Pd-NHC-catalyzed direct arylation of 1,4-disubstituted 1,2,3-triazoles with aryl halides

Article abstract of DOI:10.1002/cjoc.201100275

A highly efficient method for the synthesis of unsymmetrical multi-substituted 1,2,3-triazoles via a direct Pd-NHC system catalyzed C(5)-arylation of 1,4-disubstituted triazoles, which are readily accessible via "click" chemistry has been developed. It is

Full text of DOI:10.1002/cjoc.201100275

FULL PAPER
DOI: 10.1002/cjoc.201100275
Pd-NHC-Catalyzed Direct Arylation of 1,4-Disubstituted
1,2,3-Triazoles with Aryl Halides
He, Taoa(何涛)
Wang, Mina(王敏)
Li, Pinhuaa(李品华)
Wang, Lei*,a,b(王磊)
a Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
A highly efficient method for the synthesis of unsymmetrical multi-substituted 1,2,3-triazoles via a direct
Pd-NHC system catalyzed C(5)-arylation of 1,4-disubstituted triazoles, which are readily accessible via “click”
chemistry has been developed. It is important to note that C—H bond functionalizations of 1,2,3-triazoles with a
variety of differently substituted aryl iodides and bromides as electrophiles can be conveniently achieved through
this catalytic system at significantly milder reaction temperatures of 100 ℃ under air.
Keywords C—H activation, palladium, N-heterocyclic carbene, 1,4-disubstituted 1,2,3-triazole, C(5)-arylation
Introduction
1,2,3-triazoles with aryl bromides using NMP[10] and
PEG[11] as solvents, respectively. Using this reaction,
Oshima and Ackermann then reported a highly efficient
method for the synthesis of multi-substituted 1,2,3-
triazoles which allowed to employ aryl chlorides as
arylating agents using tricyclohexylphosphine as an ef-
ficient ligand, by using microwave[12] and conventional
heating,[13] respectively. Quite recently, Ackermann[14]
and Fukuzawa[15] reported these arylation reactions with
aryl iodides in the presence of copper catalyst system
individually.
N-Heterocyclic carbenes (NHCs) have become very
popular ligands in transition metal chemistry predomi-
nantly due to their efficiency in improving catalyst ac-
tivities.[16] NHCs were first considered as simple phos-
phane mimics in organometallic chemistry.[17] However,
their impact, often superior to that of ubiquitous
phosphines, has generally been rationalized by the co-
valent metal-carbene bond and by the strong donor abil-
ity of NHCs.[18] Because of their specific coordination
chemistry, NHCs both stabilize and activate metal cen-
ters in quite different key catalytic steps of organic syn-
theses, for example, C—C, C—H, C—O, and C—N
bond formation reactions.[19] Arduengo-type imidazoly-
lidenes have been used most widely, presumably be-
cause the free carbene is extensively stabilized by het-
eroatoms adjacent to the carbene, which makes them
easy to handle.[20] In this paper, we wish to report a
novel and highly efficient Pd(OAc)2-imidazolylidene
complex catalyzed arylation reactions of 1,4-disub-
stituted 1,2,3-triazoles with aryl iodides and bromides
through the direct C—H bond functionalization of
The transition-metal-catalyzed functionalization of
C—H bonds is a powerful synthetic strategy for the
construction of carbon-carbon bonds because of their
ecologically and economically benign nature.[1,2]
Among these, regio-selective direct arylations of (het-
ero)arenes represent a great valuable alternative to tradi-
tional cross-couplings with stoichiometric amounts of
organometallic reagents and would not require reactive
functional groups such as halogens or metal moieties.[3]
Heteroaromatic compounds, such as 1,2,3-triazoles,
due to their unique chemical and structural properties,
have received much attention and found wide applica-
tion in medicinal chemistry and material sciences.[4] The
importance of 1,2,3-triazoles has resulted in the devel-
opment of various strategies for their preparation.[5] One
of the representative methods is that the reaction of ter-
minal alkynes with organic azides gives highly regio-
selective syntheses of 1,4- or 1,5-disubstituted 1,2,3-
triazoles by using copper[6] and ruthenium[7] catalysts,
respectively. In addition, 1,4,5-trisubstituted 1,2,3-
triazoles, which also show biological activity,[8] may be
prepared by transition-metal-catalyzed reactions of in-
ternal alkynes with organic azides, but with a lack of
region-selectivity and/or generality.[9] The possibility of
taking advantage of the ready availability of 1,4-di-
substituted 1,2,3-triazoles, compounds readily accessi-
ble via the copper-catalyzed reaction, i.e., “click chem-
istry”, renders direct arylation with aryl halides prefer-
able. Recently, Gevorgyan and Ackermann independ-
ently reported palladium-catalyzed direct arylation of
*
E-mail: leiwang@chnu.edu.cn; Tel.: 0086-0561-3802069; Fax: 0086-561-03090518
Received August 24, 2011; accepted October 31, 2011 published online March 7, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201100275 or from the author.
