Tetrazole-1-acetic acid as a ligand for copper-catalyzed N-arylation of imidazoles with aryl iodides under mild conditions

Article abstract of DOI:10.1016/j.cclet.2013.05.037

Tetrazole-1-acetic acid was found to serve as a superior ligand for CuI-catalyzed N-arylation of imidazoles with aryl iodides under a low catalyst loading (5 mol% of CuI). A variety of aryl iodides could be aminated to provide the N-arylated products in good to excellent yields without the need of an inert atmosphere.

Full text of DOI:10.1016/j.cclet.2013.05.037

Chinese Chemical Letters 24 (2013) 893–896
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Chinese Chemical Letters
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Original article
Tetrazole-1-acetic acid as a ligand for copper-catalyzed N-arylation of
imidazoles with aryl iodides under mild conditions
*
Feng-Tian Wu, Ping Liu, Xiao-Wei Ma, Jian-Wei Xie , Bin Dai
School of Chemistry and Chemical Engineering/the Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University,
Shihezi 832003, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Tetrazole-1-acetic acid was found to serve as a superior ligand for CuI-catalyzed N-arylation of
imidazoles with aryl iodides under a low catalyst loading (5 mol% of CuI). A variety of aryl iodides could
be aminated to provide the N-arylated products in good to excellent yields without the need of an inert
atmosphere.
Received 3 May 2013
Received in revised form 20 May 2013
Accepted 22 May 2013
Available online 2 July 2013
ß 2013 Jian-Wei Xie. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords:
Tetrazole-1-acetic acid
N-Arylation
Imidazoles
Copper
Aryl iodides
1. Introduction
However, TZA, to our knowledge, has seldom been used as ligand in
copper-mediated cross-coupling reactions. In continuation of our
Copper-catalyzed carbon–nitrogen cross-coupling reactions
have been established as a powerful strategy for the preparation
of N-arylation of nitrogen nucleophiles, which play a vital role as
intermediates for agrochemicals, pharmaceuticals, energetic
materials and fine chemical industries [1]. Traditionally, these
reactions were often suffered from harsh reaction conditions
involving elevated temperatures and highly polar solvents, and
stoichiometric amounts of copper reagents [2]. Recently, pio-
neered by the Buchwald’s and Taillefer’s works [3], the process of
Cu-based C–N coupling reactions have reinvigorated by the
implementation of several classes of mono- and bidentate
chelating ligands [4]. However, more work still needs to be done
to identify new ligands to widen the scope of substrate tolerance,
lower copper loading, milder reaction conditions, enhanced
chemoselectivity and enantioselectivity of copper-catalyzed C–N
coupling reactions.
endeavors to develop copper-catalyzed cross couplings [10–12],
we report herein TZA as an accelerating ligand for copper-
catalyzed N-arylation of imidazoles with aryl iodides under mild
reaction conditions.
2. Experimental
All reagents were purchased from commercial suppliers and
used without further purification. All known products were
characterized by GC–MS, and 1H NMR, which were compared
with the previously reported dates. 1H NMR spectra were recorded
at room temperature on a Varian Inova-400 instrument at
400 MHz, and the chemical shifts were recorded in ppm (d) with
TMS as internal standard. Mass spectra were recorded on GC–MS
(Agilent 7890A/5975C) instrument under EI model.
General procedure for the N-arylation of imidazoles with aryl
halides: CuI (0.05 mmol), L1 (0.1 mmol), aryl halides (1.0 mmol),
imidazoles (1.5 mmol), NaOH (2 mmol), and DMSO (2 mL) were
added to a 10 mL of sealed tube. The reaction mixture was reacted
at 110 8C in a preheated oil bath for 12 h. The reaction mixture was
cooled to r.t., diluted with 10 mL H2O, and then the mixture was
extracted with ethyl acetate (3Â 20 mL). The combined organic
phases was washed with water and brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel (ethyl acetate/petro-
leum ether, 2:1 to pure ethyl acetate) to afford the target products.
On the other hand, it is well-known that carboxylate O atoms
and tetrazolyl ring N atoms have good coordination capacities [5],
and tetrazole-1-acetic acid (TZA), with both a carboxylate and
tetrazolyl ring, is a multifunctional ligand. Therefore, it could bind
to several metals via N and/or O atoms to form multi-dimensional
coordination polymers with various coordination modes [6–9].
* Corresponding author.
E-mail address: cesxjw@gmail.com (J.-W. Xie).
1001-8417/$ – see front matter ß 2013 Jian-Wei Xie. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.05.037

