Iron-catalyzed highly efficient aerobic oxidative synthesis of benzimidazoles, benzoxazoles, and benzothiazoles directly from aromatic primary amines under solvent-free conditions in the open air

Article abstract of DOI:10.1080/00397911.2014.914221

Solvent-free oxidative synthesis of benzimidazoles, benzoxazoles, and benzothiazoles from aromatic primary amines and o-phenylenediamine, o-aminophenol, and o-aminothiophenol has been achieved by using Fe(NO ₃)₃ and TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxyl). This reaction can use air as an economical and green oxidant, and a wide variety of derivatives were obtained in good to excellent yields. The reaction mechanism was proposed and this method provides a direct, practical, and efficient approach for the preparation of substituted benzimidazoles, benzoxazoles, and benzothiazoles.

Full text of DOI:10.1080/00397911.2014.914221

This article was downloaded by: [New York University]
On: 17 October 2014, At: 23:32
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Iron-Catalyzed Highly Efficient Aerobic
Oxidative Synthesis of Benzimidazoles,
Benzoxazoles, and Benzothiazoles
Directly from Aromatic Primary Amines
Under Solvent-Free Conditions in the
Open Air
a
a
a
Jiatao Yu , Yonggen Xia & Ming Lu
a
Chemical Engineering College , Nanjing , China
Accepted author version posted online: 09 Jun 2014.Published
online: 20 Aug 2014.
To cite this article: Jiatao Yu , Yonggen Xia & Ming Lu (2014) Iron-Catalyzed Highly Efficient Aerobic
Oxidative Synthesis of Benzimidazoles, Benzoxazoles, and Benzothiazoles Directly from Aromatic
Primary Amines Under Solvent-Free Conditions in the Open Air, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 44:20, 3019-3026,
DOI: 10.1080/00397911.2014.914221
To link to this article: http://dx.doi.org/10.1080/00397911.2014.914221
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“
Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.

This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

1
Synthetic Communications , 44: 3019–3026, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2014.914221
IRON-CATALYZED HIGHLY EFFICIENT AEROBIC
OXIDATIVE SYNTHESIS OF BENZIMIDAZOLES,
BENZOXAZOLES, AND BENZOTHIAZOLES DIRECTLY
FROM AROMATIC PRIMARY AMINES UNDER
SOLVENT-FREE CONDITIONS IN THE OPEN AIR
Jiatao Yu, Yonggen Xia, and Ming Lu
Chemical Engineering College, Nanjing, China
GRAPHICAL ABSTRACT
Abstract Solvent-free oxidative synthesis of benzimidazoles, benzoxazoles, and
benzothiazoles from aromatic primary amines and o-phenylenediamine, o-aminophenol,
and o-aminothiophenol has been achieved by using Fe(NO
(
3
)
3
and TEMPO
2,2,6,6-tetramethyl-1-piperidinyloxyl). This reaction can use air as an economical and
green oxidant, and a wide variety of derivatives were obtained in good to excellent yields.
The reaction mechanism was proposed and this method provides a direct, practical, and
efficient approach for the preparation of substituted benzimidazoles, benzoxazoles, and
benzothiazoles.
Keywords Aerobic oxidation; benzimidazoles; benzothiazoles; benzoxazoles; iron
INTRODUCTION
Benzimidazoles are known as important intermediates=subunits and have
received considerable attention in recent years. Benzimidazole derivatives exhibit
significant pharmacological and biological activities, such as anticonvulsant, antian-
xiety, antiulcer, antihypertensive, antiviral, antifungal, anticancer, and antihista-
[
1–5]
mine
activities. There is particular interest in their activity against several
Received February 22, 2014.
Address correspondence to Ming Lu, Chemical Engineering College, Nanjing 210094, China.
E-mail: luming302@126.com
3
019

