcd for C H N O [M+H] 299.1184,
20
14
2
MHz, DMSO-d ): δ = 8.76 (s, 1H), 8.23 (s, 1H), 8.02 (s, 1H),
6
13
found 299.1175.
7
.84 (s, 2H), 7.74–7.38 (m, 8H) ppm; C NMR (100 MHz,
DMSO-d ): δ = 150.1, 145.1, 137.6, 133.6, 132.3, 131.5, 131.3,
6
4.11 2-(pyridin-2-yl)-4,5-dip-tolyloxazole (3j): White solid;
m.p. 135.4–136.0 °C; IR (KBr): ν = 2918, 2849, 1585, 1497,
1
31.0, 130.2, 129.8, 129.2, 126.5, 125.7, 125.6, 122.5, 122.0
+
-
1 1
ppm; HRMS(ESI) calcd for C H Br N O [M+H] 454.9395,
20
12
2
2
1455, 819, 792, 714 cm ; H NMR (400 MHz, DMSO-d ): δ =
6
found 454.9391.
8
7
.78–8.72 (m, 1H), 8.20–8.16(m, 1H), 8.03–7.96 (m, 1H), 7.58–
13
.50 (m, 5H), 7.30–7.23 (m, 4H), 2.35 (s, 6H) ppm; C NMR
(
100 MHz, DMSO-d ): δ = 158.4, 149.9, 146.0, 145.2, 138.85,
6
4
.5 4,5-bis(2-fluorophenyl)-2-(pyridin-2-yl)oxazole (3d):
137.8, 137.4, 135.8, 129.5, 129.2, 128.9, 127.5, 126.5, 125.3,
White solid; m.p. 146.8–148.4 °C; IR (KBr): ν = 3055, 1580,
5

