Microwave-assisted 6π-electrocyclization in water

Article abstract of DOI:10.1016/j.cclet.2020.09.005

The recent development of microwave-assisted aqueous synthesis of polyheterocyclic-fused quinoline-2-thiones through 6π-electrocyclization was highlighted.

Full text of DOI:10.1016/j.cclet.2020.09.005

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CCLET 5834 No. of Pages 2
Chinese Chemical Letters xxx (2019) xxx–xxx
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Chinese Chemical Letters
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Microwave-assisted 6
p
-electrocyclization in water
Yan Wua, Ying-Wu Linb, Wei-Min Hec,
*
a
College of Chemistry and Chemical Engineering, Yangtze Normal University, Chongqing 408000, China
School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China
Department of Chemistry, Hunan University of Science and Engineering, Yongzhou 425100, China
b
c
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 28 July 2020
Received in revised form 24 August 2020
Accepted 31 August 2020
Available online xxx
The recent development of microwave-assisted aqueous synthesis of polyheterocyclic-fused quinoline-
2-thiones through 6p-electrocyclization was highlighted.
© 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
6p-Electrocyclization
Quinoline-2-thiones
Microwave-assisted synthesis in water
Quinoline-2-thione as a privileged structural motif has been
widely found in a wide variety of biologically active molecules,
functional materials, and synthetic intermediates. As shown in
Fig. 1, quinoline-2-thione derivatives possess remarkable pharma-
cological properties, such as mPGES-1 inhibitor, human A3
adenosine receptor antagonists, antiproliferative [1,2]. In this
context, the development of straightforward and efficient meth-
odologies toward quinoline-2-thione derivatives has successfully
gained continuous interest. Besides, imidazo[1,2-a]pyridines also
occupy an important position in natural products, pharmaceut-
icals, and optoelectronic materials [3]. From the standpoint of
synthetic chemistry, the structural combination of imidazo[1,2-a]
pyridines with quinoline-2-thiones in one single molecular
framework should be interesting for the discovery of novel
functional molecules. However, the synthesis of imidazo[1,2-a]
pyridine-fused-quinoline-2-thiones has not been reported until
recently.
solvents and external additives (e.g., 1,8-diazabicyclo[5.4.0]
undec-7-ene, In(OTf)3) were required in these procedures. In this
context, the development of an additive-free approach in water
should be valuable from the standpoint of green chemistry [7,8].
In this microwave-assisted reaction, various polyheterocyclic-
fused quinoline-2-thiones 3 were obtained in the presence of
ortho-heteroaryl anilines 1 (0.2 mmol) and carbon disulfide 2a
(0.4 mmol) in H2O (1 mL) at 140 ꢀC under irradiation of microwave
for 30 min (Scheme 2b). Moreover, the procedure showed broad
and excellent functional group compatibility. Overall, 24 examples
of polyheterocyclic-fused quinoline-2-thiones were successfully
isolated by simple filtration. Moreover, it was found that the
heteroaromatic scaffolds including indolizine, benzo[d]imidazo
Very recently, the research group of Chen and Yu at Zhengzhou
University developed a microwave-assisted aqueous reaction for
the synthesis of polyheterocyclic-fused quinoline-2-thiones
through a 6p-electrocyclization strategy (Scheme 1) [4]. This
metal- and additive-free approach features the benefits involving
catalyst-free, short reaction time, reusable and green solvent
system, and facile isolation via simple filtration. The previous
studies of 6p-electrocyclization strategies by Saito’s group [5] and
Quan’s group [6] have independently disclosed feasibility to access
highly functionalized quinoline-2-thiones. However, volatile
Fig. 1. Biologically active compounds containing quinolone-2-thione and imidazo
[1,2-a]pyridines.
* Corresponding author.
E-mail address: weiminhe2016@yeah.net (W.-M. He).
https://doi.org/10.1016/j.cclet.2020.09.005
1001-8417/© 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Y. Wu, et al., Microwave-assisted 6
10.1016/j.cclet.2020.09.005
p-electrocyclization in water, Chin. Chem. Lett. (2020), https://doi.org/

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CCLET 5834 No. of Pages 2
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Y. Wu et al. / Chinese Chemical Letters xxx (2019) xxx–xxx
[2,1-b]thiazole, imidazo[2,1-a]isoquinoline, imidazo[1,2-a]quino-
line, indole, and pyrrole could also be applied as reaction
precursors to realize the cycloaddition to give the desired products
(3s-x) (Scheme 2b).
A plausible mechanism of this microwave-assisted cyclization
reaction was proposed as shown in Scheme 2c. First, the
nucleophilic addition of the amino group in 1a reacted with CS2
to generate the intermediate A. Then the intermediate A was
converted into the intermediate B along with releasing H2S.
Scheme 1. Microwave-assisted synthesis of imidazo[1,2-a]pyridine-fused quino-
line-2-thiones in water.
Subsequently, intermediate B via 6p-electrocyclization gave the
intermediate C. Finally, the desired product 3a was obtained after
the aromatization of intermediate C.
Additionally, the recycling experiments of aqueous media for
sustainable synthesis demonstrated that comparably yields were
obtained in each recycle of water. This strategy features water as a
reused solvent at least five times without significant loss of
product yields. Finally, E-factor and EcoScale score were calculated.
The excellent scores of E-factor (0.45) and EcoScale penalty points
(14.5) demonstrated that this protocol presents great green
chemistry and environment benign metrics [9].
In conclusion, the Chen and Yu’s group recently developed a
microwave-assisted annulation for the first synthesis of a diversity
of polyheterocyclic-fused quinoline-2-thione frameworks in water
through 6p-electrocyclization without using any catalyst and
additive. C(sp2)-N and C(sp2)-C(sp2) bonds were formed in one pot.
Significantly, the green solvent water can be recycled at least for
five times, and the remarkable E-factor of 0.45 and EcoScale score
of 85.5 were observed in this protocol. Such findings will open new
routes for the application of 6p-electrocyclization in modern
organic synthesis.
Declaration of competing interest
The authors report no declarations of interest.
References
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Scheme 2. Substrate scope and proposed mechanism. a2a (4 equiv.) was used.
Please cite this article in press as: Y. Wu, et al., Microwave-assisted 6
p
-electrocyclization in water, Chin. Chem. Lett. (2020), https://doi.org/
10.1016/j.cclet.2020.09.005