The solvent-controlled chemoselective construction of C-S/S-S bonds via the Michael reaction/thiol coupling of quinoline-2-thiones

Article abstract of DOI:10.1039/c8ob02971g

K₂CO₃-catalyzed thio-Michael addition using quinoline-2-thiones and α,β-unsaturated carbonyl compounds was used to assess the chemoselective construction of C-S and S-S bonds under mild reaction conditions in different solvents. The C-S bond showed a better chemoselective construction in EtOH whereas the S-S bond showed a better chemoselective construction in 1,4-dioxane. The corresponding products, generated from the reaction, presented a significant solvent-controlling effect.

Full text of DOI:10.1039/c8ob02971g

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: X. Zhang, T.
Wang, X. Liu, X. Wang and Z. Quan, Org. Biomol. Chem., 2019, DOI: 10.1039/C8OB02971G.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Page 1 of 6
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C8OB02971G
Journal Name
ARTICLE
Solvent-Controlled Chemoselective Construction of C-S/S-S Bonds
via Michael reaction/Thiol Coupling of Quinoline-2-thiones
Xi Zhang,‡ a Tong-Lin Wang,‡ a Xiao-Jun Liu,a Xi-Cun Wang,a Zheng-Jun Quan *a
Received 00th
January 20xx,
K2CO3-catalyzed thio-Michael addition using quinoline-2-thiones and α,β-unsaturated carbonyl compounds was used to
assess chemoselective construction of C-S and S-S bonds under mild reaction conditions in different solvents. The C-S bond
showed a better chemoselective constructing in EtOH whereas the S-S bond showed a better chemoselective constructing
in 1,4-dioxane. The corresponding products, generated from the reaction, presented a significant solvent-controlling effect.
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
selectively converted into C-S bond in EtOH and S-S bond in
dioxane without any additives except the air at room
temperature.
Introduction.
As a unique nitrogen-containing heterocyclic compound, the
quinoline skeleton plays an essential role in the field of
optoelectronic functional materials,1,2 medical field3,4 and
organic synthesis.5,6 Recently, Substituted quinoline
compounds have attracted the attention of more and more
chemical researchers.
Table 1. Optimization of Reaction Conditions a.
Sulfur, it is an active non-metallic element that is ubiquitous,
especially in nature and in living organisms. Thioether and
disulfide are important unique moiety in drugs,
agrochemicals,7 materials science,8 and many functional
molecules.9 The development of a gentle and versatile method
for the formation of C-S and S-S bonds has received
considerable attention, although many synthetic methods
have been reported.10 Some of these methods have significant
limitations and require the implementation of metal-ligand
combinations or highly pre-functionalized precursors.
Therefore, an important task of chemical researchers is to find
simple ways to form C-S bonds and S-S bonds.
Entry
Base
Solvent (mL)
Yield (%)b 3a
Yield (%)b 4a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15c
16
17
18
19
20
21
22
K2CO3 (1 eq.)
K2CO3 (1 eq.)
K2CO3 (1 eq.)
K2CO3 (1 eq.)
K2CO3 (1 eq.
K2CO3 (1 eq.)
K2CO3 (1 eq.)
K2CO3 (1 eq.)
K2CO3 (1 eq.)
K2CO3 (1 eq.)
K2CO3 (1 eq.)
K2CO3 (1 eq.)
