Rhodium-catalyzed direct oxidative cross-coupling of 2-aryl pyridine with benzothiazoles

Article abstract of DOI:10.1016/j.tet.2014.07.022

A rhodium-catalyzed cross-coupling reaction of 2-aryl pyridine and benzothiazoles via dual C-H bond functionalization has been developed in the presence of copper salts. The reaction system provides a new approach to heterobiaryl species, which are ubiquitous in pharmaceuticals and nature products.

Full text of DOI:10.1016/j.tet.2014.07.022

Tetrahedron 70 (2014) 6474e6481
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Tetrahedron
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Rhodium-catalyzed direct oxidative cross-coupling of 2-aryl
pyridine with benzothiazoles
*
Hui Liu, Huan Xu, Yu Yuan
College of Chemistry and Chemical Engineering, Yangzhou University, 225002 Yangzhou, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 May 2014
Received in revised form 1 July 2014
Accepted 7 July 2014
Available online 10 July 2014
A rhodium-catalyzed cross-coupling reaction of 2-aryl pyridine and benzothiazoles via dual CeH bond
functionalization has been developed in the presence of copper salts. The reaction system provides a new
approach to heterobiaryl species, which are ubiquitous in pharmaceuticals and nature products.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Rhodium
2-Aryl pyridine
Benzothiazoles
Dehydrogenation
Cross-coupling
1. Introduction
2. Results and discussion
Heterobiaryl species are usually very important compounds in
biological, pharmaceutical, and material sciences due to the con-
struction of backbone of pharmaceuticals and nature products. The
traditional method for synthesis of these compounds is cross-
coupling reactions of aryl halides with heteroarylmetals or aryl-
metals with heteroaryl halides catalyzed by different metals.1 In the
past decades, several efficient catalytic systems have been de-
veloped in the direct arylation of heterocycle CeH bonds with aryl
halides employing Pd,2 Rh,3 Ru,4 Ir,5 Fe,6 Co,7 Ni,8 and Cu.9 A more
efficient protocol for the synthesis would be cross-
dehydrogenative-coupling of arenes and heteroarenes directly by
using palladium,10 copper,11 rhodium,12 and ruthenium13 as the
catalyst. In these cases, several heteroarene derivatives have been
studied to achieve this goal, such as oxazoles,14 thiazoles,15 imid-
azoles,16 furans,17 thiophenes,18 pyrroles.19
Among these research, Miura and co-workers developed CeH
functionalization of 2-aryl pyridine with benzoxazole in the pres-
ence of copper salt in good yields.14a You’s group realized this
transformation by using (RhCp*Cl2)2 as the catalyst in the presence
of copper salt.12j In continuing our efforts in transition metal-
catalyzed CeH functionalization,20 herein, we report rhodium (II)
acetate catalyze direct cross-dehydrogenative-coupling reaction of
2-aryl pyridine with benzothiazoles in the presence of Cu(OAc)2
(Fig. 1).
Initially, the cross-coupling reaction of 2-phenylpyridine (1a)
with benzothiozole (2a) was carried out in the presence of
3 equiv Cu(OAc)2 in N,N-dimethylacetamide (DMA) at 160 ꢀC for
9 h under an argon atmosphere, forming the desired product (3aa)
in 15% yields (Table 1, entry 1). Interestingly, while catalytic rho-
dium acetate dimmer and Xantphos (entry 4) were used in the
system, the yield was increased to 42%. The other ligands (entries
5e7) also could improve the reactivity of rhodium species and the
best ligand is triphenylphosphine (entry 7). Usually, CuI is an effi-
cient reagent in the coupling reaction of benzothiozoles,21 which
was chosen as an additive. It was found that 0.5 equiv CuI was
employed in this reaction under former conditions to obtain the
product 3aa in 81% yield (entry 11). While the amount of CuI was
increased to 1 equiv the yield could be achieved to 90% without
diheteroarylated product, which showed the good regioselectivity
and higher yield compared with the literature.14a (entry 12).