3020
J. YU, Y. XIA, AND M. LU
[6]
[7]
[8]
viruses such as HIV, influenza, and herpes (HSV-1). The excellent characteris-
tics of benzimidazole derivatives have promoted extensive studies for their synthesis.
Typically, there are two methods for the synthesis of benzimidazoles. One is the
condensation of o-phenylenediamine with carboxylic acids or their derivatives
(nitriles, imidates, orthoesters) under harsh dehydrating conditions, such as strongly
acidic conditions and high-temperature conditions.
[
9–13]
The other is oxidative cyclo-
dehydrogenation of aniline Schiff’s base, which are often generated in situ from the
condensation of o-phenylenediamines and aldehydes. Various oxidative reagents such
[
14]
[15]
[16]
as Pb(OAc) , Na S O , (NH ) S O , 2,3-dichloro-5,6-dicyanobenzoquinone
4
2
[18]
2
5
4 2
2
8
[
17]
[19]
[20]
(
DDQ), MnO2, oxone, and H O
have recently been reported. However,
2
2
from economical and environmental viewpoints, such protocol would produce an
almost equivalent amount of oxidant-derived waste and large amounts of solvents
waste, using the odorous and unstable aldehydes. Thus, development of a novel
ecofriendly and economical approach for its construction is highly desirable.
Recently, the aerobic oxidative reaction for the synthesis of heterocycles has
attracted increasing attention, due to the use of pure oxygen or air as the economical
and green oxidant, much more easily disposable catalysts, and milder reaction con-
ditions, along with generating water as the by-product. In 2008, Han and coworkers
reported the aerobic oxidative synthesis of 2-substituted benzoxazoles, benzothia-
zoles, and benzimidazoles and 2-aryl quinazolines catalyzed by 2,2,6,6-tetramethyl-
[
21,22]
piperidine N-oxyl (TEMPO) derivatives.
mild and efficient catalytic method for aerobic oxidation of indole carbinols
Fe=TEMPO=NaCl system.
In 2013, Ma and coworkers reported a
[23]
Very recently, Xu and coworkers successfully
developed a general but efficient Fe(NO ) =TEMPO catalyst system for the prep-
aration of useful imines by aerobic oxidation reactions from amines under air.
3
3
[
24]
Encouraged by these reported literatures, herein we report a simple but
efficient method for the syntheses of benzimidazoles, benzoxazoles, and benzothia-
zoles directly from aromatic primary amines and o-phenylenediamine, o-aminophe-
nol, and o-aminothiophenol catalyzed by a Fe(NO ) =TEMPO solvent-free system
3
3
using air as the oxidant. This method can tolerate a wide range of substrates and
affords the corresponding products in good yields.
RESULTS AND DISCUSSION
Our preliminary study focused on the reaction of o-phenylenediamine and
benzylamine to optimize the reaction conditions by using Fe(NO ) and TEMPO
3
3
as catalyst (Table 1). When the reaction was conducted in the absence of Fe(NO3)3
or TEMPO, it afforded a poor yield of benzimidazole (entries 1 and 2). Subse-
quently, we found that Fe(NO ) and TEMPO were both crucial for the reaction
3
3
and that their combination gave the best results (entry 4); vice versa, if neither of
them were present the reaction was not effective at all under the same conditions
(entries 1–4). Screening of the loadings of the Fe(NO ) and TEMPO revealed that
3 3
5
mol% Fe(NO ) and 5 mol% TEMPO was the most suitable proportion; more
3 3
loadings could not enhance the product yield (entries 3–6). A variety of Fe catalysts
were then examined, showing varying activities in the reaction, among which
Fe(NO ) was found to give the greatest yield (entries 5 and 7–9). The effect of
3
3
the reaction time was also tested, and it was suggested that the greatest yield was

