Visible light induced the high-efficiency spirocyclization reaction of propynamide and thiophenols via recyclable catalyst Pd/ZrO2

Article abstract of DOI:10.1016/j.cclet.2019.06.008

A new method for the synthesis of 3-thioazaspiro[4,5]trienones was developed using Pd nanoparticle catalysts, which are highly efficient, environmentally friendly and recyclable. Alkynes and thiophene phenols are effectively cyclized by Pd/ZrO₂

Full text of DOI:10.1016/j.cclet.2019.06.008

Accepted Manuscript
Title: Visible light induced the high-efficiency spirocyclization
reaction of propynamide and thiophenols via recyclable
catalyst Pd/ZrO2
Authors: Nannan Zhang, Hangdong Zuo, Chen Xu, Junyi Pan,
Jun Sun, Cheng Guo
PII:
DOI:
Reference:
S1001-8417(19)30328-6
https://doi.org/10.1016/j.cclet.2019.06.008
CCLET 5039
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Chinese Chemical Letters
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Revised date:
Accepted date:
24 April 2019
30 May 2019
5 June 2019
Please cite this article as: Zhang N, Zuo H, Xu C, Pan J, Sun J, Guo C,
Visible light induced the high-efficiency spirocyclization reaction of propynamide
and thiophenols via recyclable catalyst Pd/ZrO2, Chinese Chemical Letters (2019),
https://doi.org/10.1016/j.cclet.2019.06.008
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Communication
Visible light induced the high-efficiency spirocyclization reaction of propynamide and
thiophenols via recyclable catalyst Pd/ZrO2
Nannan Zhang, Hangdong Zuo, Chen Xu, Junyi Pan, Jun Sun, Cheng Guo*
College of Chemistry and molecular engineering, Nanjing Tech University, Nanjing 211816, China
ARTICLE INFO
ABSTRACT
Article history:
A new method for the synthesis of 3-thioazaspiro[4,5]trienones was developed using Pd
nanoparticle catalysts, which are highly efficient, environmentally friendly and recyclable.
Alkynes and thiophene phenols are effectively cyclized by Pd/ZrO2 catalyst under visible light
irradiation. The present protocol simply utilizes visible light as the safe and ecofriendly energy
source, and the Pd/ZrO2 nanocomposite as photocatalyst provides a simple and practical
approach to various 3-thioazaspiro[4,5]-trienones in moderate conditions to high yields.
Received 24 April 2019
Received in revised form 31 May 2019
Accepted 3 June 2019
Available online
Keywords:
Visible light
Spirocyclization reaction
Mild condition
Pd/ZrO2 Nanocomposite photocatalyst
Thioether spirals are a class of important structural motifs
with wide applications in organic synthesis, medicinal chemistry
and material chemistry, and their synthesis methods have
aroused great interests from relevant workers [1-8]. Recently,
organic dyes or transition metal salts have been applied in
photocatalytic or thermal reactions to obtain target products. For
example, Eosin Y Sodium was used as a photocatalyst for the
synthesis of 3-sulfonyl and 3-sulfenyl azaspiro[4,5]trienones [9],
followed by developing a AgCl catalyst in spirocyclization
reaction to get 3-thioazaspiro[4,5]trienones, a key product in
biology [10]. However, these homogeneous catalysts are
difficult to be separated from the reaction solutions thus their
recovery take additional energy. Moreover, the reaction
substrate aryl benzene requires a para-methoxy group or a
methyl group and the yields of 3-sulfenyl azaspiro[4,5]trienones
obtained by these methods is low [11-16]. Hence, it is necessary
to develop an efficient synthetic method in a greener way for
spirocyclization. In recent years, noble metal nanoparticles (NPs)
have attracted great attentions as a photocatalyst in driving
chemical reactions [17]. It has been found that palladium (Pd)
NPs can efficiently convert visible light to chemical energy in
fine organic synthesis at ambient temperatures [18]. Considering
visible light occupies a large fraction (~43%) of solar energy,
the visible light photocatalysis is a green and promising way in
driving chemical reactions [19]. Besides, the visible light is help
for forming carbon-carbon and carbon heteroatom bonds [20-30]
via catalytic oxidation route in molecules assembling. In
addition, the visible-light-induced electrons on the metal NPs
surface can be directly transferred to the anti-bonding orbital of
adsorbed molecules, which enhances the intrinsic catalytic
activity of metal NPs and triggers the reaction significantly.
When the noble metal NPs are supported on a photocatalytic
stable performance. Herein, we present the spirocyclization
reaction of alkyne can be conducted effectively at mild
conditions through using supported Pd NPs as the photocatalyst
under visible light.
Scheme 1. Various routes for the spirocyclization reactions.
We characterized the catalyst Pd/ZrO2 by XRD, TEM and
UV-vis. Initially, the TEM image (Fig 1A) demonstrates
palladium nanoparticles (Pd NPs) of spherical particles
dispersed on ZrO2. The particle size of Pd NPs supported on
ZrO2 is less than 8 nm, and most are 4-7 nm. This indicates that
the catalyst is a nanoscale catalyst (Fig. 1B). Then, it can be seen
from XRD that the introduction of the preparation method of Pd
has no effect on the structure of ZrO2. No characteristic
diffraction peaks were observed in the XRD spectrum, possibly
due to the low contents of Pd or Pd forming amorphous
nanoparticles. Finally, the UV-vis spectrum (Fig. 1C) shows that
the absorption of Pd/ ZrO2 is stronger than that of ZrO2 in the
ultraviolet and visible range, indicating that the enhanced light
absorption is due to the dispersed ZrO2 surface of the Pd
inert carrier, it can be reused as a visible light photocatalyst with
———
 Corresponding authors.
E-mail addresses: sunjun@njtech.edu.cn (J. Sun), guocheng@njtech.edu.cn (C. Guo)