1
25.1, 122.1, 20.9, 20.9 ppm; HRMS(ESI) calcd for C H N O
4.18 4,5-bis(3-bromophenyl)-2-(pyrazin-2-yl)oxazole (4a):
2
2
18
2
ACCEPTED MANUSCRIPT
White solid; m.p. 158.6–160.0 °C; IR (KBr): ν = 3065, 2962,
-1 1
+
[
M+H] 327.1497, found 327.1494.
1
=
558, 882, 787,718, 686 cm ; H NMR (400 MHz, DMSO-d ): δ
6
4
.12 4,5-di(naphthalen-2-yl)-2-(pyridin-2-yl)oxazole (3k):
9.44 (d, J= 1.1 Hz, 1H), 8.86–8.83 (m, 2H), 7.88–7.85 (m,
White solid; m.p. 175.4–177.0 °C; IR (KBr): ν = 3049, 1598,
3
-
1
1
2H), 7.73–7.64 (m, 4H),7.51–7.43 (m, 2H) ppm; C NMR (100
1
502, 1458, 1435, 826, 756, 860, 739, 706 cm ; H NMR (400
MHz, DMSO-d ): δ = 157.2, 146.1, 145.8, 144.8, 143.4, 140.7,
6
MHz, DMSO-d ): δ = 8.76 (d, J= 3.0 Hz, 1H), 8.32–8.16 (m,
3
1
6
1
35.9, 133.3, 132.5, 131.7, 131.3, 131.1, 130.2, 129.5, 129.2,
H), 7.98 (t, J= 7.4 Hz, 1H), 7.90 (s, 6H), 7.70 (d, J= 8.2 Hz,
13
126.6, 125.8, 122.3, 122.1 ppm; HRMS(ESI) calcd for
C H Br N O [M+H] 455.9347, found 455.9350.
H), 7.63 (d, J= 8.3 Hz, 1H), 7.52 (d, J= 4.1 Hz, 5H) ppm;
C
+
19
11
2
3
NMR (100 MHz, DMSO-d ): δ = 159.0, 150.0, 146.5, 145.1,
6
1
1
1
37.5, 136.6, 132.9, 132.9, 132.8, 132.7, 129.1, 128.5, 128.3,
28.2, 128.2, 127.7, 127.7, 127.2, 127.0, 127.0, 126.7, 126.6,
4.19 4,5-bis(3-bromophenyl)-2-(isoquinolin-1-yl)oxazole (4b):
Brown solid; m.p. 145.2–147.0 °C; IR (KBr): ν = 3062, 1700,
-
1 1
26.1, 125.3, 123.9, 122.3 ppm; HRMS(ESI) calcd for
1594, 1560, 1461, 890, 787, 766, 726, 696, cm ; H NMR (400
+
C H N O [M+H] 399.1497, found 399.1503.
MHz, DMSO-d ): δ = 8.56 (d, J= 8.6 Hz, 1H), 8.37–8.28 (m,
28
18
2
6
1
H), 8.18 (d, J= 8.4 Hz, 1H), 8.07 (d, J= 8.0 Hz, 1H), 7.91–7.82
4
.13 4,5-bis(4-methoxyphenyl)-2-(pyridin-2-yl)oxazole (3l):
13
(
m, 3H), 7.74–7.61 (m, 5H), 7.52–7.39 (m, 2H) ppm; C NMR
(100 MHz, DMSO-d ): δ = 159.2, 147.3, 145.7, 144.7, 137.7,
135.8, 133.5, 132.4, 131.5, 131.3, 131.0, 130.7, 130.1, 129.7,
29.4, 129.3, 128.1, 128.1, 127.9, 126.4, 126.0, 122.2, 122.0,
+
Brown solid; m.p. 131.8–131.5 °C; IR (KBr): ν = 3048, 2965,
-
1
6
2
839, 1615, 1589, 1519, 1497, 1247, 1173, 829, 792, 698 cm ;
1
H NMR (400 MHz, DMSO-d ): δ = 8.74 (d, J= 4.2 Hz, 1H),
6
1
8
.18 (d, J= 7.8 Hz, 1H), 7.99 (t, J= 7.5 Hz, 1H), 7.65–7.51 (m,
13
119.5 ppm; HRMS(ESI) calcd for C24
04.9551, found 504.9532.
H14Br N O [M+H]
2 2
5
H), 7.09–6.97 (m, 4H), 3.81 (d, J= 3.3 Hz, 6H) ppm; C NMR
5
(100 MHz, DMSO-d ): δ = 159.8, 159.2, 158.1, 149.9, 145.5,
6
1
1
45.3, 137.4, 135.0, 128.8, 128.2, 125.0, 124.1, 122.0, 120.5,
14.5, 114.1, 55.3, 55.1 ppm; HRMS(ESI) calcd for C H N O
3
4.20 2-(5-bromopyridin-2-yl)-4,5-dip-tolyloxazole (4c): White