Chin. J. Chem. 2012, 30, 979—984
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979

He et al.
FULL PAPER
1,2,3-triazoles under an atmosphere of air. The reactions
generated the corresponding 1,4,5-trisubstituted 1,2,3-
triazoles in good to excellent yields (Scheme 1).
stantially less effective and generated the desired prod-
ucts in 60%, 63% and 56% yields, respectively (Table 1,
Entries 8—10). Strong inorganic bases, such as Cs2CO3,
LiOH, t-BuOLi, t-BuONa and t-BuOK, and organic
bases, such as Et3N and DBU failed to promote the re-
action and gave a trace amount of multi-substituted
1,2,3-triazole 3a (Table 1, Entries 11—15). Moreover, a
decrease in the amount of base led to the lower yield of
1-benzyl-4,5-diphenyl-1,2,3-triazole (3a) (Table 1, En-
try 18).
The solvent also played an important role in the
model reaction. Various solvents were investigated for
the direct C—H bond functionalization of 1,2,3-triazole
and the results are listed in Table 1. From Table 1, it is
evident that DMF is suitable reaction media for the pal-
ladium-catalyzed direct arylation of 1,2,3-triazole in the
presence of L1 (Table 1, Entry 2), whereas other polar
aprotic solvents, such as DMSO and DMA, afforded
much lower isolated yields of 3a (Table 1, Entries 19
and 20). Fortunately, moderate yields of 3a were ob-
tained when the reactions were performed in NMP,
CH3CN and toluene (Table 1, Entries 21—23). How-
ever, no desired product 3a was obtained while reaction
was carried out in ClCH2CH2Cl (Table 1, Entry 24).
Optimal reaction conditions, hence, involved the use of
Pd(OAc)2 (5.0 mmol%)-L1 (10.0 mmol%) as catalyst,
K2CO3 as a base in DMF at 100 ℃ for 12 h.
After optimized the reaction conditions, we then
probed its scope in the direct arylation of 1,4-disub-
stituted-1,2,3-triazole with various aryl iodides and
bromides under the present reaction conditions. The
results of these experiments were summarized in Table
2. The direct coupling reactions of 1-benzyl-4-phenyl-
1,2,3-triazole with iodobenzene, o-iodotoluene,
m-iodotoluene, and p-iodotoluene proceeded smoothly
to generate the corresponding 5-arylated 1-benzyl-4-
phenyl-1,2,3-triazoles in excellent yields, even a more
sterically hindered group on ortho-position (Table 2,
Entries 1—4). With respect to other aryl iodides, mod-
erate to good yields of the corresponding products were
isolated for the direct coupling reactions of 1-benzyl-4-
phenyl-1,2,3-triazole with iodobenzenes with elec-
tron-withdrawing groups on the benzene rings (Table 2,
Entries 5—7). These results may suggest that the reac-
tivity of electron-riched iodobenzene was high enough
to give the corresponding coupling products in satisfac-
tory yields, while electron-deficient aryl iodides tended
to show lower reactivity toward the coupling reaction.
