Gold nanoparticles supported on titanium dioxide: An efficient catalyst for highly selective synthesis of benzoxazoles and benzimidazoles

Article abstract of DOI:10.1039/c4cc01822b

A highly efficient and selective reaction for the synthesis of 2-substituted benzoxazoles and benzimidazoles catalyzed by Au/TiO₂ has been developed via two hydrogen-transfer processes. This reaction has a good tolerance to air and water, a wide substrate scope, and represents a new avenue for practical C-N and C-O bond formation. More importantly, no additional additives, oxidants and reductants are required for the reaction and the catalyst can be recovered and reused readily. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc01822b

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Gold nanoparticles supported on titanium dioxide:
an efficient catalyst for highly selective synthesis
of benzoxazoles and benzimidazoles†
Cite this: Chem. Commun., 2014,
0, 6145
5
Received 11th March 2014,
Accepted 17th April 2014
Lin Tang,‡ Xuefeng Guo,‡ Yu Yang, Zhenggen Zha and Zhiyong Wang*
DOI: 10.1039/c4cc01822b
www.rsc.org/chemcomm
A highly efficient and selective reaction for the synthesis of 2-substituted of 2-arylbenzoxazoles from o-nitrophenols and alcohols was
5
d
benzoxazoles and benzimidazoles catalyzed by Au/TiO
developed via two hydrogen-transfer processes. This reaction has a good ineffective starting materials for this transformation.
tolerance to air and water, a wide substrate scope, and represents a new Because of the advantages of high catalytic efficiency and easy
2
has been successfully developed.
However, aliphatic alcohols are
avenue for practical C–N and C–O bond formation. More importantly, no recycling, heterogeneous catalysts have been receiving more and more
6
additional additives, oxidants and reductants are required for the reaction attention. And we have been focusing on the heterogeneous catalysis
7
and the catalyst can be recovered and reused readily.
for a long time. Recently, various heterogeneous catalytic systems for
direct C–N bond formation from nitroarenes (or amines) and alcohols
8
9
Benzoxazoles and benzimidazoles are valuable structural motifs due were successfully developed by Cao and others. Herein, we describe
to their widespread occurrence in natural products and biologically a one-pot direct synthesis of benzoxazoles and benzimidazoles
active molecules. Usually, there are two commonly used approaches using o-nitrophenols (or o-nitroanilines) and alcohols as the starting
1
for the construction of these important compounds. One is the metal- materials catalyzed by gold nanoparticles supported on titanium
2
catalyzed cross coupling reaction of o-haloanilides or their analogues dioxide (Au/TiO ). No additional additives, oxidants and reductants
2
through intramolecular or intermolecular cyclization. The other is were needed for this reaction. And various transformations, including
the condensation of 2-aminophenol with either carboxylic acid dehydrogenative oxidation of alcohols and C–N bonds, reduction of
derivatives under strong acid and high temperature conditions or the nitro group and condensation of aldehydes with amines, can be
3
aldehydes under subsequent strong oxidative conditions. Recently, achieved in this cascade reaction.
catalytic oxidative reactions for the synthesis of benzoxazoles
First of all, metal nanoparticles supported on different templates
(
or benzimidazoles) from aldehydes and o-aminophenols (or were synthesized (see detailed experiments and characterization in
4
o-phenylenediamine) were developed. In all cases, o-amino- the ESI†). Subsequently, we employed them directly to selectively
phenols (or o-phenylenediamine) and aldehydes were employed synthesize 2-phenylbenzoxazole (3aa) (Table 1). The desired product
as the starting materials. However, the direct one-pot synthesis 3aa was selectively obtained in a good yield of 90% under the
2
of benzoxazoles (or benzimidazoles) from alcohols and o-nitro- catalysis of Au/TiO , while low yields were obtained when other
5
phenols (or o-nitroanilines) is rare. Two reactions using o- supported gold catalysts were employed (Table 1, entries 1–5). These
nitrophenols and aldehydes (or trimethyl o-benzoate) as the reactants results showed that the nature of the support had a strong influence
5a,b
to prepare 2-arylbenzoxazoles were developed. Nevertheless, a large on the activity of the Au catalysts and TiO was the best support for
2
excess of metals as nitro group reductants was employed in these this reaction. When catalysts Pd/C and Pd/diatomite were employed
reactions. Besides, high reaction temperature (4200 1C) was needed in this reaction a moderate yield of 50% and 45% 3aa was obtained,
to synthesize 2-arylbenzoxazoles by reaction of o-nitrophenols respectively, and 3c was also observed (Table 1, entries 7 and 8).
