Elemental Sulfur-Mediated Decarboxylative Redox Cyclization Reaction: Copper-Catalyzed Synthesis of 2-Substituted Benzothiazoles

Article abstract of DOI:10.1055/s-0036-1589112

A S ₈ -mediated directed decarboxylative redox-cyclization strategy for the synthesis of 2-substituted benzothiazoles from o -iodoanilines, arylacetic acids, and elemental sulfur catalyzed by cheap copper metal has been developed. This reaction is operationally simple, ligand-free, compatible with a wide range of functional groups, and provides the desired products in good to excellent yields. In addition, a gram-scale experiment was carried out to furnish PMX 610, an antitumor drug.

Full text of DOI:10.1055/s-0036-1589112

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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–F
letter
A
en
X. Wang et al.
Letter
Synlett
Elemental Sulfur-Mediated Decarboxylative Redox Cyclization
Reaction: Copper-Catalyzed Synthesis of 2-Substituted Benzo-
thiazoles
Xin Wanga
I
S
S8, Cu(II)
COOH
R1
R1
Xiaotong Lia
Renhe Hua
Zhao Yanga
Ren Gua
+
R2
R2
N
NaOH, DMSO, 130 °C
NH2
29 examples
up to 93%
decarboxylative redox strategy
R
R
1 = H, Me, OMe, CH3, Cl, F
2 = H, Me, OMe, CF3, Cl, Br, F, Ph et al.
Sai Dinga
Pengyi Lia
Shiqing Han*a,b
a College of Biotechnology and Pharmaceutical Engineering,
Nanjing Tech University, Nanjing 211816, P. R. of China
hanshiqing@njtech.edu.cn
b Key Laboratory of Synthetic Chemistry of Natural Substances,
Shanghai Institute of Organic Chemistry, CAS, 345 Lingling
Road, Shanghai 200032, P. R. of China
Received: 30.07.2017
Accepted after revision: 03.09.2017
Published online: 27.09.2017
F3CO
S
NH2
N
Me
DOI: 10.1055/s-0036-1589112; Art ID: st-2017-w0598-l
H
A
N
N
OH
Abstract A S8-mediated directed decarboxylative redox-cyclization
strategy for the synthesis of 2-substituted benzothiazoles from o-iodo-
anilines, arylacetic acids, and elemental sulfur catalyzed by cheap cop-
per metal has been developed. This reaction is operationally simple, li-
gand-free, compatible with a wide range of functional groups, and
provides the desired products in good to excellent yields. In addition, a
gram-scale experiment was carried out to furnish PMX 610, an antitu-
mor drug.
O
N
O
N
Me
Me
S
B
H2N
N
N
Cl
Me
S
N
F
S
N
NH
NH2
Me
Key words benzothiazoles, decarboxylative cyclization, o-iodoanilines,
arylacetic acids, elemental sulfur
D
C
Figure 1 Biologically active benzothiazole derivatives
Among bioactive heterocyclic compounds, 2-substitut-
ed benzothiazoles and their corresponding derivatives are
ubiquitous structural blocks in pharmaceuticals, agrochem-
icals, and functional materials due to their physical, chemi-
cal, and biological properties, which have captured much
attention from organic chemists.1 Most of them have been
extensively studied for their potent biological activities and
medicinal value (Figure 1),2 such as a drug for amyotrophic
lateral sclerosis (A, Riluzole®),3a a fatty acid oxidation in-
hibitor (B, (R)-CVT-3501),3b an antitumor drug (C, 5F203),3c
and an antibacterial agent (D).3d
With their superior properties considered, many efforts
have been made to develop greener and user-friendly pro-
tocols. Over the years, these compounds are synthesized by
the condensation of 2-aminothiophenols (Scheme 1, eq. 1),4
direct arylation via C–H bond functionalization catalyzed
by transition metal between benzothiazoles and aryl ha-
lides or 2-halide-substituted benzothiazoles with aryl met-
als (Scheme 1, eq. 2).5 In 2012, a three-component reaction
of 2-iodoanilines, aldehydes, and sulfur powder to form
benzothiazoles was reported by Zhou group (Scheme 1, eq.