In addition, C6H5I(OAc)2 and 4-MeC6H4I-(OAc)2 were
found to be a good kind of arylating agent in the direct
arylation of 1,4-disubstituted-1,2,3-triazole, and good
yields of the corresponding multi-substituted 1,2,3-
triazoles were obtained under the standard reaction con-
ditions (Table 2, Entries 8 and 9). The scope of other
1,4-disubstituted 1,2,3-triazole except for 1-benzyl-4-
phenyl-1,2,3-triazole was also examined and the results
were also listed in Table 2. It was found that 4-aryl
groups in 1-benzyl-4-aryl-1,2,3-triazoles being attached
Scheme 1
+N
N
Cl-
(10 mmol%)
L1
R1
R1
Ar
N
N
Pd(OAc)2 (5 mmol%)
N
N
N
N
+
ArX
K2CO3, DMF, 100 oC, 12 h
R2
R2
Results and Discussion
In order to find a better catalytic system for the
challenging palladium-catalyzed direct arylation of
1,2,3-triazoles, a reaction of 1-benzyl-4-phenyl-1,2,3-
triazole (1a) and iodobenzene (2a) was chosen as a
model substrates for our investigation. The results were
shown in Table 1. At the outset of our studies, we
screened the effect of different N-heterocyclic carbene
precursors—imidazolium salts (L1—L4) as ligands in
Scheme 2 in the palladium-catalyzed direct arylation,
employing economical Pd(OAc)2 as palladium source,
K2CO3 as a base in DMF at significantly milder reaction
temperatures of 100 ℃ in the presence of air. Notably,
the reaction did not occur in the absence of any NHC
ligand (Table 1, Entry 1). Our studies also showed that
imidazolium salts, L1—L4 were all found to provide
satisfactory results in our reaction systems, while imi-
dazolium salt, L1 as N-heterocyclic carbene precursor
with K2CO3 as base in DMF at 100 ℃ allowed for the
best efficient catalysis (Table 1, Entries 2—5). Interest-
ingly, when increasing the temperature to 120 ℃ or
lowering to 80 ℃, the yields of 1-benzyl-4,5-diphenyl-
1,2,3-triazole (3a) was all slightly lower than that at 100
℃ (Table 1, Entries 6 and 7 vs. 2).
Scheme 2 Screening imidazolium salts L1—L4, N-heterocyclic
carbene precursors, as ligands in the reaction
+
+
N
N
N
N
Bn
Cl-
Cl-
L1
L2
+
+
N
N
N
N
Cl-
Cl-
L4
L3
Subsequently, different bases were examined for the
optimization of base in the reaction, K2CO3 was found
to be the most effective one and gave the 5-phenylated
product (3a) in 92% yield (Table 1, Entry 1). Other
bases, such as Na2CO3, K3PO4, and NaOAc, were sub-
980
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Chin. J. Chem. 2012, 30, 979—984

Pd-NHC-Catalyzed Direct Arylation of 1,4-Disubstituted 1,2,3-Triazoles with Aryl Halides
Table 1 Optimization of palladium-catalyzed direct arylation
successfully with iodobenzene (Table 2, Entries 13—
reaction conditionsa
15). Notably, 1-(p-methyl-benzyl)-4-phenyl-1,2,3-tri-
azole was also reacted with iodobenzene to give the
corresponding product in reasonable yield (Table 2, En-
try 16). In addition, it was also found that the coupling
reaction with 3,5-bis(trifluoromethyl) bromobenzene,
and 4-fluorobromo-benzene proceeded smoothly to give
the corresponding products in moderate yields despite
the fact that the reactions with bromobenzene, p-bromo-
acetophenone, or p-bromoanisole did not occur (Table 2,
Entries 17 and 18). However, no arylation product was
isolated when 1-benzyl-4-phenyl-1,2,3-triazole reacted
with aryl chlorides under the present reaction condi-
tions.
