Highly efficient ci￡n bond forming reactions in water catalyzed by copper(i) iodide with calix[4]arene supported amino acid ionic liquid

Article abstract of DOI:10.1002/cjoc.201200623

A novel and effective protocol has been developed for the Ullmann-type Ci￡N coupling reaction catalyzed by calix[4]arene supported amino acid ionic liquid and copper(I) iodide in water under microwave irradiation condition. The protocol uses calix[4]arene supported amino acid ionic liquid as double function of the ligand and phase-transfer catalyst, and shows good tolerance in good to excellent yields. A novel and effective protocol has been developed for the Ullmann-type Ci￡N coupling reaction catalyzed by calix[4]arene supported amino acid ionic liquid and copper(I) iodide in water under microwave irradiation condition. The protocol uses calix[4]arene supported amino acid ionic liquid as double function of the ligand and phase-transfer catalyst, and shows good tolerance in good to excellent yields. Copyright

Full text of DOI:10.1002/cjoc.201200623

FULL PAPER
DOI: 10.1002/cjoc. 201200623
Highly Efficient C—N Bond Forming Reactions in Water
Catalyzed by Copper(I) Iodide with Calix[4]arene
Supported Amino Acid Ionic Liquid
Huang, Li(黄利)
Jin, Can(金灿)
Su, Weike*(苏为科)
Key Laboratory of Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of
Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
A novel and effective protocol has been developed for the Ullmann-type C—N coupling reaction catalyzed by
calix[4]arene supported amino acid ionic liquid and copper(I) iodide in water under microwave irradiation condition.
The protocol uses calix[4]arene supported amino acid ionic liquid as double function of the ligand and
phase-transfer catalyst, and shows good tolerance in good to excellent yields.
Keywords calix[4]arene supported ionic liquid, copper(I) iodide, surfactant, cross-coupling, microwave irradia-
tion
Introduction
calix[4]arene skeleton for the direct aqueous Ull-
mann-type C—N coupling reaction. On that basis, we
tried to complete this reaction by microwave irradiation
with a main purpose of more quick rates and more undi-
vided selectivities.[8a] The structure of the [Emim][Pro]
based on the calix[4]arene scaffold 5 is shown in Figure
1.
Ullmann-type C—N coupling reaction is an impor-
tant way to synthesize nitrogen-containing heterocycles,
which are widely employed building blocks for the syn-
thesis of pharmaceutical and natural products.[1] Al-
though the copper catalyzed Ullmann-type C—N cou-
pling reaction is a straightforward and inexpensive ap-
proach, here are some disadvantages, such as high reac-
tion temperatures (generally 140 ℃ or higher), long
reaction time (24—60 h), the requirement of strong
bases and the need of a stoichiometric amount of copper
catalyst.[2] These facts and the moderate products yields
limit the synthetic utility of this method. In the past few
decades, more and more attentions have been paid to the
improvement of the classical Ullmann chemistry.[3]
DMF,[4] DMSO,[5] NMP,[6] CH3CN[7] are the common
solvent of Ullmann-type coupling. A few papers refer to
the procedure for Ullmann-type coupling in water re-
cently,[8] however, inefficient and inadequate mixing of the
heterogeneous reaction system limit the development of
its synthetic utility in aqueous phase. Our group has been
researched on synthesis and application of calix[4]arene
derivatives, on this basis, we attempted to design a novel
catalytic system for the assembly of N-arylated nitro-
gen-containing heterocycles in water.
O
O
O
O
Ph
Ph
N
N
N
N
-
COO
-
N
N
COO
H
H
5
Figure 1 Structure of calix[4]arene [Emim][Pro] 5.
We described that calix[4]arene supported amino acid
ionic liquids could be used as both ligand and surfactant
in the Ullmann C—N coupling reaction with aqueous
solvent. The functional group [Emim][Pro] was designed
as ligand and hydrophilic functions, simultaneously, the
calix[4]arene bearing pendant aryl chains were devised
as hydrophobic function. In order to control Hydrophilic
Lipophilic Balance[9] (HLB), 5 was synthesized as the
Results and Discussion
Herein, we described the design and use of novel
calix[4]arene supported amino acid ionic liquid catalyst
possessing both an [Emim][Pro] catalytic center and a
*
E-mail: pharmlab@zjut.edu.cn; Tel.: 0086-0571-88320752; Fax: 0086-0571-88320752
Received June 26, 2012; accepted September 13, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200623 or from the author.