Whereas only 30% yield was obtained in the reaction using CuCl as
the additive (entry 13). It was shown that the Cu(OAc)2 was nec-
essary for the reaction since the absence of Cu(OAc)2 induced the
decrease of the yield (58%) even 1 equiv CuI was added under the
conditions (entry 14). Moreover, the reaction could not carry out
without two copper salts using rhodium acetate as the catalyst
(entry 15).
With a highly active catalytic system in hand, the scope of 2-
phenylpyridines was investigated. As expected, a variety of
substituted
2-phenylpyridines
1
were
reacted
with
* Corresponding author. E-mail address: yyuan@yzu.edu.cn (Y. Yuan).
http://dx.doi.org/10.1016/j.tet.2014.07.022
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

H. Liu et al. / Tetrahedron 70 (2014) 6474e6481
6475
Fig. 1. The work on dehydrogenative cross-coupling of heteroarenes.
Table 1
Optimization of the reaction conditionsa
Entry
Cat. (mol %)
L (mol %)
Additive
Solvents
Yield (%)b
1
2
3
4
5
6
7
8
DMA
DMA
DMA
DMA
DMA
DMA
DMA
Mesitylene
DMSO
DMF
DMA
DMA
DMA
DMA
DMA
15
0
Pd(OAc)2 (10)
Xantphosc (20)
RhCl(PPh3)3 (10)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
[Rh(OAc)2]2 (5)
18
42
34
24
53
17
46
36
81
90
30
58d
Tracee
Xantphos (20)
1,10-Phenanthroline (20)
2,20-Bipyridine (20)
PPh3 (20)
PPh3 (20)
PPh3 (20)
PPh3 (20)
PPh3 (20)
PPh3 (20)
PPh3 (20)
9
10
11
12
13
14
15
CuI(0.5)
CuI(1)
CuCl(1)
CuI(1)
PPh3 (20)
PPh3 (20)
a
Reaction conditions: 1a (0.2 mmol), 2a (0.6 mmol), catalyst, copper acetate (0.6 mmol), additive, solvent (2.0 mL), 160 ꢀC, 9 h.
Yield after purification.
4,5-Bis-diphenylphosphanyl-9,9-dimethyl-9H-xanthene.
Without 3 equiv Cu(OAC)2.
Without Cu(OAc)2 and CuI.
b
c
d
e
benzothiazole 2a to evaluate the substitution effects in 2-
Next, various benzothiazole derivatives worked well under the
optimal conditions. A range of functional groups could be tolerated
in this reaction, such as alkyl, methoxy, chloro, nitro, and ester
group. Among these cases, the electro-rich substituent on the
phenyl ring of benzothiozoles benefited from the reaction (Table 3,
entries 1 and 2), whereas the electro-deficient substituents affected
the reaction efficient (entries 3 and 4). However, the reaction was
turned less active while the substituted benzothiazole with nitro
group (entry 5) was employed in the transformation. Un-
fortunately, benzoxazole was not a nice substrate under the
phenylpyridine. The electro-rich substituent on the aryl ring of
2-aryl pyridine showed good reactivities in the reaction. 94%
Yield of products could be achieved using 2-(4-methoxyphenyl)
pyridine 1e as the substrate (Table 2, entry 5). In contrast,
electro-deficient substituent on the aryl ring of 2-aryl pyridine
hindered the reaction, which induced to form moderate yield of
corresponding product (entries 7e9). Fortunately, the chloro
group was compatible with the reaction conditions in 62% yield
(entry 10).

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H. Liu et al. / Tetrahedron 70 (2014) 6474e6481
Table 2
Reaction of 2-phenylpyridine derivatives with benzothiazolea
Entry
2-Phenylpyridine 1
Product 3
Yield (%)b
1
90
1a
3aa
3ba
3ca
2
3
4
78
53
89
1b
1c
1d
3da
5
94
1e
3ea
6
81
1f
3fa

H. Liu et al. / Tetrahedron 70 (2014) 6474e6481
6477
Table 2 (continued )
Entry
2-Phenylpyridine 1
Product 3
Yield (%)b
7
8
9
76
74
72
1g
3ga
1h
3ha
1i
3ia
10
62
1j
3ja
a
Reaction conditions: 1a (0.2 mmol), 2 (0.6 mmol), [Rh(OAc)2]2 (5 mol %), PPh3 (20 mol %), Cu(OAc)2 (3 equiv), CuI (1 equiv), DMA (2.0 mL), 160 ꢀC, 9 h.