solid; m.p. 166.7–167.2 °C; IR (KBr): ν = 3031, 2917, 1571,
1495, 1458, 1103, 967, 823, 630 cm ; H NMR (400 MHz,
22
18
2
+
-1
1
[
M+H] 359.1396, found 359.1390.
CDCl ): δ = 8.83 (d, J = 2.1 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H),
3
4
.14
4,5-bis(4-(benzyloxy)phenyl)-2-(pyridin-2-yl)oxazole
7
.97 (d, J = 8.4 Hz, 1H), 7.68–7.60 (m, 4H), 7.25–7.19 (m, 4H),
(3m): White solid; m.p. 132.0–133.1 °C; IR (KBr): ν = 3047,
13
-
1
2.41 (s, 6H) ppm; C NMR (100 MHz, CDCl
147.1, 144.6, 139.5, 139.1, 138.2, 136.9, 129.4, 129.3, 129.2,
27.9, 126.9, 125.7, 123.2, 121.8, 21.46, 21.39 ppm; HRMS(ESI)
3
): δ = 157.9, 151.2,
2
919, 2877, 1609, 1516, 1494, 1455, 1240, 805, 750, 698 cm ;
1
H NMR (400 MHz, DMSO-d ): δ = 8.73 (d, J= 4.4 Hz, 1H),
6
1
8
.17 (d, J= 7.9 Hz, 1H), 8.02–7.95 (m, 1H), 7.66–7.56 (m, 4H),
.54–7.30 (m, 12H), 7.16–7.05 (m, 4H), 5.14 (d, J= 3.8 Hz, 4H)
+
calcd for C H BrN O [M+H] 404.0524, found 404.0533.
23
18
2
7
13
ppm; C NMR (100 MHz, DMSO-d ): δ = 158.9, 158.3, 158.1,
4.21 4,5-bis(3-bromophenyl)-2-(pyrimidin-2-yl)oxazole (4d):
6
1
1
1
49.9, 145.5, 145.3, 137.4, 136.9, 136.7, 135.0, 128.8, 128.4,
28.4, 128.2, 127.9, 127.9, 127.8, 127.8, 125.0, 124.3, 122.0,
White solid; m.p. 223.5–225.0 °C; IR (KBr): ν = 3055, 1552,
1492, 1415, 875, 785, 726, 710, 687 cm ; H NMR (400 MHz,
-
1 1
20.7, 115.2, 114.93, 69.4, 69.3 ppm; HRMS(ESI) calcd for
DMSO-d ): δ = 9.04 (s, 1H), 9.03 (s, 1H), 7.85 (d, J= 9.1 Hz,
6
+
13
C H N O [M+H] 511.2022, found 511.2032.
2H), 7.74–7.63 (m, 5H), 7.451–7.42 (m, 7.9 Hz, 2H) ppm;
C
34
26
2
3
NMR (125 MHz, DMSO-d ): δ = 158.2, 157.6, 153.7, 145.9,
6
4
.15 4,5-di(benzo[d][1,3]dioxol-5-yl)-2-(pyridin-2-yl)oxazole
1
36.0, 133.5, 132.6, 131.6, 131.4, 131.1, 130.2, 129.6, 129.4,
(3n): Yellow solid; m.p. 204.1–205.6 °C; IR (KBr): ν = 2897,
-
1
1
126.5, 1256.0, 122.3, 122.2, 122.0 ppm; HRMS(ESI) calcd for
1
605, 1505, 1482, 1440, 1235, 1030, 812, 793, 716 cm ; H
+
C H Br N O [M+H] 455.9347, found 455.9346.
19
11
2
3
NMR (400 MHz, DMSO-d ): δ = 8.73 (d, J= 4.0 Hz, 1H), 8.18
6
(
7
d, J= 7.8 Hz, 1H), 8.00 (t, J= 7.5 Hz, 1H), 7.57–7.51 (m, 1H),
4.22 4,5-bis(4-fluorophenyl)-2-(pyrimidin-2-yl)oxazole (4e):
.20–7.08 (m, 4H), 7.07–6.97 (m, 2H), 6.10 (d, J= 10.3 Hz, 4H)
White solid; m.p. 193.1–194.9 °C; IR (KBr): ν = 3038, 1561,
13
-1 1
ppm; C NMR (100 MHz, DMSO-d ): δ = 158.0, 149.9, 148.1,
1548, 1517, 1493, 1437, 1407, 837, 815, 740, 711, 695 cm ; H
6
1
1
1
3
47.7, 147.5, 147.3, 145.5, 145.2, 137.5, 135.2, 125.4, 125.1,
22.1, 121.6, 121.6, 121.4, 108.9, 108.6, 107.7, 106.9, 101.6+,
01.3 ppm; HRMS(ESI) calcd for C H N O [M+H]
NMR (400 MHz, DMSO-d ): δ = 9.2–8.74 (m, 2H), 7.77–7.10