AEROBIC OXIDATIVE SYNTHESIS OF BENZIMIDAZOLES
3021
a
Table 1. Optimization of reaction conditions
b
Benzylamine
(equiv.)
TEMPO
(mol%)
Temp.
ꢀ
Reaction
time (h)
Yield
(%)
Entry
[Fe] (mol%)
Oxidant
( C)
1
2
3
4
5
6
7
8
9
1
1
Fe(NO
3
)
3
(2.5)
—
2.5
—
2.5
5
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
80
80
24
24
24
24
24
24
24
24
24
12
36
24
24
24
24
24
24
24
35
31
—
—
1
80
80
12
71
1
Fe(NO
3
)
3
(2.5)
(5)
1
Fe(NO
3
)
3
80
80
86
86
1
Fe(NO
FeCl
3
)
3
(10)
10
5
1
3
(5)
(5)
80
80
69
63
1
FeCl
Fe (SO
2
2
5
1
4
)
3
3
3
3
3
3
3
3
3
3
(5)
5
80
80
78
74
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
1
Fe(NO
Fe(NO
Fe(NO
Fe(NO
Fe(NO
Fe(NO
Fe(NO
Fe(NO
Fe(NO
3
3
3
3
3
3
3
3
3
)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
5
1
)
)
)
)
)
)
)
)
5
80
80
84
82
0.8
1.2
1.4
1.2
1.2
1.2
1.2
5
5
80
80
88
88
5
5
110
120
110
110
93
93
5
5
O
2
93
Trace
5
N
2
a
3 3
Reaction conditions: A mixture of o-phenylenediamine and benzylamine, Fe(NO ) , and TEMPO were
mixed in a 5-mL, three-necked flask and then stirred rapidly in the open air for several hours. The reaction
progress was monitored by thin-layer chromatography (TLC).
b
Isolated yield.
obtained in 24 h (entries 5, 10, and 11). Additionally, we also investigated the equiva-
lent of benzylamine in the reaction, and 1.2 equiv of benzylamine was the best choice
(
entries 5 and 12–14). The effect of the reaction temperature was also tested and
ꢀ
showed that a temperature of 110 C was optimal for this reaction (entries 5, 15,
and 16). Finally, we also tested the influence of the gas, and we found that the O2
is significant for the reaction. However, when using O in the reaction, the yield
2
was equal to that using air. As an economical consideration, we chose air as the oxi-
dant (entries 15, 17, and 18).
Under the optimized conditions, the scope of the present transformation was
extended to o-phenylenediamine with various substituted benzylamines by using
the Fe(NO ) =TEMPO catalyst system and the results are shown in Table 2. In most
3
3
cases, o-phenylenediamine reacted with various benzylamines smoothly to give the
corresponding products in good to excellent yields, regardless of the presence of
electron-donating or electron-withdrawing functionalities. It seemed that benzyla-
mines bearing electron-deficient aromatic rings at the para-position gave greater
yields of products than did those bearing electron-rich aromatic rings (entries 2, 3,
and 6–9). The reason may that the strong electron-withdrawing groups (NO2)
enhanced the reaction rate (entries 6–9). The sterical hindrance of the substituted

3022
J. YU, Y. XIA, AND M. LU
a
Table 2. Synthesis of 2-substituted benzimidazoles from aromatic primary amines and o-phenylenediamines
b
Entry
X
R
1
R
2
Reaction time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
O
H
H
C
6
H
5
24
24
24
26
24
22
24
26
26
26
24
28
28
28
28
24
28
26
24
28
30
28
26
93
91
91
87
89
92
90
90
84
89
87
78
84
83
85
91
89
87
88
85
85
86
84
6 4
4-BrC H
H
4-ClC
2-ClC
6
H
H
4
4
H
6
H
2, 4-ClC
4-NO
4-(CH
4-MeOC
4-Me NC
6 3
H
H
2
C
6
H
4
H
3
)
2
CHC
6
H
4
H
6
H
4
H
2
6
H
4
1
1
1
1
1
1
1
1
1
1
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
H
3,4,5-MeOC
1-Naphtyl
Styryl
6 2
H
H
H
H
2-Furyl
5-Methyl-2-furyl
Pyridin-2-yl
H
H
4-Cl
4-NO
H
C
6
C
6
C
6
H
5
H
5
H
5
2
O
H
4-ClC
4-CH OC H
3 6 4
6 4
H
O
H
S
H
6 5
C H
S
H
4-ClC
6 4
H
S
H
2 6 4
4-NO C H
a
Reaction conditions: A mixture of 4 mmol o-phenylenediamine, 2-aminophenol, or 2-amino-
, and 5 mol% TEMPO were mixed
thiophenole and 4.8 mmol aromatic primary amine, 5 mol% Fe(NO
3
)
3
ꢀ
in a 5-mL, three-necked flask and then stirred rapidly open to air at 110 C for several hours. The reaction
progress was monitored by TLC.
b
Isolated yield.
benzylamines also influenced the reaction. For example, the more sterically hindered
ortho-chlorobenzyl amine, which reacted with o-phenylenediamine, furnished the
target product in lower yield than para-chlorobenzyl amine (entries 3 and 4).
1
-Naphthalenemethylamine was tested in the reaction and the yield was also very
good (entry 11). However, when 3-phenyl-2-propylene amine was conducted in the
reaction, the yield was lower than other aromatic amines (entry 12). Heteroaryl
amines were used in the reaction, and the yields were satisfactory (entries 13–15).
In addition, 4-chloro-o-phenylenediamine and 4-nitro-o-phenylenediamine were also
employed in the reaction, and to our delight, it resulted in good yields (entries 16 and
17). Having successfully achieved the synthesis of benzimidazoles, the Fe(NO ) =
3 3
TEMPO system was expanded to catalyze the synthesis of benzoxazoles and