Yield after purification.
b
conditions, and the corresponding product 3ag was formed only in
60% yield (entry 6).
method provided a concise access to heteroarene-containing biaryl
structure, which could be applied in pharmacy and organic synthesis.
A hypothetical mechanism for the oxidative cross-coupling of 2-
aryl pyridine with benzothiazoles is depicted in Scheme 1. First,
rhodium (II) acetate was oxidized to Rh (III) complex22 in the
presence of Cu(OAc)2 and PPh3, which is the real active species,
through the chelate-directed CeH activation of 2-aryl pyridine 1
form the intermediate A. Then rhodium complex A reacted with
copper complex B, which was confirmed by a previous report about
the reaction of benzothiazole 2 with CuI,15b,23 to produce in-
termediate C via transmetalation. The desired product 3 was ob-
tained while the intermediate C underwent reductive elimination.
Finally, the formed Rh (I) species was oxidized by Cu(OAc)2 to
regenerated Rh (III) to fulfill the catalytic cycle. Meanwhile, the
copper acetate converted to Cu (0), which could be found after
reaction.
4. Experimental section
4.1. General methods
1H NMR and 13C NMR spectra were obtained with a Bruker
AVANCE 600 spectrometer in CDCl3 with TMS as an internal stan-
dard. Chemical shifts (d) are reported in parts per million, and
coupling constants (J) are in Hertz (Hz). The following abbreviations
were used to explain the multiplicities: s¼singlet, d¼doublet,
t¼triplet, q¼quartet, m¼multiplet, br¼broad. FTIR spectra were
obtained with a Cary 610/670 spectrophotometer. HRMS were ob-
tained on a Finnigan MAT8430 instrument. All reactions were
monitored by TLC. Flash column chromatograph was carried out
using 300e400 mesh silica gel at medium pressure.
3. Conclusions
4.2. Typical procedure
In conclusion, we have developed an efficient rhodium-catalyzed
cross-dehydrogenative-coupling of 2-aryl pyridine with benzothia-
zoles in moderate to good yields in the presence of copper salts. This
[Rh(OAc)2]2 (4.4 mg, 0.01 mmol), 2-phenylpyridine 1a (31 mg,
0.2 mmol), PPh3 (10.4 mg, 0.04 mmol), CuI (38.2 mg, 0.2 mmol),

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H. Liu et al. / Tetrahedron 70 (2014) 6474e6481
Table 3
Reaction of 2-phenylpyridine with benzothiazole derivativesa
Entry
Benzothiazole 2
Product 3
Yield (%)b
1
81
3ab
2b
2
85
2c
3ac
3
4
5
93
91
85
60
2d
3ad
2e
3ae
2f
3af
6
2g
3ag
a
Reaction conditions: 1a (0.2 mmol), 2 (0.6 mmol), [Rh(OAc)2]2 (5 mol %), PPh3 (20 mol %), Cu(OAc)2 (3 equiv), CuI (1 equiv), DMA (2.0 mL), 160 ꢀC, 9 h.
Yield after purification.
b

H. Liu et al. / Tetrahedron 70 (2014) 6474e6481
6479
Scheme 1. Plausible mechanism for the oxidative cross-coupling of 2-aryl pyridine with benzothiazoles.
Cu(OAc)2 (108.6 mg, 0.6 mmol), N,N-dimethylacetamide (2.0 mL)
were placed inside a 10 mL Schlenk tube equipped with a reflux
condenser. Then, the temperature was risen to 160 ꢀC. Benzothia-
zole 2a (81 mg, 0.6 mmol) was separated into five portions and
each portion was added within 1 h. After finishing addition, the
solution was stirred under argon atmosphere at 160 ꢀC for another
4 h. After cooling to room temperature, the reaction mixture was
quenched with ethyl acetate (15 mL) and washed with water
(30 mL). The aqueous phase was extracted twice with EtOAc
(3ꢁ10 mL), and the combined organic layer was dried over anhy-
drous Na2SO4. After evaporation of the solvents in vacuo, the crude
product was purified by column chromatography on silica gel
(petroleum ether/EtOAc¼3/1) to give desire product 3aa as yellow
oil; yield: 51.8 mg (90%).
