An iron and copper system catalyzed C-H arylation of azoles with arylboronic acids

Article abstract of DOI:10.1055/s-0034-1379073

An efficient, environmentally friendly, and economical new method for arylation reactions of azoles with arylboronic acids via copper-iron-catalyzed C-H and C-B bond activation has been developed. The protocol tolerates a series of functional groups, such as methoxy, nitro, cyano, chloro, and trifluoromethyl groups.

Full text of DOI:10.1055/s-0034-1379073

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2015, 47, 0042–0048
paper
42
W.-Y. Hu et al.
Paper
Synthesis
An Iron and Copper System Catalyzed C–H Arylation of Azoles
with Arylboronic Acids
C–H Arylation of Azoles
Wei-Ye Hu
N
X
X
Cu/Fe
R
R
H
Ar
+
Pei-Pei Wang
Song-Lin Zhang*
(OH)2B
Ar
N
up to 92% yield
X = O, S
R = 5-Cl, 5-NO2
Key Laboratory of Organic Synthesis of Jiangsu Province, Col-
lege of Chemistry, Chemical Engineering and Materials Science,
Ar = Ph, 4-MeC6H4, 3,5-Me2C6H3, 3-MeOC6H4, 4-NCC6H4, 4-F3CC6H4,
2-naphthyl, 9-phenanthryl, 5-pyrimidyl, 8-quinolyl
Soochow University, Suzhou 215123, P. R. of China
+
8
6
5
(
1
2
6
)
5
6
8
0
3
5
2
zhangsl@suda.edu.cn
Received: 09.05.2014
Accepted after revision: 11.08.2014
Published online: 29.09.2014
acids.10–12 But these protocols also suffered from problems,
for example, low yields, narrow applied range, and high tox-
icity.
DOI: 10.1055/s-0034-1379073; Art ID: ss-2014-h0290-op
Considering the requirements of atom economy and en-
vironmental protection, the properties of copper and iron
as catalysts have acquired great significance.13–15 We have
recently demonstrated that an iron and copper system can
catalyzed the formation of C–C, C–O, and C–N bonds.16–19 As
a part of our continuous efforts toward the development of
an iron and copper system, we applied the iron–copper sys-
tem to the reaction of azoles with arylboronic acids. In this
paper, we report that an iron–copper catalyst system could
very efficiently catalyze the cross-coupling between azole
compounds and arylboronic acids with good yields.
The reaction of 1,3-benzoxazole (1a) with phenylboron-
ic acid (2a) was used to optimize the reaction conditions.
The results of our optimizations experiments for the copper
salt, iron salt, base, ligand, oxidant, and solvent are given in
Table 1. Initially, a copper salt was used as a single catalyst
and a series of experiments were used to identify the most
effective copper salt, base, ligand, oxidant, and solvent for
the reaction. With all other conditions identically, copper(I)
iodide gave the best result among other copper salts [CuBr,
CuCl, Cu(OAc)2, CuSO4·5 H2O, Cu(acac)2] (entries 1–6). Then,
the base was varied (NaOMe, K2CO3, KOAc, KOt-Bu, Cs2CO3)
but none gave better results than lithium tert-butoxide (en-
tries 7–11). From the experimental results, we could see
that the ligand and oxidant also have an important influ-
ence on the reaction and that no product was obtained with
certain ligand and oxidant combinations (entries 15, 16, 19,
20, and 22). The best results were obtained using di-tert-
butyl peroxide (DTBP) (entry 1). When clean oxidants, such
as oxygen or hydrogen peroxide, were used, there was no
improvement in the yield (entries 21 and 22). Next we in-
vestigated the effect of the ligand (Figure 1) and better re-
sults were obtained using 1,10-phenanthroline (L1) as the
Abstract An efficient, environmentally friendly, and economical new
method for arylation reactions of azoles with arylboronic acids via
copper–iron-catalyzed C–H and C–B bond activation has been devel-
oped. The protocol tolerates a series of functional groups, such as
methoxy, nitro, cyano, chloro, and trifluoromethyl groups.
Key words environmentally friendly, copper and iron, C–H activation,
azoles, arylboronic acids
Azoles are an important class of structures in natural
products and pharmaceuticals and they have shown a wide
range of biological activity, such as antitumor, antiviral, and
antimicrobial activity.1 Hence interest in the development
of the synthesis of azole compounds has continued.