L (10 mmol%)
Pd(OAc)2 (5 mmol%)
N
N
N
+
C6H5I
base, solvent
100 oC, 12 h
1a
2a
Ph
N
N
N
Ph
C6H5
3a
Entry Ligand Base
Solvent
Yieldb/%
1
—
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
K3PO4
NaOAc
Cs2CO3
LiOH
DMF
0
Table 2 Palladium-catalyzed direct arylations of 1,4-disub-
stituted-1,2,3-triazoles with aryl halidesa
2
L1
L2
L3
L4
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
DMF
92
3
DMF
80
R1
(10 mmol%)
L1
R1
4
DMF
82
N
N
Pd(OAc)2 (5 mmol%)
N
N
N
N
5
DMF
90
+
ArX
K2CO3, DMF
100 oC, 12 h
86c
84d
60
2
6
DMF
R2
R2
Ar
1
7
DMF
3
Entry R1
R2
ArX
Product Yieldb/%
8
DMF
9
DMF
63
1
2
3
4
5
6
7
8
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5I
3a
3b
3c
3d
3e
3f
92
86
90
91
68
67
70
81
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
DMF
56
4-MeC6H4I
3-MeC6H4I
2-MeC6H4I
4-ClC6H4I
4-FC6H4I
2-FC6H4I
DMF
15
DMF
10
t-BuOLi
t-BuONa
t-BuOK
Et3N
DMF
12
DMF
0
DMF
Trace
17
3g
3a
DMF
C6H5I(OAc)2
4-MeC6H4I-
(OAc)2
DBU
DMF
Trace
85e
26
9
Bn
C6H5
3b
83
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMF
DMSO
DMA
NMP
10 Bn
11 Bn
12 Bn
4-MeC6H4 C6H5I
4-ClC6H4 C6H5I
3h
3i
83
81
80
78
80
75
70
38
63
n-C4H9
C6H5
C6H5I
C6H5I
C6H5I
C6H5I
3j
CH3CN
C6H5CH3
CH2ClCH2Cl
70
13 n-C6H13
14 n-C8H17
15 n-C16H33
3k
3l
50
C6H5
Trace
C6H5
3m
3n
a Reaction conditions: 1a (1.0 mmol), 2a (2.0 mmol), Pd(OAc)2
16 4-MeC6H4CH2 C6H5
C6H5I
(5.0 mmol%), ligand (10.0 mmol%), base (3.0 mmol), solvent
(2.0 mL), 100 ℃, 12 h, under air. Isolated yields. At 120 ℃;
d At 80 ℃. e K2CO3 (2.0 mmol).
3,5-(CF3)2-
C6H3Br
17 Bn
18 Bn
C6H5
C6H5
3o
63
b
c
4-FC6H4Br
3p
65
a Reaction conditions: 1,4-disubstituted-1,2,3-triazole (1.0 mmol),
aryl halide (2.0 mmol), Pd(OAc)2 (0.05 mmol), L1 (0.10 mmol),
K2CO3 (3.0 mmol), DMF (2.0 mL), 100 ℃, 12 h, under air.
b Isolated yields.
either electron-donating group or electron-withdrawing
group underwent smoothly to direct arylation and good
yields of the desired products were obtained (Table 2,
Entries 10 and 11). On the other hand, the reaction of
1-benzyl-4-(n-butyl)-1,2,3-triazole with iodobenzene
also generated the corresponding product in 80% yield
(Table 2, Entry 12). It was also demonstrated that a va-
riety of 1-alkyl-4-phenyl-1,2,3-triazoles, when alkyl was
n-hexyl, n-octyl, or n-cetyl group, were shown to un-
dergo phenylation at C-5 position in 1,2,3-triazoles
Conclusions
In summary, it has been shown that a variety of un-
symmetrical fully substituted 1,2,3-triazoles could be
easily synthesized via a direct Pd-NHC system cata-
lyzed arylation of 1,4-disubstituted 1,2,3-triazoles,
Chin. J. Chem. 2012, 30, 979—984
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He et al.
FULL PAPER
which are readily accessible via “click” chemistry. It is
important to note that C—H bond functionalizations of
1,2,3-triazoles with aryl iodides and bromides can be
conveniently achieved through our catalytic system at
significantly milder reaction temperatures of 100 ℃ in
the presence of air. This methodology provides an effi-
cient, environmentally friendly, and operationally sim-
ple process for the C—H bond functionalization of
1,4-disubstituted 1,2,3-triazoles under mild reaction
conditions, comparable with the previously reported
ones.[10-15]
(3c)[14] 1H NMR (CDCl3, 400 MHz) δ: 2.29 (s, 3H),
5.38 (s, 2H), 6.87—6.90 (m, 1H), 6.94—6.95 (m, 1H),
7.01—7.04 (m, 2H), 7.21—7.32 (m, 8H), 7.55—7.58
(m, 2H); 13C NMR (CDCl3, 100 MHz) δ: 18.99, 52.14,
125.60, 126.44, 127.27, 127.57, 127.98 128.14, 128.45,
128.47, 130.04, 130.23, 130.65, 131.06, 132.74, 134.64,
138.35, 144.35.
