Highly efficient CuOx/OMS-2 catalyst for synthesis of phenoxathiin derivatives via intramolecular arylations of phenols with aryl halides

Article abstract of DOI:10.1016/j.tetlet.2019.151259

Phenoxathiin and its derivatives have attracted a great deal of interest due to their unique chemical and physical properties and their applications in fluorescent materials, antifungal activities and selective inhibitors. In the presence of copper supported on manganese oxide-based octahedral molecular sieves OMS-2 (CuO_x/OMS-2), the heterogeneously catalytic synthesis of phenoxathiinan derivatives via intramolecular arylations of phenols with aryl bromide or aryl chloride has been achieved. TEM and XRD have confirmed the CuO_x/OMS-2 catalyst has been successfully reused 8 times without a significant decrease in the yield, with simple filtration and washing as a means of separation.

Full text of DOI:10.1016/j.tetlet.2019.151259

Tetrahedron Letters 60 (2019) 151259
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Highly efficient CuOx/OMS-2 catalyst for synthesis of phenoxathiin
derivatives via intramolecular arylations of phenols with aryl halides
a,
Na Liu a, Fei Chao a, Yu Huang a, Yanlan Wang b, Xu Meng c, Long Wang a, , Xiang Liu
⇑
⇑
a College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, Material Analysis and Testing Center,
China Three Gorges University, Yichang, Hubei 443002, China
b College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, Shandong 252059, China
c State Key Laboratory for Oxo Synthesis and Selective Oxidation, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou
730000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Phenoxathiin and its derivatives have attracted a great deal of interest due to their unique chemical and
physical properties and their applications in fluorescent materials, antifungal activities and selective inhi-
bitors. In the presence of copper supported on manganese oxide-based octahedral molecular sieves OMS-
2 (CuOx/OMS-2), the heterogeneously catalytic synthesis of phenoxathiinan derivatives via intramolecu-
lar arylations of phenols with aryl bromide or aryl chloride has been achieved. TEM and XRD have con-
firmed the CuOx/OMS-2 catalyst has been successfully reused 8 times without a significant decrease in
the yield, with simple filtration and washing as a means of separation.
Received 14 August 2019
Revised 1 October 2019
Accepted 9 October 2019
Available online 11 October 2019
Keywords:
Phenoxathiin
Heterogeneous
Phenols
Ó 2019 Elsevier Ltd. All rights reserved.
Aryl halides
Introduction
have also been used as selective inhibitors of monoamine oxidase
[8]. In addition, they have attracted wide attention because of high
Sulfur-containing heterocycles and their derivatives have stim-
ulated more than a century of research aimed at exploring eco-
nomical, selective and efficient methodologies for achieving these
compounds due to their wide applications in a wide range of inter-
esting biological activities, organic functional materials, sensors,
valuable synthetic intermediates and drug industry [1]. Among
them, phenoxathiin and its derivatives have attracted a great deal
of interest due to their unique chemical and physical properties
and their applications in fluorescent materials, antifungal activities
and selective inhibitors. For instances, 3-formylphenoxathiin and
3-acetylphenoxathiin exhibited an enhancement of the emission
and a hypsochromic shift of the maxima in the presence of b-
cyclodextrin by the fluorescence spectra [2]. Hillebrand’s group
also investigated solvatochromicity, natural lifetimes and fluores-
cence quantum yields of several 3-substituted phenoxathiin
derivatives by the fluorescence spectroscopy. They found that the
emission properties of 3-acetylphenoxathiin are dependently
impacted by its substituent group [3]. Supuran’s group found that
2-aminophenoxathiin’s sulfonylamido derivatives exhibited excel-
lent antifungal activities [4]. Moreover, phenoxathiin derivatives
stability of phenoxathiin’s cation radicals [5].
The exploration of highly efficient synthetic methodologies for
phenoxathiin and its derivatives is particularly appealing [6,7].
For example, Eastmond’s group reported the synthesis of phe-
noxathiin derivatives by the cyano-activated fluoro replacement
reactions between 2,3- and 3,4-difluorobenzonitriles and the
nucleophiles (including 2-aminophenol, catechol, benzene-1,2-
dithiol either and 2-aminobenzenethiol) in DMF at 130 °C or in
DMSO at rt, in the presence of K2CO3 [8]. In 2013, Feng and Ma’s
group also described the regioselective synthesis of phenoxathiin
derivatives from the reaction of 1-halo-2-nitroarenes or 1,2-
dihaloarenes and 2-sulfanylphenol [9]. In fact, our group has long
term interest in the synthesis of heterogeneous catalysts and their
applications in cyclization reactions [10]. In 2015, we have devel-
oped the aerobic synthesis of 3-iodoimidazo[1,2-a]pyridines by
tandem cyclization/iodination of 2-aminopyridines, I2 and ace-
tophenones by using the heterogeneous and recyclable CuOx/
OMS-2 catalyst [11]. Here, in this work, we first report the highly
efficient the copper modified manganese oxide-based octahedral
molecular sieves (CuOx/OMS-2) catalyst for synthesis of phe-
noxathiin derivatives via intramolecular arylations of phenols with
aryl halides. In our study, CuOx/OMS-2 catalyst was made by
wet-impregnation of OMS-2 in copper nitrate solution followed
by filtration, washing, drying and calcination. The TEM image
⇑
Corresponding authors.
E-mail addresses: wanglongchem@ctgu.edu.cn (L. Wang), xiang.liu@ctgu.edu.cn
(X. Liu).
https://doi.org/10.1016/j.tetlet.2019.151259
0040-4039/Ó 2019 Elsevier Ltd. All rights reserved.

