2-Phenyl-2-(4-phenyl-1 H-1,2,3-triazol-1-yl)ethanol as an efficient and versatile auxiliary ligand in copper(II)-catalyzed Buchwald-Hartwig and Sharpless-Meldal C-N bond-forming reactions

Article abstract of DOI:10.1055/s-0034-1379951

A highly active, air-stable, and versatile procedure for Buchwald-Hartwig and Sharpless-Meldal C-N bond formation is reported. Under nearly solvent-free conditions using copper(II) acetate and 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol, a variety of N-heterocycles and various cyclic and noncyclic secondary amines were arylated to form N-aryl compounds in moderate to excellent yields. This methodology also provides rapid access to diverse 1,4-disubstituted 1,2,3-triazoles in good to excellent yields. All reactions are performed in short times under air.

Full text of DOI:10.1055/s-0034-1379951

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2015, 47, 1131–1146
paper
1131
H. Sharghi, P. Shiri
Paper
Synthesis
2-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol as an Efficient
and Versatile Auxiliary Ligand in Copper(II)-Catalyzed Buchwald–
Hartwig and Sharpless–Meldal C–N Bond-Forming Reactions
t-BuONa
Hashem Sharghi*
R1
HO
Cu(OAc)2/ligand
Y
Pezhman Shiri*
R3
R4
NH
or
R2
N
Z
N
X
Ph
Department of Chemistry, Shiraz University, Shiraz, 71454, Iran
shashem@chem.susc.ac.ir
ligand =
N
Het-NH
DMF
H2O
NaN3
pezhmanshiri@yahoo.com
Ph
X = C, N
Y = I, Br
R1
R2
R1, R2 = alkyl
N
N
N
3 = aryl, alkyl
4 = benzyl, allyl
R4
X
R
R
N
or
R3
Z = Br, Cl, oxiranyl
Het-N
X
Received: 02.09.2014
Accepted after revision: 02.12.2014
Published online: 17.02.2015
methylethylenediamine),3e ethyl 2-oxocyclohexanecarbox-
ylate,3f and metformin3g have been investigated in copper-
catalyzed C–N bond-forming reactions.
DOI: 10.1055/s-0034-1379951; Art ID: ss-2014-z0542-op
1,2,3-Triazoles are aromatic heterocyclic compounds
with a five-membered ring containing two carbon atoms
and three nitrogen atoms; they show biological activity, in-
cluding use as pharmaceuticals, anti-HIV, anticancer, anti-
allergic, antifungal, antibacterial, and antituberculosis
agents. The previously discovered copper(I)-catalyzed
azide-alkyne [3 + 2] Huisgen cycloaddition (CuAACs) reac-
tion is the best ‘click’ reaction to date, due to its wide range
of applications in chemistry, biochemistry, polymer chem-
istry, materials science, and fluorescent imaging.4 Recently,
1,2,3-triazoles have been successfully employed as a linker
for the attachment of metal complexes to diverse materials
and then used as heterogeneous catalysts.5 There are also
many reports of functionalized 1,2,3-triazole–metal com-
plexes due to their potential to act as nitrogen donors.6 Al-
though triazole-based ligands have already been synthe-
sized, the reported synthetic procedures for these com-
pounds involve tedious, expensive, and challenging
reaction routes.
With these considerations in mind, based on our previ-
ous studies, which focus on copper-catalyzed organic reac-
tions under ‘green’ conditions,3b,7 herein, we report our at-
tempts to increase the reaction rate of copper(II)-catalyzed
C–N bond-forming reactions using 2-phenyl-2-(4-phenyl-
1H-1,2,3-triazol-1-yl)ethanol as an inexpensive, efficient,
and versatile ligand.
At the onset of our research, we decided to carry out the
arylation of N-heterocycles and secondary amines as the
key chemical transformation because of its paramount im-
portance in the synthesis of auxiliary ligands, N-heterocy-
clic carbenes, and medicinal structures.8 For our initial
screening experiments, the cross-coupling reaction be-
tween 1H-indole (2a) and iodobenzene (1a) in a 1:1.2 mo-
Abstract A highly active, air-stable, and versatile procedure for
Buchwald–Hartwig and Sharpless–Meldal C–N bond formation is re-
ported. Under nearly solvent-free conditions using copper(II) acetate
and 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol, a variety of N-
heterocycles and various cyclic and noncyclic secondary amines were
arylated to form N-aryl compounds in moderate to excellent yields. This
methodology also provides rapid access to diverse 1,4-disubstituted
1,2,3-triazoles in good to excellent yields. All reactions are performed in
short times under air.