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F.-T. Wu et al. / Chinese Chemical Letters 24 (2013) 893–896
Table 1
Screening of the reaction conditions on the coupling reaction of 4-iodoanisole with imidazole.a
L2
L3
L4
L1
I
N
[Cu], L
N
N
N
N
N
N
N
N
N
N
H
O
Bases, solvents
N
N
N
N
O
COOH
COOH
COOH
COOH
b
Entry
[Cu]
Ligand
Solvent
Base
T (8C)
Yield (%)
1
2
CuI
L1
L2
L3
L4
–
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
KOH
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
100
80
93
CuI
84
3
CuI
77
4
CuI
88
5
CuI
75
6
CuO
CuSO4
Cu(OAc)2
CuCl
CuBr
–
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
81
7
71
8
83
9
87
10
11
12
13
14
15
16
17
18
19
20
21
22
23
89
0
CuI
48
CuI
DMAC
80
CuI
1,4-Dioxane
H2O
40
CuI
Trace
79
CuI
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CuI
K3PO4
Cs2CO3
K2CO3
NaOH
NaOH
NaOH
NaOH
88
CuI
81
CuI
11
CuI
88
CuI
16
CuI
110
110
92c (70d)
80e
CuI
a
Reaction conditions: 4-iodoanisole (0.5 mmol), imidazole (0.75 mmol), [Cu] (10 mmol%), L (20 mmol%), base (1.0 mmol), solvent (1 mL), 12 h.
b
c
Isolated yield.
5 mol% CuI, 10 mol% L1.
5 mol% CuI, ligand-free.
2.5 mol% CuI, 5 mol% L1.
d
e
Table 2
CuI-catalyzed N-arylation of imidazoles with aryl iodides using tetrazole-1-acetic acid as ligand under mild conditions.a
5 mol% CuI
N
N
X
N-Het
10 mol% L1
N
N
R1
R1
Het-NH
L1 =
NaOH, DMSO
110 oC, 12 h
COOH
1-13
Entry
ArX
Het-NH
Product
MeO
Yield (%)b
92 (70c)
1
I
I
N
N
N
N
H
MeO
1
2
3
90
85
N
N
N
N
H
EtO
Me
EtO
2
3
I
N
N
N
N
N
H
Me
4
5
84 (71c)
91 (81c)
I
N
N
N
H
4
Me
I
N
N
Me
N
N
H
Me
5
Me

F.-T. Wu et al. / Chinese Chemical Letters 24 (2013) 893–896
895
Table 2 (Continued )
Entry
6
ArX
Het-NH
Product
Yield (%)b
76
MeO
I
N
N
MeO
N
N
H
6
7
8
75d (50c,d
75 (38c)
84
)
I
N
N
N
N
H
OMe
OMe
7
8
I
N
N
N
N
H
NH
2
NH
2
9
I
N
N
N
N
N
H
Ph
Cl
Ph
Cl
9
10
96 (83c)
I
N
N
N
H
10
11
12
82e
I
N
N
N
N
H
O N
2
O N
2
11
12
79 (0c)
N
N
I
I
N
N
H
Cl
Cl
Cl
13
74 (28c)
35 (15c)
N
N
N
H
Cl
13
14
Br
N
N
N
N
H
MeO
MeO
1
a
Reaction conditions: aryl halides (1.0 mmol), imidazoles (1.5 mmol), CuI (0.05 mmol), L1 (0.1 mmol), NaOH (2.0 mmol), DMSO (2 mL), 12 h.
b
c
Isolated yields.
Ligand-free.
d
e
Reaction time: 18 h.
90 8C, 6 h.
3. Results and discussion
and NaOH gave the best yields (entries 1, 16–19). Lowering the
reaction temperature can markedly decelerate the reaction rate
and led to lower yields (entries 1, 20 and 21). In addition, when the
loading of CuI was reduced from 10 mol% to 5 mol%, the excellent
yield was also afforded. However, when 2.5 mol% of CuI was
employed, the reaction yield decreased to 80% (entries 1, 22 and
23). In summary, the optimal conditions for the N-arylation of
imidazole with 4-iodoanisole involves the use of 5 mol% of CuI,
10 mol% of L1, and 2 equiv. of NaOH in DMSO at 110 8C for 12 h.
The scope of the CuI/L1 catalytic system was probed by using a
wide range of aryl iodides and N-heterocyclic substrates under the
optimized conditions, and the results are listed in Table 2. In
general, the N-arylation of imidazoles with most of electron-rich,
electron-neutral, and electron-poor aryl iodides afforded the
desired products in yield ranging from 74% to 96%. It is worth
noting that the sterically hindered o-iodoanisole reacted smoothly
only with prolonging the reaction time to 18 h (entry 7). In
addition, when other potentially reactive functional groups (e.g.,
amino) are present, high level of chemoselectivity was observed
Initially, 4-iodoanisole and imidazole were selected as the
model substrates to optimize the coupling reaction conditions
including copper source, ligand, solvent, bases and temperature
without the protection by an inert gas. The results are shown in
Table 1. Among the ligands used, TZA was more beneficial to the
catalysis than other N-heterocyclic-1-acetic acid, which gave the
desired product in 93% isolated yield (entries 1–4). This could be
attributed to the excellent coordination capacity of L1. In contrast,
the reaction was also carried out in the absence of ligand, and the
N-arylation product was obtained in moderate yield (entry 5).
Nevertheless, the effect of the ligands is obvious (entry 1 vs entry 5,
and entry 22). By using L1 as the ligand, different copper source
have then been examined, and CuII or CuI were more or less active,
and CuI demonstrated the highest yields (entries 6–10). Observa-
tion of the solvent indicated that DMSO is the most favorable
solvent for the model reaction (entries 1, 12–15). The bases,
including NaOH, KOH, K3PO4, Cs2CO3, and K2CO3 were explored,

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F.-T. Wu et al. / Chinese Chemical Letters 24 (2013) 893–896
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nucleophiles with differently substituted aryl iodides under mild
conditions. The low catalyst loading (5 mol% of CuI), the
commercial availability of the ligand and without the protection
of an inert gas are expected to be useful for a variety of synthetic
chemists.
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This work was supported financially by the National Basic
Research Program of China (973 Program, No. 2012CB722603) and
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