2
N. Liu et al. / Tetrahedron Letters 60 (2019) 151259
bases including KOH, Na2CO3, K2CO3 and Cs2CO3 (Entries 2–5),
we found the yield of 2a increased to 89% by using Cs2CO3. Then,
we investigated different loadings of Cs2CO3, in the amount of
1 eq and 3 eq, and obtained 66% and 89% yields, respectively
(Entries 6 and 7). Next, the reactions were conducted in different
solvent, such as DMF and Toluene, and the reactions did not afford
more higher yields (Entries 8 and 9). We also investigated the reac-
tion at different temperatures (Entries 10 and 11), the yield of 2a
was also influenced by the reaction temperature. Next, the dosages
of CuOx/OMS-2 were examined, we found 8 mg of CuOx/OMS-2
gave the highest yield, while 4 and 12 mg only provided 48% and
85% yield, respectively (Entries 12 and 13). As a comparative
experiment, OMS-2 (instead of CuOx/OMS-2) was tested under
the same condition. The result shows OMS-2 itself only gave 26%
yield (Entry 14). In addition, commercial CuO and Cu2O were also
investigated, we found both CuO and Cu2O gave the excellent yield
(85%) as that of CuOx/OMS-2 (Entries 15 and 16). It is clear that the
significant catalytic activity of CuOx/OMS-2 catalyst is taken into
account to its superficial highly active copper species. Finally, the
reaction was also conducted without catalyst, and only gave 26%
yield (Entry 17). Based on the above-studied results, 2 eq of Cs2CO3,
8 mg of CuOx/OMS-2 130 °C and DMSO are the optimal conditions
for this reaction.
Fig. 1. The TEM image of CuOx/OMS-2.
showed that CuOx/OMS-2 are short nanorods (Fig.1). In addition,
the CuOx/OMS-2 catalyst has been reused 8 times without a signif-
icant decrease in the yield of 2a (83–89%), with simple filtration.
Results and discussion
Under the optimized reaction conditions, we extended the
study with 2-((2-bromophenyl)thio)phenol with different
substituting groups for the synthesis of various phenoxathiine
derivatives. The results have been shown in Table 2. Various
2-((2-bromophenyl)thio)phenols have afforded the desired phe-
noxathiine derivatives in moderate to good yields. It is obvious that
the nature of the substituent on the aromatic rings showed few
influence on the yields of the desired phenoxathiine derivatives
(Table 2, entries 1–12). The aromatic ring with whether electron-
withdrawing groups (fluoro and chloro group) or electron-donat-
ing groups (methyl and methoxy group) gave more than 82% yields
(Table 3, entry 1–5).
First, the reaction conditions were optimized using 2-((2-bro-
mophenyl)thio)-5-chlorophenol (1a) as model substrates. As
shown in Table 1, the reaction was conducted with 2-((2-bro-
mophenyl)thio)-5-chlorophenol (1a) (0.5 mmol) in the presence
of 1 mmol of NaOH in DMSO (2 mL) at 130 °C under air for 10 h.
The desired product 3-chlorophenoxathiine (2a) was obtained
from intramolecular arylations of phenols with aryl halides in only
68% yield (Table 1, entry 1). When the intramolecular arylations of
phenols reactions were carried out in the presence of different
Table 1
The recyclability of the CuOx/OMS-2 catalyst has also been
examined in Scheme 1. 2-((2-bromophenyl)thio)-5-chlorophenol
(1a) was chosen as the model substrates, and the reaction was con-
ducted under the previously optimized conditions: DMSO (2 mL) at
130 °C under air for 10 h in the presence of CuOx/OMS-2 (8 mg)
and Cs2CO3 (2 equiv.). As shown in Scheme 1, the CuOx/OMS-2 cat-
Optimization of the reaction condition.a
Table 2
Reactions of 2-((2-bromophenyl)thio)phenol with different substituting groups.a
Entry
Catalyst
Base
Solvent
Yield [%]b
1
2
3
4
5
6
7
8
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (8 mg)
CuOx/OMS-2 (4 mg)
CuOx/OMS-2 (12 mg)
OMS-2 (8 mg)
NaOH (2 eq)
KOH (2 eq)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
Toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
68
5
Na2CO3 (2 eq)
K2CO3 (2 eq)
Cs2CO3 (2 eq)
Cs2CO3 (1 eq)
Cs2CO3 (3 eq)
Cs2CO3 (2 eq)
Cs2CO3 (2 eq)
Cs2CO3 (2 eq)
Cs2CO3 (2 eq)
Cs2CO3 (2 eq)
Cs2CO3 (2 eq)
Cs2CO3 (2 eq)
Cs2CO3 (2 eq)
Cs2CO3 (2 eq)
Cs2CO3 (2 eq)
70
64
89
66
89
55
0
42
91
48
85
26
85
85
26
Entry
Product
R1
R2
Yield [%]b
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2i
5-Cl
5-F
3-Cl
5-OCH3
3-CH3
5-F
H
H
H
H
89
83
92
94
61
84
90
81
78
80
87
82
9
10c
11d
12
13
14
15
16
17
H
4-CH3
4-CH3
4-CH3
4-CH3
4-Cl
H
5-Cl
5-CH3
5-OCH3
5-Cl
H
5-Cl
CuO (2 mg)
Cu2O (1.8 mg)
none
9
10
11
12
2j
2k
2l
a
Reaction conditions: 1a (0.5 mmol), base (1.0 mmol), CuOx/OMS-2 (8 mg), sol-
3-CH3
vent (2 mL), 130 °C, 10 h.
a
b
Reaction conditions: 1 (0.5 mmol), Cs2CO3 (1.0 mmol), CuOx/OMS-2 (8 mg),
Isolated yield.
The reaction was carried out at 110 °C.
c
solvent (2 mL), 130 °C, 10 h.
b
d
Isolated yield.
The reaction was carried out at 150 °C.