Key words 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol,
Buchwald–Hartwig reaction, Sharpless–Meldal reaction, copper cataly-
sis, N-arylation
One possible choice to accelerate metal-catalyzed or-
ganic reactions, especially copper- and palladium-catalyzed
reactions is to use auxiliary ligands.1 Over the past few de-
cades, the formation of the C–N bond has been of great stra-
tegic importance because of their interesting and abun-
dance in various natural compounds as well as in synthetic
organic products that exhibit diverse biological properties.2
The Buchwald–Hartwig and Sharpless–Meldal C–N bond-
forming reactions are catalyzed by different copper and
palladium sources and a variety of ligands. The prominence
in accelerating ligands in these reactions has promoted ex-
tensive experimental studies toward their synthesis and
functionalization. In this respect, the acceleratory effect of
some ligands such as phosphoramidites,3a hybrid tris(het-
erocycle-methyl)amines (mixing 1,2,3-triazolyl, benzimid-
azol-2-yl, and 2-pyridyl donors on the ligand arms),1a 7,8-
dihydroxy-4-methylcoumarin,3b homogeneous dinuclear
copper catalysts,3c tris(triazolyl)methane ligands,3d simple
diamine ligands (such as trans-cyclohexane-1,2-diamine,
trans-N,N′-dimethylcyclohexane-1,2-diamine, and N,N′-di-
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H. Sharghi, P. Shiri
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Synthesis
lar ratio was studied (Scheme 1) considering various pa-
rameters such as different copper sources, solvents, and
bases in the presence of 2-phenyl-2-(4-phenyl-1H-1,2,3-
triazol-1-yl)ethanol.
(Table 1). Copper(II) acetate was the most effective copper
source in terms of reaction rate and isolated yield of the
product 3aa. The optimized loading level of this catalytic
system is at a concentration of 1 mol% of 2-phenyl-2-(4-
phenyl-1H-1,2,3-triazol-1-yl)ethanol (L) and 1 mol% of cop-
per(II) acetate (entries 6 and 15). During the optimization
studies, the effect of various solvents was examined and di-
methyl sulfoxide and N,N-dimethylformamide were the
most suitable (entries 6, 9, and 15); lower yields were ob-
served for 3aa when using other solvents, such as acetoni-
trile, ethanol, and toluene (entries 12–14) and no 3aa was
detected when the reaction was performed in water–ace-
tone or water (entries 10 and 11). In order to reduce level of
toxic chemicals and environmental pollution, all reactions
were performed in 0.3 mL of solvent (entry 15).
I
copper source
ligand, base
N
+
N
H
2a
OH
N
1a
3aa
N
Ph
N
Ph
ligand (L)
Having optimized the solvent, the effect of various inor-
ganic and organic bases was screened and the results
showed that sodium tert-butoxide was the best base (en-
tries 15–20). To highlight the auxiliary effect of 2-phenyl-2-
(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol (L), the reaction
was performed in the absence of the ligand and the yield of
Scheme 1 The reaction between 1a and 2a as a model reaction
In the first step, a series of copper sources, including
copper(II) acetate, copper(II) nitrate, copper(II) chloride,