The traditional methods for the synthesis of aryl-substi-
tuted azole compounds consist of cyclization of functional
groups containing the heteroatom2 and cross-coupling of 2-
chloro-1,3-benzoxazoles or 2-chloro-1,3-benzothiazoles
with arylboronic acids.3 Among these methods, the palladi-
um-catalyzed Suzuki–Miyaura reaction is one of the most
powerful and convenient methods for the synthesis of aryl-
substituted azole compounds.4 In recent year, direct C–H
bond functionalization has become a popular topic in
chemical research. Compared with traditional reactions, di-
rect C–H bond functionalization of azoles represents an en-
vironmentally and economically attractive strategy, which
is a potential alternative to traditional reactions because it
avoids the extra introduction of functional groups in one of
the coupling partners. Much progress has been made in the
C–H activation of azoles with aryl halides or pseudoha-
lides.5–9 In addition, some metal-catalyst systems (such as
Ni, Pd/Cu, and microwave/Mn) have been reported for the
direct reaction between azole compounds and arylboronic
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 42–48

43
W.-Y. Hu et al.
Paper
Synthesis
Table 1 Optimization of the Reaction Conditionsa
B(OH)2
O
O
Cu/Fe
H
+
N
N
1a
2a
3a
Entry
Copper salt
Iron salt
Base
LiOt-Bu
Ligandb
Oxidant
Solvent
Yieldc (%)
1
CuI
–
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L6
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
I2
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
50
44
42
10
23
27
16
13
27
42
26
40
20
18
0
2
CuBr
CuCl
Cu(OAc)2
CuSO4·5 H2O
Cu(acac)2
CuI
–
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
NaOMe
K2CO3
3
–
4
–
5
–
6
–
7
–
8
CuI
–
9
CuI
–
KOAc
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
CuI
–
KOt-Bu
Cs2CO3
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
LiOt-Bu
CuI
–
CuI
–
CuI
–
CuI
–
CuI
–
CuI
–
0
CuI
–
24
31
0
CuI
–
TBHP
NBS
CuI
–
CuI
–
DDQ
O2
0
CuI
–
40
0
CuI
–
H2O2
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
–
CuI
–
44
35
52
41
87
83
73
80
0
CuI
–
NMP
CuI
–
toluene
benzene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CuI
–
CuI
Fe2O3
Fe3O4
FeCl2
FeCl3
Fe2O3
Fe2O3
Fe2O3
Fe2O3
CuI
CuI
CuI
–
CuI
45d
60e
77f
CuI
CuI
a Reaction conditions: 1a (0.5 mmol), phenylboronic acid (2a, 2 equiv), copper salt (20 mol%), iron salt (20 mol%), base (3 equiv), ligand (20%), oxidant (2 equiv),
solvent (3 mL), 110 °C, 12 h.
b Isolated yield based on 1a after silica gel chromatography.
c See Figure 1.
d Using 1.5 equiv of phenylboronic acid (2a).
e Using 1.7 equiv of phenylboronic acid (2a).
f Using 2 equiv of Fe2O3.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 42–48

44
W.-Y. Hu et al.
Paper
Synthesis
oxidant compared to TMEDA (L2), DMEDA (L3), and 2,2′-bi-
pyridyl (L4) (entries 12–14). Therefore, 1,10-phenanthro-
line (L1) was selected as the optimal ligand for its catalytic
effect and inexpensive price. Finally, the solvent was varied
and toluene was found to be the best choice (entries 23–
26).
or quinoline rings as well. The results of the reactions of 4-
methylphenylboronic acid (2b) and 3,5-dimethylphenylbo-
ronic acid (2c) show that electron-donating groups may re-
duce the yield of the products (entries 2–4); the methoxy
group affects the yield with a stronger electron-donating
ability than methyl. When arylboronic acids linked with
electron-withdrawing groups in the para position, such as
4-(trifluoromethyl)phenylboronic acid (2f) and 4-cyano-
phenylboronic acid (2e), were used, the yields of products
dropped sharply (entries 5 and 6). Polycyclic arylboronic
acid like naphthalen-2-ylboronic acid (2g) and phenan-
thren-9-ylboronic acid (2h) also reacted with 1,3-benzox-
azole to provide the products 3g and 3h in 80% and 63%
yields, respectively (entries 7 and 8). Pyrimidin-5-yl- or
quinolin-8-yl-substituted boronic acids gave the products
3j and 3k, respectively, in acceptable yields (entries 10 and
11). The optimized reaction conditions were also applicable
in the reactions of 5-chloro-1,3-benzoxazole (1b), 5-nitro-
1,3-benzoxazole (1c), and 4-phenyloxazole (1d) with aryl-
boronic acids (entries 12–16).
Me2N
NMe2
MeHN
NHMe
N
N
N
L1
L4
L2
L5
L3
H
O
N
OH
OH
N
OH
L6
Figure 1
Table 2 Reaction of Oxazoles with Arylboronic Acidsa
Although a great number of experiments have been per-
formed to improve the yield, we have not achieved our aim
as the copper salt was the only catalyst. Interestingly, when
an iron salt was added to work jointly with the copper salt,
the yield rose sharply (entries 27 and 28). From the results,
we could see that the iron salt is indispensable for a high
yield and iron(III) oxide was the best from several common
iron salts (Fe2O3, Fe3O4, FeCl2, FeCl3) (entries 27–30).