2394
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Chin. J. Chem. 2012, 30, 2394—2400

Highly Efficient C—N Bond Forming Reactions in Water Catalyzed by Copper(I) Iodide
ligand and phase transfer catalyst.
neously, L-proline played an important role[5a] in the
Calix[4]arene [Emim][Pro] 5 can be prepared from
the already reported p-t-butyl-25,27-bis-O-(2-bromo-
ethoxy) calix[4]arene (2).[10] The process is outlined in
Scheme 1. Treatment of 2 with benzyl bromide in the
presence of LiH gave compound 3 in cone conformation.
3 was transformed into intermediate 4 by treatment with
10 equiv. of 1-methyl-1H-imidazole. Then, calix[4]arene
imidazolium hydroxide could easily be obtained by an
anion exchange reaction of 4 with 201×7 Styrene-
DVB. Lastly, L-proline was used to neutralize
calix[4]arene imidazolium hydroxide and gave the ob-
function of ligand. To prove that both the L-proline and
the calix[4]arene skeleton on 5 were the same important
groups in the aqueous phase Ullmann coupling reaction,
we used L-proline or 3 separately as ligand. It was con-
firmed that there was hardly any response to this reaction
in water with 3 or L-proline respectively (Table 1, Entries
4 and 8). To compare the reaction method, CuI/5 (10
mol%)/K2CO3/H2O was used as the reaction system, this
Ullmann coupling reaction was performed under conven-
Table 1 Some representative results from the screening of reac-
tion conditions for the N-arylation of imidazole with 1-bromo-4-
methylbenzenea
1
jective product 5 which was confirmed by H and 13C
NMR spectra, and ESI-MS spectrometry.
As we know, L-proline is an effective catalyst and
ligand in many types of reaction, such as asymmetric
Michael addition, aza-Diels-Alder cyclization, Ullmann
coupling reaction, and so on.[11] However, it has never
been reported for synthesis and application of calix[4]-
arene-[Emim][Pro].
N
CuI/ligand/K2CO3
Br
N
N
N
solvent
H
Entry
1c
Ligand/mol%
Solvent Time/min
Yieldb/%
5 (10)
H2O
48 h
10
85
A preliminary survey of reaction conditions was
conducted using 1-bromo-4-methylbenzene and imida-
zole as model arylating substrate (Table 1, Entries 1—8).
As shown in Table 1, the best result was obtained in
H2O at 140 ℃ for 10 min under microwave irradiation
and N2 atmosphere, using 2.4 equiv. of K2CO3 as the
base in the presence of a catalyst system generated from
10 mol% of CuI and 10 mol% of 5 (Table 1, Entry 3).
Compared with TBAB,[8b] 5 has higher catalytic per-
formance in water: 1-bromo-4-methylbenzene could be
activated by 5 to react with imidazole to afford 95% of
the corresponding product, however, the yield was only
40% when TBAB was used (compare Entry 3 to Entry
9). We suspected that the suitable HLB of 5 resulted in the
well water-solubility and the micellar effects,[12] simulta-
2
5 (5)
H2O
15
3
5 (10)
H2O
10
95
4
L-Pro (20)
L-Pro (20)
5 (10)
H2O
10
Trace
50
5
DMF
DMF
DMSO
H2O
10
6
7d
5
72
5 (10)
48 h
10
80
8
3 (10)
Trace
40
9
TBAB (10)
H2O
10
a
CuI (9.5 mg, 0.05 mmol), ligand, K2CO3 (165 mg, 1.2 mmol),
imidazole (0.5 mmol), 1-bromo-4-methylbenzene (0.6 mmol),
and H2O (2 mL) under N2, microwave irradiation under 140 ℃.
b Isolated yields based on imidazole. c Traditional heating under
85 ℃ for 48 h. d Traditional heating under 120 ℃ for 48 h.
Scheme 1 Synthesis of the calix[4]arene [Emim][Pro] 5
BrCH2CH2Br
LiH, BnBr
K2CO3, CH3CN
CH3CN
O
O
O
O
O
O
OH
OH
HO
OH OH
OH
Bn
Bn
3 (93%)
1
Br
Br
Br
Br
2 (72%)
N
N
(1) ionic change resin
O
O
O
O
toluene, reflux
(2) L-proline, CH3OH/H2O
O
O
O
O
Bn
Bn
Bn
+
N
+
N
Bn
N
Br
N
N
N
Br
N
N
COO -
5 (81%)
COO-
4 (90%)
N
N
H
H
Chin. J. Chem. 2012, 30, 2394—2400
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Huang, Jin & Su
FULL PAPER
tional heating condition at 85 ℃ for 48 h, giving 85%
yield (Table 1, Entry 1). It illustrated that the method of
microwave condition has a higher efficiency than
conventional heating. When DMF was chosen as the
solvent under microwave condition, only 72% of the
corresponding product was obtained (Table 1, Entry 6).