K2CO3 (20%)
K2CO3 (20%)
K2CO3 (20%)
DBU (20%)
DCE
Acetone
EtOAc
1,4-Dioxane
1,3-Dioxolane
Dibutyl ether
THF
DME
PEG-400
EtOH
MeOH
DMF
EtOH
1,4-Dioxane
1,4-Dioxane
EtOH
trace
10
30
35
25
83
76
72
53
62
10
trace
trace
trace
trace
80
13
trace
15
18
13
10
26
trace
trace
trace
trace
12
15
67
92
85
88
90
trace
trace
88
42
45
73
76
It is well known that the Michael addition reaction is an
essential reaction in organic chemistry, an important primary
method for constructing C-C,11 C-N,12 and C-S bonds,13
However, the strategy for constructing C-S remains the
interest of chemists The thia-Michael addition reaction is a
simple and effective method for forming C-S bonds and is
widely used in organic synthesis.13
Herein, based on our previous work,14 we reported the
solvent-controlled selective construction of C-S and S-S bonds
on the quinoline skeleton by using K2CO3 as a catalyst under
mild conditions. The C=S bond in quinoline-2-thione were
Et3N (20%)
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
DABCO (20%)
NaOH (20%)
Cs2CO3 (20%)
K3PO4 (20%)
Na2S (20%)
53
47
31
a
Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), K2CO3 (20 mol%), EtOH (2
mL), rt., 5 hours. bIsolated yield. c Under N2 atmosphere.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2018, 00, 1-3 | 1

Organic & Biomolecular Chemistry
Page 2 of 6
ARTICLE
Journal Name
a yield of 13%, when the dioxane that excluded oxygen was
used (Table 1, entry 15), indicating that the process of forming
Results and discussion
View Article Online
DOI: 10.1039/C8OB02971G
4a required oxygen to participate. Thus, we got the optimal
conditions: K2CO3 (20%) was used as base at room temperature.
When EtOH was used as a solvent, the compound 3a was isolated
in a yield of 90% by reacting for 5 hours (Table 1, entry 13).
Meanwhile, in the case of using dioxane as the solvent, 4a can be
obtained in an 80% yield after 5 hours (Table 1, entry 14).
With the optimized conditions in hand, we firstly studied the
Michael addition range of differential quinoline-2-thiones 1
and acrylonitrile 2a (Scheme 1). The results indicate that when
acrylonitrile is used as a receptor, both electron-donating and
electron-withdrawing substitution at the 2-position, 3-position,
4-position of the aromatic ring provided moderate to good
yields of the thia-Michael addition products (3a-3o). The halide
(-F) substituent was well tolerated under these conditions.
However, it is unsatisfactory that the yield of naphthyl
quinoline-2-thiones (3k, 3l) is relatively low. This may be
caused by the high electron-withdrawing nature of the
naphthyl group. Acrylates were also tested in this reaction,
where both methyl acrylates (3m) and butyl esters (3o) gave
addition products in good yields. This shows that the chain
length of the acrylate does not affect the yield. The structure
of 3a was clearly determined by single crystal X-ray
diffraction.15
Scheme 1. Substrate scope of 4-arylquinoline-2(1H)-thione.
Our investigation was initiated by using quinoline-2-thione 1a
and acrylonitrile 2a as the model substrates. First, we screened
a series of solvents in the presence of 1 equivalent of K2CO3 as
the base (Table 1, entries 1-12). When a common polar aprotic
solvent was used (Table 1, entries 1-8), the target Michael
addition product 3a was obtained in a low yield, while the thiol
coupling product 4a was separated in moderate to a good
yield, especially in ether solvents (Table 1, entries 4-8). 1,4-
dioxane yielded a disulfide 4a in 83% yield. The reaction in 1,3-
dioxolane and dibutyl ether were able to give 4a in 76% and 68%
yield, and trace amounts of 3a were detected (Table 1, entries
5-6). 4a was obtained in a yield of 53% and 62% in THF or DME
as a solvent, while a low yield of compound 3a (Table 1,
entries 7-8) was isolated. Next, we tested the common polar
protic solvents (Table 1, entries 9-12) which showed that both
polar protic solvents (EtOH, MeOH) and polar inert protic
solvents (PEG-400, DMF) delivered compound 3a in a
moderate to good yield. Based on these results, we indicated
that disulfide 4a selectively obtained in a polar aprotic solvent,
while the thia-Michael addition product 3a can be
advantageously obtained in a polar protic solvent. Finally, we
screened the amount and type of base(Table 1, entries 16-22).
The target products 3a and 4a were still obtained in 90% and
80% yields when a catalytic amount of K2CO3 (20 mol%) was
used (Table 1, entries 13-14). Although DBU, NaOH, Cs2CO3
and some other bases gave target compound 3a in moderate
yield, K2CO3 remained the best one and 4a has isolated only in
Scheme 2. Substrate scope of the symmetric disulphide. a Reaction conditions: 1
(0.2 mmol), K2CO3 (20 mol%), dioxane (2 mL), rt., 4-5 hours. b Isolated yield. c 4h,
d 5h.