The highest yield was obtained using the conditions in
entry 27 and several experiments were performed varying
the proportions of the reactants. We have reason to believe
that the iron salt functions as a pre-oxidant. The reaction
was carried out solely using the iron salt to ascertain
whether the copper salt and iron salt were working jointly
or separately; no product was obtained in the absence of
the copper salt (entry 31). It follows that iron salt and cop-
per salt are a collaborative catalyst in the reaction. The reac-
tion with iron(III) oxide (2 equiv) in the absence of di-tert-
butyl peroxide gave the product in 77% yield (entry 34). Re-
ducing the amount of phenylboronic acid gave the product
in lower yields (entries 32 and 33). We selected copper(I)
iodide (20% mmol), iron(III) oxide (20% mmol), lithium tert-
butoxide (3.0 equiv), 1,10-phenanthroline (20% mmol), di-
tert-butyl peroxide (2.0 equiv), and toluene (3.0 mL) as the
optimal reaction conditions.
N
O
O
N
Cu/Fe
H
+
(OH) B
Ar
Ar
R
R
2
1
2a–k
3a–p
Entry
R
Ar
Product
Yieldb (%)
1
H
Ph (2a)
4-MeC6H4 (2b)
3a
3b
3c
3d
3e
3f
87
78
74
50
42
58
80
63
52
60
62
73
67
57
45
64
2
H
H
H
H
H
H
H
H
H
H
3
3,5-Me2C6H3 (2c)
3-MeOC6H4 (2d)
4-NCC6H4 (2e)
4-F3CC6H4 (2f)
2-naphthyl (2g)
9-phenanthryl (2h)
4-PhC6H4 (2i)
5-pyrimidyl (2j)
8-quinolyl (2k)
Ph (2a)
4
5
6
7
3g
3h
3i
8
9
10
11
12
13
14
15
16
3j
3k
3l
5-Cl
5-Cl
4-MeC6H4 (2b)
4-F3CC6H4 (2f)
Ph (2a)
3m
3n
3o
3p
5-Cl
5-NO2
c
–
4-MeC6H4 (2b)
With the optimized reaction conditions in hand, we
next explored the substrate scope of the reactions of diver-
sified azoles with arylboronic acids. To evaluate the gener-
ality of this reaction, 1,3-benzoxazole (1a) was reacted with
a range of arylboronic acids and the results are summarized
in Table 2. The results show that 1,3-benzoxazole reacts
well with arylboronic acids. Electron-poor or -rich arylbo-
ronic acids containing functionalities such as methyl, meth-
oxy, cyano, or trifluoromethyl were studied and pyrimidine
a Reaction conditions: oxazole 1 (0.5 mmol), CuI (20 mol%), Fe2O3 (20
mol%), L1 (20 mol%), LiOt-Bu (1.5 mmol), DTBP (1.0 mmol), arylboronic
acid (1.0 mmol), toluene (3 mL), 110 °C, 12 h.
b Isolated yield based on 1 after silica gel chromatography.
c The substrate was 4-phenyloxazole.
In view of the results above, substrates were further
broadened from 1,3-benzoxazoles to 1,3-benzothiazole (4)
and the results are listed in Table 3. From the results we can
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 42–48

45
W.-Y. Hu et al.
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Synthesis
2 FeO
see that our catalytic system is well suited to 1,3-benzothi-
azole. Similar to the results for 1,3-benzoxazoles 1, in the
reaction of 1,3-benzothiazole (4) the use of arylboronic
acids containing electron-withdrawing groups resulted in a
decrease in the yield (entries 5 and 6); the use of arylboron-
ic acids containing electron-donating groups gave only
slightly lower yields of product (entries 1–3). Naphthalen-
2-yl- and phenanthren-9-ylboronic acids also reacted un-
der these conditions in satisfactory yields (entries 7 and 8).
t-BuOOt-Bu
N
O
Fe2O3
CuI2
CuI
PhB(OH)2
N
ICuPh
CuI
A
Table 3 Reaction of 1,3-Benzothiazole with Arylboronic Acidsa
Cu(Ph)I
O
CuI2
C
N
S
S
N
Cu/Fe
H
+
(OH)2B
2a–h
Ar
Ar
I2CuPh
B
4
5a–h
N
Li
Entry
Ar
Product
Yieldb (%)
O
Scheme 1 Proposed reaction mechanism for the iron and copper sys-
tem catalyzed C–H arylation of azoles with arylboronic acids
1
2
3
4
5
6
7
8
Ph (2a)
4-MeC6H4 (2b)
5a
5b
5c
5d
5e
5f
92
83
82
45
37
55
72
59
3,5-Me2C6H3 (2c)
3-MeOC6H4 (2d)
4-NCC6H4 (2e)
All reagents and solvents were used directly as obtained commercial-
ly unless otherwise noted. Petroleum ether (PE) used refers to the
fraction with bp 60–90 °C. Column chromatography was performed
4-F3CC6H4 (2f)
1
2-naphthyl (2g)
9-phenanthryl (2h)
5g
5h
with 300–400 mesh silica gel using flash column techniques. H and
13C NMR spectra were determined in CDCl3 or DMSO-d6 on a Varian-
Inova 400 MHz spectrometer referenced to internal TMS. Chemical
shifts in 13C NMR spectra are reported relative to the central line of
the CDCl3 (δ = 77.22). IR spectra were recorded on Varian F-1000
spectrometer in KBr. HRMS were obtained with a GCT-TOF instru-
ment.