3).6 Then later, the Wang group described an efficient meth-
od for the 2-substituted benzothiazoles from 2-iodoani-
lines, benzylamines, and sulfur powder (Scheme 1, eq. 4).7
However, most of these methods required prefunctionaliza-
tion of the starting materials, ligand, or drastic reaction
conditions. It is highly desirable to develop a simple, mild,
and green approach for the synthesis of valuable 2-substi-
tuted benzothiazoles.
As we all know, decarboxylative reactions have attract-
ed much attention in organic synthesis due to arylacetic ac-
ids are common, stable, and nontoxic, which can serve as
versatile arylation reagents through metal-mediated decar-
boxylation to generate aryl-metal intermediates.8 They
have been highlighted by their occurrence in a myriad of
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

B
X. Wang et al.
Letter
Synlett
Previous work
SH
S
PhCHO
R
Ph
Ph
R
R
(1)
(2)
condensation
N
S
NH2
S
PhX
R
X
direct arylation
N
N
I
CHO
S
N
S8, ligand
Cu
+
+
R2
R2
R1
R1
R1
(3)
(4)
R2
NH2
I
S
N
NH2
S8, ligand
Cu
R1
NH2
R2
This work
I
S
N
S8
COOH
R2
(5)
R1
+
R1
R2
Cu
NH2
Scheme 1 Different routes for the synthesis of 2-substituted benzothiazoles
natural products and wide applications in pharmaceutical
chemistry. Moreover, it is a well-known fact that elemental
sulfur can promote the electron transfer in a redox reaction
depending on its numerous oxidation states, ranging from –2
to +6. With advances in sulfur-mediated/-catalyzed/-partic-
ipated reactions, the formation for the construction of C–C
and C–X bonds has become a hot spot.9 As a case study, we
disclose herein the development of novel and user-friendly
S8-mediated decarboxylative redox cyclization of o-iodoani-
lines, arylacetic acids, and elemental sulfur to synthesize 2-
substituted benzothiazoles (Scheme 1, eq. 5).
Our initial efforts commenced with the treatment of o-
iodoaniline (1a), arylacetic acid (2a), and elemental sulfur
using Cu(OAc)2·H2O as catalyst and K2CO3 as base in DMSO
I
S
COOH
R
S8, NaOH, Cu(OAc)2⋅H2O
+
R
N
NH2
DMSO, 130 °C, 24 h
3aa–av
1a
2a–v
S
S
S
N
S
N
N
N
CF3
Br
OMe
3aa 98%
3ab 43%
S
3ac 88%
S
3ad 74%
S
S
OMe
Cl
N
N
N
N
3ag 88%
3ae 59%
3af 48%
3ah 68%
F
S
S
S
S
F
Br
N
N
N
N
3aj 93%
3ai 62%
3al 71%
3ak 84%
Br
S
S
S
S
N
N
N
N
N
3an 81%
3am trace
3ao 62%
3ap 71%
S
S
O
S
S
S
OMe
OMe
Cl
N
N
N
N
3aq 72%
3ar 75%
3as 77%
3at 52%
Cl
S
N
R
R3 = Me 3au not detected
4 = Et 3av not detected
R
Scheme 2 ·Scope of substituted arylacetic acids. Reagents and conditions: 1a (0.5 mmol, 1 equiv), 2a–v (0.6 mmol), S8 (3 equiv), Cu(OAc)2·H2O
(20 mmol%), and NaOH (2 equiv) in DMSO (3 mL) under a nitrogen atmosphere at 130 °C for 24 h. All reported yields are isolated yields.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