Scheme 3. Substrate scope of the asymmetric disulphide. a Reaction conditions: 1 (0.2
mmol), 2 (0.3 mmol), K2CO3 (20 mol%), Dioxane (2 mL), rt., 5 hours. b Isolated yield.
In view of the optimum conditions (Table 1, entry 17), we
tested the coupling reaction of a series of quinolin-2-thiones.
As shown in Scheme 2, a variety of disulfides were obtained in
good yields and the functional groups are well-tolerated, and
2 | J. Name., 2018, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx

Page 3 of 6
Organic & Biomolecular Chemistry
Journal Name
the position of the substituent does not influence the yield.
ARTICLE
were removed in vacuum. The residue wasViepwuArritficieledOnlbinye
recrystallization (EtOH) to give the quinoDlinOeI:-120-.t1h03io9n/Ce8sO. B02971G
17
Based on our previous work,
asymmetric heterocyclic
disulfides have different reaction sites, so we tried to
synthesize asymmetric disulfides with quinoline-2-thione and
simple thiols (Scheme 3). It was found that asymmetric
disulfide compounds can be obtained in about 50% yield. And
that the symmetric disulfides (4a, 4d) were obtained in a yield
of 15% to 25%, and about 30% yield of the simple disulfides
7a-d was isolated.
Typical Procedure for the Synthesis of 3a
The mixture of quinoline-2-thione 1a (0.2 mmol, 50 mg),
acrylonitrile 2a (0.24 mmol, 13 mg) and K2CO3 (20%, 6 mg) in
EtOH (2 mL) was stirred at room temperature for 5 hours
under air atmosphere. After the reaction was complete
according to TLC detection, 2.0 mL of saturated aq. NH4Cl was
added to the mixture to quench the reaction. The mixture was
extracted with ethyl acetate (3×25 mL). The organic layer was
washed with aqueous NaHCO3 and brine, dried over MgSO4,
filtered, and the volatiles were removed in vacuum. Then the
mixture was purified by using silica gel column
chromatography with a different eluent (ethyl acetate:
petroleum ether = 1:30) thus yielding a pure 3a was obtained
as a white solid (55 mg, 90% yield).
The possible reaction mechanism was obtained by comparing
with the literature precedent (Scheme 4).13,16 Initially, owing to
the substrate has higher activity in this reaction, a thio
18
intermediate A is formed by tautomerization of 1.
Next,
K2CO3 captures the protons in thiol A to generate KHCO3 and
sulfur-anion intermediates B. Usually, Michael reaction is
carried out in a protic solvent,19a hydrogen bond formation
among solvent (EtOH) and substrates increased the
electrophilicity of
2
and nucleophilicity of 1, thus,
simultaneous activation of the 1 and 2. 13 So, in a protic solvent
the addition reaction of an intermediate B to an unsaturated
carbonyl compound produces a carbon anion intermediate C.
Finally, C obtained the proton in KHCO3, generating the target
product 3 and K2CO3 which was continued to enter the
catalytical cycle. Meanwhile, it is more favourable that in a
aprotic solvent A can be oxidized by O2 (air) to form a disulfide
4 or 6. 19b-d
Typical Procedure for the Synthesis of 6a
The mixture of quinoline-2-thione 1a (0.2 mmol, 50 mg),
thiophenol 5a (0.3 mmol, 13 mg) and K2CO3 (20%, 6 mg) in 1,4-
dioxane (2 mL) was stirred at room temperature for 5 hours
under air. After the completion of the reaction monitored by
TLC detection, 2.0 mL of saturated aq. NH4Cl was added to the
mixture to quench the reaction and extracted with ethyl
acetate (3×25 mL). The organic layer was washed with
aqueous NaHCO3 and brine, dried over MgSO4, filtered, and
the volatiles were removed in vacuum. Then, the mixture was
purified by using silica gel column chromatography with
different eluent (ethyl acetate: petroleum ether = 1:30) thus
yielding a pure 6a as a colourless oil (40 mg, 55% yield).
Scheme 4. Proposed mechanism.
Conflicts of interest
There are no conflicts to declare.
Conclusions
In summary, we have reported a solvent-dependent selectively
construction of C-S and S-S bonds in good yields under mild
conditions. The thioether compounds could be obtained in
high yields in EtOH with high efficiency. Particularly interesting
is that the reaction could also produce the symmetric or
asymmetric disulfides product in dioxane with chemical
selectivity.