The reason for lower yield was that DMF was easily
decomposed under microwave heating condition.
Inspired by these results, we decided to focus on the
scope of the reaction by the standard reaction condition.
We were delighted to find that the N-arylation of imida-
zole with a broad range of aryl or heteroaryl bromides
could be conducted smoothly to afford the correspond-
ing products in good to excellent yields (Table 2, Entries
1—7). Notably, our catalyst system showed very high
activity with electron-deficient aryl chloride (Table 2,
Entries 8). It is more interesting that the substrates that
contain certain functional groups (for example ester,
carbonyl, amido and nitro), could be sustained in our
catalytic system and reaction condition (Table 2, Entries
3—5, 7). To our knowledge, the substrates that contain
certain functional groups always have some problem in
the N-arylation of imidazoles. Only a few literatures had
reported the reaction previously.[13]
Table 2 Microwave-assisted CuI/5 catalyzed coupling reactions of aryl halides with anilines in water a
R3
R3
5 (10 mol%), CuI (10 mol%), K2CO3
R1
N
R1
X
HN
R2
R2
H2O, MW, 140 oC, 10 min
Entry
1
R1—X
Amines
Products
Yieldb/%
95
H
N
N
Br
N
93, 91, 90c
N
6a
H
N
N
Br
N
2
3
4
5
87
85
85
91
N
6b
6c
N
H
N
Br
Br
OHC
H2N
N
OHC
N
N
H
N
N
H2N
N
6d
H
N
N
Br
EtOOC
N
EtOOC
N
6e
N
Br
N
H
N
6
75
94
N
6f
N
H
N
S
N
Br
7
S
N
6g
H
N
N
Cl
O2N
O2N
N
8d
98
97
O2N
N
6h
H
Br
N
N
9
O2N
6i
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Chin. J. Chem. 2012, 30, 2394—2400

Highly Efficient C—N Bond Forming Reactions in Water Catalyzed by Copper(I) Iodide
Continued
Yieldb/%
Entry
10
R1—X
Amines
Products
N
N
N
Br
Br
N
N
N
N
95
77
N
H
6j
11
12
N
H
6k
Br
90
N
H
6l
N
I
N
N
HN
N
N
13
14
96
92
6m
N
Br
Br
N
N
HN
6n
N
N
N
15
16
73
HN
6o
Br
N
HN
N
—
Trace
a CuI (9.5 mg, 0.05 mmol), K2CO3 (165 mg, 1.2 mmol), 5 (51 mg, 0.05 mmol), imidazole (0.5 mmol), aryl halides (0.6 mmol), and H2O
(2 mL) under N2, microwave irradiation under 140 ℃ for 10 min. b Isolated yields based on imidazole. c Recycle first, second, third time.
d Microwave irradiation under 100 ℃ for 15 min.
On the other hand, our catalytic system and reaction
condition showed high activity and an extensive struc-
tural range of other nitrogen heterocycles. To our delight,
the π-electron-deficient nitrogen heterocycles showed
higher activity in our protocol (Table 2, Entries 9 and
10). However, π-electron-rich nitrogen heterocycles
such as 2-methyl-1H-indole and 3,4-dimethyl-1H-
pyrazole were proved to be less reactive (Table 2, En-
tries 11 and 15). It is worthy to indicate that the reaction
of 1H-1,2,4-triazole and 1-iodo-4-methyl benzene could
be in the process successfully, and give an excellent
yield (Table 2, Entry 13). But no reaction forwarded
when 1-iodo-4-methylbenzene was replaced by
1-bromo-4-methylbenzene (Table 2, Entry 16).
and water. Consequently, 5 that played the role of phase
transfer catalyst and ligand simultaneously had an impor-
tant effect in the catalytic system. Further, the catalytic
activity of 5 did not show significant decrease after be-
ing reused three times (Table 2, Entry 1).