C
X. Wang et al.
Letter
Synlett
at 130 ℃ for 24 hours under a nitrogen atmosphere
(Table 1). To our delight, the reaction afforded the expected
product 3aa in 61% (Table 1, entry 1). Encouraged by this re-
sult, we explored the effect of temperature (Table 1, entry
2), and 130 ℃ was better. To determine the most efficient
base for this reaction, various bases were examined (Table
1, entries 3–5), and the results indicated that NaOH is the
best one for this redox reaction (Table 1, entry 4). Then a va-
riety of copper salts were screened including Cu(I), Cu(II),
and Cu powder. We found that the Cu(II) salts were all ex-
cellent (Table 1, entries 6–12), and we chose Cu(OAc)2·H2O
as the best base. Besides, the amount of 2a was investigated,
and it was inferred that 1.2 equivalents of 2a were more ef-
ficient for the reaction (Table 1, entries 13 and 14). When a
lower amount of elemental sulfur was tested, three equiva-
lents of elemental sulfur was found to be the best choice
(Table 1, entries 15 and 16).
Different solvents were checked, which suggested
DMSO performed better as solvent for this reaction (Table 1,
entries 17–19). In addition, the yield of 3aa decreased to
84% when the reaction time was shortened to 12 hours (en-
try 20). Finally, the product 3aa was obtained in 54% yield
under an air atmosphere (Table 1, entry 21).
With the optimal reaction conditions in hand, the gen-
erality of this copper-catalyzed decarboxylative reaction
was examined. At first, we investigated the substrate scope
of arylacetic acids (Scheme 2). The results showed that aryl-
acetic acids containing not only electron-donating but also
electron-withdrawing functional groups can be employed
to afford the corresponding benzothiazoles in moderate to
excellent yields. Furthermore, in contrast with the yields of
methyl-substituted (3ab, 3ac, and 3ad) and bromo-substi-
tuted benzothiazoles (3ai, 3ak, and 3am), we speculated
the position of the substituent has some effect on the yield
of this coupling reaction. Both 4-biphenylacetic acid and 2-
naphthylacetic acid reacted well and gave 3an and 3ao in
81% and 62%, respectively. In addition, heteroaromatic aryl-
acetic acids also worked well under standard conditions
and offered 3ap–ar in good isolated yields. Besides, disub-
stituted arylacetic acids also led to the corresponding 2-
substituted benzothiazoles smoothly in moderate to good
yields (3as and 3at). The expected products were not de-
tected when alkyl carboxylic acids were used as substrates
(3au and 3av).
Table 1 Optimization of the Reaction Conditionsa
I
S
COOH
S8, catalyst
+
base, solvent
NH2
N
2a
1a
3aa
Entry
Catalyst
Temp (°C) Solvent
Base
Yield (%)b
1
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
CuCl2·H2O
130
120
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
K2CO3
K2CO3
61
51
52
95
91
93
92
92
80
90
85
76
96
92
88
65
23
trace
36
84
54
2
3
CS2CO3
NaOH
KOH
4
5
6
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
7
Cu(OH)2
To extend the potential of this transformation further, a
library of o-iodoanilines was investigated under the opti-
mized conditions (Scheme 3). The results demonstrated
that o-iodoanilines bearing electron-rich functional groups
could smoothly undergo the transformation in moderate to
8
CuO
9
Cu2O
10
CuCl
11
CuI
12
Cu powder
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
13c
14d
15c,e
16c,f
17c,e
18c,e
19c,e
20c,e,g
21c,e,h
I
S
S8, NaOH,
Cu(OAc)2⋅H2O
COOH
R
R
+
N
NH2
DMSO,
130 °C, 24 h
3ba–ia
1b–i
2a
S
S
S
N
N
3da 86%
S
N
O
F
toluene
NMP
3ca 87%
3ba 52%
S
S
N
N
DMSO
DMSO
N
F
Cl
3ga 89%
F
3ea 88%
F3C
3fa 92%
S
N
S
a The reaction was carried out with 1a (0.5 mmol, 1 equiv), 2a (2 equiv), S8
(4 equiv), base (2 equiv), and Cu source (20 mmol%) in 3 mL solvent under a
N
nitrogen atmosphere for 24 h.
3ha 88%
3ia trace
b Isolated yields.
c 2a (1.2 equiv).