6
13
(m, 9H) ppm; C NMR (100 MHz, DMSO-d ): δ = 163.8, 163.3,
6
161.3, 160.9, 158.1, 157.2, 153.9, 146.0, 135.8, 129.8, 129.7,
22
14
2
5
87.0981, found 387.0980.
129.4, 129.3, 127.8, 127.8, 124.2, 122.1, 116.4, 116.2, 116.0,
+
1
3
15.7 ppm; HRMS(ESI) calcd for C H F N O [M+H]
36.0948, found 336.0943.
19 11 2 3
4
.16 4,5-bis(3-nitrophenyl)-2-(pyridin-2-yl)oxazole
(3o):
Yellow solid; m.p. 236.2–237.1 °C; IR (KBr): ν = 3079, 1527,
1
-
1 1
349, 862, 792, 706, 681 cm ; H NMR (400 MHz, DMSO-d ):
4.23 4,5-bis(4-chlorophenyl)-2-(pyrimidin-2-yl)oxazole (4f):
6
δ = 8.80 (d, J= 4.3 Hz, 1H), 8.52 (s, 1H), 8.48 (s, 1H), 8.36–8.27
White solid; m.p. 200.0–202.0 °C; IR (KBr): ν = 3044, 1562,
-
1 1
(
m, 3H), 8.14–8.09 (m, 2H), 8.06 (t, J= 7.7 Hz, 1H), 7.85–7.76
1498, 1415, 831, 718 cm ; H NMR (400 MHz, DMSO-d ): δ =
6
13
(m, 2H), 7.66–7.60 (m, J= 7.4, 4.9 Hz, 1H) ppm; C NMR (100
9.02 (d, J= 4.8 Hz, 2H), 7.70–7.61 (m, 5H), 7.57–7.48 (m, 4H)
13
MHz, DMSO-d ): δ = 159.6, 150.2, 148.2, 148.2, 145.1, 144.6,
ppm; C NMR (100 MHz, DMSO-d ): δ = 158.2, 157.4, 153.8,
6
6
1
1
37.7, 135.7, 133.8, 132.9, 132.7, 131.0, 130.7, 128.9, 125.8,
146.1, 136.1, 134.3, 133.4, 131.1, 130.1, 129.3, 129.0, 128.6,
+
24.2, 123.6, 122.6, 122.2, 121.3 ppm; HRMS(ESI) calcd for
126.4, 122.2 ppm; HRMS(ESI) calcd for C H Cl N O [M+H]
19
11
2
3
+
C H Cl N O [M+H] 389.0886, found 389.0875.
368.0357, found 368.0352.
20
12
2
4
5
4
.17
4,5-bis(4-(methylsulfonyl)phenyl)-2-(pyridin-2-
4.24 4,5-bis(4-bromophenyl)-2-(pyrimidin-2-yl)oxazole (4g):
yl)oxazole (3p): White solid; m.p. 280.1–281.0 °C; IR (KBr): ν
White solid; m.p. 240.3–242.0 °C; IR (KBr): ν = 3061, 1553,
-
1
-
1
1
=
2988, 2912, 1597, 1306, 1149, 954, 847, 833, 774, 712 cm ;
1
492, 1437,1413, 823, 713, 690 cm ; H NMR (400 MHz,
1
H NMR (400 MHz, DMSO-d ): 8.77 (d, J = 4.2 Hz, 1H), 8.24
6
DMSO-d ): δ = 9.01 (d, J= 3.8 Hz, 2H), 7.74–7.54 (m, 9H) ppm;
6
(d, J = 7.9 Hz, 1H), 8.08–8.00 (m, 5H), 7.96–7.89 (m, 4H), 7.62–
13
C NMR (100 MHz, DMSO-d ): δ = 158.2, 157.5, 153.8, 146.2,
6
7
.51 (m, 1H), 3.30 (d, J = 1.1 Hz, 6H), 3.30 (s, 3H), 3.30 (s, 3H).
13
136.2, 132.3, 131.9, 130.5, 129.6, 128.8, 126.7, 123.1, 122.2,
ppm; C NMR (100 MHz, DMSO-d ): δ = 160.2, 150.6, 146.3,
1
1
6
+
1
4
4
22.0 ppm; HRMS(ESI) calcd for C H Br N O [M+H]
19 11 2 3
45.1, 141.6, 141.3, 138.1, 137.2, 136.6, 132.6, 129.1, 128.4,
28.1, 127.9, 126.3, 123.1, 43.9, 43.8 ppm; HRMS(ESI) calcd
55.9347, found 455.9361.
.25 2-(pyrimidin-2-yl)-4,5-di(thiophen-2-yl)oxazole (4h):
Yellow solid; m.p. 193.0–194.2 C; IR (KBr): ν = 3094, 3072,
+
for C H N O S [M+Na] 477.0555, found 477.0572.
22
18
2
5 2
o
6

