PTSA-catalyzed green synthesis of 1,3,5-triarylbenzene under solvent-free conditions

Article abstract of DOI:10.1039/c0gc00158a

An economical and green conversion of acetophenones into 1,3,5-triarylbenzenes catalyzed by PTSA is described. The present method is facile and chemo-selective without using any metal catalyst or solvent.

Full text of DOI:10.1039/c0gc00158a

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www.rsc.org/greenchem | Green Chemistry
PTSA-catalyzed green synthesis of 1,3,5-triarylbenzene under solvent-free
conditions†
Yanan Zhao,a Jian Li,a Chunju Li,a Kun Yin,a Dongyan Yea and Xueshun Jia*a,b
Received 31st May 2010, Accepted 21st June 2010
First published as an Advance Article on the web 19th July 2010
DOI: 10.1039/c0gc00158a
Table 1 Catalyst and temperature screening for the triple condensation
of 1aa
An economical and green conversion of acetophenones into
1,3,5-triarylbenzenes catalyzed by PTSA is described. The
present method is facile and chemo-selective without using
any metal catalyst or solvent.
Screening green methods for chemical synthesis is urgent and
challenging in the long term to avoid the adverse consequences
of the substances used and generated.1 A green chemical process
for sustainable development always involves considerations such
as using cost-effective catalysts without any additives, employing
water as a solvent or with a solvent-free system. In addition, a
simple workup procedure is also desirable.
Entry
Catalyst
Temperature/◦C
Time/h
Yield (%)b
1
2
3
4
5
6
7
8
FeCl3
FeCl3
ZnCl2
CuCl2
CAN
TiCl4
Fe3O4
I2
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
130
130
130
130
130
130
130
130
130
130
80
10
10
10
10
10
10
10
10
10
10
12
24
65 c
78
40
38
>10
50
0
1,3,5-Triarylbenzenes are very useful compounds used as elec-
troluminescing materials, electrode devices,2 resisting materials3
or conducting polymers.4 These compounds can also serve
as versatile intermediates for the synthesis of buckminster-
fullerenes, pharmaceuticals and conjugated star polyaromatics.5
As a result, the synthesis of 1,3,5-triarylbenzenes has attracted
much attention and a variety of methodologies have been
developed. To our knowledge, triple condensations of alkynes
catalyzed by transition metal complexes (such as Nb,6 Co,7 Ir,8
Pd9 and Rh10) have been widely investigated. Metal-catalysed
cross-coupling reactions between 1,3,5-trihalobenzenes with
organometallic partners also act as an alternative.11 Of the
methodologies mentioned above, however, alkynes are some-
what expensive and not readily available. Meanwhile, the triple
self-condensation of alkynes always involves precious metal
catalysts together with ligands.6–10 Moreover, the triple conden-
sation of alkynes always produces 1,3,5-triarylbenzenes as minor
products or by-products.7,8,9,10 Comparatively, cross-coupling
reactions from 1,3,5-trihalobenzenes can give better yields
without the employment of precious metals. On the other hand,
syntheses of 1,3,5-triarylbenzenes from aryl methyl ketones have
been regarded as more straightforward methods and many
methodologies have been developed.2,12,13 Of these protocols
used in this manner, however, most suffer from using precious
metal catalysts, lower yields or harsh operating conditions. Due
to their expensive nature, inadequate accessibility, toxicity of the
additives often used and the generation of toxic waste as well as
0
9
85
10
11
12
91d
e
rt
0
a Conditions: 1 (3 mmol), catalyst (5 mol%), solvent free. b Isolated yield.
c 2% catalyst was used. d 10% catalyst was used. e Trace product was
obtained.
the use of organic solvent, there is an urgent need to develop a
powerful method to meet the requirement of green chemistry.
More recently, PTSA (TsOH·H2O) has attracted much atten-
tion from synthetic organic chemists and has been extensively
applied for a plethora of organic transformations14 because
of it’s relative nontoxicity, ready availablility, and is fairly
insensitive. As a continuation of our ongoing efforts to explore
environmentally benign synthetic reactions,15 herein we wish to
report a simple and green method for the synthesis of 1,3,5-
triarylbenzenes from aryl methyl ketone catalyzed by PTSA
under solvent-free conditions.
Initially, we chose acetophenone 1a as the model substrate.
Firstly, the reaction was carried out in the presence of FeCl3
(2%) under solvent-free conditions (Table 1, entry 1). To our