Acknowledgements
We are thankful for the financial support from the National
Nature Science Foundation of China (No. 21562036) and the
Scientific and Technological Innovation Engineering program of
Northwest Normal University (NWNU-LKQN-15-1).
Experiment
References and notes
Synthesis of quinoline-2-thiones 1a-1o
1
(a) J. P. Michael, Nat. Prod. Rep., 2008, 25, 166; (b) A. P.
Gorka, A. de Dios and P. D. Roepe, J. Med. Chem., 2013,
56, 5231; (c) M. Rouffet, C. A. F. de Oliveira,Y. Udi, A.
Agrawal, I. Sagi, J. A. McCammon and S. M. Cohen, J.
Am. Chem. Soc., 2010, 132, 8232; (d) S. Andrews, S. J.
Burgess, D. Skaalrud, J. X. Kelly and D. H. Peyton, J. Med.
Chem., 2010, 53, 916.
Under an atmosphere of air, 2-(1-phenylvinyl) aniline (0.5
mmol, 0.0095 g), CS2 (1.2 eq. 0.6 mmol, 0.0046 g), DBU (5
mol%, 0.00018 g) were added to a tube. DMF (3.0 mL) was
added by dropper and the mixture was stirred for 8 h at 140
and the reaction was monitored by TLC analysis. Then, 2.0 mL
ammonium chloride were added to the mixture to quench the
reaction and extracted with ethyl acetate (3×25 mL). The
combined organic layers were washed with saturated aq.
NH4Cl and brine, dried over MgSO4, filtered, and the volatiles
2
(a) V. Bhalla, V. Vij, M. Kumar, P. R. Sharma and T. Kaur,
Org. Lett., 2012, 14, 1012; (b) M. Velusamy, C. H. Chen,
Y. S. Wen, J. T. Lin, C. C. Lin, C. H. Lai and P. T. Chou,
Organometallics., 2010, 29, 3912; (c) S. Tao, L. Li, J. Yu,
Y. Jiang, Y. Zhou, C. S. Lee, S. T. Lee, X. Zhang and O.
Kwon, Chem. Mater., 2009, 21, 1284; (d) J. L. Kim, I. S.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2018, 00, 1-3 | 3

Organic & Biomolecular Chemistry
Page 4 of 6
ARTICLE
Journal Name
Shin and H. Kim, J. Am. Chem. Soc., 2005, 127, 1614; (e)
H. Xu, R. Chen, Q. Sun, W. Lai, Q. Su, W. Huang and X.
Liu, Chem. Soc. Rev., 2014, 43, 3259; (f) A. Danel, E.
Gondek and I. Kityk, Opt. Mater., 2009, 32, 267.
Surolia, T. Owa and B. Bhatta-charyya, J.VMieweAdr.ticClehOenmlin.e,
2005, 48, 547.
DOI: 10.1039/C8OB02971G
8
9
(a) H. K. Cui, Y. Guo, Y. He, F. L. Wang, H. N. Chang, Y. J.
Wang, F. M. Wu, C. L. Tian and L. Liu, Angew. Chem. Int.
Ed., 2013, 52, 9558; (b) H. Grönbeck, A. Curioni and W.
Andreoni, J. Am. Chem. Soc., 2000, 122, 3839; (c) S. P.
Stratton, E. R. Sharlow, A. Baker and , T. Dragovich, Clin.
Cancer Res., 2007, 13, 2109; (d) A. R. Murphy and J. M.
J. Fre ´chet, Chem. Rev., 2007, 107, 1066.
3
(a) S. S. Zhu, W. Y. Lin and L. Yuan, Dyes Pigm., 2013, 99,
465; (b) C. J. Fahrni and V. V. O’Halloran, J. Am. Chem.
Soc., 1999, 121, 11448; (c) V. R. Solomon and H. Lee,
Curr. Med. Chem., 2011, 18, 1488; (d) K. Kaur, M. Jain,
R. P. Reddy and R. Jain, Eur. J. Med. Chem., 2010, 45,
3245; (e) R. Musiol, M. Serda, S. Hensel-Bielowka and J.
Polanski, Curr. Med. Chem., 2010, 17, 1960; (f) J. P.