5
c
with benzylic amines. Recently, a new iron-catalyzed synthesis However, the reaction could hardly afford the product 3aa (5%), and
a and 3b were obtained in very low yields when Pt/C was employed
3
as the catalyst (Table 1, entry 6). No product was obtained in the
presence of TiO or KAuCl (Table 1, entries 9 and 10). After catalyst
Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory
of Soft Matter Chemistry & Collaborative Innovation Center of Suzhou Nano
Science and Technology, University of Science and Technology of China, Hefei,
2
4
screening, Au/TiO showed the best catalytic activity and selectivity
2
2
30026, P. R. China. E-mail: zwang3@ustc.edu.cn; Fax: +86 551-360-3185
for this reaction. Unexpectedly, water was also a good solvent
†
Electronic supplementary information (ESI) available: Experimental details,
(Table 1, entry 11). These results implied that this reaction could
characterization of catalysts and characterization of products. See DOI: 10.1039/
c4cc01822b
tolerate water well. After the catalyst optimization, the reaction
‡
These authors contributed equally to this work.
conditions were optimized (see Table S1 in the ESI†).
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 6145--6148 | 6145

View Article Online
Communication
ChemComm
a
a
Table 1 Synthesis of 2-phenylbenzoxazole catalyzed by various catalysts
Table 2 Synthesis of benzoxazoles from alcohols and o-nitrophenols
1
6
2
b
Entry
R
R
Product
Yield (%)
1
2
3
4
5
6
7
8
9
C
H
5
H
H
H
H
H
H
H
H
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
99 (90)
98
4-MeC
3-MeC
4-MeOC
3-MeOC
2-MeC
2-MeOC
6
H
H
4
b
6
4
97
Yield (%)
6
H
4
4
99 (91)
91
Entry
3a
3b
3c
3aa
6
H
6
H
4
81
85
1
2
3
4
5
6
7
8
9
2
O
3
5
4
7
2
3
13
3
4
n.d.
n.d.
3
6
13
8
14
5
21
5
3
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
21
40
41
53
32
90 (88)
5
50
45
n.d.
n.d.
81
6
H
4
4-FC
3-FC
6
H
H
4
95 (85)
94
6
4
H
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
4-ClC
4-BrC
4-CF
1-Napthyl
Me
6
4
H
H
H
H
H
H
H
H
4-Me
5-Me
4-MeO
5-F
4-F
4-Cl
H
3ja
3ka/3aa
3la
98
63/17
70
95
52
63 (55)
56
60
96
95 (84)
97
4
3
4
3ma
3na
3oa
3pa
3qa
3ab
3ac
3ad
3ae
3af
17
c
n.d.
n.d.
4
n.d.
n.d.
n.d.
d
d
d
t-Bu
1
1
0
1
n-C
5
H
c
Cyclohexyl
a
18
C
6
C
6
C
6
C
6
C
6
C
6
C
6
H
H
H
H
H
H
H
5
5
5
5
5
5
5
The reactions were carried out with 1a (2.0 equiv., 1.0 mmol), 2a
19
(
2
1.0 equiv., 0.25 mmol), solvent of toluene (1.0 ml) and a catalyst (metal:
mol%) for 24 h under a N atmosphere. GC yield of the product is
2
c
b
20
21
98
99
95
80 (75)
based on 2a, n.d. = not detected, isolated yield in parentheses. Water
2
2
2
2
3
4
as the solvent.
3ag
3aa
e
a
The reactions were carried out with the alcohol (1.5 equiv.,
With the optimized conditions in hand, the scope of the alcohols
and o-nitrophenols in the reaction was extended (Table 2). The and a catalyst (Au/TiO , Au: 2 mol%) for 24 h under a N atmosphere.
electronic properties of a series of benzylic alcohols were found to
have little influence on the reaction. Reactions with benzylic alcohols
bearing both electron-donating groups (Table 2, entries 2–5) and
electron-withdrawing groups (Table 2, entries 8–10) in the aromatic
0
.75 mmol), 2a (1.0 equiv., 0.25 mmol), solvent of toluene (1.0 ml)
2
2
b
Yield of the isolated product is based on 2, water as the solvent in
c
parentheses. 2.0 mmol alcohol and 0.05 mmol K
2
CO
3
were used.
d
e
1
.0 mmol alcohol and 0.05 mmol K CO were used. Under air.
2 3
ring could effectively afford the desired products in excellent yields (Table 2, entry 24), which delivered a good tolerance to water and
490%). However, the steric hindrance of the substituents had a air. These results indicated that the reaction was highly efficient for
negative influence on the reaction. Relatively low yields of the the synthesis of a wide range of benzoxazoles.