-
1
1
1
567, 1540, 1437, 847, 813, 706 cm ; H NMR (400 MHz,
140.6, 140.4, 139.4, 133.7, 129.6, 128.5, 128.2, 127.9, 127.5,
121.6, 44.6, 21.6 ppm; HRMS(ESI) calcd for C H N O
4
ACCEPTED MANUSCRIPT
DMSO-d ): δ = 9.04 (d, J= 4.8 Hz, 2H), 7.88 (d, J= 4.9 Hz, 1H),
.76–7.70 (m, 2H), 7.68 (t, J= 4.8 Hz, 1H), 7.62 (d, J= 3.2 Hz,
H), 7.29 (t, J= 4.2 Hz, 1H), 7.25–7.18 (m, 1H) ppm; C NMR
100 MHz, DMSO-d ): δ = 158.2, 156.8, 153.6, 141.3, 132.9,
6
21 15
3
+
7
1
(
[M+Na] 414.0888, found 414.0887.
4.32 5-(4-nitrophenyl)-2-(pyrimidin-2-yl)-4-p-tolyloxazole
(5e): Yellow solid; m.p. 275.0–275.4 °C; IR (KBr) ν = 3056,
13
6
-
1 1
1
31.5, 129.2, 128.3, 128.2, 127.9, 127.8, 127.6, 126.4, 122.2
1596, 1547, 1509, 1404, 1335, 851, 831, 702 cm ; H NMR (400
+
ppm; HRMS(ESI) calcd for C H N OS [M+H] 312.0265,
MHz, CDCl ): δ = 8.98 (d, J= 1.1 Hz, 1H), 8.97 (d, J= 1.1 Hz,
15
9
3
2
3
found 312.0260.
.26 4,5-bis(4-(methylsulfonyl)phenyl)-2-(pyrimidin-2-
yl)oxazole (4i): White solid; m.p. 277.1–277.6 °C; IR (KBr): ν =
1H), 8.24 (d, J= 1.3 Hz, 1H), 8.22 (t, J= 1.6 Hz, 1H), 7.95 (d, J=
1.0 Hz, 1H), 7.94 (d, J= 1.9 Hz, 1H), 7.64 (s, 1H), 7.62 (s, 1H),
4
7.43 (t, J= 4.9 Hz, 1H), 7.26 (s, 1H), 7.24 (s, 1H), 2.42 (s, 3H)
-
1
1
13
2
988, 2901, 1558, 1309, 1150, 963, 772, 719, 712 cm ; H NMR
ppm; C NMR (100 MHz, CDCl ): δ = 158.5, 158.2, 154.8,
3
(
400 MHz, DMSO-d ): δ = 9.04 (s, 1H), 9.03 (s, 1H), 8.09–8.01
147.6, 145.3, 141.1, 139.6, 134.6, 129.7, 128.6, 128.2, 127.4,
124.2, 121.7, 21.58 ppm; HRMS(ESI) calcd for C H N O
3
6
(m, 4H), 7.97–7.89 (m, 4H), 7.69 (d, J = 9.8 Hz, 1H), 3.31 (s,
2
0
14
4
13
+
3
1
1
H), 3.31 (s, 3H) ppm; C NMR (100 MHz, DMSO-d ): δ =
[M+Na] 381.0964, found 381.0943.
4.34 5-(3-nitrophenyl)-2-(pyrimidin-2-yl)-4-p-tolyloxazole
(5f): Yellow solid; m.p. 239.4–240.2 °C; IR (KBr) ν = 3057,
6
58.7, 158.6, 154.1, 147.0, 141.9, 141.3, 137.5, 136.4, 132.4,
29.0, 128.4, 128.2, 128.1, 122.9, 43.9, 43.8 ppm; HRMS(ESI)
+
-1
1
calcd for C H N O S [M+H] 456.0688, found 456.0682.
1550, 1400, 1345, 823, 748, 701 cm ; H NMR (400 MHz,
21
17
3
5 2
4
.27 2-(pyrimidin-2-yl)-4,5-dip-tolyloxazole (4j): White solid;
CDCl ): δ = 8.89 (d, J= 4.9 Hz, 2H), 8.57 (t, J= 1.8 Hz, 1H),
3
m.p. 176.1–176.6 °C; IR (KBr): ν = 3061, 3032, 2974, 2916,
8.16–8.10 (m, 1.3 Hz, 1H), 7.98 (d, J= 7.9 Hz, 1H), 7.56 (d, J=
8.1 Hz, 2H), 7.49 (t, J= 8.0 Hz, 1H), 7.35 (t, J= 4.9 Hz, 1H), 7.16
(d, J= 7.9 Hz, 2H), 2.33 (s, 3H). ppm; C NMR (100 MHz,
-
1 1
1
558, 1549, 1407, 1128, 817, 737, 715 cm ; H NMR (400 MHz,
13
CDCl ): δ = 8.91 (d, J = 4.9 Hz, 2H), 7.68–7.60 (m, 4H), 7.33 (t,
3
J = 4.9 Hz, 1H), 7.20–7.14 (m, 4H), 2.36 (s, 3H), 2.36 (s, 3H)
CDCl ): δ = 158.1, 154.7, 148.7, 145.0, 139.9, 139.4, 132.6,
3
13
ppm; C NMR (100 MHz, CDCl ): δ = 1157.9, 157.1, 155.0,
130.2, 129.9, 129.6, 128.28, 128.0, 127.6, 123.7, 121.9, 121.6,
3
+
1
1
47.9, 139.3, 138.2, 137.5, 129.4, 129.1, 128.9, 128.1, 127.2,
25.6, 120.9, 21.5, 21.4 ppm; HRMS(ESI) calcd for C H N O
21.58. ppm; HRMS(ESI) calcd for C H N O [M+H]
20
14
4
3
359.1144, found 359.1146.
21
17
3
+
[
M+H] 328.1450, found 328.1461.
4.35 N-(2-oxo-1,2-dip-tolylethyl)picolinamide (F): White solid;
m.p. 137.9–138.5 °C; IR (KBr): ν = 3387, 2919, 1681, 1665,
4
.28
4-(4-methoxyphenyl)-5-(4-nitrophenyl)-2-(pyridin-2-
-1 1
yl)oxazole (5a): Yellow solid; m.p. 220.0–221.4 °C; IR (KBr) ν
1640, 1568, 1498, 769, 655 cm ; H NMR (400 MHz, CDCl ): δ
3
-
1 1
=
2929, 2834, 1600, 1512, 1483, 1335, 838, 707 cm ; H NMR
= 9.37 (d, J = 7.4 Hz, 1H), 8.59 (d, J = 4.7 Hz, 1H), 8.14 (d, J =
7.8 Hz, 1H), 7.94 (d, J = 8.2 Hz, 2H), 7.83–7.74 (m, 1H), 7.39 (t,
(
400 MHz, CDCl ): δ = 8.80 (d, J= 4.2 Hz, 1H), 8.31–8.20 (m,
3
3
7
H), 7.94–7.83 (m, 3H), 7.67–7.62 (m, 2H), 7.46–7.40 (m, 1H),
.02–6.96 (m, 2H), 3.88 (s, 3H) ppm; C NMR (100 MHz,
J = 7.5 Hz, 3H), 7.20 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 7.9 Hz,
13
13
2H), 6.69 (d, J = 7.6 Hz, 1H), 2.34 (s, 3H), 2.25 (s, 3H) ppm;
C
CDCl ): δ = 160.6, 160.2, 150.5, 147.3, 145.8, 144.1, 140.5,
NMR (100 MHz, CDCl ): δ = 194.9, 163.6, 149.7, 148.3, 144.6,
3
3
1
5
37.3, 134.9, 130.1, 126.9, 125.3, 124.3, 123.9, 122.9, 114.6,
138.2, 137.1, 134.5, 132.0, 129.9, 129.4, 129.3, 128.2, 126.2,
122.2, 58.3, 21.7, 21.1 ppm; HRMS(ESI) calcd for C H N O
[M+Na] 367.1422, found 367.1417.
+
5.57 ppm; HRMS(ESI) calcd for C H N O [M+H] 374.1141,
21
15
3
4
22 20
2
2
+
found 374.1125.
4
.29
4-(4-fluorophenyl)-5-(4-nitrophenyl)-2-(pyridin-2-
yl)oxazole (5b): Yellow solid; m.p. 232.1–233.4 °C; IR (KBr) ν
-
1
1
=
3064, 1593, 1509, 1339, 854, 842, 740 cm ; H NMR (400
Acknowledgements
MHz, CDCl ): δ = 8.82 (d, J= 4.4 Hz, 1H), 8.25 (t, J= 8.5 Hz,
3
3
7
1
1
1
H), 7.94–7.85 (m, 3H), 7.75–7.65 (m, 2H), 7.49–7.41 (m, 1H),
We are grateful for financial support of the National Natural
Science Foundation of China (No. 21372174); Young National
Natural Science Foundation of China (No. 21202113); Young
Natural Science Foundation of Jiangsu Province (BK2012174);
the PH.D. Programs Foundation of Ministry of Education of
China (2013201130004); PAPD.
13
.17 (t, J= 8.6 Hz, 2H) ppm; C NMR (100 MHz, CDCl ): δ =
3
64.6, 162.2, 160.3, 150.5, 147.5, 145.6, 144.6, 139.5, 137.3,
34.5, 130.6, 130.5, 128.5, 127.7, 127.7, 127.1, 125.4, 124.3,
22.9, 116.4, 116.2 ppm; HRMS(ESI) calcd for C H FN O
3
20
12
3
+
[
M+H] 362.0941, found 362.0936.
4
.30
5-(4-(methylsulfonyl)phenyl)-2-(pyridin-2-yl)-4-p-
tolyloxazole (5c): White solid; m.p. 216.2–216.8 °C; IR (KBr): ν
3063, 3016, 2962, 2920, 1310, 1148, 1088, 957, 777, 753, 738,
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7
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8