AEROBIC OXIDATIVE SYNTHESIS OF BENZIMIDAZOLES
3023
benzothiazoles using o-aminophenol and o-aminothiophenol respectively with ben-
zylamines as the starting materials. Benzoxazoles and benzothiazoles were also con-
verted from corresponding o-aminophenol and o-aminothiophenol in good yields.
Preliminary mechanistic studies of the reaction were also conducted. First, we
turn our attention to the reaction of benzylamine and aniline to synthesize the cross
imines as shown in Table 3. After optimizing the reaction condition, we found that
almost no 3a occurred in the absence of both Fe(NO ) and TEMPO. Either (1)
3
3
2
.5 mol% of either Fe(NO ) or TEMPO or (2) both 2.5 mol% of Fe(NO ) and
3 3 3 3
TEMPO resulted only in incomplete conversion of the substrates. Then, unreacted
a decreased in degrees when increasing the amounts of Fe(NO ) and TEMPO,
and the yields of 3a were increased up to 85%. On the other hand, when the amounts
1
3
3
of Fe(NO ) and TEMPO were increased to 10 mol%, the yield stayed at 85%. These
3
3
mean that the catalytic ability was not improved obviously by increasing the amounts
of the catalysts. In addition, when we tried to explore the reaction under N , the con-
2
version of 1a and the yield of product were much less. Therefore, this reaction was an
aerobic oxidative step catalyzed by Fe(NO ) and TEMPO, using air as the oxidant.
3
3
Encouraged by these results, we speculated, in the imine formation step, that
o-phenylenediamine with benzylamine took place to form imine, and then the imine
further reacted with another amine group of o-phenylenediamine to form benzimida-
zoline. In the cyclo-dehydrogenation of benzimidazoline step, preliminary studies of
the reaction were conducted, and the result is shown in Table 4. When benzimidazo-
ꢀ
line was treated with 5 mol% Fe(NO3)3 and 5 mol% TEMPO at 110 C under
solvent-free conditions for 12 h, the desired 2-phenylbenzimidazole was isolated in
9
7% yield (entry 3). In the absence of one of them, the yield decreased substantially
entries 1–3). Besides, we also tried this reaction under N , and the result was not sat-
(
isfactory. Therefore, Fe(NO ) , TEMPO, and air were essential for the reaction.
2
3
3
Table 3. Fe(NO
a
3
)
3
=TEMPO-catalyzed aerobic oxidation of benzylamine and aniline to
imine under air
Fe(NO
3
)
3
TEMPO
(mol%)
1a (%)
(unreacted)
b
Entry
(mol%)
Oxidant
Yield (%)
1
2
3
4
5
6
7
—
2.5
—
2.5
5
—
—
2.5
2.5
5
98
40
57
15
<1
<1
68
Air
Air
Air
Air
Air
Air
—
5
13
27
85
85
16
10
5
10
5
N
2
a
3 3
Reaction conditions: A mixture of 4 mmol aniline and 4 mmol benzylamine, Fe(NO ) ,
and TEMPO were mixed in a 5-mL, three-necked flask and then stirred rapidly while open
ꢀ
to air at 110 C for 24 h.
b
Isolated yield.

3024
J. YU, Y. XIA, AND M. LU
a
Table 4. Cyclo-dehydrogenation of benzimidazoline to benzimidazole
Fe(NO
3
)
3
TEMPO
(mol%)
b
Entry
(mol%)
Oxidant
Yield (%)
1
2
3
4
5
–
5
5
–
5
5
5
Air
Air
Air
39
78
97
23
N
2
a
Reaction conditions: A mixture of 4 mmol benzimidazoline, Fe(NO
3
)
3
, and TEMPO was mixed in a
ꢀ
5
-mL, three-necked flask and then stirred rapidly while open to air at 110 C for 12 h.
b
Isolated yield.
Based on these results and the literature reports about the aerobic oxidation of
[28,29]
[25–27]
primary amines to imines
and Fe=TEMPO system, a plausible reaction path-
way for the formation of benzimidazole is shown in Scheme 1. First, the aerobic oxidat-
ive synthesis of benzimidazoline proceeds via the coupling of o-phenylenediamine with
3 3
Scheme 1. Possible mechanism for Fe(NO ) =TEMPO aerobic catalytic oxidative synthesis of
benzimidazoles.