728, 692 cmꢂ1; HRMS: calcd for C19H14N2S: 302.0878, found:
302.0876.
4.2.3. 2-(2,4-Dimethyl-6-(pyridin-2-yl)phenyl)benzothiazole
(3ca). Yield: 53%. Yellow oil. 1H NMR (600 MHz, CDCl3)
d 8.54e8.50
(m, 1H), 8.05 (d, J¼8.2 Hz, 1H), 7.74 (d, J¼7.8 Hz, 1H), 7.48e7.43 (m,
1H), 7.37 (s, 1H), 7.36e7.31 (m, 2H), 7.19e7.14 (m, 2H), 7.02 (m, 1H),
2.42 (s, 3H), 2.28 (s, 3H); 13C NMR (150 MHz, CDCl3)
d
167.8, 158.6,
153.3, 149.4, 141.2, 140.0, 138.1, 136.9, 135.9, 131.6, 129.6, 128.5,
126.0, 125.1, 124.7, 123.5, 121.9, 121.6, 21.5, 20.5; IR (KBr)
n¼3058,
2922, 2856, 1586, 1565, 1520, 1456, 1436, 1313, 1277, 1219, 1086,
1038, 861, 792, 759, 687 cmꢂ1; HRMS: calcd for C20H16N2S:
316.1034, found: 316.1039.
4.2.4. 2-(3-Methoxy-2-(pyridin-2-yl)phenyl)benzothiazole
Yield: 89%. Yellow oil. 1H NMR (600 MHz, CDCl3)
(3da).-
8.64 (d,
4.2.1. 2-[2-(Pyridin-2-yl)phenyl] benzothiazole (3aa). Yield: 90%.
d
Yellow oil. 1H NMR (600 MHz, DMSO-D6)
d
8.52 (d, J¼4.8 Hz, 1H),
8.03e7.90 (m, 3H), 7.78 (t, J¼11.6 Hz, 1H), 7.71e7.59 (m, 3H), 7.41
(m, 4H); 13C NMR (150 MHz, DMSO-D6)
167.0, 157.6, 152.6, 149.2,
140.4, 136.6, 135.8, 132.2, 130.6, 130.4, 130.4, 128.7, 126.2, 125.2,
J¼4.7 Hz, 1H), 7.94 (d, J¼8.2 Hz, 1H), 7.72e7.64 (m, 3H), 7.49 (dd,
J¼10.7, 5.5 Hz, 1H), 7.41e7.37 (m, 1H), 7.34 (d, J¼7.8 Hz, 1H), 7.26 (m,
2H), 7.11 (d, J¼8.3 Hz, 1H), 3.78 (s, 3H); 13C NMR (150 MHz, CDCl3)
d
d
167.3, 157.6, 155.6, 153.5, 149.7, 136.7, 136.3, 134.7, 129.9, 126.9,
124.5, 122.8, 122.7, 121.9; IR (KBr)
n
¼3059, 1585, 1562, 1522, 1457,
126.1, 125.1, 123.5, 122.7, 122.7, 121.4, 113.1, 56.3; IR (KBr)
n
¼3060,
1434, 1312, 1268, 1218, 1022, 964, 794, 759, 690, 616, 437 cmꢂ1
HRMS: calcd for C18H12N2S: 288.0721, found: 288.0725.
;
2930, 2851, 1592, 1495, 1461, 1431, 1380, 1312, 1260, 1083, 992, 800,
759, 664 cmꢂ1; HRMS: calcd for C19H14N2OS: 318.0827, found:
318.0831.