(
corresponding products were obtained when the substituent groups
To further establish the general utility of these transformations,
appeared in the ortho-position of the benzene ring (Table 2, entries 6 the o-nitrophenols were replaced with different o-nitroanilines
and 7). As expected, the yield of 3ka decreased to 63% and 3aa was for the synthesis of benzimidazoles (Table 3). Firstly, the reaction
obtained in 17% yield when 4-bromobenzyl alcohol was employed of o-nitroaniline with benzyl alcohol was carried out smoothly to
as the substrate because 4-bromobenzyl alcohol could be reduced to give the desired product in a good yield of 78% (Table 3, entry 1).
benzyl alcohol by its liberating hydrogen (Table 2, entry 11). An
alcohol bearing strong electron-withdrawing group could also be
used as starting material to afford the desired product in good yield Table 3 Reactions of benzyl alcohol with various 2-nitroanilines
a
(
Table 2, entry 12). Moreover, an excellent yield of 95% was obtained
when the benzene ring was replaced by a hindered naphthyl group
Table 2, entry 13). It is worth noting that aliphatic alcohols were
(
successfully employed as the substrates to give the corresponding
products with good yields (Table 2, entries 14–17). In contrast, the
scope of the substrates was limited to aromatic alcohols in the
previous report. After this alcohol screening, the scope of various
o-nitrophenols was investigated. Pleasingly, all these reactions could
proceed smoothly to give the desired product in excellent yields
regardless of electron-donating groups or electron-withdrawing
groups on the aromatic ring (Table 2, entries 18–23). Also, good
yields were obtained when water was used as the solvent (Table 2,
entries 1, 4, 8, 15 and 19) and when the reaction was performed
b
Entry
R
1
X
Product
Yield (%)
1
2
3
4
5
6
H
H
4-Me
4-MeO
4-F
NH
5aa
5ab
5bb
5cb
5db
5eb
78 (70)
84
5d
NMe
NMe
NMe
NMe
NMe
83
86 (81)
86
79 (70)
4-Cl
a
The reactions were carried out with the alcohol (1.5 equiv.,
.75 mmol), 2-nitroaniline (1.0 equiv., 0.25 mmol), solvent of toluene
, Au: 2 mol%) for 24 h under a N
atmosphere. Yield of the isolated product is based on 2-nitroaniline,
0
(1.0 ml) and a catalyst (Au/TiO
2
2
b
under an air atmosphere a good yield could still be achieved water as the solvent in parentheses.
6
146 | Chem. Commun., 2014, 50, 6145--6148
This journal is ©The Royal Society of Chemistry 2014

View Article Online
ChemComm
Communication
a
Table 4 Recycling of Au/TiO
2
for the synthesis of 2-phenylbenzoxazole
hydrogen-transfer process. In the whole catalytic cycle, the
alcohol and the intermediate 2-phenyl-2,3-dihydrobenzoxazole
are used as reductants (hydrogen donor) once and 2-nitrophenol
is used as the oxidant (hydrogen acceptor) twice.
In summary, we have developed a highly efficient protocol
for one-pot synthesis of 2-substituted benzoxazoles and benzi-
midazoles from cheap and readily available starting materials
c
Run
1
2
3
4
5
6
7
b
Yield (%)
99
99
99
98
98
96
99
a
The reactions were carried out with 1a (1.5 equiv., 0.75 mmol), 2a (nitro compounds and alcohols) via two hydrogen-transfer pro-
(
(
1.0 equiv., 0.25 mmol), a solvent (1.0 ml) and an initial catalyst
cesses. To the best of our knowledge, this is the first example of
b
Au/TiO
2
, Au: 2 mol%) for 24 h under a N
2
atmosphere. Yield of the
c
these transformations to form new C–N and C–O bonds catalyzed by
a heterogeneous gold catalyst. Depending on these catalytic systems,
a wide scope of alcohols and nitro compounds is extended to give
the desired products. And these reactions can tolerate air and water
well. It is noteworthy that no additional additives, oxidants and
reductants are required for this reaction, and this catalyst can be
recovered and reused readily without loss of its catalytic activity.
Detailed mechanistic studies and other applications in organic
reactions of this catalyst are in progress within our laboratory.
We are grateful to National Nature Science Foundation of
China (2127222, 91213303, 21172205, and J1030412).
2
isolated product is based on 2a. Catalyst (Au/TiO , Au: 2 mol%).
