Facile C–H arylation using catalytically active terminal sulfurs of 2 dimensional molybdenum disulfide

Article abstract of DOI:10.1016/j.tetlet.2018.09.054

The first methodology of C–H arylation of heteroarene via 2D transition metal dichalcogenides that have catalytically active edge functional groups was described. The terminal sulfur groups could effectively catalyze a formation of an azo-linked intermediate with aryl diazonium salts, leading to produce heteroarenes with good yields. This novel methodology using bulk 2D transition metal dichalcogenides that have catalytically active edge functional groups can apply for various reactions to achieve C–C bond formation in the fields of heterogeneous catalysis that is easily separable, highly reusable, and inexpensive method.

Full text of DOI:10.1016/j.tetlet.2018.09.054

Accepted Manuscript
Facile C–H Arylation using Catalytically Active Terminal Sulfurs of 2 Dimen-
sional Molybdenum Disulfide
Eunhee Hwang, Sae Mi Lee, Sora Bak, Hee Min Hwang, Hyunjung Kim,
Hyoyoung Lee
PII:
S0040-4039(18)31156-0
https://doi.org/10.1016/j.tetlet.2018.09.054
TETL 50293
DOI:
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
13 August 2018
19 September 2018
20 September 2018
Please cite this article as: Hwang, E., Mi Lee, S., Bak, S., Min Hwang, H., Kim, H., Lee, H., Facile C–H Arylation
using Catalytically Active Terminal Sulfurs of 2 Dimensional Molybdenum Disulfide, Tetrahedron Letters (2018),
doi: https://doi.org/10.1016/j.tetlet.2018.09.054
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Facile C–H Arylation using Catalytically Active Terminal
Sulfurs of 2 Dimensional Molybdenum Disulfide
a, b, †
a, b, †
a, b
a, c
a, d
Eunhee Hwang
Hyoyoung Lee
, Sae Mi Lee
, Sora Bak , Hee Min Hwang , Hyunjung Kim , and
a, b, c, d
*
a
Centre for Integrated Nanostructure Physics (CINAP), Institute of Basic Science (IBS), 2066
Seoburo, Jangan-gu, Suwon 16419, Republic of Korea
b
Department of Chemistry, Sungkyunkwan University, 2066 Seoburo, Jangan-gu, Suwon
1
6419, Republic of Korea
c
Department of Energy Science, Sungkyunkwan University, 2066 Seoburo, Jangan-gu, Suwon
1
6419, Republic of Korea
d
Skku Advanced Institute of Nanotechnology(SAINT), Sungkyunkwan University, 2066
Seoburo, Jangan-gu, Suwon 16419, Republic of Korea.
†
These authors contributed equally to this work.
*
0
Corresponding Author, E-mail: hyoyoung@skku.edu; Fax: +82-031-290-5934; Tel: +82-
31-299-4566.
Abstract
The first methodology of C-H arylation of heteroarene via 2D transition metal
dichalcogenides that have catalytically active edge functional groups was described. The
terminal sulfur groups could effectively catalyze a formation of an azo-linked
intermediate with aryl diazonium salts, leading to produce heteroarenes with good
yields.This novel methodology using bulk 2D transition metal dichalcogenides that have

catalytically active edge functional groups can apply for various reactions to achieve C-
C bond formation in the fields of heterogeneous catalysis that is easily separable, highly
reusable, and inexpensive method.
Keywords: aryl (benzene) diazonium salts, C-H activation, molybdenum disulfide, cross
coupling, edged sulfur
Introduction
Functionalization reactions of C–H bonds have received great attention as synthetic
routes for natural products and pharmaceuticals.[1] Particularly, carbon–carbon cross
coupling is a beneficial technique for transformation in organic synthesis. [2, 3] Especially,
Meerwein’s method[4] which is a copper catalyzed C–H arylation using diazonium salts and
unsaturated compounds still has disadvantages such as its low yield (20–40%) and the
various byproducts produced under its aqueous conditions. Many researchers are trying to
improve the yield or replace substrates for making carbon-carbon coupling through modified
Meerwein type arylation.[5, 6] However, most of improved Meerwein reaction in the
diazonium salts-based C-H activation have required cocatalysts or photocatalysts.[7-9]
However, the development of easily and entirely separable and recyclable catalysts remains a
big challenge in both homogeneous and heterogeneous catalytic systems.
Recently, catalysts based on atomically thin layers of transition metal dichalcogenides
(
TMDs) have been pursued because of their distinctive optical, electrical, and physical
properties.[10] Among TMDs, the most interesting two-dimensional (2D) layered material is
molybdenum disulfide (MoS ) due to its easy preparation as monolayered or few-layered
forms, and its high stability compared with analogous TMDs.
2