4.2.2. 2-(4-Methyl-2-(pyridin-2-yl)phenyl)benzothiazole
(3ba).-
8.63 (d,
Yield: 78%. Yellow oil. 1H NMR (600 MHz, CDCl3)
d
4.2.5. 2-(5-Methoxy-2-(pyridin-2-yl)phenyl)benzothiazole
Yield: 94%. Yellow oil. 1H NMR (600 MHz, CDCl3)
(3ea).-
8.59 (d,
J¼3.3 Hz, 1H), 7.96 (d, J¼8.1 Hz, 1H), 7.85 (d, J¼7.9 Hz, 1H), 7.72 (d,
J¼8.0 Hz, 1H), 7.54 (td, J¼7.7, 1.7 Hz, 1H), 7.45 (s, 1H), 7.43e7.39
(m, 1H), 7.34 (dd, J¼7.8, 0.8 Hz, 1H), 7.32e7.27 (m, 1H), 7.26e7.23
(m, 1H), 7.20 (m, 1H), 2.45 (s, 3H); 13C NMR (150 MHz, CDCl3)
d
J¼4.2 Hz, 1H), 8.00 (d, J¼8.1 Hz, 1H), 7.74 (d, J¼7.9 Hz, 1H), 7.58 (d,
J¼8.5 Hz, 1H), 7.51 (t, J¼7.7 Hz, 1H), 7.48e7.41 (m, 2H), 7.32 (t,
J¼7.5 Hz, 1H), 7.21 (d, J¼7.8 Hz, 1H), 7.18e7.14 (m, 1H), 7.11 (dd,
d
167.9, 158.6, 153.4, 149.7, 140.8, 140.6, 136.6, 136.2, 131.5, 130.8,
130.1, 129.7, 126.1, 125.4, 125.0, 123.4, 122.5, 121.5, 21.6; IR (KBr)
¼3060, 2972, 2901, 1559, 1456, 1430, 1313, 1263, 1065, 962, 761,
J¼8.5, 2.0 Hz, 1H), 3.91 (s, 3H); 13C NMR (150 MHz, CDCl3)
d 167.9,
159.9, 158.2, 153.5, 149.7, 136.7, 136.2, 134.0, 133.5, 132.2, 126.2,
n
125.4, 125.3, 123.6, 122.1, 121.6, 116.9, 115.3, 55.9; IR (KBr)
n
¼3059,

6480
H. Liu et al. / Tetrahedron 70 (2014) 6474e6481
2923, 2853, 1603, 1502, 1461, 1428, 1318, 1265, 1239, 1172, 1044,
1018, 886, 788, 758 cmꢂ1; HRMS: calcd for C19H14N2OS: 318.0827,
found: 318.0826.
1266, 1217, 1062, 1022, 969, 884, 760 cmꢂ1; HRMS: calcd for
19H14N2S: 302.0878, found: 302.0877.
C
4.2.12. 6-Methoxy-2-(2-(pyridin-2-yl)phenyl)benzothiazole
(3ac). Yield: 85%. Yellow oil. 1H NMR (600 MHz, CDCl3)
8.59 (d,
4.2.6. 2-(5-(Benzyloxy)-2-(pyridin-2-yl)phenyl)benzothiazole
d
(3fa). Yield: 81%. Yellow oil. 1H NMR (600 MHz, CDCl3)
d
8.59 (d,
J¼4.2 Hz, 1H), 8.00 (d, J¼8.1 Hz, 1H), 7.74 (d, J¼7.9 Hz, 1H), 7.58 (d,
J¼8.5 Hz, 1H), 7.51 (t, J¼7.7 Hz, 1H), 7.48e7.41 (m, 2H), 7.32 (t,
J¼7.5 Hz, 1H), 7.21 (d, J¼7.8 Hz, 1H), 7.18e7.14 (m, 1H), 7.11 (dd,
J¼4.5 Hz, 1H), 8.00 (d, J¼8.1 Hz, 1H), 7.74 (d, J¼7.9 Hz, 1H), 7.57 (dd,
J¼10.2, 5.5 Hz, 2H), 7.52 (m, 1H), 7.47e7.42 (m, 3H), 7.39 (t,
J¼7.5 Hz, 2H), 7.33 (t, J¼7.3 Hz, 2H), 7.21 (d, J¼7.8 Hz, 1H), 7.19e7.15
J¼8.5, 2.0 Hz, 1H), 3.91 (s, 3H); 13C NMR (150 MHz, CDCl3)
d 167.9,
(m, 2H), 5.18 (s, 2H); 13C NMR (150 MHz, CDCl3)
d
167.8, 159.0,
159.9, 158.2, 153.3, 149.7, 136.7, 136.2, 134.0, 133.5, 132.2, 126.2,
158.1, 153.3, 149.7, 136.7, 136.2, 134.0, 133.7, 132.3, 128.9, 128.3,
127.9, 127.8, 126.2, 125.3, 125.3, 123.6, 122.3, 122.2, 121.6, 121.5,
125.4, 125.3, 123.6, 122.1, 121.6, 116.9, 115.3, 55.9; IR (KBr)
n
¼3061,
2931, 1723, 1602, 1559, 1464, 1435, 1318, 1265, 1226, 1118, 1025, 892,
827, 794, 758, 702 cmꢂ1; HRMS: calcd for C19H14N2OS: 318.0827,
found: 318.0832.