N. Liu et al. / Tetrahedron Letters 60 (2019) 151259
3
Table 3
Reactions of 2-((2-chlorophenyl)thio)phenol with different substituting groups.a
Entry
Reactant
R1
R2
Yield [%]b
1
2
3
4
5
1m
1n
1o
1p
1q
5-Cl
5-OCH3
5-Cl
5-OCH3
H
H
H
4-CH3
4-CH3
H
87
95
82
86
83
a
Reaction conditions: 1 (0.5 mmol), Cs2CO3 (1.0 mmol), CuOx/OMS-2 (8 mg),
solvent (2 mL), 130 °C, 10 h.
b
Isolated yield.
Fig. 2. (a) TEM and (b) XRD of 8th used CuOx/OMS-2 catalyst.
Scheme 1. Recyclability of the CuOx/OMS-2 catalyst.
alyst has been recycled 8 times without a significant decrease in
the yield of 3-chlorophenoxathiine (2a) (83–89%), with simple fil-
tration and washing as a means of separation. The separated CuOx/
OMS-2 catalyst after the 8th run of reaction has been further exam-
ined by using XRD and TEM. Both TEM and XRD of the 8th recycled
CuOx/OMS-2 do not exhibit any apparent structural changes in
comparison with the images of the fresh catalyst (Fig. 2), confirm-
ing the high stability and recyclability of CuOx/OMS-2 catalyst.
Based on the analogous mechanisms discussed in literature
[12], a plausible mechanism for the intramolecular arylations of
phenols with aryl halides has been proposed as shown in Scheme 2.
The catalytic cycle starts with the formation of the intermediate 3
by the attack of [CuOx] to 2-((2-bromophenyl)thio)phenol 1a. The
intermediate 4 is produced from the 3 via another intramolecular
oxidative addition. In the presence of Cs2CO3, subsequently, the
intermediate 5 is obtained from intermediate 4 after removal of
HBr. Finally, concomitant CAO coupling via a concerted process
inside the aggregate would then lead to the formation of the
intramolecular coupling product 2a.
Scheme 2. Proposed mechanism for synthesis of phenoxathiins.
(CuOx/OMS-2) nanocomposite for synthesis of phenoxathiinan
derivatives via intramolecular arylations of phenols with aryl
halides has been successfully developed. The intramolecular aryla-
tions of phenols reactions with aryl bromide or aryl chloride toler-
ated a large number of substrates and gave moderate to great
yields of phenoxathiinan derivatives that could be applied in fluo-
rescent materials, antifungal activities and selective inhibitors. In
addition, the CuOx/OMS-2 catalyst has been successfully reused 8
times without a significant decrease in the yield, with simple filtra-
tion and washing as a means of separation.
Conclusion
In summary, a highly efficient and heterogeneous the copper
modified manganese oxide-based octahedral molecular sieves

