Visible-light-induced aerobic thiocyanation of indoles using reusable TiO2/MoS2 nanocomposite photocatalyst

Article abstract of DOI:10.1016/j.tetlet.2016.03.028

TiO₂/MoS₂ nanocomposite photocatalyst was prepared via simple one-step hydrothermal process. This nontoxic and inexpensive photocatalyst exhibited high activity toward the thiocyanation of indoles under visible light irradiation at room temperature. Simple work-up, good yields, as well as reusability of the catalyst are the major advantages of the present method.

Full text of DOI:10.1016/j.tetlet.2016.03.028

Accepted Manuscript
Visible-light-induced aerobic thiocyanation of indoles using reusable TiO2/
MoS2 nanocomposite photocatalyst
Liang Wang, Cancan Wang, Wenjie Liu, Qun Chen, Mingyang He
PII:
S0040-4039(16)30251-9
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.03.028
TETL 47416
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
27 January 2016
7 March 2016
9 March 2016
Please cite this article as: Wang, L., Wang, C., Liu, W., Chen, Q., He, M., Visible-light-induced aerobic thiocyanation
of indoles using reusable TiO2/MoS2 nanocomposite photocatalyst, Tetrahedron Letters (2016), doi: http://
dx.doi.org/10.1016/j.tetlet.2016.03.028
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Graphical Abstract
Visible-light-induced aerobic thiocyanation
of indoles using reusable TiO2/MoS2
nanocomposite photocatalyst
Leave this area blank for abstract info.
Liang Wang,* Cancan Wang, Wenjie Liu, Qun Chen, and Mingyang He*

1
Tetrahedron Letters
journal h omepage: www.els evier. com
Visible-light-induced aerobic thiocyanation of indoles using reusable TiO2/MoS2
nanocomposite photocatalyst
Liang Wang,* Cancan Wang, Wenjie Liu, Qun Chen, and Mingyang He*
School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Changzhou University, Changzhou, 213164, P. R.
China.
*Corresponding author. Tel.: +86-519-86330263; fax: +86-519-86330251. E-mail address: lwcczu@126.com; hemingyangjpu@yahoo.com
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
TiO2/MoS2 nanocomposite photocatalyst was prepared via simple one-step hydrothermal
process. This nontoxic and inexpensive photocatalyst exhibited high activity towards the
thiocyanation of indoles under visible light irradiation at room temperature. Simple work-up,
good yields, as well as reusability of the catalyst are the major advantages of the present method.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Photocatalysis
Thiocyanation
Indoles
TiO2/MoS2
µmol h-1 g-1) was observed with only 1 wt% loading of MoS2.17
Xiang et al18 prepared a composite material consisting of TiO2
nanocrystals grown in the presence of a layered MoS2/graphene
hybrid, which reached a high H2 production rate (up to 165.3
µmol h-1 g-1). Shen et al19 also disclosed an efficient MoS2
nanosheet/TiO2 nanowire hybrid nanostructure for visible light