117.4, 116.5, 70.5; IR (KBr)
n
¼3061, 2925, 2857, 1602, 1562, 1499,
1459, 1429, 1381, 1318, 1288, 1235, 1126, 1042, 1015, 893, 816, 759,
731, 697 cmꢂ1; HRMS: calcd for C25H18N2OS: 394.1140, found:
394.1141.
4.2.13. Methyl 2-(2-(pyridin-2-yl)phenyl)benzothiazole-5-
carboxylate (3ad). Yield: 93%. Yellow oil. 1H NMR (600 MHz,
4.2.7. 2-(2-(Pyridin-2-yl)-5-(trifluoromethyl)phenyl)benzothiazole
CDCl3)
2H), 7.79 (d, J¼8.4 Hz, 1H), 7.59 (m, 4H), 7.31 (d, J¼7.8 Hz, 1H),
7.24e7.21 (m, 1H), 3.94 (s, 3H); 13C NMR (150 MHz, CDCl3)
169.18,
167.13, 158.35, 153.29, 149.74, 141.37, 140.91, 136.39, 132.52, 130.93,
130.9, 130.8, 129.0, 128.5, 125.8, 125.2, 125.1, 122.7, 121.4, 52.5; IR
d
8.61 (s, 1H), 8.59 (d, J¼4.7 Hz, 1H), 7.98 (dd, J¼18.6, 8.0 Hz,
(3ga). Yield: 76%. Yellow oil. 1H NMR (600 MHz, CDCl3)
d 8.64 (d,
J¼4.5 Hz, 1H), 8.27 (s, 1H), 8.01 (d, J¼8.2 Hz, 1H), 7.81 (d, J¼8.0 Hz,
d
1H), 7.79e7.73 (m, 2H), 7.60 (t, J¼7.7 Hz, 1H), 7.45 (t, J¼7.6 Hz, 1H),
7.37e7.25 (m, 3H); 13C NMR (150 MHz, CDCl3)
d 165.9, 157.1, 153.2,
145.0, 136.7, 136.4, 133.7, 131.4, 127.34 (q, J¼148.5 Hz), 125.6, 125.2,
(KBr)
n
¼3059, 2954, 2851, 1720, 1586, 1562, 1462, 1432, 1303, 1243,
123.8, 123.1, 121.6; IR (KBr)
n
¼3061, 1587, 1522, 1492, 1457, 1404,
1149, 1092, 904, 794, 759, 694 cmꢂ1; HRMS: calcd for C20H14N2O2S:
346.0776, found: 346.0778.
1331, 1260, 1211, 1129, 1085, 1037, 899, 792, 758, 728, 704 cmꢂ1
HRMS: calcd for C19H11F3N2S: 356.0595, found: 356.0590.