and copper sulfate were tested in this N-arylation reaction
Table 1 Optimization of the Reaction Conditions (Scheme 1)a
Entry
Copper (mol%)
Lb (mol%)
Base
t-BuONa
Solvent (mL)
Temp (°C)
Time (h)
Yieldc (%)
1
2
Cu(OAc)2 (10)
Cu(NO3)2 (10)
CuCl2 (10)
10
10
10
10
5
DMF (3)
120
0.5
3.0
3.0
3.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
3.0
3.0
3.0
0.5
4.0
4.0
4.0
0.5
4.0
5.0
98
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
CsCO3
DMF (3)
120
78
3
DMF (3)
120
81
4
CuSO4 (10)
DMF (3)
120
61
5
Cu(OAc)2 (5)
Cu(OAc)2 (1)
Cu(OAc)2 (0.5)
Cu(OAc)2 (0.05)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (5)
DMF (3)
120
98
6
1
DMF (3)
120
120
120
98 (83d)
90
7
0.5
0.05
1
DMF (3)
8
DMF (3)
69
9
DMSO (3)
H2O–acetone (3)
H2O (3)
120
97
10
11
12
13
14
15
16
17
18
19
20
21
1
reflux
reflux
reflux
reflux
reflux
120
120
0
1
CsCO3
0
1
t-BuONa
t-BuONa
t-BuONa
t-BuONa
K2CO3
MeCN (3)
EtOH (3)
toluene (3)
DMF (0.3)
DMF (0.3)
DMF (0.3)
DMF (0.3)
DMF (0.3)
DMF (0.3)
DMF (0.3)
16
1
12
1
7
1
98 (81d)
33
1
1
Et3N
120
40
1
NaOAc
120
70
1
CsCO3
120
97
1
NaOH
120
70
–
t-BuONa
120
34
a Reaction conditions: 1a (1.0 mmol), 2a (1.2 mmol), base (1.2 mmol).
b L = 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol.
c Molar yield calculated by 1H NMR.
d Isolated yield.
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H. Sharghi, P. Shiri
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Synthesis
3aa was considerably lower; this indicates that the ligand
plays an important role in accelerating the rate of this reac-
tion (entry 21).
These results prompted us to investigate the generality
and versatility of this procedure. The reaction was extended
to various N-heterocyclic compounds 2a–g and secondary
amines 2h–m and different organic halides 1a–d. In all
cases, C–N cross-coupling reactions were completed in a
reasonable time and N-substituted products 3 were isolated
in moderate to excellent yields (Table 2).
Table 2 Buchwald–Hartwig Reaction of Various Structurally Diverse N-Unsubstituted Compoundsa
Entry
1
Aryl halide
N-Unsubstituted compound
Product
Time (min) Yieldb (%)
N
Ph
1a
1a
PhI
2a
3aa
30
45
98
97
N
H
N
N
N
2
2b
3ab
N
H
Ph
3
4
1a
1a
2c
3ac
3ad
45
30
96
99
NH
N
Ph
N
N
N
Ph
2d
2e
NH
N
N
N
NH
5
6
1a
1a
3ae
3af
45
98
67
Ph
NH
S
N
Ph
2f
120
S
7
8
1a
1b
1c
1c
2g
2a
2e
2b
3ag
3ba
3ce
3cb
60
30
30
30
49
98
97
97
N
N
H
Ph
N
4-MeC6H4I
9
N
N
N
N
N
Br
N
N
10
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Table 2 (continued)
Entry
Aryl halide
N-Unsubstituted compound
Product
Time (min) Yieldb (%)
11
1c
2d
2a
3cd
30
30
98
97
N
N
N
N
12
13
14
1c
3ca
3dd
3ah
OMe
1d
1a
4-MeOC6H4Br
2d
2h
180
60
70
63
N
O
N
O
N
H
Ph
15
16
1a
1a
2i
2j
Et2NH
3ai
3aj
Et2NPh
Bu2NPh
60
60
33
62
Bu2NH
Ph
N
Ph
N
17
1a
2k
3ak
60
75
N
N
H
Ph
18
19
1a
1a
2l
[Ph(CH2)2]BnNH
3al
[Ph(CH2)2]BnNPh
60
60
67
51
H
N
2m
3ak
N
H
N
N
20
21
1c
1a
2k
2a
3ck
3aa
45
60
87
N
Ph
91c
a Reaction conditions: N-unsubstituted compounds 2 (1.0 mmol), aryl halides 1 (1.2 mmol), t-BuONa (1.2 mmol), Cu(OAc)2 (1 mol%), 2-phenyl-2-(4-phenyl-1H-
1,2,3-triazol-1-yl)ethanol (1 mol%), DMF (0.3 mL).
b Molar yield calculated by 1H NMR.
c The reaction was performed on a 10-mmol scale.