Scheme 3 Scope of substituted o-iodoanilines. Reagents and condi-
tions: 1b–i (0.5 mmol, 1 equiv), 2a (0.6 mmol), S8 (3 equiv),
Cu(OAc)2·H2O (20 mmol%), and NaOH (2 equiv) in DMSO (3 mL) under
a nitrogen atmosphere at 130 °C for 24 h. All reported yields are iso-
lated yields.
d 2a (1.0 equiv).
e S8(3 equiv).
f S8 (2 equiv).
g 12 h.
h The reaction was carried out under an air atmosphere.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

D
X. Wang et al.
Letter
Synlett
I
MeO
MeO
S8, NaOH, Cu(OAc)2⋅H2O
S
COOH
+
OMe
OMe
DMSO, 130 °C, 24 h
N
F
NH2
F
1f (5 mmol)
2s (6 mmol)
PMX 610 76%
Scheme 4 A grame-scale experiment of PMX 610
excellent yields (3ba–da). Moreover, electron-deficient
groups on the aromatic ring also furnished the desired
products in 88–92% yields (3ea–ha).
strates was reacted for one hour under standard conditions,
3aa and diaryl disulfide 4 were obtained in 19% and 61%,
respectively (Scheme 5, eq. 2).
Exceptionally, only a trace amount of product 3ia was
obtained when 3-fluoro-2-iodoaniline was used as the sub-
strate, which indicates that the reaction might be affected
by steric hindrance.10
Then the reaction time was prolonged to three hours
and the yield of 3aa was increased to 47%, accordingly the
yield of 4 was decreased to 40% (Scheme 5, eq. 3). Thus it
showed that diaryl disulfide 4 may be the key intermediate
for the reaction. In addition, we conducted the cross-cou-
pling reaction involving diaryl disulfide 4 with arylacetic
acid 2a (Scheme 5, eq. 4–6): 3aa was obtained in 92% in the
presence of elemental sulfur and Cu(OAc)2·H2O (Scheme 5,
eq. 4). By treatment of 4 with 2a, 4 was transformed into
3aa in 88% yield mediated by elemental sulfur (Scheme 5,
eq. 5). The yield of 3aa decreased to 44% in the absence of
elemental sulfur and Cu(OAc)2·H2O (Scheme 5, eq. 6). It
proved that elemental sulfur served not only as sulfur
source but also as reaction promoter.5,6,11 According to pre-
vious literature,12 an approach to 2-substituted benzo-
With the consideration of the efficiency of this reaction,
a gram-scale experiment was carried out under the stan-
dard reaction conditions (Scheme 4). Compound PMX610
(3fs), which shows potent and selective inhibitory activity
against lung, colon, and breast cancer cell lines, could be
achieved on a 5 mmol scale in 76% isolated yield.6,10
Several control experiments were carried out in order to
shed light on the possible mechanism of the reaction, as
shown in Scheme 5. First of all, o-iodoaniline (1a) was sub-
jected to elemental sulfur, and diaryl disulfide 4 was
formed (Scheme 5, eq. 1). When the mixture of all sub-
H2N
S
I
NaOH, Cu(OAc)2⋅H2O
S
(1)
S8
+
DMSO, 130 °C, 1 h
NH2
I
NH2
1a
1a
H2N
4 69%
S8, NaOH, Cu(OAc)2⋅H2O
S
S
N
COOH
COOH
S
+
+
DMSO, 130 °C, 1 h
(2)
(3)
NH2
NH2
2a
3aa 19%
4 61%
H2N
I
S8, NaOH, Cu(OAc)2⋅H2O
S
S
S
+
+
DMSO, 130 °C, 3 h
NH2
N
NH2
1a
2a
2a
3aa 47%
4 40%
S
COOH
NaOH, Cu(OAc)2⋅H2O
+
4
S8
(4)
(5)
N
DMSO, 130 °C, 24 h
3aa 92%
S
NaOH
COOH
COOH
4
+
S8
DMSO, 130 °C, 24 h
N
2a
3aa 88%
S
N
NaOH
4
+
(6)
(7)
DMSO, 130 °C, 24 h
2a
3aa 44%
I
S
NaOH, Cu(OAc)2⋅H2O
S
N
H
DMSO, 130 °C, 24 h
N
5
3aa
Scheme 5 Control experiments
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