a Reaction conditions: 1,3-benzothiazole (4, 0.5 mmol), CuI (20 mol%),
Fe2O3 (20 mol%), L1 (20 mol%), LiOt-Bu (1.5 mmol), DTBP (1.0 mmol), aryl-
boronic acid (1.0 mmol), toluene (3 mL), 110 °C, 12 h.
b Isolated yield based on 4 after silica gel chromatography.
To gain insight into whether the reaction is a radical re-
action or not, a model reaction was carried out with
2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO, 2.0 equiv) as
an additive under standard conditions; the arylation prod-
uct was obtained with similar yield and no radicals were
captured with TEMPO. Referring to previously reported
mechanisms,15,20 a reaction mechanism was proposed as
shown in Scheme 1. Copper(I) iodide is oxidized to cop-
per(II) iodide by iron(III) oxide, which is itself reoxidized by
di-tert-butyl peroxide. Then a transmetalation from phen-
ylboronic acid with copper(II) iodide occurred which forms
an arylcopper(II) species A. Intermediate A is oxidized to
arylcopper(III) intermediate B. Then, the other transmeta-
lation gives intermediate C. Finally, the desired cross-
coupling product is obtained via a reductive elimination re-
action.
In summary, an inexpensive and nonpoisonous iron and
copper catalytic system has been successfully used, replac-
ing noble metals like palladium salts which are costly and
nocuous to the environment, in the reaction of azoles with
arylboronic acids. From synthetic point of view, an effec-
tive, facile, and environmentally friendly method for the
preparation of azoles has been developed.
2-Phenyl-1,3-benzoxazole (3a);12 Typical Procedure
CuI (19 mg, 0.1 mmol), Fe2O3 (16 mg, 0.1 mmol), 1,10-phenanthroline
(18 mg, 0.1 mmol), LiOt-Bu (180 mg, 1.5 mmol), and di-tert-butyl
peroxide (146 mg, 1.0 mmol) were added to a solution of toluene (3
mL) containing phenylboronic acid (1.0 mmol) and 1,3-benzoxazole
(0.5 mmol). The mixture was stirred at 110 °C for 12 h. The resulting
mixture was then cooled to r.t. and the solvent was removed in vacuo
and the remaining residue was purified by column chromatography
(silica gel, PE–EtOAc, 20:1) to yield 3a (84.8 mg, 87%) as a light yellow
solid; mp 105–107 °C.
IR (KBr): 3060, 1616, 1551, 1489, 1472, 1446, 1343, 1278, 1241, 1052,
1021, 923, 807, 747, 702, 687 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.23–8.21 (m, 2 H), 7.75–7.73 (m, 1 H),
7.55–7.47 (m, 4 H), 7.32–7.30 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 163.24, 150.96, 142.30, 131.72,
129.11, 127.82, 127.36, 125.31, 124.78, 120.22, 110.80.
HRMS (EI): m/z [M]+ calcd for C13H9NO: 195.0684; found: 195.0685.
2-p-Tolyl-1,3-benzoxazole (3b)12
Yellow solid; yield: 81.5 mg (78%); mp 115–117 °C.
IR (KBr): 3026, 2918, 2306, 1622, 1555, 1501, 1450, 1243, 1177, 1055,
1017, 820, 745, 726, 501 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.16 (d, J = 8.0 Hz, 2 H), 7.78–7.71 (m, 1
H), 7.59–7.51 (m, 1 H), 7.36–7.22 (m, 4 H), 2.43 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 42–48

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W.-Y. Hu et al.
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Synthesis
13C NMR (100 MHz, CDCl3): δ = 163.49, 150.88, 142.37, 142.25,
129.84, 127.79, 125.06, 124.67, 124.60, 120.03, 110.69, 21.85.
HRMS (EI): m/z [M]+ calcd for C14H11NO: 209.0841; found: 209.0844.
13C NMR (100 MHz, CDCl3): δ = 163.34, 151.00, 142.36, 134.89,
131.11, 129.10, 128.93, 128.30, 128.06, 127.95, 127.05, 125.34,
124.80, 124.52, 124.10, 120.18, 110.76.