We were pleased to find that a wide range of N-hetero-
cyclic compounds [such as 1H-benzimidazole (2e), 1H-im-
idazole (2b), 3,5-dimethyl-1H-pyrazole (2c), 1H-pyrrole
(2d), 1H-indole (2a), 2-methyl-1H-indole (2f), and 10H-
phenothiazine (2g)] can efficiently produce the corre-
sponding products 3 (entries 1–13). Various cyclic and non-
cyclic secondary amines including morpholine (2h), di-
ethylamine (2i), dibutylamine (2j), 1-phenylpiperazine
(2k), N-benzyl-2-phenylethanamine (2l), and piperazine
(2m) also reacted with aryl halides to afford the desired
products in moderate yields (entries 14–20).
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Owing to the wide range of properties of morpholine9
and pyridine8k,10 derivatives, these compounds have be-
come ideal targets in laboratory and industrial syntheses.
Also, pyridine derivatives are attractive due to their appli-
cations as sensors,10a their importance in the synthesis of
pyridine-based multi-dentate ligands, their use as a unique
class of ligands for copper- and palladium-catalyzed organ-
ic reactions,8k–m and their use as sensitizers in dye-sensi-
tized solar cells.10b Working on the envisaged strategy, we
successfully accomplished the synthesis of N-substituted
compounds bearing pyridine and morpholine using cop-
per(II)-catalyzed C–N bond-forming reactions (entries 9–
12, 14, and 20).
This methodology was then extended to the click syn-
thesis of diverse 1,4-disubstituted 1,2,3-triazoles and β-hy-
droxy 1,4-disubstituted 1,2,3-triazoles using various struc-
turally diverse organic halides or organic epoxides, differ-
ent nonactivated terminal alkynes, and sodium azide.
In order to establish the optimum reaction conditions,
the three component and 1,3-dipolar cycloaddition reac-
tion between benzyl bromide (4a), phenylacetylene (5a),
and sodium azide in a 1:1:1.1 molar ratio was studied un-
der various conditions (temperature, solvent, and amount
of catalyst) (Scheme 3).
N
N
N
Considering the literature focusing on the catalytic ac-
tivity of copper sources and a variety of ligands, as well as
metal complexes of triazole-based ligands,8 we proposed a
mechanism for this C–N bond-forming reaction (Scheme 2),
in this the 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)eth-
anol ligand is coordinated to copper(II). Subsequently, oxi-
dative addition and subsequent complexation with aryl ha-
lide results in the formation of a further intermediate B. At
this stage, the intermediate B may react with the NH com-
pound in the presence of a base, leading to the formation of
the N-substituted compounds and the intermediate A again
completing the catalytic cycle.
Br
+
+ NaN3
4a
5a
6aa
Scheme 3 The reaction between 4a, 5a and sodium azide as a model
reaction
We studied the efficiency of this catalytic system for the
Sharpless–Meldal C–N bond-forming reaction at various
temperatures in water (Table 3). The reaction can be carried
out at room temperature (entry 1), but to accelerate the
‘click’ reaction it was carried out at 40 °C (entry 2). A com-
parison of the efficiency of organic solvents versus water in
this reaction showed that water was the best choice (en-
tries 1 and 2 vs 5–11).
In the next step, the metal-to-ligand ratio was opti-
mized and the results showed that the optimum was 3
mol% copper(II) acetate and 6 mol% 2-phenyl-2-(4-phenyl-
1H-1,2,3-triazol-1-yl)ethanol (L) (entries 1, 2 vs 12–15).
The scope and generality of this one pot and click reac-
tion catalyzed by copper(II) acetate and 2-phenyl-2-(4-phe-
nyl-1H-1,2,3-triazol-1-yl)ethanol was explored using a
broad range of structurally diverse organic halides 4a–f or
organic epoxides 4g–i, nonactivated terminal alkynes 5a–m,
and sodium azide to afford the desired triazoles 6, as ex-
pected, as only one of the possible regioisomers (Table 4).