photocatalytic hydrogen evolution reaction. Just recently, Zhang
et al20 successfully applied a similar MoS2/TiO2 composite on the
degradation of methyl orange. Acknowledged to the pioneer
work that using modified semiconductor photocatalysts in
hydrogen evolution area and photo-degradation of organic
wastes, there is still much room to apply this appealing strategy
to organic synthesis.
Recently, titanium dioxide (TiO2) as an attractive
heterogeneous photocatalyst has received much attention since it
is very cheap, readily accessible, stable and nontoxic.1,2 More
importantly, it benefits the photo-induced catalysis with
heterogeneous features including stability and recyclability.
Despite these impressive advantages of TiO2 over conventional
homogeneous photocatalysts, their utilization in organic
transformations is still quite limited, especially under visible
light irradiation.3-6 The limiting factors to the applications of
TiO2 as a photocatalyst lies in its wide band gap energy (~3.2 eV)
and high recombination rate of photo-induced e-/h+ pairs at or
near the catalyst surface.7-9 Much efforts have been made in
recent years to narrow the band gap of TiO2 and reduce the hole-
electron pair recombination. Among them, modification of TiO2
with other metal oxide nanoclusters such as NiO, FeOx, CuO etc.
have proven to be one of the most effective methods.3,10-13
Thiocyano groups widely exist in natural products and
pharmaceutical ingredients. They also serve as useful blocks to
construct sulfur-containing heterocycles (Figure 1).21
Additionally, they are often considered as organic pseudohalides
and can be easily converted to other functional groups.
Electrophilic thiocyanation using thiocyanate salts in the
presence of an oxidant is the major approach to deliver organic
thiocyanates.22 However, a large excess amount of oxidants was
usually required. Photocatalyzed thiocyanation reaction was also
been reported, while these photocatalysts were expensive and
could not be recovered and reused.23 To our literature,
thiocyanation reaction utilizing cheap and reusable
semiconductor photocatalyst has not been reported yet. Herein,
we disclosed the preparation of a TiO2/MoS2 nanocomposite
During the past decades, layered molybdenum disulfide
(MoS2) has been extensively investigated in photocatalysis due
to its narrow band gap (1.3~1.8 eV), which provides not only
visible-light-harvesting function but also high stability against
photocorrosion.14,15 Moreover, high chemical stability as well as
quantum confinement effects make it a suitable photosensitizer
in heterogeneous semiconductor system. For instance, Zong et
al16 reported the enhancement of photocatalytic H2 production
activity of CdS by loading MoS2 as cocatalyst. Liu et al reported
a one-step solvothermal synthesis of MoS2/TiO2 nanocomposites
and excellent photocatalytic activity for H2 evolution (119.5