HRMS (EI): m/z [M]+ calcd for C17H11NO: 245.0841; found: 245.0839.
2-(3,5-Dimethylphenyl)-1,3-benzoxazole (3c)21
2-(Phenanthren-9-yl)-1,3-benzoxazole (3h)25
White solid; yield: 82.5 mg (74%); mp 122–124 °C.
White solid; yield: 92.9 mg (63%); mp 162–164 °C.
IR (KBr): 2916, 2382, 2303, 1600, 1551, 1452, 1243, 1229, 1183, 1003,
929, 863, 741, 682 cm–1
.
IR (KBr): 1615, 1542, 1523, 1447, 1242, 1135, 999, 949, 902, 770, 728
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.78 (s, 2 H), 7.70–7.61 (m, 1 H), 7.46–
7.44 (m, 1 H), 7.25–7.22 (m, 2 H), 7.04 (s, 1 H), 2.29 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 163.56, 150.82, 142.23, 138.72,
133.44, 126.99, 125.51, 125.08, 124.63, 120.02, 110.64, 21.38.
1H NMR (400 MHz, CDCl3): δ = 9.55–9.52 (m, 1 H), 8.80–8.71 (m, 3 H),
8.03 (d, J = 8.0 Hz, 1 H), 7.92–7.89 (m, 1 H), 7.77–7.73 (m, 3 H), 7.68–
7.65 (m, 2 H), 7.43–7.41 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 162.93, 150.40, 142.50, 131.95,
131.82, 131.01, 130.75, 130.00, 128.92, 128.88, 127.83, 127.34,
127.32, 125.60, 124.75, 123.15, 122.91, 122.76, 120.54, 110.72.
HRMS (EI): m/z [M]+ calcd for C15H13NO: 223.0997; found: 223.0998.
2-(3-Methoxyphenyl)-1,3-benzoxazole (3d)22
HRMS (EI): m/z [M]+ calcd for C21H13NO: 295.0997; found: 295.0994.
White solid; yield: 56.3 mg (50%); mp 70–72 °C.
IR (KBr): 2833, 2385, 1602, 1555, 1488, 1452, 1243, 1043, 859, 784,
2-(Biphenyl-4-yl)-1,3-benzoxazole (3i)12
748, 725, 682 cm–1
.
White solid; yield: 70.5 mg (52%); mp 142–143 °C.
1H NMR (400 MHz, CDCl3): δ = 7.98–7.93 (m, 2 H), 7.67–7.65 (m, 1 H),
7.46–7.44 (m, 1 H), 7.30–7.20 (m, 4 H), 2.33 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 163.11, 160.08, 150.89, 142.20,
130.17, 128.48, 125.34, 124.77, 120.77, 120.17, 118.51, 112.02,
110.78, 55.68.
IR (KBr): 3027, 1568, 1482, 1446, 1406, 1289, 1245, 1057, 847, 744,
700 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.55–7.54 (m, 2 H), 7.42–7.35 (m, 8 H),
7.06 (d, J = 8.0 Hz, 2 H), 6.73 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 163.12, 150.97, 146.76, 144.42,
140.92, 128.89, 128.28, 128.08, 127.35, 127.00, 126.33, 125.33,
124.82, 120.16, 110.79.
HRMS (EI): m/z [M]+ calcd for C14H11NO2: 225.0790; found: 225.0795.
4-(1,3-Benzoxazol-2-yl)benzonitrile (3e)23
HRMS (EI): m/z [M]+ calcd for C19H13NO: 271.0997; found: 271.0993.
White solid; yield: 46.2 mg (42%); mp 204–206 °C.
IR (KBr): 3060, 2227, 1613, 1493, 1474, 1450, 1410, 1341, 1242, 1096,
2-(Pyrimidin-5-yl)-1,3-benzoxazole (3j)26
1055, 927, 843, 816, 760, 692, 548 cm–1
.
White solid; yield: 59.1 mg (60%); mp 137–139 °C.
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 8.0, 2 H), 7.64 (d, J = 8.0 Hz,
1 H), 7.45–7.42 (m, 2 H), 7.39–7.31 (m, 2 H), 7.23 (d, J = 7.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 161.12, 151.09, 142.05, 132.90,
131.32, 128.17, 126.37, 125.34, 121.72, 120.77, 114.93, 111.09.
HRMS (EI): m/z [M]+ calcd for C14H8N2O: 220.0637; found: 220.0639.
IR (KBr): 3407, 3060, 1549, 1512, 1489, 1458, 1431, 1343, 1216, 1241,
1052, 1019, 912, 824, 755, 693, 675 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.17 (s, 1 H), 7.97–7.87 (m, 4 H), 7.51
(s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 138.61, 133.94, 132.86, 128.72,
128.44, 127.88, 126.56, 126.32, 126.21, 125.94.