Benzyl halides with electron-donating groups reacted at a
faster rate than benzyl halides substituted with electron-
withdrawing groups (entry 4 vs 5). The reaction of 2-hy-
Cu
O
N
N
oxidative addition
N
Ph
Ph
A
Ar-N-compound
reductive elimination
X
Ar
Cu
O
N
N
N
Ph
Ph
B
N-compound
Cu
Ar
droxybenzaldehyde derivative 4e containing
a single
base
chloromethyl group with sodium azide led to the formation
of the corresponding 1,2,3-triazole derivative 6ea in good
yield (entry 6). The use of this method in the reaction of dif-
ferent terminal alkynes, sodium azide, and allyl halides in-
stead of benzyl halides also produced the desired products
in satisfactory yields (entries 7–9, 15, and 21). Various ali-
phatic terminal alkynes, such as hex-1-yne (5c), prop-2-
ynol (5d), 2-methylbut-3-yn-2-ol (5b), prop-2-ynyl benzo-
ates 5g–l, and (prop-2-ynyloxy)benzene 5e,11 were carried
out with different organic halides to afford the desired tri-
azoles under the same reaction conditions (entries 9–21).
O
N
N
N
Ph
Ph
C
Scheme 2 Proposed mechanism for the synthesis of N-substituted
compounds
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H. Sharghi, P. Shiri
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Table 3 Optimization of the Reaction of Benzyl Bromide (4a), Phenylacetylene (5a), and Sodium Azide (Scheme 3)a
Entry
Conditionsb
Solvent
Temp (°C)
Time (min)
Yieldc (%)
H2O
81 (71d)
1
2
L (6 mol%), Cu(OAc)2·H2O (3 mol%)
L (6 mol%), Cu(OAc)2·H2O (3 mol%)
L (6 mol%), Cu(OAc)2·H2O (3 mol%)
L (6 mol%), Cu(OAc)2·H2O (3 mol%)
L (6 mol%), Cu(OAc)2·H2O (3 mol%)
L (6 mol%), Cu(OAc)2·H2O (3 mol%)
L (6 mol%), Cu(OAc)2·H2O (3 mol%)
L (6 mol%), Cu(OAc)2·H2O (3 mol%)
L (10 mol%), Cu(OAc)2·H2O (5 mol%)
L (10 mol%), Cu(OAc)2·H2O (5 mol%)
L (10 mol%), Cu(OAc)2·H2O (5 mol%)
L (12 mol%), Cu(OAc)2·H2O (6 mol%)
L (18 mol%), Cu(OAc)2·H2O (8 mol%)
L (3 mol%), Cu(OAc)2·H2O (1 mol%)
L (1 mol%), Cu(OAc)2·H2O (1 mol%)
25
40
70
100
40
40
40
40
40
25
25
40
40
40
40
90
30
H2O
85 (73d)
85
3
H2O
15
4
H2O
7
85
5
neat
180
180
180
180
180
180
180
30
15
6
toluene
DMF
5
7
32
8
DMSO
EtOH
DMSO–H2O
BuOH–H2O
H2O
37
9
43
10
11
12
13
14
15
45
49
82
H2O
30
82
H2O
30
75
H2O
30
47
a Reaction conditions: 4a (1.0 mmol), 5a (1.0 mmol), NaN3 (1.1 mmol), solvent (1.0 mL).
b L = 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol.
c Molar yield calculated by 1H NMR.
d Isolated yield.
Because of their highly strained structure that is easy to
Herein, we proposed a mechanism for the triazole-
cleavage with nucleophiles, epoxide rings are used as im-
portant starting materials in synthetic organic chemistry
especially in the CuAAC click reaction. In this aspect, no
modifications to the above-optimized experimental proce-
dure were required to verify that organic epoxides 4g–i,
nonactivated terminal alkyne 5a, and sodium azide in a
1:1:1.1 molar ratio smoothly react to form β-hydroxy 1,2,3-
triazoles 6ga–ia in excellent yields. Using styrene oxide (4g)
as the epoxide gave primary alcohol 1,4-disubstituted
1,2,3-triazole derivatives 6ga by cleavage of styrene oxide
with sodium azide in a regioselective manner, with attack
at the more stable benzylic carbon (i.e. electronic factors
predominate over steric factors) (entry 22). The triazoles
from aliphatic epoxides such as cyclohexene oxide (4h) and
2-[(phenoxy)methyl]oxirane (4i) were also obtained from
the attack of azide at the less hindered carbon (entries 23
and 24).7b To assess the feasibility of applying these C–N
bond-forming reactions in a large-scale synthesis, we car-
ried out the reaction of benzyl bromide (4a), phenylacety-
lene (5a), and sodium azide, as well as the condensation of
1H-indole (2a) and iodobenzene (1a), on a 10-mmol scale
in the presence of this catalytic system. As expected, the re-
action gave similar yields to those obtained on a smaller
scale (Table 3, entry 21 and Table 4, entry 25), and the de-
sired 1,2,3-triazole 6aa and N-substituted compound 3aa
were obtained in good yields.