Michael, Nat. Prod. Rep., 2008, 25, 166; (g) X. Z. Yang, Y.
J. Feng, S. Duffy, V. M. Avery, D. Camp, R. J. Quinn and
R. A. Davis, Planta Med., 2011, 77, 1644; (h)B. Leon, J. C.
N. Fong, K. C. Peach, W. R. Wong, F. H. Yildiz and R. G.
Linington, Org. Lett., 2013, 15, 1234; (i)D. A. Ibrahim, D.
A. Abou El Ella, A. M. El-Motvvally and R. M. Aly, Eur. J.
Med. Chem., 2015, 102, 115; (j) K. Gopaul, S. A Shintre
and N. A Koorbanally, Anti-Cancer Agents Med Chem.,
2015, 15, 631; (k) M. Orhan Puskullu, B. Tekiner and S.
Suzen, Mini. Rev. Med. Chem., 2013, 13, 365.
(a) S. S. Zhu, W. Y. Lin and L. Yuan, Dyes Pigm., 2013, 99,
465; (b) C. J. Fahrni and V. V. O’Halloran, J. Am. Chem.
Soc., 1999, 121, 11448; (c) V. R. Solomon and H. Lee,
Curr. Med. Chem., 2011, 18, 1488; (d) K. Kaur, M. Jain,
R. P. Reddy and R. Jain, Eur. J. Med. Chem., 2010, 45,
3245; (e) R. Musiol, M. Serda, S. Hensel-Bielowka and J.
Polanski, Curr. Med. Chem., 2010, 17, 1960; (f) J. P.
Michael, Nat. Prod. Rep., 2008, 25, 166; (g) X. Z. Yang, Y.
J. Feng, S. Duffy, V. M. Avery, D. Camp, R. J. Quinn and
R. A. Davis, Planta Med., 2011, 77, 1644; (h)B. Leon, J. C.
N. Fong, K. C. Peach, W. R. Wong, F. H. Yildiz and R. G.
Linington, Org. Lett., 2013, 15, 1234; (i) D. A. Ibrahim, D.
A. Abou El Ella, A. M. El-Motvvally and R. M. Aly, Eur. J.
Med. Chem., 2015, 102, 115; (j) K. Gopaul, S. A Shintre
and N. A Koorbanally, Anti-Cancer Agents Med Chem.,
2015, 15, 631; (k) M. Orhan Puskullu, B. Tekiner and S.
Suzen, Mini. Rev. Med. Chem., 2013, 13, 365.
(a) J. P. Michael, Nat. Prod. Rep., 2007, 24, 223; (b) J. P.
Michael, Nat. Prod. Rep., 2008, 25, 166; (c) T. Eicher, S.
Hauptamann and A. Speicher in The Chemistry of
Heterocycles, II ed. Wiley-VCH: 2003; (d) Q. A. Zou, H. L.
Duan, M. M. Ning, J. Liu, Y. Feng, L. M. Zhang, J. J. Zhu,
Y. Leng and J. H. Shen, Eur. J. Med. Chem., 2011, 46,
3639; (e) P. Dziedzic, J. A. Cisneros, M. J. Robertson, A.
A. Hare, N. E. Danford, R. H. G. Baxter and W. L.
Jorgensen, J. Am. Chem. Soc., 2015, 137, 2996.
(a) R. Y. Zhu, T. G. Saint-Denis, Y. Shao, J. He, J. D.
Sieber, C. H. Senanayake and J. Q. Yu, J. Am. Chem. Soc.,
2017, 139, 5724; (b) P. X. Shen, X. C. Wang, P. Wang, R.
Y. Zhu and J. Q. Yu, J. Am. Chem. Soc., 2015, 137, 11574;
(c) G. Rouquet and N. Chatani, Angew. Chem. Int. Ed.,
2013, 52, 11726; Angew. Chem., 2013, 125, 11942; (d)
M. Corbet and F. De Campo, Angew. Chem. Int. Ed.,
2013, 52, 9896; Angew. Chem., 2013, 125, 10080; (e) Y.
Zhang and M. S. Sigman, J. Am. Chem. Soc., 2007, 129,
3076; (f) M. M. Biddle, M. Lin and K. A. Scheidt, J. Am.