1-Benzyl-4-phenyl-5-(2-tolyl)-1H-1,2,3-triazole
(3d)[14] 1H NMR (CDCl3, 400 MHz) δ: 1.60 (s, 3H),
5.23—5.37 (m, 2H), 6.92—6.95 (m, 2H), 7.07—7.09
(m, 1H), 7.15—7.30 (m, 8H), 7.38—7.42 (m, 1H),
7.52—7.55 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ:
18.99, 52.14, 125.60, 126.44, 127.27, 127.57, 127.98,
128.14, 128.45, 128.47, 130.04, 130.23, 130.65, 131.06,
132.74, 134.64, 138.35, 144.35.
Experimental
General remarks
All 1H NMR and 13C NMR spectra were recorded on
a Bruker-DMX-400 MHz FT-NMR spectroscopy.
Chemical shifts were given as δ value with reference to
tetramethylsilane (TMS) as internal standard. High
resolution mass spectroscopy data of the product were
collected on a Waters Micro-mass GCT instrument.
Products were purified by flash column chromatography
on 230—400 mesh silica gel, SiO2.
1-Benzyl-4-phenyl-5-(4-chlorophenyl)-1H-1,2,3-
triazole (3e)[14] 1H NMR (CDCl3, 400 MHz) δ: 5.40 (s,
2H), 7.00—7.07 (m, 4H), 7.23—7.29 (m, 6H),
7.36—7.40 (m, 2H), 7.50—7.54 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 52.12, 126.29, 126.71, 127.33,
127.86, 128.24, 128.49, 128.76, 129.48, 130.58, 131.41,
132.63, 135.16, 135.95, 144.79.
1-Benzyl-4-phenyl-5-(4-fluorophenyl)-1H-1,2,3-
triazole (3f)[14] 1H NMR (CDCl3, 400 MHz) δ: 5.40 (s,
2H), 7.00—7.03 (m, 2H), 7.09—7.12 (m, 4H),
7.25—7.28 (m, 6H), 7.51—7.54 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 52.13, 116.45 (d, J＝21.04 Hz),
123.74 (d, J＝3.2 Hz), 126.64, 127.46, 127.88, 128.27,
128.54, 128.73, 130.77, 132.01 (d, J＝8.20 Hz), 132.80,
135.23, 144.83, 163.34 (d, J＝250.0 Hz).
The chemicals were purchased from commercial
suppliers (Aldrich, USA and Shanghai Chemical Com-
pany, China) and used without purification prior to use.
Representative procedure for Pd-NHC system cata-
lyzed direct arylations of 1,4-disubstituted
1,2,3-triazoles: the preparation of triazole 3a (Table
2, Entry 1)
1-Benzyl-4-phenyl-5-(2-fluorophenyl)-1H-1,2,3-
triazole (3g) 1H NMR (CDCl3, 400 MHz) δ: 5.41 (s,
2H), 6.94—7.02 (m, 3H), 7.11—7.27 (m, 8H),
7.43—7.49 (m, 1H), 7.54—7.56 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 52.51 (d, J＝1.20 Hz), 115.72 (d,
J＝15.2 Hz), 116.31 (d, J＝21.2 Hz), 124.77 (d, J＝3.2
Hz), 126.39, 127.51, 127.76, 127.84, 128.10, 128.43,
128.53, 130.59, 132.03 (d, J＝2.0 Hz), 132.13 (d, J＝
8.2 Hz), 134.63, 145.66, 159.94 (d, J＝250.0 Hz).
HRMS (ESI) ([M]＋) calcd for C21H16FN3 329.1328,
found 329.1327.
1-Benzyl-4-(4-tolyl)-5-phenyl-1H-1,2,3-triazole
(3h)[12] 1H NMR (CDCl3, 400 MHz) δ: 2.28 (s, 3H),
5.39 (s, 2H), 6.99—7.08 (m, 4H), 7.11—7.15 (m, 2H),
7.21—7.27 (m, 3H), 7.39—7.47 (m, 5H); 13C NMR
(CDCl3, 100 MHz) δ: 21.13, 51.98, 126.61, 127.45,
127.99, 128.05, 128.62, 129.06, 129.08, 129.53, 130.10,
133.51, 135.40, 137.42, 144.60.