4
N. Liu et al. / Tetrahedron Letters 60 (2019) 151259
(l) L. Wang, Y.-B. Xie, N.-Y. Huang, J.-Y. Yan, W.-M. Hu, M.-G. Liu, M.-W. Ding,
Declaration of Competing Interest
ACS Catal. 6 (2016) 4010;
(m) L. Wang, M. Sun, M.-Wu Ding, Eur. J. Org. Chem. 18 (2017) 2568;
(n) L. Wang, Z.-R. Guan, M.-W. Ding, Org. Biomol. Chem. 14 (2016) 2413;
(o) Y.-W. Liu, Y.-B. Xie, D.-J. Li, L. Wang, Russ. J. Gen. Chem. 85 (2015) 2163;
(p) L. Wang, Y.-B. Xie, Q.-Li Yang, M.-G. Liu, K.-B. Zheng, Y.-L. Hu, N.-Y. Huang,
J. Iran. Chem. Soc. 13 (2016) 1797;
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
(q) Z.-L. Ren, L. Su, S. Cai, W.-T. Lu, Y. Qiao, P. He, M.-W. Ding, Asian J. Org.
Chem. 8 (2019) 1394–1397;
(r) F. Zou, Y. Huang, L. Wang, Z. Ren, X. Cheng, Y. Sun, J. Wu, P. He, Synlett 30
(2019) 717;
Acknowledgments
Financial support from the National Natural Science Foundation
of China (Nos. 21602123, 21805166 and 21403256), the 111 Pro-
ject of Hubei Province (No. 2018-19-1), the Foundation of Hubei
Key Laboratory of Natural Products Research and Development
(NPRD 2018007), the Youth Innovation Promotion Association
CAS (2018456) and China Three Gorges University is gratefully
acknowledged.
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Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2019.151259.
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