Despite recent investigations,[11-16] there have been few reports regarding the use of
MoS catalyst for organic coupling reactions even though it has potential catalytic active sites
including molybdenum that is able to have a unsaturated coordination and also sulfurs located
at the edge sites.[17] Recently, a 2D heterostructured catalyst, Cu S/MoS , was introduced
for use in the Ullmann coupling organic reaction, a well-known copper-catalyzed arylation
reaction.[18] Unfortunately, however, there has been no report on the direct use of MoS for
C–H arylation of heteroarenes. MoS substrates have been used as supporters,[18, 19] but
2
2
2
2
2
not as the catalyst. Therefore, it is expected that understanding the active sites of edge sulfur
or molybdenum should be useful for the development of future catalysts.
Herein we report a new and easy-to-use organic coupling heterogeneous catalyst, 2D
MoS , as an efficient catalyst of the C–H arylation reaction for the production of aryl-linked
2
heteroarene compounds. We carefully chose benzene diazonium salts and furan as starting
materials for C-H arylation to give heteroarene compounds.
Results and discussion
Background research was investigated with 4-cholorobenzene diazonium
tetrafluoroborate (1a), furan (2) and commercially available MoS
powder). Table 1 lists the conditions and resulting yields. Reacting 4-cholorobenzene
diazonium tetrafluoroborate (1a) and furan (2) over MoS catalyst gave the target product
without solvent (25%, entry 1), (3a). And the yield was low in the absence of MoS catalyst
22%, entry 2). It indicates that MoS promotes the reaction efficiency to produce 3a. The
target compound, 3a, could be obtained moderately when both solvent and MoS were
included. To optimize the reaction condition, various solvents were tried in the presence of
MoS . Using acetonitrile (ACN) and tetrahydrofuran (THF) (entries 3, 4) yielded only trace
amounts of the target product, consistent with a previous report on the trace yields provided
2
(Alfa Aesar, 325 mesh
2
2
(
2
2
2

by polar aprotic solvents.[7] Isopropanol (IPA) was the most successful solvent used, giving
the arylated heteroarene in 87% isolated yield after 4 h, even without the use of base
additives (Table 1, entry 11). Other alcohols (entries 5, 6) and dimethyl formamide (DMF;
entry 7) also gave the target compound, 3a, but in poorer yields. The influence of base was
also investigated (entries 13–15). The arenediazonium tetrafluoroborates are used in our
reaction system. According to previous reports, bases are helpful to minimize the undesirable
-
spontaneous degradation when BF4 is the counteranion.[20] However, in our reaction
condition, no arylated heteroarenes were obtained even with several different bases,
indicating that the bases may hinder the photo catalytic radical intermediate coupling reaction
by blocking of active catalytic sites. Based on our previous research,[21] the base additives
are helpful for exfoliation of MoS2 powder by a covalent bonding between edged sulfurs of
MoS2 and arene molecules, which means that the bases facilitate the S-arene bond but block
the generation of arene radical intermediate that is a competition reaction of the edged sulfur
,
groups to form C-C coupling bond via S-N=N-arene.[22] [23] So, we can confidently assume
that this phenomenon blocks the reaction sites. We also investigated the effect of radical
scavengers (entries 16, 17) to understand the reaction mechanism; their use was found to
inhibit the arylation of benzene diazonium salts through radical trapping.
a
Table 1 Optimization of reaction conditions
b
Entry
Reaction condition
No solvent
IPA (2 mL), no catalyst
ACN (2 mL)
THF (2 mL)
MeOH (2 mL)
EtOH (2 mL)
Yield [%]
25
22
10
12
48
52
53
1
2
3
4
5
6
7
DMF (2 mL)