1-Benzyl-4-(4-chlorophenyl)-5-phenyl-1H-1,2,3-
triazole (3i)[21] 1H NMR (CDCl3, 400 MHz) δ: 5.39 (s,
2H), 6.99—7.03 (m, 2H), 7.10—7.14 (m, 2H),
7.19—7.26 (m, 5H), 7.39—7.50 (m, 5H); 13C NMR
(CDCl3, 100 MHz) δ: 52.02, 127.48, 127.50, 127.90,
128.18, 128.63, 128.68, 129.25, 129.39, 129.84, 129.96,
133.53, 133.98, 135.15, 143.50.
1-Benzyl-4-(n-butyl)-5-phenyl-1H-1,2,3-triazole
(3j) 1H NMR (CDCl3, 400 MHz) δ: 0.84 (t, J＝8.0 Hz,
3H), 1.25—1.33 (m, 2H), 1.56—1.68 (m, 2H), 2.62 (t,
A suspension of palladium acetate (11.2 mg, 0.05
mmol), 1a (240 mg, 1.0 mmol), 2a (408 mg, 2.0 mmol),
K2CO3 (412 mg, 3.0 mmol) and L1 (36 mg, 0.1 mmol)
in DMF (2.0 mL) was stirred under air for 12 h at 100
℃. The reaction mixture was diluted with ethyl acetate
(10 mL), washed with water (20 mL) and brine (10 mL),
dried over Mg2SO4 and concentrated in vacuum. The
remaining residue was purified by column chromatog-
raphy on silica gel (hexane∶EtOAc, 10∶1) to afford
72 mg of 3a as pure compound (yield 92%). Then 3a
was fully characterized by 1H NMR and 13C NMR spec-
troscopy.
1-Benzyl-4,5-diphenyl-1H-1,2,3-triazole
(3a)[7]
1H NMR (CDCl3, 400 MHz) δ: 5.40 (s, 2H), 7.00—7.03
(m, 2H), 7.12—7.14 (m, 2H), 7.21—7.27 (m, 6H),
7.36—7.48 (m, 3H), 7.53—7.56 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 51.99, 126.65, 127.43, 127.65,
127.73, 128.08, 128.38, 128.63, 129.11, 129.63, 130.03,
130.78, 133.84, 135.26, 144.42.
1-Benzyl-4-phenyl-5-(4-tolyl)-1H-1,2,3-triazole
(3b)[12] 1H NMR (CDCl3, 400 MHz) δ: 2.41 (s, 3H),
5.38 (s, 2H), 7.02—7.07 (m, 4H), 7.20—7.27 (m, 8H),
7.56—7.57 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ:
21.38, 51.83, 124.69, 126.65, 127.44, 127.56, 128.04,
128.35, 128.63, 129.84, 129.90, 131.04, 133.97, 135.50,
139.71, 144.37.
1-Benzyl-4-phenyl-5-(3-tolyl)-1H-1,2,3-triazole
982
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 979—984

Pd-NHC-Catalyzed Direct Arylation of 1,4-Disubstituted 1,2,3-Triazoles with Aryl Halides
J＝8.0 Hz, 2H), 5.40 (s, 2H), 6.96—7.04 (m, 2H),
7.09—7.14 (m, 2H), 7.20—7.24 (m, 3H), 7.37—7.46
(m, 3H); 13C NMR (CDCl3, 100 MHz) δ: 13.65, 22.24,
24.67, 31.62, 51.82, 127.23, 127.51, 127.87, 128.53,
128.72, 129.10, 129.59, 134.26, 135.58, 145.94. HRMS
(ESI) ([M] ＋ ) calcd for C19H21N3 291.1735, found
291.1737.
hui Province’s Higher Education (No. KJ2009B212Z).