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Supporting Information
Metal-free One-pot Domino Reaction: Chemoselective
Synthesis of Polyarylated Oxazoles
Hua Meng, You Zi, Xiao-Ping Xu,* and Shun-Jun Ji*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry
Chemical Engineering and Materials Science & Collaborative Innovation Center of
Suzhou Nano Science and Technology, Soochow University, Suzhou 215123,
People’s Republic of China
Fax : (+86)-512-65880307; phone: (+86)- 512-65880307; E-mail: xuxp@suda.edu.cn;
shunjun@suda.edu.cn
Table of Contents
Crystal structure of 3a
page S2
page S3
page S4
page S5
Optimization of reaction condition
The structure determination of 5e according to HMBC spectrum
1
13
The H and C NMR spectra of compounds
S1

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Figure S1: crystal structure of 3a
Crystal Number: CCDC 1047167
Empirical formula: C20
Formula weight: 356.1301
Unit cell parameters: a = 7.5076(13) Å, b = 10.0815(16) Å, c = 22.685(4) Å,
2 2
H12Br N O

= 90.00,  = 94.653(4), = 90.00, space group P 21/n
Temperature: 223(2) K
Wavelength: 0.71075 Å
Crystal system: Monoclinic
Volume: 1711.3(5) Å
Z: 4
3
Calculated density: 1.770 Mg/m
-1
Absorption coefficient: 4.747 mm
F (000): 896
3
Crystal size: 0.40×0.28× 0.26 mm
Correction-type: multi-scan
h, k, l max: 8, 11, 29
S2