8
9
1
1
1
1
1
1
1
1
1
IPA (2 mL)
IPA (2 mL)
IPA (0.1 mL)
IPA (1 mL)
IPA (1 mL), H
IPA (1 mL), pyridine (2 equiv)
IPA (1 mL), potassium tert-butoxide (2 equiv) <10
IPA (1 mL), sodium acetate (2 equiv)
IPA (1 mL), galvinoxyl free radical (1 equiv)
IPA (1 mL), TEMPO (1 equiv)
62
<10
10
87
48
c
0
1
2
3
4
5
6
7
2
O (2 equiv)
<10
<10
27
35
0
d
d
8[21]
IPA (1 mL), edge blocked MoS2
a
Standard reaction conditions: 0.2 mmol of 1a, 2 mL of 2, 0.2 mmol of MoS , 2 mL of
2
b
c
solvent under N
of 2. Radical scavenger.
2
atmosphere. Isolated yield after column chromatography. 0.2 mL
d
To optimize the yield, we investigated various reaction conditions, adjusting the amount of
catalyst (Table S1) and using various solvents. The amount of catalyst used did not greatly
affect the yield; the reaction worked well even when a tiny amount of MoS
Supporting Information Table S1). However, the yield strongly depended on the solvent
quantity (entries 7–10), implying that the reaction requires a proper dispersion state to get the
maximum catalytic active sites of MoS powder. The optimum solvent amount was 1 mL of
2
was added
(
2
IPA (Table 1, Entry 10) in the presence of 2 mL of furan, 2.[22, 23] The influence of light on
the reaction was also investigated; the reaction conditions and yields are listed in Supporting
Information Table S2. The use of light appeared to affect the yield very little, meaning that
light does not have an important effect on the reaction.

Figure 1. Kinetic investigation of the reaction. (a) FT-IR spectra of 1a with 2 in the presence
of MoS during reaction. Spectra shown: MoS , 4-chlorobenzene diazonium salt (1a), 1a and
in the presence of MoS after 20 min, 90 min, and 4 h. (b) Product yield versus reaction
time. (c) UV-vis absorbance spectra used for investigation of reaction kinetics at 400 nm after
h. Spectra shown: 1a in the presence of MoS (red line), 1a and 2 in the presence of MoS
blue line), and 4-chlorobenzene diazonium salt (green line); all samples were in isopropyl
2
2
2
2
4
2
2
(
alcohol. (d) Absorbance at 400 nm versus reaction time.
Fourier transform infrared spectroscopy (FT-IR) was carried out to confirm the reaction
−
1
−1
kinetics. Figure 1a shows the typical absorptions of N≡N (2289 cm ), C=C (1564 cm ), and
−
1
C–N (1465 cm ) bonds in aryldiazonium salts (1a).[24] As the reaction time increased, a
−
1
new C–H stretching absorption band appeared at 2978 cm and typical absorption of N≡N
−
1
disappeared at 2289 cm after 4 h, meaning that the starting material has fully participated in
the reaction to form an arylated furan. Contrastingly, FT-IR spectra of 4-chlorobenzene

diazonium salt with MoS
2
catalyst showed no change for the same reaction time (Supporting
is remained in the reaction,
Information Figure S1). It indicates that only azo linked MoS
2
which is related with UV-vis spectra as we will discuss below (Supporting Information
Figure S2). To investigate the reaction kinetics, the product yield was checked. It
dramatically increased during the first 2 h (Figure 1b). According to the literature, the color
change of the solution from colorless to yellow is associated with generation of the
intermediate state, namely, the formation of the azo functional group. The azo intermediate
state can be detected using UV-vis spectroscopy by means of the π–π* transition of the azo
functional moiety.[7, 25, 26] UV-vis spectroscopy can be used to monitor the reaction easily
because the starting material and product have no absorptions in the visible region.
As expected, no absorption by a solution of 1a was observed (Figures 1c, S2c), but a
solution of 1a with MoS
S2a), which continuously increased throughout the reaction time (Figure 1d). This confirmed
that the absorption was related to an azo-linked MoS intermediate. Furthermore, after the
addition of 2 into a mixed solution of 1a and MoS , the azo-MoS intermediate absorption
2
showed an enhanced absorption peak at near 400 nm (Figures 1c,
2
2
2
peak near 380 nm bathochromically shifted to a new absorption peak at 410 nm (Figures 1c,
S2b), which eventually saturated with increasing reaction time (Figure 1d). The absorbance
peak of the reaction of 1a, 2, and the MoS
is eventually saturated, while that of 1a and MoS
there being no consumption of the azo-MoS intermediate.
2
catalyst shows the dramatic enhancement, which
2
without 2 increases continuously due to
2

Figure 2. X-ray photoelectron spectroscopy analyses. (a) Spectra from as prepared MoS
Mo 3d at various reaction times; (b) S 2p core levels. (c) Quantitative analyses of as-prepared
MoS versus reaction time. (d) Mo 3d and S 2p peak positions versus reaction time.
2
and
2
To examine the stability of MoS
2
and find evidence of interactions between MoS and the
2
benzene diazonium salt of 1a, X-ray photoelectron spectroscopy (XPS) was conducted
(
(
Figure 2). Importantly, the Mo 3d and S 2p peaks were shifted to lower binding energies
~0.3 eV for Mo 3d and ~0.2 eV for S 2p) after reaction for 1 h, compared with pristine MoS
2
,
in a manner consistent with a previous report.[27] The azo-functional moiety was shown at
99.2 eV in XPS of N 1s, indicating that azo-functional group was involved as an
intermediate by interacting with active site of MoS (Supporting Information S3).[28] We
3
2
also carried out additional investigation to clarify active sites between Mo and edge sulfur for
our C-H synthetic arylation system. To find active catalytic sites between Mo and sulfur of
MoS , we carried out additional control experiment to block the possible active sites of the
2