To our delight, when N-methyl-o-nitroaniline was employed as
the substrate, the corresponding yield was improved to 84%
(
nitroaniline with benzylic alcohols bearing a series of groups
including methyl, methoxy, fluoro and chloro were investigated
and good yields of these products were obtained as shown in
Table 3, entries 3–6. Similarly, these transformations could be
performed smoothly in water to afford the desired products
Table 3, entry 2). Subsequently, the reactions of N-methyl-o-
(
Table 3, entries 1, 4 and 6).
2
The recovery and reuse of the developed Au/TiO catalyst in
Notes and references
the reaction could be achieved by a simple phase separation. A
little loss of the catalytic activity was observed after the sixth
round, as shown in Table 4. When we added some additional
catalyst to maintain the Au loading of 2 mol% (run 7), we are
pleased to find that an excellent yield of 99% was obtained
again. These results showed that the catalyst could be reused at
least 7 times without loss of its activity.
1 (a) L. Zirngibl, Antifungal Azoles: A Comprehensive Survey of Their
Structures and Properties, Wiley-VCH, Weinheim, 1998; (b) A. A. Nagel,
D. R. Liston, S. Jung, M. Mahar, L. A. Vincent, D. Chapin, Y. L. Chen,
S. Hubbard, J. L. Ives, S. B. Jones, J. A. Nielsen, A. Ramirez, I. A. Shalaby,
A. Villalobos and W. F. White, J. Med. Chem., 1995, 38, 1084;
(
c) T. Kusumi, T. Ooi, M. R. W ¨a lchli and H. Kakisawa, J. Am. Chem.
Soc., 1988, 110, 2954; (d) M. O. Chaney, P. V. Demarco, N. D. Jones and
J. L. Occolowitz, J. Am. Chem. Soc., 1974, 96, 1932.
Based on control experiments (see Scheme S1 in the ESI† for
2 (a) R. D. Viirre, G. Evindar and R. A. Batey, J. Org. Chem., 2008,
73, 3452; (b) B. Zou, Q. Yuan and D. Ma, Angew. Chem., Int. Ed., 2007,
5
d,7g,i,8,9
detailed analysis) and previous reports,
the possible
4
6, 2598; (c) J. Bonnamour and C. Bolm, Org. Lett., 2008, 10, 2665;
d) S. Ueda and H. Nagasawa, Angew. Chem., Int. Ed., 2008, 47, 6411;
mechanism is depicted in Scheme 1. First of all, dehydrogena-
(
tive oxidation of the alcohol (1a) to its corresponding carbonyl
(e) P. Saha, M. A. Ali, P. Ghosh and T. Punniyamurthy, Org. Biomol.
Chem., 2010, 8, 5692; ( f ) P. Saha, T. Ramana, N. Purkait, M. A. Ali,
R. Paul and T. Punniyamurthy, J. Org. Chem., 2009, 74, 8719.
For some recent examples, see: (a) Y. Riadi, R. Mamouni, R. Azzalou,
M. Haddad, S. Routier, G. Guillaumet and S. Lazar, Tetrahedron Lett.,
2011, 52, 3492; (b) D. S. Bose and M. Idrees, Synthesis, 2010, 398;
0
8b,c,9d,e,10
compound (1a ) generates the gold-hydride species (b)
and 2-nitrophenol (2a) is reduced to 2-aminophenol (2a ) in situ
0
3
4
0
by b. This is the first hydrogen-transfer process. Then, 2a can
0
readily react with 1a to afford the corresponding imine (c).
(
(
c) F. Chen, C. Shen and D. Yang, Tetrahedron Lett., 2011, 52, 2128;
d) C. Praveen, K. H. Kumar, D. Muralidharan and P. T. Perumal,
c is selectively converted to the intermediate 2-phenyl-2,3-
dihydrobenzoxazole (d) under the catalysis of a gold catalyst.
Subsequently, d can be rapidly oxidized to the product 3aa in
the presence of a gold catalyst accompanied by the generation
Tetrahedron, 2008, 64, 2369.
(a) Y. Kawashita, N. Nakamichi, H. Kawabata and M. Hayashi, Org.
Lett., 2003, 5, 3713; (b) M. Kidwai, V. Bansal, A. Saxena, S. Aerry and
S. Mozumdar, Tetrahedron Lett., 2006, 47, 8049; (c) Y. X. Chen,
L. F. Qian, W. Zhang and B. Han, Angew. Chem., Int. Ed., 2008,
0
of b. And 2a is again reduced to 2a by b. This is the second
47, 9330; (d) A. J. Blacker, M. M. Farah, M. I. Hall, S. P. Marsden,
O. Saidi and J. M. J. Williams, Org. Lett., 2009, 11, 2039; (e) W. Yoo,
H. Yuan, H. Miyamura and S. Kobayashi, Adv. Synth. Catal., 2011,
3
53, 3085.