E
X. Wang et al.
Letter
Synlett
I
I
Cu
NH
S
Cu
S
N
5
I
CO2
path A
NH2
1a
S
O–
COOH
COO
S8
S
O
6
N
3aa
2a
H2N
CO2
H2S
I
S
S
Cu
S8
NH2
NH2
oxidation
1a
4
path B
S
S
2
N
N
CH
8
7
Scheme 6 Plausible mechanism
thiazoles by the intramolecular coupling reaction of o-iodo-
thiobenzanilide 5 was reported, therefore we put forward
another hypothesis (Scheme 6, Path A). However, the reac-
tion of o-iodothiobenzanilide 5 catalyzed by a copper salt
failed to afford the target product 3aa under standard con-
ditions (Scheme 5, eq. 7). This result indicates that com-
pound 5 may not be the intermediate.
Funding Information
We thank the National High Technology Research and Development
Program of China (863 Program 2014AA022100), Six Talent Peaks
Project in Jiangsu Province (No. 2015-SWYY-016) and Graduate Stu-
dent Innovation Project in Jiangsu Province (Grant No. SJCX17_0287)
for supporting this research.
)(
On the basis of above-mentioned observations and pre-
vious work,10,13 a tentative mechanism for the product for-
mation is proposed (Scheme 6, Path B). At first, arylacetic
acid 2a was deprotonated under alkaline conditions and
then reacted with elemental sulfur to sulfide 6,14 and at the
same time the copper-catalyzed coupling of o-iodoaniline
(1a) with elemental sulfur provided diaryl disulfide prod-
uct 4. Then, compound 6 reacted with 4 to yield intermedi-
ate 7 by a decarboxylative nucleophilic addition–elimina-
tion reaction. Subsequently, intermediate 8 was generated
by intramolecular nucleophilic addition, which followed by
oxidation reaction to furnish the target product 3aa.15
To sum up, we have developed a novel and efficient cop-
per-catalyzed decarboxylative redox cyclization of readily
available o-iodoanilines, arylacetic acids, and elemental sul-
fur to synthesize 2-substituted benzothiazoles without the
addition of a ligand or additive.16 This methodology pro-
vides a three-component reaction to afford the correspond-
ing benzothiazoles in moderate to excellent yields. In addi-
tion, the approach exhibited good functional-group toler-
ance. Further study and extension of the present results are
underway in our laboratory.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1589112.
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References and Notes
(1) (a) Evindar, G.; Batey, R. A. J. Org. Chem. 2006, 71, 1802.
(b) Samanta, S.; Das, S.; Biswas, P. J. Org. Chem. 2013, 78, 11184.
(c) Nguyen, T. B.; Ermolenko, L.; Al-Mourabit, A. Org. Lett. 2013,
15, 4218. (d) Banerjee, M.; Chatterjee, A.; Kumar, V.; Bhutia, Z.
T.; Khandare, D. G.; Majik, M. S.; Roy, B. G. RSC Adv. 2015, 74,
39606. (e) Urzúa, J. I.; Contreras, R.; Salas, C. O.; Ricardo, A. T.
RSC Adv. 2016, 85, 82401. (f) Hu, R.; Li, X.; Tong, Y.; Miao, D.;
Pan, Q.; Jiang, Z.; Gan, H.; Han, S. Synlett 2016, 27, 1387. (g) He,
K.; Tan, F.; Zhou, C.; Zhou, G.; Yang, X.; Li, Y. Angew. Chem. Int.
Ed. 2017, 56, 3080.