AEROBIC OXIDATIVE SYNTHESIS OF BENZIMIDAZOLES
3025
benzylamine to form imine, which is then transformed to the intermediary benzimidazo-
line. Finally, the aerobic oxidative cyclo-dehydrogenation of benzimidazoline affords
the product benzimidazole. The whole process was catalyzed by Fe(NO ) =TEMPO.
3
3
In conclusion, we have developed a green protocol for aerobic oxidative coup-
ling of aromatic primary amines and o-phenylenediamine, o-aminophenol, or
o-aminothiophenol catalyzed by Fe(NO ) =TEMPO under solvent-free conditions
3
3
ꢀ
in open air at 110 C, and yields were satisfactory. This simple Fe(NO ) =TEMPO
3
3
system uses air as the oxidant and may find a wide range of applications in green
oxidation chemistry. The extension of this catalytic system for the preparation of
other heterocycles is under way in the laboratory.
EXPERIMENTAL
All starting materials were purchased from commercial sources and used with-
out further treatment. Melting points were determined on a Thomas Hoover capil-
lary apparatus and were uncorrected. All known compounds are identified by
1
appropriate techniques such as H NMR and compared with previously reported
1
data. H NMR (500 MHz) was recorded on a Bruker 500 spectrometer with tetra-
methylsilane (TMS) as an internal standard. Mass spectra were recorded on an Agi-
lent technologies 6110 quadrupole LC=MS equipped with an electrospray ionization
(ESI) probe operating in positive ion mode. Analytical TLC was performed on pre-
coated silica-gel 60 F254 plates. Yields refer to the isolated yields of the products
after purification by silica-gel column chromatography (300 mesh). All starting che-
micals are commercially available.
Typical Procedure for Synthesis of Benzimidazoles, Benzoxazoles, or
Benzothiazoles
A mixture of 4 mmol o-phenylenediamine, 2-aminophenol, or 2-amino-
thiophenole and 4.8 mmol amine, 5 mol% Fe(NO ) , and 5 mol% TEMPO were
3
3
mixed in a 5-ml, three-necked flask and then stirred rapidly while open to air at
ꢀ
110 C for several hours. The reaction progress was monitored by TLC. After com-
pletion of the reaction, the residue was directly purified by column chromatography
on silica gel using hexane = ethyl acetate (7:3) as eluent to afford the pure product.
SUPPLMENTAL MATEIAL
Supplemental data for this article can be accessed on the publisher’s website.
REFERENCES
1
2
3
. Soderlind, K.-J.; Gorodetsky, B.; Singh, A. K.; Bachur, N.; Miller, G. G.; Loun, J. W.
Anti-cancer Drug Des. 1999, 14, 19.
. Gravatt, G. L.; Baguley, B. C.; Wilson, W. R.; Denny, W. A. J. Med. Chem. 1994, 37,
4338.
. Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893.