nanoparticles.
a small amount of the target product 3a was examined in the
absence of visible light irradiation (entry 12) under the standard
conditions.
Table 1
Optimization of the reaction conditions.a
Fig. 1. (A) TEM image of 3 wt% Pd/ZrO2 (B) The X-ray diffraction patterns
for pure 3 wt% Pd/ZrO2 (red) and ZrO2 (black). (C) UV–vis spectra of pure
ZrO2 (black), 3 wt% Pd/ZrO2 (red).
In our preliminary investigation, we investigated the different
reaction conditions under the induction of visible light with 1a
and 2a as the reaction substrates. The results were summarized
in Table 1. The solvents such as DMF, ethanol, dioxane and
THF were filtered by us. As a result, the yield of the target
product 3a was found to be not greatly improved. In order to
investigate the role of Pd in the reaction, we investigated the
effect of Pd(OAC)2 (entry 13) and PdCl2 (entry 14) as catalysts
on the reaction under the standard conditions. And it was found
that the recyclable Pd nanoparticles acted as a catalyst to
strengthen the reaction compared with the Pd salt catalyst.
Pd/ZrO2 (3%wt, 10 mol%) was used as photocatalyst in CH3CN
under the exposure of an incandescent lamp at air conditions for
12 h which is the optimal conditions to produce the product 3a
(3-thioazaspiro[4,5]trienones). After that, the mass fraction ratio
and content of the catalyst were investigated (Table 1). And only
Entry
1
2
3
4
5
6
7
8
Catalyst
Solvent
DMSO
DMF
Ethanol
Dioxane
THF
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Time
12h
12h
12h
12h
12h
12h
12h
12h
12h
12h
12h
12h
12h
12h
Yield (%)
27
trace
trace
trace
trace
92
3wt%Pd/ZrO2
3wt%Pd/ZrO2
3wt%Pd/ZrO2
3wt%Pd/ZrO2
3wt%Pd/ZrO2
3wt%Pd/ZrO2
3wt%Pd/CeO2
2wt%Pd/ZrO2
4wt%Pd/ZrO2
5wt%Pd/ZrO2
ZrO2
80
82
85
83
9
10
11
12
13
14
trace
3wt%Pd/ZrO2
Pd(OAC)2
PdCl2
22b
46
50
a Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), photocatalyst
(2–5 wt%), irradiation with one halogen tungsten lamp in solvent (3
mL) at 30 °C for 12 h.
b In dark.
100
100
C
Dark
Light
A
B
100
90
80
90
80
70
60
50
40
30
20
10
0
90
80
70
60
50
40
70
Light
Dark
70%
67%
60
50
40
68%
61%
49%
30
20
10
0
30
20
10
0
0.3
0.4
0.5
0.6
0.7
25
30
35
40
45
0
1
2
3
4
5
Reaction temperature (oC)
Light intensity (w/cm2)
Recycle time
Fig. 2. (A) The photocatalytic activity of the Pd/ZrO2 catalyst after being recycled five times. (B) Light and dark reaction yields under different
temperature conditions. (C) Dependence of the catalytic activity of Pd/ZrO2 photocatalyst for the spirocyclization reaction of the aromatic
alkyne with the sulfhydryl group on the intensity of irradiation. The light contribution = [(Ylight – Ydark)/Ylight]× 100%, where Ylight and Ydark
are the product yields under irradiation and controlled in the dark, respectively.
A key advantage of heterogeneous catalysis is the possibility
of catalyst recovery. A series of spirocyclization reactions of N-
methyl-N, 3-diphenylpropanamide 1a and thiophenol 2a were
studied under visible light irradiation, demonstrating that
Pd/ZrO2 is a recyclable catalyst. At the end of each reaction
cycle, the Pd/ZrO2 catalyst was separated by a centrifuge and
thoroughly washed twice with ethanol and dried for subsequent
reaction. We have reused five times of Pd/ZrO2 catalyst to carry
out the catalysis of the reaction under the same reaction
conditions and obtained some research data. As shown in Fig.
2A, the Pd/ZrO2 catalyst was reused for several cycles without
significantly exhibiting low and moderate activity.
between the yields under visible light and the dark reaction
yields, to found that this reaction system is more efficient, green
and energy efficient at 30 °C (Fig 2B).
We studied the relationship between photocatalytic activity
and incident light intensity (irradiance). The spirocyclization
reactions of the aromatic alkyne with the sulfhydryl group are
carried out at different irradiances. The product yield is also
correspondingly increased when the intensity of light is
enhanced (Fig 2C). The contribution of irradiation to the
reaction is manifested by calculating the reaction conversion rate
obtained by subtracting the reaction yield obtained in the dark
under the same reaction conditions, and the yield of the product
obtained in the dark is considered to be heat contribution.
The products yields tend to be stable when the reaction
temperature exceeds 30 °C. And the conversion rate at different
temperatures has been obtained by calculating the difference