(2) (a) Bradshaw, T. D.; Westwell, A. D. Curr. Med. Chem. 2004, 11,
1009. (b) Choi, S. J.; Park, H. J.; Lee, S. K.; Kim, S. W.; Han, G.;
Choo, H. Y. P. Bioorg. Med. Chem. 2006, 4, 1229. (c) Weekes, A. A.;
Weatwell, A. D. Curr. Med. Chem. 2009, 19, 2430. (d) Shi, H.; Ji, S.;
Bian, B. Dyes Pigm. 2007, 73, 394. (e) Sharma, H.; Singh, N.; Jang,
D. O. Green Chem. 2014, 12, 4922.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

F
X. Wang et al.
Letter
Synlett
(3) (a) Bryson, H. M.; Fulton, B.; Benfield, P. M. Drugs 1996, 52, 549.
(b) Ding, Q.; Huang, X.; Wu, J. J. Comb. Chem. 2009, 11, 1047.
(c) Mortimer, C. G.; Wells, G.; Crochard, J. P.; Stone, E. L.;
Bradshaw, T. D.; Stevens, M. F. G.; Westwell, A. D. J. Med. Chem.
2006, 49, 179. (d) Gao, Y.; Song, Q.; Cheng, G.; Cui, X. Org.
Biomol. Chem. 2014, 12, 1044.
(4) (a) Sakamoto, T.; Mori, K.; Akiyama, T. Org. Lett. 2012, 14, 3312.
(b) Liao, Y.; Qi, H.; Chen, S.; Jiang, P.; Zhou, W.; Deng, G. Org.
Lett. 2012, 14, 6004. (c) Sun, Y.; Jiang, H.; Wu, W. Org. Lett. 2013,
15, 1598. (d) Tong, Y.; Pan, Q.; Jiang, Z.; Miao, D.; Shi, X.; Han, S.
Tetrahedron Lett. 2014, 55, 5499.
(5) (a) Do, H. Q.; Khan, R. M.; Daugulis, O. J. Am. Chem. Soc. 2008,
130, 15185. (b) Li, B.; Yang, S.; Shi, Z. Synlett 2008, 949.
(c) Huang, J.; Chan, J.; Chen, Y.; Borths, C. J.; Baucom, K. D.;
Larsen, R. D.; Faul, M. M. J. Am. Chem. Soc. 2010, 132, 3674.
(d) Liu, B.; Guo, Q.; Cheng, Y.; Lan, J.; You, J. Chem. Eur. J. 2011,
17, 13415. (e) Nishino, M.; Hirano, K.; Satoh, T.; Miura, M.
Angew. Chem. 2012, 124, 7099.
(6) Deng, H.; Li, Z.; Ke, F.; Zhou, X. Chem. Eur. J. 2012, 18, 4840.
(7) Wang, R.; Ding, Y.; Liu, H.; Peng, S.; Ren, J.; Li, L. Tetrahedron Lett.
2014, 55, 945.
(8) (a) Wang, Q.; Zhang, S.; Guo, F.; Zhang, B.; Hu, P.; Wang, Z. J. Org.
Chem. 2012, 77, 11161. (b) Qin, X.; Sun, D.; You, Q.; Cheng, Y.;
Lan, J.; You, J. Org. Lett. 2015, 17, 1762. (c) Yang, B.; Xu, X.; Qing,
F. Org. Lett. 2016, 18, 5956. (d) Biafora, A.; Krause, T.;
Hackenberger, D.; Belitz, F.; Gooßen, L. Angew. Chem. 2016, 55,
14752. (e) Vandamme, M.; Bouchard, L.; Gilbert, A.; Keita, M.;
Paquin, J. Org. Lett. 2016, 18, 6468. (f) Liu, L.; Wang, Z. Green
Chem. 2017, 19, 2076.
(9) (a) Huang, Y.; He, X.; Lin, X.; Rong, M.; Weng, Z. Org. Lett. 2014,
16, 3284. (b) Nguyen, T. B.; Ermolenko, L.; Retailleau, P.; Al-
Mourabit, A. Angew. Chem. Int. Ed. 2014, 53, 13808. (c) Zhang,
G.; Yi, H.; Chen, H.; Bian, C.; Liu, C.; Lei, A. Org. Lett. 2014, 16,
6156. (d) Xu, J.; Zhang, L.; Li, X.; Gao, Y.; Tang, G.; Zhao, Y. Org.