terminal sulfur groups through benzene diazonium mediated functionalization with an amine
base catalyst at only edge sites.[21] Noticeably, edge sulfurs that were blocked with 4-
carboxybenzene functional groups could not give the final product, 3a. Based on this control
experiment, we strongly assume that the terminal sulfur is considered as main catalytic active
sites to produce arylated heteroarene. According to previous reports, 1T phase of MoS
2
which
is functionalized with organic molecules or chemical treatments has excess electrons on the
surface.[29, 30] It indicates that the electron rich surface of MoS
interact with positively charged diazonium salts.[31, 32]
2
can electrostatically
For further investigation of radical generation in MoS
measurements were performed (Figure S4). The ESR signal in the region of ~3500 G (g =
.003~2.008) was attributed to free radicals localized on sulfur atoms.[33] And the ESR
signal of radicals derived from benzene diazonium salt was overwrapped with g=2.003.[34, 35]
The intensity of the ESR signal increased when MoS reacted with the benzene diazonium
salt of 1a by generating aryl radicals on sulfur of MoS , a process that releases nitrogen.
2
, electron spin resonance (ESR)
2
2
2
Therefore, the intensity of the signal was enhanced continuously until furan 2 participated in
the reaction. After furan 2 was started to involve in the reaction, an intermediate can release
nitrogen to give product 3a. Accordingly, the peak was decreased dramatically, which meant
that the formation of 3a occurred by means of an interaction between compound 2 and the
azo-linked MoS intermediate.
2

Figure 3. Postulated mechanism of the MoS -catalyzed direct arylation
2
Based on our results and considering previous reports[36-38], we assume that the terminal
sulfurs of MoS act as reactive sites to form an intermediate state of the arylated heteroarene;
the azo-containing intermediate is reduced by MoS to generate the aryl radical via
2
2
electrostatical interaction between the terminal sulfur and the positively charged diazonium
ion.[31, 32] Then, the following addition reaction of the aryl radical to the heteroarene 2
gives the radical-containing arylated heteroarene. Our proposed mechanism also appears
favorable for following a radical chain mechanism with radical generated aryl moiety.
Rearomatization of the radical-containing arylated heteroarene leads to the formation of the
product 3. A recycling test was also carried out for reactivity over MoS ; this showed good
2
recyclability with over 80% yield (Supporting Information Table S3). Finally, various
benzene diazonium salts were also used as substrates under the optimized conditions, giving
various arylated heteroarene products in good yields, as listed in Table 2. Arylated

heteroarenes with both electron-donating (Table 2, compounds 3f and 3h) and electron-
withdrawing substituents (3a–3e and 3g) were obtained. Differently located substituents of
aryldiazonium salt were also examined (3i–3j). Various representative substituents in the
pyridine system were also obtained (5a–5k).
a
Table 2 MoS -catalyzed C–H heteroarylation: diazonium salt and heteroarene scope
2
a
Yield of isolated product (0.2 mmol diazonium salt, 2 mL heteroarene). See the Supporting
Information for detailed experimental procedures.
Conclusions
In summary, we developed a new direct C-H arylation in the synthesis of heteroarene
compounds by using 2D MoS2 catalyst. The catalytically active terminal sulfur groups acted
as a nucleophile could effectively catalyze a formation of an azo-linked intermediate with

aryl diazonium salts to give heteroarenes with high yields. The transformation of diazonium
salts with both electron-rich and electron-poor functional tail groups gave high yields. The
best yield was about 87 % with good recyclability. Our new development of C-H activation
using heterogeneous 2D TMD catalyst is easy, rapid, and simple one-pot synthesis of
heteroarenes, which can offer a blueprint for facile synthesis of biaryl compounds.
Acknowledgements
This work was supported by the Institute for Basic Science (IBS-R011-D1).
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the online version,
at doi:
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Highlights



Unprecedented MoS
Catalytically active terminal sulfurs of MoS
High reusability and simple separation of heterogeneous catalyst
2
catalyzed for direct C–H Arylation
2
for C–H arylation

Facile C–H Arylation using Catalytically Active Terminal Sulfurs of 2 Dimensional Molybdenum
Disulfide