based ligand–copper(II) acetate catalyzed preparation of
triazoles (Scheme 4), which is in analogy to the established
mechanism reported in the literature.4 Firstly, the one-pot
multicomponent coupling/cycloaddition reaction involves
the formation of organic azide and Cu–acetylide D interme-
diates under heating and stirring conditions. Subsequently
the azide intermediate binds to the copper to form inter-
mediate E. Finally, the cyclization reaction of azide and
alkyne provides corresponding triazole as the desired prod-
uct.
An extremely efficient and inexpensive auxiliary ligand
was prepared via the click strategy in only aqueous phase at
room temperature. Diverse N-substituted compounds and
1,4-disubstituted 1,2,3-triazoles were synthesized using 2-
phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol as a ver-
satile auxiliary ligand in copper(II)-catalyzed Buchwald–
Hartwig and Sharpless–Meldal C–N bond-forming reac-
tions. This method not only offers substantial improve-
ments in the reaction yields and rates, but also avoids or re-
duces the use of toxic solvents and expensive catalysts in
terms of cost and for environmental reasons. This proce-
dure offers a diverse scope for drug discovery and material
chemistry.
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Table 4 The One-Pot Three-Component Synthesis of 1,4-Disubstituted 1,2,3-Triazoles in the Presence of the Catalytic System in Watera
Entry Halide
Alkyne
Product
Time (h) Yieldb (%)
N
N
Ph
1
2
4a
BnBr
BnCl
5a
5a
PhC≡CH
6aa
6aa
0.5
1.5
85
80
N
Ph
4a′
Br
3
4
5
4b
4c
4d
4-BrC6H4CH2Br
4-MeC6H4CH2Cl
5a
5a
5a
6ba
6ca
6da
1.5
1.3
83
82
79
N
N
N
N
N
Ph
Ph
N
N
NO2
4-O2NC6H4CH2Cl
10
N
N
Ph
Ph
N
N
Cl
N
6
4e
5a
6ea
0.5
83
HO
O
HO
O
H
H
N
N
Br
Cl
7
8
4f
5a
5a
6fa
6fa
0.5
93
90
N
Ph
4f′
0.75
N
N
OH
HO
9
4f
5b
6fb
N
1.0
83
N
N
N
Ph
10
11
4a
4a
5c
BuC≡CH
6ac
6ad
4.30
3.3
80
81
N
N
N
Ph
Ph
5d
HOCH2C≡CH
N
HO
HO
N
N
12
13
4a
4a
5b
5e
6ab
6ae
4.0
80
75
OH
O
OH
O
Ph
O
N
Ph
6.30
O
N
N
Ph
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1131–1146

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Synthesis
Table 4 (continued)
Entry Halide
Alkyne
Product
Time (h) Yieldb (%)
O
O
H
H
14
4a
5f
6af
4.0
80
O
O
N
N
O
N
O
Ph
O
O
N
15
16
4f
5g
6fg
5.0
5.0
80
79
N
N
Cl
Cl
O
O
4a
5h
6ah
O
O
N
Ph
N
N
Br
Br
O
Ph
N
O
N
O
N
17
4a
5i
6ai
5.0
77
O
Br
Br
N
N
Ph
O
O
N
O
O
Cl
Cl
18
4a
5j
6aj
6.30
79
NO2
NO2
O
O
N
O
O
N
19
20
4a
4a
5k
5l
6ak
6al
5.0
5.0
81
79
N
NO2
NO2
Ph
O
O
N
O
O
N
N
MeO
MeO
Ph
Ph
N
21
4f
5m
PhN(CH2C≡CH)2
6fm
10
69
N
N
N
N
N
N
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1131–1146

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H. Sharghi, P. Shiri
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Synthesis
Table 4 (continued)
Entry Halide
Alkyne
Product
Time (h) Yieldb (%)
HO
O
N
N
N
22
23
4g
4h
5a
6ga
0.5
1.3
96
95
N
Ph
Ph
Ph
HO
O
N
N
5a
6ha
N
Ph
Ph
N
N
PhO
O
24
25
4i
5a
6ia
2.30
0.75
94
HO
OPh
4a
5a
6aa
77c
a Reaction conditions: organic halide or organic epoxide 5 (1.0 mmol), alkyne 6 (1.0 mmol), NaN3 (1.2 mmol), Cu(OAc)2 (3 mol%), 2-phenyl-2-(4-phenyl-1H-1,2,3-
triazol-1-yl)ethanol (6 mol%), water (1.0 mL), 40 °C.