Lett. 2016, 18, 1266. (e) Meng, L.; Fujikawa, T.; Kuwayama, M.;
Segawa, Y. J. Am. Chem. Soc. 2016, 138, 10351. (f) Ravi, C.; Reddy,
N. N. K.; Pappula, V.; Samanta, S.; Adimurthy, S. J. Org. Chem.
2016, 81, 9964.
(10) Gan, H.; Miao, D.; Pan, Q.; Hu, R.; Li, X.; Han, S. Chem. Asian J.
2016, 11, 1770.
(11) (a) Ray, S.; Das, P.; Banerjee, B.; Bhaumikb, A.;
Mukhopadhyayet, C. RSC Adv. 2015, 5, 72745. (b) Liu, B.; Zhu, N.;
Hong, H.; Han, L. Tetrahedron 2015, 71, 9287. (c) Du, G.; Zhu, N.;
Han, L.; Hong, H.; Suo, Q. Heterocycles 2015, 91, 1723.
(12) (a) Downer, N. K.; Jackson, Y. A. Org. Biomol. Chem. 2004, 2,
3039. (b) Bose, S. D.; Idrees, M.; Srikanth, B. Synthesis 2007, 819.
(c) Cheng, Y.; Peng, Q.; Fan, W.; Li, P. J. Org. Chem. 2014, 79,
5812.
(13) (a) Antonello, S.; Daasbjerg, K.; Jensen, H.; Taddei, F.; Maran, F.
J. Am. Chem. Soc. 2003, 125, 12905. (b) Jiang, Y.; Qin, Y.; Xie, S.;
Zhang, X.; Dong, J.; Ma, D. Org. Lett. 2009, 11, 5250. (c) Park, N.;
Heo, Y.; Kunar, M. R.; Kim, Y.; Song, K. H.; Lee, S. Eur. J. Org.
Chem. 2012, 43, 1984.
(14) Guntreddi, T.; Vanjari, R.; Singh, K. N. Org. Lett. 2014, 16, 3624.
(15) (a) Song, Q.; Feng, Q.; Zhou, M. Org. Lett. 2013, 15, 5990.
(b) Dang, P.; Zeng, W.; Liang, Y. Org. Lett. 2015, 17, 34. (c) Fan, L.;
Shang, Y.; Li, X.; Hua, W. Chin. Chem. Lett. 2015, 26, 77.
(16) General Procedure for the Synthesis of Benzothiazoles
A mixture of o-iodoaniline (0.5 mmol, 1 equiv), arylacetic acid
(0.6 mmol), elemental sulfur (1.5 mmol), Cu(OAc)2·H2O (20
mmol%), and NaOH (1.0 mmol) in DMSO (3 mL) was put into a
sealed pressure vessel (25 mL) containing a magnetic stirring
bar. The tube was purged with nitrogen three times, and then
capped and stirred in a preheated oil bath at 130 °C for 24 h. The
reaction mixture then cooled to r.t. and extracted with EtOAc
(3 × 10 mL), the organic layer was washed with sat. NaCl
(2 × 10 mL), dried over anhydrous Na2SO4, evaporated under
vacumm, and then purified by silica gel column chromato-
graphy (PE–EtOAc 200:1) to give pure compound 3aa in 98%
yield.
Selected Spectral Data for 2-Phenylbenzothiazole (3aa)
1H NMR (300 MHz, CDCl3): δ = 8.09–8.11 (m, 3 H), 7.90 (d, J =
7.8 Hz, 1 H), 7.48–7.52 (m, 4 H), 7.38 (t, J = 7.5 Hz, 1 H). 13C NMR
(75 MHz, CDCl3): δ = 168.0, 154.1, 135.1, 133.6, 130.9, 129.0,
127.5, 126.2, 125.1, 123.2, 121.6.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F