3026
J. YU, Y. XIA, AND M. LU
4
5
6
. Kim, J. S.; Gatto, B.; Yu, C.; Liu, A.; Liu, L. F.; LaVoie, E. J. J. Med. Chem. 1996, 39,
92.
. Roth, T.; Morningstar, M. L.; Boyer, P. L.; Hughes, S. H.; Bukheit, R. W.; Michejda, C.
J. J. Med. Chem. 1997, 40, 4199.
. Porcari, A. R.; Devivar, R. V.; Kucera, L. S.; Drach, J. C.; Townsend, L. B. J. Med.
Chem. 1998, 41, 1252.
9
7
8
. Hisano, T.; Ichikawa, M.; Tsumoto, K.; Tasaki, M. Chem. Pharm. Bull. 1982, 30, 2996.
. Migawa, M. T.; Giradet, J. L.; Walker, J. A.; Koszalka, G. W.; Chamberlain, S. D.;
Drach, J. C.; Townsend, L. B. J. Med. Chem. 1998, 41, 1242.
9. Wang, Y.; Sarris, K.; Sauer, D. R.; Djuric, S. W. Tetrahedron Lett. 2006, 47, 4823.
1
0. (a) Huang, W.; Scarborough, R. M. Tetrahedron Lett. 1999, 40, 2665; (b) Chi, Y.-C.; Sun,
C.-M. Synlett. 2000, 5, 591; (c) Kumar, D.; Jacob, M. R.; Reynolds, M. B.; Kerwin, S. M.
Bioorg. Med. Chem. 2002, 10, 3997; (d) Gong, B.; Hong, F.; Kohm, C.; Bonham, L.;
Klein, P. Bioorg. Med. Chem. Lett. 2004, 14, 1455; (e) Huang, S.-T.; Hsei, I.-J.; Chen,
C. Bioorg. Med. Chem. 2006, 14, 6106.
1
1
1. (a) Dunwell, D. W.; Evans, D.; Smith, C. E.; Williamson, W. R. N. J. Med. Chem. 1975,
18, 692; (b) Dzvinchuk, I. B.; Vypirailenko, A. V.; Lozinskii, M. O. Russ. J. Org. Chem.
1998, 34, 685.
2. (a) Barni, E.; Savarino, P. J. J. Heterocycl. Chem. 1979, 16, 1583; (b) Hendrickson, J. B.;
Hussoin, M. S. J. Org. Chem. 1987, 52, 4137; (c) Gungor, T.; Fouquet, A.; Teulon, J.-M.;
Provost, D.; Cazes, M.; Cloarec, A. J. Med. Chem. 1992, 35, 4455; (d) White, A. W.;
Almassy, R.; Calvert, A. H.; Curtin, N. J.; Griffin, R. J.; Hostomsky, Z.; Maegley, K.;
Newell, D. R.; Srinivasan, S.; Golding, B. T. J. Med. Chem. 2000, 43, 4084; (e) Biasotti,
B.; Dallavalle, S.; Merlini, L.; Farina, C.; Gagliardi, S.; Parini, C.; Belfiore, P. Bioorg.
Med. Chem. 2003, 11, 2247.
1
3. (a) Bougrin, K.; Loupy, A.; Soufiaoui, M. Tetrahedron 1998, 54, 8055; (b) Ben-Alloum,
A.; Bakkas, S.; Soufiaoui, M. Tetrahedron Lett. 1998, 39, 4481; (c) Reddy, G. V.; Rao,
V. V. V. N. S. R.; Narsaiah, B.; Rao, P. S. Synth. Commun. 2002, 2467; (d) Mao, Z.;
Wang, Z.; Li, J.; Song, X.; Luo, Y. Synth. Commun. 2010, 40, 1963.
1
1
4. Stephens, F. F.; Bower, J. D. J. Chem. Soc. 1949, 2971.
5. Lombardy, R. L.; Tanious, F. A.; Ramachandran, K.; Tidwell, R. R.; Wilson, W. D. J.
Med. Chem. 1996, 39, 1452.
1
1
6. Bahrami, K.; Khodaei, M. M.; Nejati, A. Green Chem. 2010, 12, 1237.
7. (a) Vanden Eynde, J. J.; Delfosse, F.; Lor, P.; Van Haverbeke, Y. Tetrahedron 1995, 51,
5813; (b) Lee, K. J.; Janda, K. D. Can. J. Chem. 2001, 79, 1556.
1
1
2
2
2
8. Bhatnagar, I.; George, M. V. Tetrahedron 1968, 24, 1293.
9. Beaulieu, P. L.; Hache, B.; von Moos, E. Synthesis 2003, 11, 1683.
0. Bahrami, K.; Khodaei, M. M.; Kavianinia, I. Synthesis 2007, 4, 547.
1. Chen, Y.; Qian, L.; Zhang, W.; Han, B. Angew. Chem. Int. Ed. 2008, 47, 9330.
2. Han, B.; Wang, C.; Han, R.; Yu, W.; Duan, X.; Fang, R.; Yang, X. Chem. Commun. 2011,
47, 7818.
2
2
2
2
2
3. Liu, J.; Ma, S. Org. Biomol. Chem. 2013, 11, 4186.
4. Zhang, E.; Tian, H.; Xu, S.; Yu, X.; Xu, Q. Org. Lett. 2013, 11, 2704.
5. Liu, L.; Zhang, S.; Fu, X.; Yan, C. Chem. Commun. 2011, 47, 10148.
6. Patil, R. D.; Adimurthy, S. Adv. Synth. Catal. 2011, 353, 1695.
7. Huang, H.; Huang, J.; Liu, Y. M.; He, H. Y.; Cao, Y.; Fan, K.-N. Green Chem., 2012, 14,
930.
2
2
8. Wang, N.; Liu, R.; Chen, J.; Liang, X. Chem. Commun. 2005, 5322.
9. Lu, T.; Lu, M. J. Chin. Chem. Soc. 2012, 59, 899.