can inhibited the occurrence of the reaction when it is added to
the reaction system in other things being equal. And the
TEMPO-trapped complex (PhS-TEMPO) was detected by Mass
Spectrometry analysis (Scheme 3, d), which supports that ArS
radical may involve in the reaction and promote reaction
pathway to gain further insight the mechanism of this process.
Through the investigation of the above experimental results
and previous experimental reports [31-38],
a
possible
mechanism was proposed as shown in Scheme 4 [39]. Initially,
the high-energy electrons excited on the surface of the metal
palladium nanoparticles enter the deductive band through the
band transition to the surface, thereby entering the molecular
anti-bond orbital under the irradiation of visible light. So the
thiophenol adsorbs on the surface of the catalyst to form a
complex [40]. Then, the electron holes are converted into each
other and the electrons enter the hydrogen in the sulfhydryl
group. Subsequently, the hydrogen of thiophenol is extracted by
Pd/ZrO2 nanoparticles to form a radical 4 (ph-S) and the
removed hydrogen is adsorbed on the surface of nano-palladium
to form H-Pd NPs, which attacks the acetylenic bond of the
substrate 1 to form a radical intermediate 5 (detected by MS in
the Supporting information). Then, the intramolecular
spirocyclization of the radical intermediate 5 with aromatic ring
may result in a radical intermediate 6 which forms a free radical
intermediate 7 under the oxidation of oxygen in the air while
losing one H positive ion. Next the radical intermediate 7 is
transferred to Pd/ZrO2 nanoparticles to form intermediate 8
(detected by MS in the Supporting information). After that, the
1/2 oxygen anion is removed to form a radical intermediate 9.
Meanwhile, the oxygen anion reacts with the H positive ion to
form water. Subsequently, the radical intermediate 9 forms the
final product 3 and the activation site on the photocatalyst return
to the state before starting the reaction (Scheme 4).
Scheme 2. Visible-light-induced alkynes and thiols to form 3-
sulfenyl azaspiro[4,5]trienonesa.
Based on the optimization research, some extended researchs
on this new spirocyclization reaction, and the results are
summarized in Scheme 2. First, whether the substituent on the
thiophenol is an electron withdrawing group (F, Cl or Br) or an
electron donating group (Me or MeO), the reaction proceeds
well and has a good yield (3b-3k). Afterwards, we studied
different substituents of the aniline moiety of N-
arylpropiolamides, mainly the ortho and meta positions are
compatible with this reaction, and a good yield can be obtained
(3l-3o), The desired spirocyclization product can also be
obtained by replacing N-Me with N-H, as is the substitution on
the alkyl alkyne (3p).
Scheme 3. Control experiments.
We conducted several experiments in order to investigate the
reaction mechanism of this reaction and the source of oxygen in
the product (Scheme 3). The results indicate that the oxygen in
the product is derived from air rather than H2O (Scheme 3, a and
b). Interestingly, we did not get the desired product when we
added the group at the para position of the aniline which further
confirmed that product 3 has a change in the para position
(Scheme 3, c). Then we conducted several sets of experiments
and discussed, no new products were produced in the respective
independent reactions of 1a and 2a under the same conditions,
this result indicates that the original reaction occurred due to the
interaction of 1a and 2a. Moreover, a well-known radical
trapping agent TEMPO (2, 2, 6, 6-tetramethyl-1-piperidinyloxy)
Scheme 4. Plausible reaction pathway.

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synthesizing various 3-sulfenyl azaspiro[4,5]trienones can be
driven in visible light irradiation at 30 °C. During this
photocatalytic process, Pd NPs loaded on ZrO2 contributes
activation of the reactants and may reveal a new spirocyclic
oxygenation pathway. This reaction pathway reveals a class of
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conservation, lower environmental impact for the synthesis of
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Graphical Abstract
A simple, highly efficient spirocyclization reaction without additional additives and oxidizing agents, and the photocatalyst
Pd/ZrO2 can be recycled. It is a green environmentally friendly reaction pathway.