Chem. Soc., 2007, 129, 3830.
(a) J. X. Gong, X. Shen, L. G. Yao, H. Jiang, K. Krohn and
Y. W. Guo, Org. lett., 2007, 9, 1715; (b) C. S. Jiang, W. E.
G. Müller, H. C. Schröder and Y. W. Guo, Chem. Rev.,
2012, 112, 2179; (c) S. A. Caldarelli, M. Hamel, J. F.
Duckert, M. Ouattara, M. Calas, M. Maynadier, S. Wein,
C. Périgaud, A. Pellet, H. J. Vial and S. Peyrottes, J. Med.
Chem., 2012, 55, 4619; (d) S. S. Mansy and J. A. Cowan,
Acc. Chem. Res., 2004, 37, 719; (e) N. S. Li, J. K.
Frederiksen and J. A. Piccirilli, Acc. Chem. Res., 2011, 44,
1257; (f) P. Chauhan, S. Mahajan and D. Enders, Chem.
Rev., 2014, 114, 8807; (g) J. S. Yu, H. M. Huang, P. G.
Ding, X. S. Hu, F. Zhou and J. Zhou, ACS Catal., 2016, 6,
5319; (h) C. Shen, P. F. Zhang, Q. Sun, S. Q. Bai, T. S. A.
Hor and X. G. Liu, Chem. Soc. Rev., 2015, 44, 291; (i) Z.
Huang, D. Zhang, X. Qi, Z. Yan, M. Wang, H. Yan and A.
Lei, Org. Lett., 2016, 18, 2351; (j) K. L. Dunbar, D. H.
Scharf, A. Litomska and C. Hertweck, Chem. Rev., 2017,
117, 5521; (k) C.-F. Lee, Y.-C. Liu and S. S. Badsara,
Chem. Asian J., 2014, 9, 706.
4
10 (a) C. Shen, and X. G. Liu, Chem. Soc. Rev., 2015, 44,
291; (b) E. Schaumann, Top. Curr. Chem., 2007, 274, 1;
(c) D. Uraguchi, N. Kinoshita, D. Nakashima and T. Ooi,
Chem. Sci., 2012, 3, 3161; (d) X. Wu, Y. Chen, M. Li, M.
Zhou and S. K. Tian, J. Am. Chem. Soc., 2012, 134,
14694; (e) A. Sakakura, H. Yamada and K. Ishihara, Org.
Lett., 2012, 14, 2972; (f) J. F. Hartwig, Nature., 2008,
314; (g) Y. M. Xi, J. L. Petersen and X. D. Shi, Angew.
Chem. Int. Ed., 2014, 53, 4657; (h) Q. Q. Lu, and A. W
Lei, J. Am. Chem. Soc., 2013, 135, 11481; (i) Q. Lu, J.
Zhang, and A. W. Lei, Angew. Chem., Int. Ed., 2013, 52,
7156; (j) M. Arisawa, K. Fujimoto, S. Morinaka and M.
Yamaguchi, J. Am. Chem. Soc., 2005, 127, 12226; (k) X.
Xiao, M. H. Feng, X. F. Jiang, Angew. Chem. Int. Ed.,
2016, 55, 14121; (l) F. Dénès, M. Pichowicz, G. Povie
and P. Renaud, Chem. Rev., 2014, 114, 2587.
5
6
11 R. Yeab, F. F. Faucher and G. A. Somorjai, Mol. Catal.,
2018, 447, 65.
12 (a) R. S. Varma and R. K. Saini, Synlett., 1997, 7, 857; (b)
T. K. Roy, B. Parhi and P. Ghorai, Angew. Chem. Int. Ed.,
2018, 57, 9397.
13 (a) S. Lauzon, M. Li, H. Keipour and T. Ollevier, Eur. J.
Org. Chem., 2018, 2018, 4536; (b) C. Berthonneau, F.
Buttard, M. A. Hiebel, F. Suzenet and J. F. Brière, Adv.
Synth. Catal., 2017, 359, 4106; (c) P. Wadhwa and A.
Sharma, Asian J. Org. Chem., 2018, 7, 634; (d) E. H.
Krenske, R. C. Petter, Z. D. Zhu and H. K. N, J. Org.
Chem., 2011, 76, 5074; (e) J. R. Christopher, H. K.