Conclusions
In summary, A novel calix[4]arene [Emim][Pro] (5)
was prepared successfully as the supported ionic liquid
catalysis primarily. The Ullmann-type C—N coupling
reaction was proceeded smoothly by using the catalytic
system of CuI/5/K2CO3 in water under microwave irra-
diation to afford the corresponding products in good to
excellent yields. The catalytic activity of 5 did not show
significant decrease after being reused three times. In
addition, effects are in progress to extend to other ap-
plications of calix[4]arene [Emim][Pro] as surfactant
and ligand.
A variety of nitrogen heterocycles could be
N-arylated with aryl or heteroaryl halides effectively
under the corresponding experimental conditions. It is
reasonable that the significantly enhanced catalytic ac-
tivity may stem from high micellar effects[14] between 5
Chin. J. Chem. 2012, 30, 2394—2400
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Huang, Jin & Su
FULL PAPER
Experimental
General methods
(m, 8H), 3.83 (t, J＝6.4 Hz, 4H), 3.32 (d, J＝13.1 Hz,
4H), 1.29 (s, 18H), 0.95 (s, 18H); 13C NMR (100 MHz,
CDCl3) δ: 153.5, 151.6, 145.5, 144.5, 136.8, 135.1,
131.6, 129.4, 128.7, 128.4, 125.5, 124.5, 78.6, 73.6,
34.2, 33.7, 31.8, 31.3, 31.2, 29.5; IR νmax: 2961, 1480,
All the reagents were from commercial sources. All
microwave irradiation experiments were carried out in a
Discover-CEM mono mode microwave apparatus.
Melting points (m.p.) were recorded on a WRS-1B
－
1
1202, 1122, 1010, 993, 697 cm ; MS (ESI) m/z: 1060.6
(M＋NH＋4 ). HRMS (ESI) calcd for C62H78Br2 NO＋ [M＋
4
1
NH＋4 ]: 1060.4277, found 1060.4271.
digital melting point apparatus and uncorrected. H
NMR and 13C NMR spectra were obtained on a Varian
Mercury plus-400 spectrometer using CDCl3 as the sol-
vent with TMS as the internal standard. Mass spectra
were measured with a Finnigan Trace DSQ spectrome-
ter. IR spectra were recorded using KBr pellets on a
Nicolet Aviatar-370 instrument. Mass spectra were
measured with Thermo Finnigan LCQ-Advantage. High
resolution mass spectral (HRMS) analysis was per-
formed on a Bruker micrOTOF-QⅡ using ESI tech-
niques.
Calix[4]arene supported [Emim][Br] (4): A mixture
of 1-methyl-1H-imidazole (0.79 g, 9.6 mmol) with 3
(0.51 g, 0.48 mmol) in toluene (5 mL) was stirred at 100
℃ for 11 h. After cooling the reaction mixture to room
temperature, the suspension was filtered off and the
solid dissolved in MeOH (30 mL). The solvent was then
distilled off, and the solid residue was recrystallized
with CH2Cl2/CH3OH (5∶1) to afford 4 (0.52 g, 90%)
as white solid: m.p. 285—286 ℃; 1H NMR (400 MHz,
CDCl3) δ: 9.43 (s, 1H), 7.57 (d, J＝11.2 Hz, 2H),
7.46—7.32 (m, 8H), 7.29—7.20 (m, 3H), 7.09 (s, 4H),
6.74 (s, 2H), 6.41 (s, 4H), 4.79 (s, 4H), 4.67 (t, J＝7.2
Hz, 4H), 4.36 (t, J＝6.5 Hz, 4H), 4.17—4.06 (m, 10H),
3.09 (d, J＝12.8 Hz, 4H), 1.34 (s, 18H), 0.81 (s, 18H);
13C NMR (100 MHz, CDCl3) δ: 151.8, 150.9, 146.4,
144.8, 137.0, 136.7, 135.1, 131.3, 129.7, 128.7, 128.1,
125.6, 124.5, 123.5, 121.3, 78.3, 70.3, 48.6, 36.9, 34.2,
33.6, 31.7, 31.2, 31.0; IR νmax: 2960, 1480, 1193, 1174,
Experimental procedure and physical data
p-t-Butyl-25,27-bis-O-(2-bromoethoxy)calix[4]-
arene (2): p-t-Butyl-calix[4]arene (1) (1.0 g, 1.5 mmol),
K2CO3 (2.07 g, 15 mmol) were dissolved under nitrogen
in CH3CN (100 mL) for 30 min. Then 1,2-dibro-
moethane (8.7 g, 46 mmol) was added and the mixture
was stirred under nitrogen at 80 ℃ for 10 h. After
quenched with aqueous HCl (20 mL), the mixture was
stirred for ten more minutes. After the removal of
CH3CN by evaporation, the aqueous layer was extracted
with CH2Cl2 (30 mL×3). The organic layer was then
washed with brine (30 mL) and H2O (20×2 mL), dried
over Na2SO4, filtrated and evaporated. The obtained
solid was dissolved in ethyl acetate (20 mL), filtrated off.
