2
A. R. Hajipour, F. Mohammadsaleh / Tetrahedron Letters xxx (2014) xxx–xxx
X
10 mol% Cu
2
O, 2 equiv. NaN
3
results. This can be attributed to the higher solubility of the start-
ing materials in EtOH/EG (7:3) compared with EG.
N3
4
0 mol% TEAP,
The concentration of TEAP was also found to be important in
this reaction system (Table 1, entry 9). A low TEAP concentration
usually led to a long reaction and an increased amount of TEAP
shortened the reaction time. We also examined catalyst loading
and found that 10 mol % was the optimum catalyst concentration
R
R
EtOH/EG (7:3), 95 oC
X= I, Br
TEAP:
NEt4
OOC
N
H
(
Table 1, entries 8, 10, and 11). However, interestingly, it was
observed that in the absence of Cu O, the reaction afforded a 35%
yield of the azide product after 10 h (Table 1, entry 11).
As shown in Table 1 (entry 12), the use of -proline (40 mol %)
Scheme 1.
2
L
organic reactions.18–20 The efficiency of these systems is due to the
metal nanoparticles stabilized by quaternary salts and/or the for-
mation of a new catalytic system. Moreover, in some cases, quater-
nary salts act as phase-transfer catalysts to facilitate the migration
of reactants in the reaction mixture.
and NaOH (40 mol %) instead of TEAP gave a relatively lower yield
(72%).
In addition, the efficiency of CuI as a catalyst was also investi-
gated in this reaction system. Treatment of 4-bromoanisole with
3
NaN , CuI (10 mol %), and TEAP (40 mol %) in EtOH/EG (7:3) affor-
TEAP is an amino acid based ionic liquid. The synthesis and
investigation of such materials have attracted considerable atten-
tion due to their remarkable properties.21 Ohno et al. have devel-
oped novel task-specific ionic liquids by focusing on the amino
acids, because these ionic materials can behave as anions with var-
ious characteristics. Following these results, it would be interesting
to evaluate the efficiency of these materials in catalytic systems,
especially for metal-catalyzed coupling reactions.
ded the corresponding azide in 60% yield (Table 1, entry 13).
According to the experimental results, the optimized conditions
are as follows: EtOH/EG (7:3) as the solvent system, Cu O
2
(10 mol %) as the catalyst, and TEAP (40 mol %) as the co-catalyst
at 95 °C.
We next explored the scope and limitations of this transforma-
tion (Table 2). Various aryl iodides and bromides reacted efficiently
to give the corresponding aryl azides in moderate to excellent
yields. We examined the electronic effects on the resulting yields
and conversion times of the reactions. Electron-rich aryl halides
in comparison to electron-poor aryl halides gave better conver-
sions in shorter times. The reaction of nitro-aryl halides afforded
low yields, while in contrast, methoxy-aryl halides required
shorter reaction times and gave excellent yields. In these reactions,
I- and Br-substituted aryl halides were reactive, and the reactions
22
Here, Cu
reaction of an aryl halide with NaN
of 4-bromoanisole with sodium azide as a model to begin this
investigation. It was found that by employing Cu O (10 mol %)
and TEAP (40 mol %) in the mixed solvent EtOH/H O (7:3), the cor-
2
O/TEAP has been applied as a catalytic system for the
3
. At first, we chose the reaction
2
2
responding azide was obtained in 40% yield after 2 h. In order to
optimize the reaction conditions, we examined the effect of differ-
ent reaction parameters such as solvent, temperature, Cu
ing and TEAP concentration on the model system (Table 1). It is
noteworthy that the solvent system played an important role in
2
O load-
of both electron-rich aryl bromides and iodides with NaN
promoted efficiently by this system.
As previously reported by other groups, different catalytic sys-
tems based on copper(I) catalysts combined with a ligand promote
the reaction of aryl halides with NaN . Reaction temperature, reac-
3
tion rate, and selectivity (azide or amine product) are important
factors that must be considered in this transformation.
3
were
this reaction. Among the different solvents tested including H
EtOH, DMSO, ethylene glycol (EG), polyethylene glycol (PEG), and
mixed solvents EtOH/H O (7:3), DMSO/H O (9:1), and EtOH/EG
7:3), EtOH/EG (7:3) gave the best result (Table 1, entries 1–8).
2
O,
2
2
(
Although with 4-bromoanisole both EG and EtOH/EG (7:3) gave
good results, for solid aryl halides EtOH/EG (7:3) afforded better
2
We have shown that the use of Cu O as the catalyst combined
with TEAP as a co-catalyst in the EtOH/EG solvent system, greatly
improved the rate and selectivity of this transformation compared
to previously reported conditions. Our system compared to the
Table 1
10
procedure described by Ma was generally faster. Also, compared
Optimization of the reaction conditions
Br
catalyst
N
3
Table 2
+
NaN3
MeO
solvent, temp.
Scope of the aryl halides in the reaction with NaN
3
MeO
N
3
X
2 3
10 mol% Cu O, 2 equiv. NaN
Entry
Solvent
TEAP
Time
(h)
Catalyst
(mol %)
Conversiona,b
(%)
4
0 mol% TEAP
R
(
mol %)
R
EtOH/EG (7:3), 95 oC
1
2
3
4
5
6
7
8
9
DMSO
DMSO/H
PEG
EG
EtOH
40
40
40
40
40
40
40
40
20
40
40
0
2
2
2
2
2
2
2
2
2
10
10
10
10
10
10
10
10
10
5
40
15
70
90
45
5
40
90
45
70
35
72
60
X= I, Br
2
O (9:1)
Yielda,b
Entry
R
X
Time (h)
1
2
3
4
5
6
7
8
9
4-OCH
4-OH
4-NH
4-Br
4-BrC
4-OCH
4-CH
4-NH2
4-I
3
Br
Br
Br
Br
Br
I
2
2
2
1.5
2
1.5
1
2
1.5
1.5
2
90
91
80
85
10
92
90
87
70
50
0
H
2
O
EtOH/H
2
O (7:3)
2
EtOH/EG (7:3)
EtOH/EG (7:3)
EtOH/EG (7:3)
EtOH/EG (7:3)
EtOH/EG (7:3)
EtOH/EG (7:3)
6
H
4
10
11
12
13
2
10
2
3
0
10
10
3
I
I
I
I
c
d
40
2
10
3-NO
4-NO2
2
a
Isolated yield.
11
I
b
3 2
Reaction conditions: aryl halide (0.1 mmol), NaN (0.2 mmol), TEAP, Cu O,
a
3
Reaction conditions: aryl halide (0.1 mmol), NaN (0.2 mmol), TEAP (40 mol %),
solvent (2 mL), 95 °C.
c
Cu O (10 mol %), EtOH/EG (7:3), 95 °C.
L-Proline (40 mol %) and NaOH (40 mol %) were used instead of TEAP.
2
b
d
Isolated yield.
CuI was used as the catalyst.