b Molar yield calculated by 1H NMR.
c The reaction was performed on a 10-mmol scale.
Further investigations on the application of this tri-
azole-based ligand as an auxiliary ligand for the accelera-
tion of other transition-metal-catalyzed reactions are in
progress.
1-Phenyl-1H-indole (3aa)2c
Dark brown oil; yield: 150 mg (81%).
IR (KBr): 694 (m), 748 (m), 1018 (w), 1027 (w), 1134 (w), 1227 (m),
1327 (m), 1458 (m), 1504 (m), 1596 (m), 2923 (w), 3055 cm–1 (w).
1H NMR (250 MHz, CDCl3): δ = 6.59–6.63 (m, 1 H), 7.06–7.17 (m, 2 H),
7.25–7.30 (m, 2 H), 7.39–7.47 (m, 4 H), 7.47–7.52 (m, 1 H), 7.59–7.64
(m, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 103.6, 110.5, 120.4, 121.1, 122.4,
124.4, 126.4, 128.0, 129.3, 129.4, 135.8, 139.8.
All chemicals and solvents were obtained from Fluka, Aldrich, and
Merck and used without further purification. The purity determina-
tion of the substrates and reaction monitoring were accomplished by
TLC on silica gel PolyGram SILG/UV 254 plates. Column chromatogra-
phy was carried out on short columns of silica gel 60 (70–230 mesh)
in glass columns. Mass spectra were determined on a Shimadzu
GCMS-QP 1000 EX instrument at 70 or 20 eV. IR spectra were ob-
tained using a Shimadzu FT-IR 8300 spectrophotometer. Melting
points were determined by Buchi Melting point B-545 electrical melt-
ing point apparatus.
MS: m/z (%) = 196 (M+ + 2, 94.8), 195 (M+ + 1, 28.7), 194 (M+, 35.1),
168 (89.1), 140 (24.1), 114 (22.4), 97 (32.2), 78 (100), 51 (68.4).
Anal. Calcd for C14H11N (193.248): C, 87.01; H, 5.75; N 7.25. Found: C,
87.5.9; H, 5.90; N, 7.40.
1-Phenyl-1H-imidazole (3ab)2b
Dark brown oil; yield: 110 mg (79%).
N-Substituted Compounds 3; General Procedure
1H NMR (250 MHz, CDCl3): δ = 7.14–7.45 (m, 7 H), 7.80 (s, 1 H).
A mixture of N-unsubstituted compound 2 (1.0 mmol), aryl halide 1
(1.2 mmol), and t-BuONa (1.2 mmol) was stirred in DMF (0.3 mL) in
the presence of Cu(OAc)2·H2O (1 mol%) and 2-phenyl-2-(4-phenyl-
1H-1,2,3-triazol-1-yl)ethanol (1 mol%) at 120 °C for the time given in
Table 2. The mixture was washed with EtOAc; after removal of the
solvent, the residue was purified by column chromatography (silica
gel, petroleum ether–EtOAc).
13C NMR (62.9 MHz, CDCl3): δ = 118.2, 121.5, 127.5, 129.9, 130.4,
135.5, 137.4.
MS: m/z (%) = 145 (M+ + 1, 9.3), 144 (M+, 28.0), 117 (45.0), 97 (33.3),
81 (82.7), 57 (100.0).