Elizabeth, H. K. N and W. Peter., Org. Lett., 2013, 15,
1076; (f) L. K. Gopal, K. Raj and K. C. Asit, Org. Lett.,
2006, 8, 6433; (g) F. H. Rosemarie and D. R. Seth, J. Org.
Chem., 2006, 71, 6342; (h) A. C. Valeria van, B.
Fernando, D. C. Antonella, M. Luigi, R. Ivan and S. Luca,
J. Org. Chem., 1999, 64, 8122.
14 (a) T. L. Wang, X. J. Liu, C. D. Huo, X. C. Wang and Z. J.
Quan, Chem. Commun., 2018, 54, 499; (b) X. Zhang, T. L.
Wang, C. D. Huo, X. C. Wang and Z. J. Quan, Chem.,
Commun. 2018, 54, 3114.
15 The structure of 3a was determined by X-ray
crystallographic. CCDC No. CCDC 1877268.
7
(a) A. Casini, J. Y. Winum, J.-L. Montero, A. Scozzafava
and C. T. Supuran, Bioorg. Med. Chem. Lett., 2003, 13,
837; (b) M. Mellah, A. Voituriez and E. Schulz, Chem.
Rev., 2007, 107, 5133; (c) H. Haruki, M. G. Pedersen, K.
I. Gorska, F. Pojer and K. Johnsson, Science., 2013, 340,
987; (d) A. Natarajan, H. Aktas, M. Chorev and J. A.
Halperin, J. Med. Chem., 2004, 47, 4979; (e) D. C. Cole,
G. Zhang, J.Coupet and L. E. Schechter, J. Med. Chem.,
2005, 48, 353; (f) M. Banerjee, A. Poddar, G. Mitra, A.
4 | J. Name., 2018, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx

Page 5 of 6
Organic & Biomolecular Chemistry
Journal Name
16 (a) S. Lauzon, H. Keipour, V. Gandon and T. Ollevier,
ARTICLE
View Article Online
Org. Lett., 2017, 19, 6324; (b) F. Hampel, and S. B.
Tsogoeva Chem. Eur. J., 2018, 24, 6551.
DOI: 10.1039/C8OB02971G
17 (a) K. J. Wei, Z. J. Quan and X. C. Wang, Org. Biomol.
Chem., 2016, 14, 2395; (b)K. J. Wei, Z. J. Quan and X. C.
Wang, RSC Adv., 2016, 6, 78059; (c)K. J. Wei, Z. J. Quan
and X. C. Wang, Synlett., 2016, 27, 1743.
18 T. Y. Yang, Z. J. Quan and X. C. Wang, Synlett., 2017, 28,
847.
19 (a) D. J. Macquarrie, Tetrahedron Lett., 1998, 39, 4125;
(b) M. Oba, K. Nishiyama and W. Ando, J. Org. Chem.,
2011, 76, 4173; (c) A. Dhakshinamoorthy, M. Alvaroa
and H. Garcia, Chem. Commun., 2010, 46, 6476; (d) S.
Song, J. Z. Liu and N. Jiao., Angew. Chem. Int. Ed. 2017,
56, 1.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2018, 00, 1-3 | 5

Organic & Biomolecular Chemistry
Page 6 of 6
View Article Online
DOI: 10.1039/C8OB02971G
Table of contents entry
Solvent-Controlled Chemoselective Construction of C-S/S-S Bonds via Michael
reaction/Thiol Coupling of Quinoline-2-thiones
Xi Zhang,‡a Tong-Lin Wang,‡a Xiao-Jun Liu,a Xi-Cun Wang,a Zheng-Jun Quan*ab
Solvent-controlled selectively constructing C-S and S-S bonds containing quinoline
skeleton under mild conditions from quinoline-2-thione.
EWG
R1
R1
S
S
N
S
N
S
R
S
N
HN
R-SH
EWG
or
Dioxane, rt
EtOH, rt
R2
R2
R1
R1
R2
R2
2
15 examples
up to 90% yield
12 examples
up to 80% yield
EWG= -CN, -COOR
Keywords: Solvent-controlled; Thio-Michael addition; Quinoline-2-thione; C-S and
S-S; Thioether; Symmetric/asymmetric disulfide.