The filtrate was evaporated to give crude product that
was purified by recrystallisation in CH2Cl2/MeOH (1∶
5) to give 2. (0.74 g, 72%) as white crystal: m.p. 277—
－
－
1
1124, 1044 cm ; MS (ESI) m/z: 1127.6 (M－Br ).
HRMS (ESI) calcd for
C70H86BrN4 NO4
1127.5074, found 1127.5768.
＋ [M－Br－]:
Calix[4]arene supported [Emim][Pro] (5): The 4 (1.0
g, 0.83 mmol) was stirred with anion ion resin (201×7
Styrene-DVB, 10 equiv. based on the imidazolium
group) in MeOH for 40 h at room temperature. The re-
sulting 5 was separated and evaporated, followed by a
stirring in MeOH/H2O (10∶1, 20 mL) of L-proline (1
mol/L, 100 equiv. based on the imidazolium group) for
40 h at room temperature. The solution was then added
acetonitrile (50 mL), standing stillness for 30 min. The
residue was added to acetonitrile, and then filtered
through a plug of silica gel. The filter was washed with
acetonitrile, and then the filtrate was distilled off. This
process was repeated for three times. The resulting
residue was dried in vacuo for 24 h to afford 5 (0.85 g,
1
280 ℃ [Lit.[15] m.p. 278—280 ℃]; H NMR (400
MHz, CDCl3) δ: 7.04 (s, 4H), 6.93 (s, 2H), 6.77 (s, 4H),
4.35—4.25 (m, 8H), 3.83 (t, J＝6.4 Hz, 4H), 3.32 (d,
J＝13.0 Hz, 4H), 1.29 (s, 18H), 0.95 (s, 18H); 13C NMR
(100 MHz, CDCl3) δ: 150.3, 149.1, 147.0, 141.4, 132.2,
127.5, 125.5, 125.0, 75.3, 34.0, 33.9, 31.8, 31.0, 29.4;
MS (ESI) m/z: 885.4 (M＋Na＋).
1
p-t-Butyl-25,27-bis-O-(2-bromoethoxy)-26,28-bis-
81%) as white solid: m.p. 143.6—145.0 ℃; H NMR
O-benzyloxycalix[4]arene (3): To
p-t-butyl-25,27-bis(2-bromoethoxy)calix[4]arene
a
solution of
(2)
(400 MHz, CDCl3) δ: 7.50—7.48 (m, 1H), 7.36—7.35
(m, 4H), 7.30—7.27 (m, 12H), 7.10—7.07 (m, 3H),
6.73—6.71 (m, 1H), 6.43—6.41 (m, 3H), 4.77 (s, 4H),
4.65 (t, J＝6.7 Hz, 4H), 4.31 (t, J＝6.7 Hz, 4H), 4.18—
4.15 (m, 4H), 4.03 (s, 6H), 3.70—3.67 (m, 2H), 3.05—
3.04 (m, 5H), 2.93—2.90 (m, 1H), 2.13—2.07 (m, 2H),
1.98 (s, 1H), 1.94—1.86 (m, 2H), 1.73—1.68 (m, 4H),
1.33 (s, 18H), 0.83—0.81 (m, 18H); 13C NMR (100
MHz, CDCl3) δ: 152.3, 151.2, 146.6, 145.1, 137.3,
135.2, 131.5, 129.9, 129.7, 128.7, 128.5, 128.3, 128.0,
125.8, 124.7, 123.6, 121.6, 78.3, 77.4, 77.3, 76.8, 70.8,
61.9, 61.4, 48.8, 36.4, 34.2, 33.7, 31.8, 31.7, 31.5, 31.1;
(11.2 g, 13.0 mmol) and LiH (1 g, 130 mmol, 98% con-
tent) in CH3CN (300 mL) was added benzyl bromide
(22.2 g, 130 mmol) at room temperature. The reaction
mixture was stirred for 2 h at room temperature and then
quenched with aqueous HCl (150 mL). After the re-
moval of CH3CN by evaporation, organic materials
were extracted with CH2Cl2 (70 mL×3) and the organic
extracts were dried with MgSO4. Evaporation of sol-
vents and purification of the residue by recrystallization
with CH2Cl2/MeOH afforded 3 (9.4 g, 83%) as white
crystal: m.p. 242—243 ℃; 1H NMR (400 MHz, CDCl3)
δ: 7.04 (s, 4H), 6.94 (s, 2H), 6.77 (s, 4H), 4.34—4.25
－
1
IR νmax: 3380, 2960, 1617, 1577, 1480, 1416, 1193 cm ;
MS (ESI) m/z: 1160.2 (M－C5H8NO－2 ), 1388.3 (M＋
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Chin. J. Chem. 2012, 30, 2394—2400

Highly Efficient C—N Bond Forming Reactions in Water Catalyzed by Copper(I) Iodide
C5H8NO－2 ). HRMS (ESI) calcd for
－ [M－
C75H94 N5O6
165.6, 140.7, 135.6, 131.7 (2C), 131.2, 129.5, 120.7
(2C), 118.0, 61.6, 14.8; MS (EI) m/z: 216 (M＋, 90), 171
(100).