2
Tetrahedron Letters
photocatalyst and its application in the thiocyanation of indoles
DMF, DMSO, DCE, 1,4-dioxane, or CH3OH led to decreased
under visible light irradiation at room temperature.
yields (Table 1, entries 9-13). A much lower yield was also
obtained by decreasing the catalyst amount to 10 mg.
Replacement of NH4SCN with KSCN gave unsatisfactory yield
(48%, Table 1, entry 15). Decreasing the amount of NH4SCN to
2 equiv also led to a lower yield (73%, Table 1, entry 15).
Finally, rather poor yield was observed under N2 atmosphere,
indicating O2 is critical for this reaction (Table 1, entry 16).
Table 1 Optimized the reaction conditions.a
Fig. 1Thiocyano group-containing natural products and bioactive
compounds.
The TiO2/MoS2 nanocomposite was prepared by slightly
modifying the reported literature17 via a simple hydrothermal
process using cheap and readily available TiCl4, sodium
molybdate and thioacetamide as starting materials (see
Supplementaty Material). The as-prepared TiO2/MoS2
nanocomposite was characterized by XRD, UV-vis and TEM.
Entry
1
Catalyst
Solvent
Yield(%)b
TiO2 (Anatase)
TiO2 (Rutile)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
n.r.
n.r.
2
3
TiO2/MoS2 (100: 1)
TiO2/MoS2 (50: 1)
TiO2/MoS2 (20: 1)
TiO2/MoS2 (10: 1)
TiO2/MoS2 (5: 1)
MoS2
42
4
55
5
79
6
93
7
85
8
63
9
TiO2/MoS2 (10: 1)
TiO2/MoS2 (10: 1)
TiO2/MoS2 (10: 1)
TiO2/MoS2 (10: 1)
TiO2/MoS2 (10: 1)
TiO2/MoS2 (10: 1)
TiO2/MoS2 (10: 1)
TiO2/MoS2 (10: 1)
48
10
11
12
13
14
15
16
DMSO
DCE
41
58
1,4-dioxane
MeOH
53
84
CH3CN
CH3CN
CH3CN
46c, 90d
48e, 73f
11g, 92h
a Reaction conditions: 1a (0.2 mmol), catalyst (20 mg, the ratio in parenthesis
is the molar ratio of Ti to Mo), NH4SCN (0.6 mmol, 3 equiv), solvent (2
b
mL), air, irradiation under a 14 W CFL at room temperature for 16 h.
d
e
Isolated yields. c 10 mg catalyst was used. 40 mg catalyst was used.
3
h
f
equiv of KSCN was used. 2 equiv of NH4SCN was used. g N2 atmosphere.
Fig. 2 (a) XRD patterns of pure TiO2 (red), pure MoS2 (black) and
TiO2/MoS2 (10: 1, molar ratio) nanocomposite (blue). (b) UV-vis spectra of
pure TiO2 (black), MoS2 (red) and TiO2/MoS2 (10: 1, molar ratio)
nanocomposite (blue). (c) TEM image of MoS2. (d) TEM image of
TiO2/MoS2 (10: 1, molar ratio) nanocomposite.
O2 atmosphere.
With these results in hand, we began to examine the scope and
generality of the present method (Table 2).25
Table 2. Reaction scope for indoles.a
Fig. 2 (a) presents the X-ray diffraction patterns for pure TiO2,
MoS2 and TiO2/MoS2 (10: 1, molar ratio) nanocomposite. The
characteristic diffraction peaks clearly indicate that the hybrid
nanostructures with well-defined crystallinity consist of both
MoS2 and Anatase TiO2. In the UV-vis study, TiO2/MoS2
nanocomposite exhibits intense absorption in both ultraviolet and
visible-light regions (Fig. 2, b). The band gap energy (Eg) is
estimated to be 2.99 eV based on the absorption spectrum and
the (Ahv) = K(hv–Eg)n formula.24 The TEM analyses show that
the MoS2 has a layered structure (Fig. 2, c), and TiO2
nanoparticles (ca. 3~5 nm) disperse uniformly on the surface of
the MoS2 layer.
With the TiO2/MoS2 nanocomposite in hand, we start to
explore its photocatalytic activity towards thiocyanation of
indoles, and the results are summarized in Table 1. As shown
from Table 1, no reaction occurred in the presence of either
Anatase TiO2 or Rutile TiO2 under visible-light irradiation. A 42%
yield of product 2a was obtained by employing TiO2/MoS2 (100:
1, molar ratio of Ti to Mo) nanocomposite as the photocatalyst,
indicating the hybridization structure have a synergistic effect in
the present process. Further studies clearly showed that
TiO2/MoS2 (10: 1, molar ratio of Ti to Mo) nanocomposite was
the most suitable catalyst, providing 2a in 93% yield (Table 1,
entry 6). Only moderate yield was obtained in the presence of
pure MoS2 (Table 1, entry 8). Reactions in other solvents such as