;
4.2.14. 5-Chloro-2-(2-(pyridin-2-yl)phenyl)benzothiazole
4.2.8. Methyl
4-(benzothiazol-2-yl)-3-(pyridin-2-yl)benzoate
(3ae). Yield: 91%. Yellow oil. 1H NMR (600 MHz, CDCl3)
d 8.59 (d,
(3ha). Yield: 74%. Yellow oil. 1H NMR (600 MHz, CDCl3)
d
8.62 (d,
J¼4.5 Hz, 1H), 7.93 (dd, J¼7.8, 1.5 Hz, 2H), 7.66e7.56 (m, 4H), 7.54
J¼4.1 Hz, 1H), 8.29 (s, 1H), 8.18 (d, J¼8.0 Hz, 1H), 8.07 (d, J¼8.1 Hz,
1H), 7.99 (d, J¼8.2 Hz, 1H), 7.75 (d, J¼8.0 Hz, 1H), 7.62 (t, J¼7.6 Hz,
1H), 7.44 (t, J¼7.6 Hz, 1H), 7.34 (t, J¼7.6 Hz, 2H), 7.28e7.24 (m, 1H),
(m, 1H), 7.29 (dd, J¼8.5, 1.9 Hz, 1H), 7.22 (m, 1H); 13C NMR
(150 MHz, CDCl3)
d 169.8, 158.4, 154.2, 149.7, 141.5, 140.9, 136.4,
134.9, 132.6, 132.2, 130.9, 130.7, 129.0, 125.7, 125.1, 123.3, 122.6,
122.3; IR (KBr)
¼3060, 1590, 1494, 1457, 1428, 1393, 1314, 1255,
1099, 1037, 895, 782, 759, 729, 691 cmꢂ1; HRMS: calcd for
C18H11ClN2S: 322.0331, found: 322.0333.
3.94 (s, 3H); 13C NMR (150 MHz, CDCl3)
d
166.5, 166.5, 157.7, 153.3,
n
149.9,140.9,136.9,136.7,136.6,132.1,131.8,131.1,129.8,126.4,125.6,
125.3, 123.8, 122.9, 121.6, 52.6; IR (KBr)
¼3060, 2960, 2870, 1691,
1590, 1494, 1462, 1314, 1259, 1093, 1019, 798 cmꢂ1; HRMS: calcd for
20H14N2O2S: 346.0776, found: 346.0778.
n
C
4.2.15. 6-Nitro-2-(2-(pyridin-2-yl)phenyl)benzothiazole
(3af). Yield: 85%. Yellow oil. 1H NMR (600 MHz, CDCl3)
8.68 (d,
d
4.2.9. 1-(3-(Benzothiazol-2-yl)-4-(pyridin-2-yl)phenyl)ethanone
(3ia). Yield: 72%. Yellow oil. 1H NMR (600 MHz, CDCl3)
8.63 (d,
J¼2.3 Hz, 1H), 8.57 (d, J¼4.4 Hz, 1H), 8.29 (dd, J¼8.9, 2.3 Hz, 1H),
d
8.02 (t, J¼8.4 Hz, 2H), 7.66 (td, J¼7.7, 1.8 Hz, 1H), 7.62 (d, J¼3.9 Hz,
J¼4.6 Hz, 1H), 8.52 (s, 1H), 8.15 (dd, J¼8.0, 1.4 Hz, 1H), 8.00 (d,
J¼8.2 Hz, 1H), 7.76 (d, J¼8.0 Hz, 2H), 7.59 (t, J¼7.7 Hz, 1H), 7.45 (t,
J¼7.8 Hz, 1H), 7.34 (t, J¼7.6 Hz, 1H), 7.29 (d, J¼7.8 Hz, 1H), 7.24 (t,
2H), 7.60e7.55 (m, 1H), 7.37 (d, J¼7.8 Hz, 1H), 7.28e7.24 (m, 1H); 13
C
NMR (150 MHz, CDCl3) d 173.8, 158.1, 157.0, 149.8, 145.0, 141.1, 136.9,
136.7, 132.1, 131.4, 131.0, 129.1, 125.0, 123.7, 122.9, 121.7, 118.2; IR
J¼6.3 Hz, 1H), 2.69 (s, 3H); 13C NMR (150 MHz, CDCl3)
d
197.3, 166.7,
(KBr)
n
¼3061, 1566, 1513, 1463, 1439, 1339, 1261, 968, 794, 748,
157.5, 153.4,145.0,144.9,137.3,136.7, 136.4,133.5,131.4, 131.2, 129.7,
692 cmꢂ1
333.0578.