C5H8NO－2 ]: 1160.7204, found 1160.7210.
Ullmann coupling reaction experimental procedure
and physical data
1-(Naphthalen-1-yl)-1H-imidazole (6f): Yield 75%;
white solid; m.p. 62—64 ℃ [Lit.[16] m.p. 61—63 ℃];
1H NMR (400 MHz, CDCl3) δ: 7.91 (d, J＝7.9 Hz, 2H),
7.73 (s, 1H), 7.60—7.45 (m, 4H), 7.41 (dd, J＝7.2, 1.0
Hz, 1H), 7.27 (d, J＝6.9 Hz, 1H), 7.22 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ: 138.4, 134.1, 134.0, 129.6,
129.4, 129.2, 128.3, 127.6, 126.9, 125.2, 123.6, 122.3,
121.7; MS (EI) m/z: 194 (M＋, 100), 193 (32), 167 (34),
166 (37).
1-(Thiophen-2-yl)-1H-imidazole (6g): Yield 94%;
yellow oil;[16] 1H NMR (400 MHz, CDCl3) δ: 7.74 (s,
1H), 7.21—7.09 (m, 3H), 7.03—6.92 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ: 138.8, 136.8, 130.0, 126.1,
121.6, 120.1, 118.8; MS (EI) m/z: 150 (M＋, 100), 96
(38).
1-(4-Nitrophenyl)-1H-imidazole (6h): Yield 98%;
yellow solid; m.p. 204—206 ℃ [Lit.[20] m.p. 202—204
℃]; 1H NMR (400 MHz, CDCl3) δ: 8.37 (d, J＝8.8 Hz,
2H), 7.99 (s, 1H), 7.59 (d, J＝8.8 Hz, 2H), 7.38 (s, 1H),
7.27 (s, 1H); 13C NMR (100 MHz, CDCl3) δ: 146.0,
141.7, 135.2, 131.5, 125.6 (2C), 120.9 (2C), 117.5; MS
(EI) m/z: 189 (M＋, 100).
In a 10 mL pressurized vial “snap-on” cap with a
magnetic stirring bar was charged with CuI (9.5 mg,
0.05 mmol), calix[4]arene [Emim][Pro] 5 (64 mg, 0.1
mmol of L-proline), K2CO3 (165 mg, 1.2 mmol), nitro-
gen-containing heterocycle (0.5 mmol), aryl or hetero-
aryl halide (0.6 mmol) and H2O (2 mL) under N2. A
rubber septum was replaced with a glass stopper, and
the system was then evacuated three times and refilled
with N2. The reaction mixture was stirred for 30 min at
room temperature, and then was irradiated for 10 min at
140 ℃. The resulting mixture was cooled to ambient
temperature, diluted with ethyl acetate (2—3 mL), fil-
tered through a plug of silica gel, and washed with ethyl
acetate (10—20 mL). The filtrate was concentrated and
the resulting residue was purified by column chroma-
tography on silica gel to provide the desired product.
Then, 5 was eluted with pole solvent (such as ethyl ace-
toacetate) for reuse in the next cycle of aqueous reaction
directly.