HRMS (EI): m/z [M]+ calcd for C11H7N3O: 197.0589; found: 197.0586.
2-[4-(Trifluoromethyl)phenyl]-1,3-benzoxazole (3f)24
White solid; yield: 76.3 mg (58%); mp 154–156 °C.
IR (KBr): 3054, 1917, 1614, 1590, 1482, 1433, 1404, 1321, 1169, 1109,
8-(1,3-Benzoxazol-2-yl)quinoline (3k)27
1064, 1011, 967, 859, 754, 731, 675, 617, 587 cm–1
.
Brown oil; yield: 76.3 mg (62%).
1H NMR (400 MHz, CDCl3): δ = 8.38 (d, J = 8.12 Hz, 2 H), 7.82–7.80 (m,
3 H), 7.63–7.60 (m, 1 H), 7.43–7.38 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 161.70, 151.08, 142.11, 133.37,
133.04, 130.65, 128.08, 126.15 (q, J = 3.78), 126.0499, 125.16, 120.62,
111.02.
IR (KBr): 3057, 1654, 1593, 1542, 1494, 1452, 1381, 1320, 1242, 1177,
1125, 1066, 924, 832, 793, 746, 653, 624 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 9.18–9.16 (m, 1 H), 8.51–8.49 (m, 1 H),
8.25–8.22 (m, 1 H), 8.01–7.98 (m, 1 H), 7.95–7.92 (m, 1 H), 7.69–7.62
(m, 2 H), 7.52–7.49 (m, 1 H), 7.40–7.37 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 162.37, 151.95, 151.04, 145.97,
142.39, 136.74, 132.82, 131.83, 128.87, 126.36, 126.09, 125.38,
124.50, 121.81, 120.84, 110.88.
HRMS (EI): m/z [M]+ calcd for C14H8NOF3: 263.0558; found: 263.0554.
2-(Naphthalen-2-yl)-1,3-benzoxazole (3g)12
White solid; yield: 98 mg (80%); mp 117–119 °C.
HRMS (EI): m/z [M]+ calcd for C16H10N2O: 246.0793; found: 246.0795.
IR (KBr): 3050, 2359, 1541, 1452, 1362, 1244, 1178, 1049, 950, 866,
760, 750, 740, 472 cm–1
.
5-Chloro-2-phenyl-1,3-benzoxazole (3l)28
1H NMR (400 MHz, CDCl3): δ = 8.75 (s, 1 H), 8.29 (d, J = 8.0 Hz, 1 H),
7.94 (d, J = 8.0 Hz, 2 H), 7.85–7.79 (m, 2 H), 7.55–7.53 (m, 3 H), 7.36 (s,
2 H).
Yellow solid; yield: 83.6 mg (73%); mp 108–111 °C.
IR (KBr): 3062, 1611, 1553, 1465, 1334, 1262, 1053, 1023, 918, 864,
809, 701, 683, 593 cm–1
.
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1H NMR (400 MHz, CDCl3): δ = 8.17 (d, J = 6.32 Hz, 2 H), 7.68 (s, 1 H),
13C NMR (100 MHz, CDCl3): δ = 168.21, 154.28, 135.20, 133.75,
7.48–7.43 (m, 4 H), 7.19 (s, 1 H).
131.12, 129.17, 127.70, 126.47, 125.34, 123.38, 121.77.
13C NMR (100 MHz, CDCl3): δ = 164.57, 149.55, 143.35, 132.15,
HRMS (EI): m/z [M]+ calcd for C13H9NS: 211.0456; found: 211.0448.
130.24, 129.21, 127.96, 126.89, 125.59, 120.18, 111.52.
2-p-Tolyl-1,3-benzothiazole (5b)12
HRMS (EI): m/z [M]+ calcd for C13H8ClNO: 229.0294; found: 229.0292.
Yellow solid; yield: 93.4 mg (83%); mp 86–89 °C.
IR (KBr): 3056, 2954, 1591, 1447, 1217, 955, 751, 447 cm–1
5-Chloro-2-p-tolyl-1,3-benzoxazole (3m)22
.
Yellow solid; yield: 81.4 mg (67%); mp 139–141 °C.
1H NMR (400 MHz, CDCl3): δ = 8.07 (d, J = 7.72 Hz, 2 H), 7.69–7.67 (m,
IR (KBr): 2963, 1615, 1559, 1498, 1449, 1260, 1199, 1104, 1016, 916,
1 H), 7.50–7.48 (m, 1 H), 7.26 (s, 4 H), 2.36 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.40, 154.33, 141.62, 135.00,
131.12, 129.91, 127.66, 126.52, 125.19, 123.22, 121.76, 21.72.