; HRMS: calcd for C18H11N3O2S: 333.0572, found:
126.4, 125.5, 125.2, 123.9, 123.1, 121.6, 27.0; IR (KBr)
n
¼3060, 2924,
1687, 1600, 1498, 1543, 1431, 1357, 1314, 1252, 1206, 1095, 1025, 904,
790, 758, 694 cmꢂ1; HRMS: calcd for C20H14N2OS: 330.0827, found:
330.0824.
4.2.16. 2-[2-(Pyridin-2-yl)phenyl]benzoxazole (3ag). Yield: 60%.
Yellow oil. 1H NMR (600 MHz, CDCl3)
d
8.54 (d, J¼4.8 Hz, 1H), 8.12
(dd, J¼7.7, 1.1 Hz, 1H), 7.71e7.59 (m, 4H), 7.55 (td, J¼7.6, 1.3 Hz, 1H),
4.2.10. 2-(5-Chloro-2-(pyridin-2-yl)phenyl)benzothiazole
(3ja).-
8.61 (d,
7.33 (d, J¼7.8 Hz, 1H), 7.31e7.24 (m, 3H), 7.23e7.20 (m, 1H); 13C
Yield: 62%. Yellow oil. 1H NMR (600 MHz, CDCl3)
d
NMR (150 MHz, CDCl3) d 163.8, 158.8, 150.9, 149.5, 142.0, 141.3,
J¼4.7 Hz, 1H), 7.99 (dd, J¼7.9, 5.1 Hz, 2H), 7.74 (d, J¼8.0 Hz, 1H),
136.4, 131.3, 131.1, 130.9, 128.8, 126.6, 125.1, 124.5, 123.9, 122.3,
7.60e7.52 (m, 3H), 7.44 (t, J¼7.5 Hz, 1H), 7.33 (t, J¼7.6 Hz, 1H), 7.23
120.4, 110.7; IR (KBr)
n
¼3060, 1586, 1564, 1453, 1344, 1302, 1242,
(m, 2H); 13C NMR (150 MHz, CDCl3)
d
166.2, 157.4, 153.3, 149.9,
1074, 1031, 925, 795, 747, 679 cmꢂ1; HRMS: calcd for C18H12N2O:
272.0950, found: 272.0949.
139.2, 136.7, 136.3, 135.0, 134.4, 132.2, 130.7, 130.4, 126.4, 125.5,
125.3, 123.8, 122.8, 121.6; IR (KBr)
n
¼3060, 1590, 1494, 1457, 1428,
1393, 1314, 1255, 1099, 1037, 895, 782, 759, 729, 691 cmꢂ1; HRMS:
calcd for C18H11ClN2S: 322.0331, found: 322.0329.
Acknowledgements
This work was supported by the Priority Academic Program
Development of Jiangsu Higher Education Institutions.
4.2.11. 4-Methyl-2-(2-(pyridin-2-yl)phenyl)benzothiazole
(3ab). Yield: 81%. Yellow oil. 1H NMR (600 MHz, CDCl3)
d
8.65 (s,
1H), 7.99 (s, 1H), 7.71e7.52 (m, 5H), 7.37e7.18 (m, 4H), 2.60 (s, 3H);
13C NMR (150 MHz, CDCl3)
166.2, 159.1, 153.1, 149.6, 140.8, 133.6,
133.1, 130.9, 130.9, 130.2, 128.9, 126.6, 125.2, 125.1, 122.3, 118.9, 18.4;
IR (KBr)
¼3057, 2922, 2852, 1584, 1560, 1520, 1464, 1425, 1315,
Supplementary data
d
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.07.022.
n

H. Liu et al. / Tetrahedron 70 (2014) 6474e6481
6481
V.; Duarte, M. T.; Veiros, L. F.; Gois, P. M. P.; Afonso, C. A. M. Tetrahedron 2010,
66, 8494e8502; (i) Wang, P.; Rao, H.; Hua, R.; Li, C.-J. Org. Lett. 2012, 14,
902e905; (j) Dong, J.; Long, Z.; Song, F.; Wu, N.; Guo, Q.; Lan, J.; You, J. Angew.
Chem., Int. Ed. 2013, 52, 580e584.
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