3
a Reaction conditions: 1 (0.2 mmol), TiO2/MoS2 (10: 1 molar ratio) (20 mg),
NH4SCN (0.6 mmol, 3 equiv), CH3CN (2 mL), air, irradiation under a 14 W
CFL at room temperature for 16 h, isolated yields. b Reaction for 36 h.
confinement effects of nanoscale MoS2. The photogenerated
electrons were then transferred into CB of anatase TiO2, thereby
the photoinduced electrons and holes can be efficiently separated.
The produced holes oxidized thiocyanate anion to thiocyanate
radical, which attacked indole to generate radical intermediate A.
Subsequently, intermediate A was oxidized to the intermediate B,
which afforded the final product 2a via deprotonation.
As illustrated in Table 2, a series of functional groups
including chloro, bromo, methoxyl, methyl, as well as phenyl
were well tolerated under the standard conditions. Substrates
with electron-withdrawing groups, however, were inert towards
the reaction even at a prolonged reaction time (2f, 48%; 2g, 27%;
2h, 12%; 2i, 21%, respectively). For N-methyl indole, the
corresponding 3-thiocyano products were obtained in 94 and 84%
yields respectively (2l and 2n), while N-Boc indole gave trace
amount of the desired product (2o). It was worth noting that 3-
methyl indole also reacted smoothly to deliver the 3-methyl-3-
thiocyanatoindolin-2-one (2p) in 86% yield.
To demonstrate the utility of the present protocol, a scale-up
reaction (10 mmol scale) was performed (Scheme 1). To our
delight, this transformation afforded the desired product 2a in 83%
yield (1.44 g) with a prolonged time (48 h).
Scheme 2 Control experiments.
Scheme 1 Gram-scale thiocyanation of 1a.
Another advantage of this developed protocol is the
opportunity to recycle the nanocatalyst. Once the reaction is
complete, in-flask extraction and centrifugal separation allows
for isolation of the desired product, while the catalyst can be
washed with ethanol and water. The recycled photocatalyst, as
expected, showed good reusability in eight consecutive cycles
with slight decrease in its activity (Fig. 3, a). Meanwhile, the
recovered catalyst was examined by TEM and it was obvious
that aggregation of TiO2 was observed and the size of TiO2
nanoparticles increased, which might accounted for the
decreased activity after several runs (Fig. 3, b).
Scheme 3. Proposed mechanism.
In summary, we have developed a mild, inexpensive, and
nontoxic visible-light-mediated photocatalytic system for
thiocyanation of indoles by using TiO2/MoS2 nanocomposite.
MoS2 works as an efficient photosensitizer, and the hybridization
structure exhibits
a
synergistic effect to enhance the
photocatalytic activity under visible light irradiation. Good
isolated yield and substrate compatibility, easy-to-hand workup
process, and recyclability of the catalyst enable this protocol a
more practical and environmentally benign alternative to known
methods.
Fig. 3 Recycling experiment (a) and the TEM image of recovered TiO2/MoS2
(10: 1) nanocomposite after eight runs.
To gain insight into the mechanism, several control
experiments were performed (Scheme 2). It was observed that
the reaction was quenched when 3 equiv of radical scavenger,
2,2,6,6-tetramethylpiperidine N-oxide (TEMPO), was added to
the reaction mixture under standard conditions (Scheme 2, a).
The reaction also did not take place in the absence of visible
light, which strongly supports the radical mechanism (Scheme 2,
b). Furthermore, the reaction was not quenched in the presence
Acknowledgments
We gratefully acknowledge financial support from the
National Natural Science Foundation of China (21302014), the
Natural Science Foundation of Jiangsu Province (BK20130247),
the Jiangsu Key Laboratory of Advanced Catalytic Materials and
Technology (BM2012110), the Priority Academic Program
Development (PAPD) of Jiangsu Higher Education Institutions,
and Advanced Catalysis and Green Manufacturing Innovation
center of Changzhou University.
of
1
equiv of 1,4-Diazabicyclo[2.2.2]octane (DABCO),
indicating that singlet oxygen is not involved in the reaction
(Scheme 2, c).26
On the basis of above experimental results, a plausible
mechanism for this reaction was proposed (Scheme 3). Under
visible-light irradiation, the CB of nanoscale MoS2 is more
positive than that of Anatase TiO2 due to the quantum

4
Tetrahedron Letters
and ammonium thiocyanate (0.6 mmol) in CH3CN (2 mL)
References and notes
was added TiO2/MoS2 (10: 1, molar ratio, 20 mg). The
reaction mixture was stirred under a 14 W CFL irradiation
at room temperature for a certain time. After reaction
(monitored by TLC), ethyl acetate was added, and the solid
catalyst was recovered by centrifugation. The reaction
mixture was extracted with ethyl acetate and washed with
water. The combined organic phase was then dried over
Na2SO4 and concentrated under reduced pressure to give
the crude residue, which was purified by column
chromatography with petroleum ether/ethyl acetate to
afford the pure thiocyanated product 2. The recovered
catalyst was then washed with ethanol and deionized water,
dried under vacuum, and reused for the next run.
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5
Highlights
Nontoxic and inexpensive TiO2/MoS2
photocatalyst is prepared.
Green thiocyanation of indoles is developed.
Good yields and substrate compatibilities.
Reaction can be scaled up to gram scale.