HRMS (EI): m/z [M]+ calcd for C14H11NS: 225.0612; found: 225.0618.
893, 792, 726, 703, 498 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.12 (d, J = 8.0 Hz, 2 H), 7.73 (d, J = 7.04
Hz, 1 H), 7.48 (d, J = 8.0 Hz, 1 H), 7.35–7.29 (m, 3 H), 2.45 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.52, 154.28, 139.05, 132.00,
2-(3,5-Dimethylphenyl)-1,3-benzothiazole (5c)31
Yellow solid; yield: 98 mg (82%); mp 72–75 °C.
129.10, 128.17, 126.47, 125.31, 125.05, 123.34, 121.78, 21.54.
HRMS (EI): m/z [M]+ calcd for C13H10ClNO: 243.0451; found:
243.0452.
IR (KBr): 2915, 1773, 1598, 1506, 1432, 1309, 1277, 1184, 1040, 874,
842, 754, 725, 686 cm–1
.
5-Chloro-2-[4-(trifluoromethyl)phenyl]-1,3-benzoxazole (3n)29
White solid; yield: 84.6 mg (57%); mp 147–149 °C.
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.08 Hz, 1 H), 7.76 (d, J =
7.84 Hz, 1 H), 7.60 (s, 2 H), 7.37 (t, J = 7.53 Hz, 1 H), 7.25 (t, J = 7.42 Hz,
1 H), 7.00 (s, 1 H), 2.29 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 168.99, 154.22, 138.84, 135.11,
133.54, 132.90, 126.38, 125.47, 125.18, 123.22, 121.71, 21.38.
IR (KBr): 2936, 2359, 1557, 1501, 1453, 1412, 1325, 1261, 1163, 1112,
1072, 1014, 919, 848, 806, 752, 700, 589 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.35 (d, J = 8.24 Hz, 2 H), 7.80–7.77 (m,
3 H), 7.53 (d, J = 8.6 Hz, 1 H), 7.35 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 162.97, 149.63, 143.19, 133.40,
130.66, 130.16, 128.22, 126.33, 126.21 (q, J = 3.69), 125.21, 122.50,
120.55, 111.75.
HRMS (EI): m/z [M]+ calcd for C14H13NS: 239.0769; found: 239.0766.
2-(3-Methoxyphenyl)-1,3-benzothiazole (5d)32
White solid; yield: 54.2 mg (45%); mp 84–87 °C.
HRMS (EI): m/z [M]+ calcd for C14H7ClF3NO: 297.0168; found:
297.0166.
IR (KBr): 3060, 2833, 1604, 1470, 1289, 1047, 995, 871, 761, 727, 684
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.07 (d, J = 8.04, 1 H), 7.88 (d, J = 7.84
Hz, 1 H), 7.64 (m, 2 H), 7.48 (t, J = 7.64, Hz, 1 H), 7.39–7.35 (m, 2 H),
7.02 (d, J = 7.56 Hz, 1 H), 3.89 (s, 3 H).
5-Nitro-2-phenyl-1,3-benzoxazole (3o)29
White solid; yield: 54 mg (45%); mp 167–169 °C.
IR (KBr): 2963, 1615, 1553, 1527, 1449, 1350, 1261, 1067, 1023, 890,
13C NMR (100 MHz, CDCl3): δ = 168.08, 160.10, 154.20, 135.23,
135.03, 130.18, 126.46, 125.37, 123.38, 121.76, 120.37, 117.47,
112.17, 55.63.
820, 736, 704, 685 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.66 (s, 1 H), 8.34–8.27 (m, 3 H), 7.79
(d, J = 8.0 Hz, 1 H), 7.62–7.55 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 166.22, 154.48, 143.15, 132.85,
HRMS (EI): m/z [M]+ calcd for C14H11NOS: 241.0561; found: 241.0556.
4-(1,3-Benzothiazol-2-yl)benzonitrile (5e)25
130.56, 129.38, 128.27, 126.19, 121.37, 116.52, 110.96.
HRMS (EI): m/z [M]+ calcd for C13H8N2O3: 240.0535; found: 240.0539.
White solid; yield: 43.7 mg (37%); mp 163–165 °C.
IR (KBr): 3062, 2227, 1603, 1495, 1476, 1450, 1412, 1343, 1245, 1061,
4-Phenyl-2-p-tolyloxazole (3p)30
834, 679, 618, 553 cm–1
.
Yellow solid; yield: 75.2 mg (64%); mp 113–115 °C.
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 8.44 Hz, 2 H), 7.57 (d, J =
8.20 Hz, 1 H), 7.36 (d, J = 8.44 Hz, 2 H), 7.31–7.24 (m, 2 H), 7.16 (d, J =
7.04 Hz, 1 H).
IR (KBr): 3047, 2934, 2418, 1676, 1571, 1483, 1421, 1214, 1165, 1035,
983, 810, 733, 710, 482 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 8.70 (s, 1 H), 7.96–7.86 (m, 4 H),
13C NMR (100 MHz, CDCl3): δ = 146.91, 138.70, 133.35, 132.49,
7.46–7.37 (m, 5 H), 2.38 (s, 3 H).