References
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Weinheim, Germany, 2009; (b) Handbook of C—H Transformations,
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1-n-Hexyl-4,5-diphenyl-1H-1,2,3-triazole (3k)
1H NMR (CDCl3, 400 MHz) δ: 0.78—0.82 (t, J＝7.2
Hz, 3H), 1.17—1.26 (m, 6H), 1.73—1.82 (m, 2H),
4.17—4.20 (t, J＝7.2 Hz, 2H), 7.22—7.28 (m, 3H),
7.30—7.34 (m, 2H), 7.50—7.55 (m, 5H); 13C NMR
(CDCl3, 100 MHz) δ: 13.85, 22.29, 26.02, 29.97, 30.97,
48.29, 126.75, 127.62, 128.06, 129.40, 129.32, 129.65,
129.92, 130.82, 133.70, 144.10. HRMS (ESI) ([M]＋)
calcd for C20H23N3 305.1892, found 305.1895.
1-n-Octyl-4,5-diphenyl-1H-1,2,3-triazole
(3l)[22]
1H NMR (CDCl3, 400 MHz) δ: 0.85 (t, J＝7.2 Hz, 3H),
1.17—1.26 (m, 10H), 1.73—1.80 (m, 2H) 4.19 (t, J＝
7.6 Hz, 2H), 7.21—7.28 (m, 3H), 7.30—7.35 (m, 2H),
7.49—7.56 (m, 5H); 13C NMR (CDCl3, 100 MHz) δ:
14.01, 22.53, 26.35, 28.79, 28.91, 30.03, 31.63, 48.23,
126.73, 127.53, 128.23, 128.36, 129.30, 129.58, 129.94,
131.03, 133.59, 144.12.
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1,2,3-triazoles, inhibitors of tumor necrosis factor-α (TNT-α) and
antagonists for GABA receptors have been reported. (a) Tullis, J. S.;
VanRens, J. C.; Natchus, M. G.; Clark, M. P.; De, B.; Hsieh, L. C.;
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8680 and references cited therein.
1-n-Cetyl-4,5-diphenyl-1H-1,2,3-triazole (3m) 1H
NMR (CDCl3, 400 MHz) δ: 0.87 (t, J＝6.8 Hz, 3H),
1.15—1.26 (m, 26H), 1.73—1.82 (m, 2H), 4.19 (t, J＝
7.2 Hz, 2H), 7.22—7.28 (m, 3H), 7.30—7.35 (m, 2H),
7.49—7.55 (m, 5H); 13C NMR (CDCl3, 100 MHz) δ:
14.08, 22.64, 26.35, 28.83, 29.26, 29.31, 29.44, 29.54,
29.59, 29.60, 29.62, 29.64, 29.65, 30.03, 31.88, 48.23,
126.73, 127.53, 128.22, 128.36, 129.29, 129.58, 129.93,
131.01, 133.59, 144.11. HRMS (ESI) ([M]＋) calcd for
C30H43N3: 445.3457, found 445.3459.
1-(4-Methylbenzyl)-4,5-diphenyl-1H-1,2,3-triazole
(3n) 1H NMR (CDCl3, 400 MHz) δ: 2.29 (s, 3H), 5.35
(s, 2H), 6.91 (d, J＝8.2 Hz, 2H), 7.04 (d, J＝7.8 Hz,
2H), 7.13—7.17 (m, 2H), 7.21—7.26 (m, 3H),
7.39—7.48 (m, 3H), 7.52—7.56 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 21.04, 51.75, 126.66, 127.43,
127.60, 127.81, 128.35, 129.08, 129.27, 129.60, 130.07,
130.85, 132.26, 133.77, 137.86, 144.40. HRMS (ESI)
([M]＋) calcd for C22H19N3 325.1579, found 325.1583.
1-Benzyl-4-phenyl-5-(3,5-bis(trifluoromethyl))-
phenyl-1H-1,2,3-triazole (3o) 1H NMR (CDCl3, 400
MHz) δ: 5.40 (s, 2H), 7.01—7.08 (m, 2H), 7.22—7.29
(m, 6H), 7.36—7.40 (m, 2H), 7.50—7.54 (m, 2H), 7.95
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ: 52.87, 118.51,
121.22, 123.94, 126.70, 127.23, 128.47 (d, J＝24.0 Hz),
128.81 (d, J＝26.8 Hz), 129.75, 130.57, 131.01 (d, J＝
102.0 Hz), 132.52 (d, J＝33.8 Hz), 134.49, 145.57.
HRMS (ESI) ([M]＋) calcd for C23H15F6N3 447.1170,
found 447.1168.
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This work was supported by the National Natural
Science Foundation of China (No. 20972057) and An-
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984
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 979—984