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Table S1 Optimization of reaction conditionsa
entry
substrate
a:2a
temp.
time
(h)
solvent
yield
(%)
o
1
( C)
1
2
3
4
5
6
7
8
9
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
4:1
130
150
170
170
170
170
170
170
170
170
170
170
170
170
170
10
10
10
12
7
AcOH
AcOH
trace
30
AcOH
60
AcOH
60
AcOH
40
5
AcOH
21
3
AcOH
trace
41
10
10
10
10
10
10
10
10
AcOH
2:1
AcOH
35
1
0
1
1:1
AcOH
56
1
1:2
AcOH
58
1
1
1
1
2
3
4
5
1:2.5
1:2.5
1:2.5
1:2.5
TFA
messy
messy
trace
29
TfOH
Oxalic acid
Propionic
acid
1
6
1:2.5
170
10
Pivalic acid
9
a
Reaction conditions: 4.0 mmol 3-bromobenzaldehyde in 3.0 mL HOAc.
S3

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The structure determination of 5e according to HMBC spectrum
Figure S2
S4

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1
13
The H and C NMR spectra of compounds
4,5-bis(3-bromophenyl)-2-(pyridin-2-yl)oxazole (3a)
S5

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4,5-bis(2-bromophenyl)-2-(pyridin-2-yl)oxazole (3b)
S6

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S7

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4,5-bis(4-bromophenyl)-2-(pyridin-2-yl)oxazole (3c)
S8

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4,5-bis(2-fluorophenyl)-2-(pyridin-2-yl)oxazole (3d)
S9

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S10

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4,5-bis(4-fluorophenyl)-2-(pyridin-2-yl)oxazole (3e)
S11

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4,5-bis(3-chlorophenyl)-2-(pyridin-2-yl)oxazole (3f)
S12

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4,5-bis(4-chlorophenyl)-2-(pyridin-2-yl)oxazole (3g)
S13

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S14

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4,5-bis(2,4-dichlorophenyl)-2-(pyridin-2-yl)oxazole (3h)
S15

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4,5-diphenyl-2-(pyridin-2-yl)oxazole (3i)
S16

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2-(pyridin-2-yl)-4,5-dip-tolyloxazole (3j)
S17

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S18

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4,5-di(naphthalen-2-yl)-2-(pyridin-2-yl)oxazole (3k)
S19

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4,5-bis(3-nitrophenyl)-2-(pyridin-2-yl)oxazole (3l)
S20