1-p-Tolyl-1H-imidazole (6a): Yield 95%; white
solid; m.p. 45—47 ℃ [Lit.[16] m.p. 45—46 ℃]; H
1
5-Nitro-1-phenyl-1H-indole (6i): Yield 97%; yellow
1
solid; m.p. 82—83 ℃ [Lit.[21] m.p. 83 ℃]; H NMR
NMR (400 MHz, CDCl3) δ: 7.81 (s, 1H), 7.25—7.24 (bs,
4H), 7.19 (s, 1H), 7.17 (s, 1H), 2.39 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 137.4, 135.6, 134.9, 130.3 (2C) ,
130.2, 121.4 (2C), 118.3, 21.2; MS (EI) m/z: 158 (M＋,
100), 130 (35).
1-Phenyl-1H-imidazole (6b): Yield 87%; yellow
oil;[16] 1H NMR (400 MHz, CDCl3) δ: 7.84 (s, 1H),
7.50—7.42 (m, 2H), 7.41—7.32 (m, 3H), 7.29—7.24
(m, 1H), 7.19 (s, 1H); 13C NMR (100 MHz, CDCl3) δ:
137.1, 135.3, 130.2, 129.6 (2C), 127.2, 121.3 (2C),
118.0; MS (EI) m/z: 144 (M＋, 100), 117 (45).
4-(1H-Imidazol-1-yl)benzaldehyde (6c): Yield 85%;
pale yellow solid; m.p. 144—145 ℃ [Lit.[17] m.p.
147—148 ℃]; 1H NMR (400 MHz, CDCl3) δ: 10.03 (s,
1H), 8.10—7.90 (m, 3H), 7.57 (d, J＝8.4 Hz, 2H), 7.37
(s, 1H), 7.26 (d, J＝5.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ: 190.3, 141.5, 135.2, 134.7, 131.4 (2C), 131.1,
120.9 (2C), 117.5; MS (EI) m/z: 172 (M＋, 100), 171
(20).
4-(1H-Imidazol-1-yl)aniline (6d): Yield 85%; pale
yellow solid; m.p. 141—143 ℃ [Lit.[18] m.p. 143—147
℃]; 1H NMR (400 MHz, CDCl3) δ: 7.70 (s, 1H), 7.14 (t,
J＝5.8 Hz, 4H), 6.72 (d, J＝8.5 Hz, 2H), 3.82 (s, 2H);
13C NMR (100 MHz, CDCl3) δ: 145.9, 135.6, 129.5,
128.5, 123.1 (2C), 118.7, 115.3 (2C); MS (EI) m/z: 159
(M＋, 100), 132 (20).
(400 MHz, CDCl3) δ: 8.62 (d, J＝2.1 Hz, 1H), 8.09 (dd,
J＝9.1, 2.2 Hz, 1H), 7.59—7.41 (m, 7H), 6.84 (d, J＝
3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 142.2,
138.8, 138.7, 131.4, 130.1 (2C), 128.6, 127.9, 124.8
(2C), 118.4, 118.1, 110.7, 105.8; MS (EI) m/z: 238 (M＋,
100), 192 (45), 191 (71).
1-Phenyl-1H-benzo[d][1,2,3]triazole (6j): Yield 95%;
white solid; m.p. 92—93 ℃ [Lit.[22] m.p. 85—87 ℃];
1H NMR (400 MHz, CDCl3) δ: 8.13 (d, J＝8.3 Hz, 1H),
7.75 (dd, J＝14.7, 8.3 Hz, 3H), 7.59 (t, J＝7.6 Hz, 2H),
7.56—7.45 (m, 2H), 7.41 (t, J＝7.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ: 145.9, 136.4, 131.7, 129.3, 128.1,
127.7, 123.9, 122.3, 119.8, 109.9; MS (EI) m/z: 195
(M＋, 20), 167 (100), 166 (50).
2-Methyl-1-phenyl-1H-indole (6k): Yield 77%; yel-
low oil;[21] 1H NMR (400 MHz, CDCl3) δ: 7.57—7.45
(m, 3H), 7.40 (t, J＝7.1 Hz, 1H), 7.31 (d, J＝7.7 Hz,
2H), 7.12—7.02 (m, 3H), 6.38 (s, 1H), 2.28 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ: 138.0, 137.8, 136.8, 129.2
(2C), 128.0, 127.8 (2C), 127.5, 120.9, 119.9, 119.4,
109.9, 101.2, 13.5; MS (EI) m/z: 207 (M＋, 100), 206
(75).