delight, a large amount of 1,3,5-triphenylbenzene was afforded
as white solid.11 Since Fumiaki Ono et al. 2 didn’t obtain the same
product using FeCl3, AlCl3 or TiCl4 in toluene under reflux, we
thus deduced the presence of solvent may disfavor the triple con-
densation. When 5% FeCl3 was used, the above conversion got a
substantial increase to 78% yield (Table 1, entry 2). A variety of
experimental parameters including catalysts and their loadings
were screened to optimize the reaction conditions. Many other
catalysts such as I2, ZnCl2, CuCl2, TiCl4, (NH4)2Ce(NO3)6 and
Fe3O4 were also tested for this transformation, only to produce
aShanghai Univesity, 99 Shangda Road, Shanghai, 200444, P. R. China.
E-mail: xsjia@mail.shu.edu.cn; Fax: +86-21-66132408
bKey Laboratory of Synthetic Chemistry of Natural Substances,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai, 200032, P. R. China
† Electronic Supplementary Information (ESI) available: General ex-
perimental details and characterisation data for compounds. See
DOI:10.1039/c0gc00158a/
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Table 2 Cyclotrimerization of aryl methyl ketone catalyzed by
TsOH·H2O a
Entry Ar
Product Temperature/◦C Time/h Yield (%)b
1
2
3
4
5
6
7
8
C6H5
2a
p-CH3C6H4 2b
p-NH2C6H4 2c
p-OCH3C6H4 2d
p-NO2C6H4 2e
130
146
142
148
140
143
145
130
128
136
140
145
146
10
13
16
25
24
24
13
18
22
24
18
16
19
91
87
71
68
c
-
p-FC6H4
p-ClC6H4
p-BrC6H4
p-IC6H4
o-CH3C6H4 2j
m-CH3C6H4 2k
2f
2g
2h
2i
90
74
82
84
70
85
71
61
9
10
11
12
13
Scheme
1
Possible mechanism for the cyclotrimerization of
m-ClC6H4
o-ClC6H4
2l
2m
acetophenones.
a Conditions: 3 mmol of aryl methyl ketone, 0.3 mmol of TsOH·H2O, no
solvent. b Isolated yields. c No reaction.
tives. Importantly, water was the only by-product in the whole
process, which added to its attractiveness.
In conclusion, we have developed a simple and green method
for the synthesis of 1,3,5-triarylbenzenes catalyzed by PTSA
under solvent-free conditions.16 The major advantages of the
method lie in the cheap catalyst, easy work up and avoidance
of using harmful solvent. This could be an economical protocol
for the preparation of 1,3,5-arylbenzenes compared with other
reported methods. Furthermore, water is afforded as the by-
product in this reaction, which makes the present process
environmentally benign.
somewhat lower yields (Table 1, entries 3–8). However, the
triple condensation reaction became quite sluggish with poor
yields when p-OCH3 and o-CH3 substituted acetophenones
were used. Elevating the reaction temperature didn’t bring any
improvement. To solve this problem, we paid attention to other
new catalysts. Fortunately, the reaction afforded an 85% yield
of 2a using 5% PTSA. Using 10% PTSA (TsOH·H2O), the
yield was enhanced to 91%. Effect of reaction temperature was
also studied, and the results showed that lower temperatures
disfavored the reaction (Table 1, entries 10–12).
Acknowledgements
After optimization of conditions, we investigated the scope
and the limitation of this trimerization reaction. As shown
in Table 2, acetophenones containing either electron-donating
or electron-withdrawing groups reacted smoothly to afford
1,3,5-arylbenzenes in good yields. When the para-substituents
were chloro, bromo and iodo, the yields increased as their
electronegativity decreased (Table 2, entries 7, 8, 9). On the
other hand, strong electron-donating groups such as -NH2 and
-OCH3 provided lower yields (Table 2, entry 3, 4) than other
groups such as alkyls or halogens. When substrates with a
strong electron-withdrawing nitro group were used, no reaction
occurred even after enhancing the loading of TsOH·H2O to 1
equivalent (Table 2, entry 5). The steric effect was significant,
and the reactions of para- or meta- substituted chloroacetophe-
nones afford little higher yields than sterically hindered ortho-
substituted acetophenone. The results also indicate the reactivity
order of substituted acetophenones: para- > meta- > ortho-
(Table 2, entries 2, 7, 10, 11, 12, 13).
The authors thank the National Natural Science Foundation of
China (No: 20872087 and 20902057), the Key Laboratory of
Synthetic Chemistry of Natural Substances, Chinese Academy
of Sciences, Leading Academic Discipline Project of Shanghai
Municipal Education Commission (No: J50101) and the Inno-
vation Fund of Shanghai University for financial support.
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©