(a) A. Hari, C. Karan, W. C. Rodrigues and B. L. Miller, J. Org. Chem.,
001, 66, 991; (b) J. J. Lee, J. Kim, Y. M. Jun, B. M. Lee and B. H. Kim,
5
6
7
2
Tetrahedron, 2009, 65, 8821; (c) H. Nishioka, Y. Ohmori, Y. Iba,
E. Tsuda and T. Harayama, Heterocycles, 2004, 64, 193; (d) M. Wu,
X. Hu, J. Liu, Y. Liao and G. J. Deng, Org. Lett., 2012, 14, 2722.
For reviews on heterogeneous catalysts, see: (a) N. Mizuno and
M. Misono, Chem. Rev., 1998, 98, 199; (b) R. Akiyama and S. Kobayashi,
Chem. Rev., 2009, 109, 594; (c) S. Ikegami and H. Hamamoto, Chem. Rev.,
2
009, 109, 583; (d) M. J. Climent, A. Corma and S. Iborra, Chem. Rev.,
2011, 111, 1072, and references therein.
(a) Z. Zhang and Z. Wang, J. Org. Chem., 2006, 71, 7485; (b) J. Zhang,
C. Yu, S. Wang, C. Wan and Z. Wang, Chem. Commun., 2010,
46, 5244; (c) Y. Wang, G. Ouyang, J. Zhang and Z. Wang, Chem.
Commun., 2010, 46, 7912; (d) Y. Wang, D. Zhu, L. Tang, S. Wang and
Z. Wang, Angew. Chem., Int. Ed., 2011, 50, 8917; (e) H. Sun, Y. Zhang,
Scheme 1 Plausible reaction mechanism.
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 6145--6148 | 6147

View Article Online
Communication
ChemComm
F. Guo, Z. Zha and Z. Wang, J. Org. Chem., 2012, 77, 3563; ( f ) H. Sun,
Q. Hua, F. Guo, Z. Wang and W. Huang, Adv. Synth. Catal., 2012,
Green Chem., 2011, 13, 2672; (e) H. Huang, J. Huang, Y. M. Liu,
H. Y. He, Y. Cao and K. N. Fan, Green Chem., 2012, 14, 930.
3
2
54, 569; (g) L. Tang, H. Sun, Y. Li, Z. Zha and Z. Wang, Green Chem.,
012, 14, 3423; (h) L. Tang, X. Guo, Y. Li, S. Zhang, Z. Zha and
9 (a) C. Gonzalez-Arellano, K. Yoshida, R. Luque and P. L. Gai, Green
Chem., 2010, 12, 1281; (b) A. Corma, T. R ´o denas and M. J. Sabater,
Chem. – Eur. J., 2010, 16, 254; (c) X. Cui, Y. Zhang, F. Shi and Y. Deng,
Chem. – Eur. J., 2011, 17, 2587; (d) X. Cui, C. Zhang, F. Shi and
Y. Deng, Chem. Commun., 2012, 48, 9391; (e) Q. Peng, Y. Zhang,
F. Shi and Y. Deng, Chem. Commun., 2011, 47, 6476.
Z. Wang, Chem. Commun., 2013, 49, 5213; (i) X. Guo, L. Tang,
Y. Yang, Z. Zha and Z. Wang, Green Chem., 2014, 16, 2443.
(a) H. Sun, F. Z. Su, J. Ni, Y. Cao, H. Y. He and K. N. Fan, Angew. Chem.,
Int. Ed., 2009, 48, 4390; (b) L. He, X. B. Lou, J. Ni, Y. M. Liu, Y. Cao,
8
H. Y. He and K. N. Fan, Chem. – Eur. J., 2010, 16, 13965; (c) C. H. Tang, 10 (a) A. Abad, C. Almela, A. Corma and H. Garcia, Chem. Commun.,
L. He, Y. M. Liu, Y. Cao, H. Y. He and K. N. Fan, Chem. – Eur. J., 2011,
7, 7172; (d) J. Huang, L. Yu, L. He, Y. M. Liu, Y. Cao and K. N. Fan,
2006, 3178; (b) F. Z. Su, L. He, J. Ni, Y. Cao, H. Y. He and K. N. Fan,
Chem. Commun., 2008, 3531.
1
6
148 | Chem. Commun., 2014, 50, 6145--6148
This journal is ©The Royal Society of Chemistry 2014