1-p-Tolyl-1H-indole (6l): Yield 90%; yellow oil;[21]
1H NMR (400 MHz, CDCl3) δ: 7.66 (d, J＝7.7 Hz, 1H),
7.51 (d, J＝8.1 Hz, 1H), 7.37 (d, J＝8.2 Hz, 2H),
7.32—7.27 (m, 3H), 7.16 (dt, J＝14.7, 7.1 Hz, 2H),
6.65 (d, J＝3.2 Hz, 1H), 2.43 (s, 3H); 13C NMR (100
MHz, CDCl3) δ: 137.4, 136.3, 136.1, 130.3 (2C), 129.3,
128.2, 124.5 (2C), 122.4, 121.2, 120.3, 110.7, 103.4,
21.46; MS (EI) m/z: 207 (M＋, 100), 206 (36).
Ethyl 4-(1H-imidazol-1-yl)benzoate (6e): Yield 91%;
pale white solid; m.p. 101 —103 ℃ [Lit.[19] m.p.
1
101—103 ℃]; H NMR (400 MHz, CDCl3) δ: 8.15 (d,
J＝8.4 Hz, 2H), 7.94 (s, 1H), 7.45 (d, J＝8.4 Hz, 2H),
7.34 (s, 1H), 7.23 (s, 1H), 4.40 (q, J＝7.1 Hz, 2H), 1.42
(t, J＝7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
1-p-Tolyl-1H-1,2,4-triazole (6m): Yield 96%; white
Chin. J. Chem. 2012, 30, 2394—2400
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2399

Huang, Jin & Su
FULL PAPER
solid; m.p. 66—67 ℃ [Lit.[23] m.p. 67—67.5 ℃]; H
NMR (400 MHz, CDCl3) δ: 8.50 (s, 1H), 8.07 (s, 1H),
7.53 (d, J＝8.2 Hz, 2H), 7.28 (d, J＝8.1 Hz, 2H), 2.40
(s, 3H); 13C NMR (100 MHz, CDCl3) δ: 152.1, 140.5,
138.0, 134.5, 130.0 (2C), 119.8 (2C), 21.1; MS (EI) m/z:
159 (M＋, 100), 105 (70).
1
Catal. 2010, 352, 3241.
[6] (a) Sperotto, E.; Van Klink, G. P. M.; De Vries, J. G.; Van Koten, G.
Tetrahedron 2010, 66, 3478; (b) De Lange, B.; Lambers-Verstappen,
M. H.; Van De Vondervoort, S. L. Synlett 2006, 3105.
[7] (a) Weng, B.-J.; Li, J.-H. Appl. Organomet. Chem. 2009, 9, 375; (b)
Xu, L.; Zhu, D.; Wu, F.; Wang, R.-L.; Wan, B.-S. Tetrahedron 2005,
61, 6553.
1-Phenyl-1H-pyrazole (6n): Yield 92%; colorless
oil;[21] 1H NMR (400 MHz, CDCl3) δ: 7.91—7.90 (m,
1H), 7.71—7.67 (m, 3H), 7.43 (t, J＝7.8 Hz, 2H), 7.28
—7.24 (m, 1H), 6.45 (t, J＝1.6 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ: 140.9, 140.0, 129.3 (2C), 126.6, 126.3,
119.1 (2C), 107.5; MS (EI) m/z: 144 (M＋, 100).
3,4-Dimethyl-1-phenyl-1H-pyrazole (6o): Yield
73%; colorless oil;[24] 1H NMR (400 MHz, CDCl3) δ:
7.99—7.89 (m, 2H), 7.72—7.64 (m, 3H), 7.61 (s, 1H),
2.10 (s, 3H), 2.00 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ: 149.1, 139.9, 132.5, 129.7 (2C), 128.0, 119.9 (2C),
119.4, 12.2, 7.2; MS (EI) m/z: 172 (M＋, 50), 171 (100).
[8] (a) Zhu, X.-H.; Su, L.; Huang, L.-Y.; Chen, G.; Wang, J.-L.; Song,
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H. L.; Chan, A. S. C.; Fwong, F. Y. Tetrahedron Lett. 2009, 50, 5868.
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41, 359.
[10] Bozkurt, S.; Durmaz, M.; Yilmaz, M.; Sirit, A. Tetrahedron: Asym-
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Kozikowski, A. P.; Mugrage, B. B. J. Org. Chem. 1989, 54, 2274; (c)
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Acknowledgement
We gratefully acknowledge financial support from
the National Natural Science Foundation of China (No.
21176222).
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(Pan, B.; Qin, X.)
2400
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2394—2400