129.82, 129.14, 128.95, 126.86, 119.17, 118.40, 111.94, 100.48.
13C NMR (100 MHz, DMSO-d6): δ = 161.65, 141.39, 141.19, 135.73,
HRMS (EI): m/z [M]+ calcd for C14H8N2S: 241.0561; found: 241.0556.
131.28, 130.25, 129.32, 128.57, 126.56, 125.73, 124. 62, 21.56.
2-[4-(Trifluoromethyl)phenyl]-1,3-benzothiazole (5f)25
White solid; yield: 76.7 mg (55%); mp 161–163 °C.
HRMS (EI): m/z [M]+ calcd for C16H13N2O: 235.0997; found: 235.0994.
2-Phenyl-1,3-benzothiazole (5a)12
IR (KBr): 3056, 1919, 1617, 1484, 1435, 1407, 1323, 1173, 1109, 1066,
Yellow solid; yield: 97 mg (92%); mp 110–113 °C.
971, 842, 760, 678, 620, 589 cm–1
.
IR (KBr): 3061, 1897, 1597, 1306, 1228, 1067, 958, 756, 684, 552 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.17 (s, 2 H), 7.69 (s, 1 H), 7.50–7.43
.
1H NMR (400 MHz, CDCl3): δ = 8.18 (d, J = 8.0 Hz, 2 H), 8.09 (d, J = 8.0
Hz, 1 H), 7.90 (d, J = 8.0 Hz, 1 H), 7.73 (d, J = 8.0 Hz, 2 H), 7.51 (t, J = 8.0
Hz, 1 H), 7.41 (t, J = 8.0 Hz, 1 H).
(m, 4 H), 7.28 (s, 2 H).
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Synthesis
13C NMR (100 MHz, CDCl3): δ = 166.26, 154.25, 136.98, 135.41,
132.50, 127.98, 126.87, 126.23 (q, J = 3.7), 126.00, 123.84, 121.96.
HRMS (EI): m/z [M]+ calcd for C14H8F3NS: 279.0330; found: 279.0332.
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2-(Naphthalen-2-yl)-1,3-benzothiazole (5g)12
Yellow solid; yield: 94 mg (72%); mp 126–128 °C.
IR (KBr): 3045, 2347, 1527, 1442, 1353, 1224, 1164, 1030, 939, 857,
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2, 1403.
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1H NMR (400 MHz, CDCl3): δ = 8.57 (s, 1 H), 8.22 (d, J = 8.0 Hz, 1 H),
8.12 (d, J = 8.0 Hz, 1 H), 7.99–7.93 (m, 3 H), 7.90–7.88 (m, 1 H), 7.57–
7.54 (m, 2 H), 7.51 (d, J = 8.0 Hz, 1 H), 7.41 (t, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 168.34, 154.43, 135.32, 134.81,
133.39, 131.18, 129.04, 128.08, 127.79, 127.68, 127.10, 126.60,
125.46, 124.64, 123.44, 122.24, 121.86.
HRMS (EI): m/z [M]+ calcd for C17H11NS: 261.0612; found: 261.0615.
2-(Phenanthren-9-yl)-1,3-benzothiazole (5h)33
Yellow oil; yield: 91.7 mg (59%).
IR (KBr): 1627, 1554, 1533, 1450, 1254, 1147, 1012, 958, 921, 787,
741 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.92 (d, J = 8.0 Hz, 1 H), 8.79 (d, J = 8.0
Hz, 1 H), 8.74 (d, J = 8.0 Hz, 1 H), 8.22 (d, J = 8.0 Hz, 2 H), 7.99 (t, J = 8.0
Hz, 2 H), 7.77–7.64 (m, 4 H), 7.58 (t, J = 8.0 Hz, 1 H), 7.48 (t, J = 8.0 Hz,
1 H).
13C NMR (100 MHz, CDCl3): δ = 167.78, 154.28, 135.58, 131.37,
131.25, 131.01, 130.86, 130.01, 129.60, 129.42, 128.37, 127.66,
127.42, 127.31, 126.89, 126.54, 125.60, 123.78, 123.10, 122.90,
121.63.
HRMS (EI): m/z [M]+ calcd for C21H13NS: 211.0769; found: 211.0771.
Acknowledgment
We gratefully acknowledge A Project Funded by the Priority Academic
Program Development of Jiangsu Higher Education Institutions, The
Project of Scientific and Technologic Infrastructure of Suzhou
(SZS201207) and the National Natural Science Foundation of China
(No. 21072143) for financial support.
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379073.
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