Anal. Calcd for C9H8N2 (144.176): C, 74.98; H, 5.59; N, 19.43. Found: C,
75.50; H, 5.40; N, 20.92.
3,5-Dimethyl-1-phenyl-1H-pyrazole (3ac)2g
Brown oil; yield: 140 mg (83%).
IR (KBr): 748 (m), 1226 (w), 1465 (m), 2923 (w), 3055 cm–1 (w).
1H NMR (250 MHz, CDCl3): δ = 2.22 (s, 6 H), 5.92 (s, 1 H), 7.18–7.40
(m, 5 H).
1,4-Disubstituted 1,2,3-Triazole Derivatives 6; General Procedure
To a solution of 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol
(6 mol%) and Cu(OAc)2·H2O (3 mol%) in water (1 mL), a mixture of or-
ganic halide 4 (1.0 mmol), terminal alkyne 5 (1.0 mmol), and NaN3
(1.2 mmol) was added. The mixture was heated for the time given in
Table 4. The mixture was washed with EtOAc; after removal of the
solvent, the residue was purified by column chromatography (silica
gel, petroleum ether–EtOAc).
13C NMR (62.9 MHz, CDCl3): δ = 12.4, 13.5, 106.9, 124.7, 127.2, 129.0,
139.3, 140.0, 149.0.
MS: m/z (%) = 171 (18.3), 149 (26.7), 105 (51.7), 69 (100.0).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1131–1146

1140
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Synthesis
N
R2
N
Cu
R
N
R1
O
N
N
H+
N
H+
Ph
Ph
N
R2
N
A
R
N
R1
Cu
Cu
O
O
N
N
N
N
N
O
N
Ph
Ph
Ph
Ph
D
G
N3
N
N
R1
N
Br
N
R1
N
N
R2
N
N
N
N
R1
•
N
R2
Cu
N
Cu
O
O
N
N
Ph
Ph
N
Ph
F
Ph
E
Scheme 4 Proposed mechanism for the synthesis of 1,4-disubstituted 1,2,3-triazoles
Anal. Calcd for C11H12N2 (172.229): C, 76.71; H, 7.02; N, 16.27. Found:
C, 76.77; H, 7.50; N, 16.01.
Anal. Calcd for C13H10N2 (194.235): C, 80.39; H, 5.19; N, 14.42. Found:
C, 80.10; H, 5.35; N, 14.99.
1-Phenyl-1H-pyrrole (3ad)2d
2-Methyl-1-phenyl-1H-indole (3af)2h
Dark brown oil; yield: 120 mg (85%).
Dark brown oil; yield: 100 mg (49%).
1H NMR (250 MHz, CDCl3): δ = 6.27 (t, J = 4.5 Hz, 2 H), 7.00 (t, J = 4.5
Hz, 2 H), 7.11–7.18 (m, 1 H), 7.28–7.36 (m, 4 H).
IR (KBr): 694 (m), 748 (m), 1226 (w), 1319 (w), 1380 (w), 1458 (m),
1496 (m), 1569 (m), 1712 cm–1 (w).
13C NMR (62.9 MHz, CDCl3): δ = 110.6, 115.9, 119.4, 120.6, 125.7,
1H NMR (250 MHz, CDCl3): δ = 2.22 (s, 3 H), 6.32 (s, 1 H), 7.00–7.10
129.7, 132.4, 140.9.
(m, 3 H), 7.24–7.29 (m, 2 H), 7.32–7.51 (m, 4 H).
MS: m/z (%) = 143 (M+, 10.4), 129 (17.1), 105 (30.3), 81 (62.6), 57
13C NMR (62.9 MHz, CDCl3): δ = 13.4, 101.3, 110.02, 119.6, 120.0,
(100.0).
121.0, 127.7, 128.0, 128.2, 129.4, 137.0, 138.2.
Anal. Calcd for C10H9N (143.188): C, 83.88; H, 6.34; N, 9.78. Found: C,
83.02; H, 6.01; N, 9.60.
MS: m/z (%) = 208 (M+ + 1, 56.4), 207 (M+, 80.0), 195 (41.8), 77 (49.1),
57 (100.0).
Anal. Calcd for C15H13N (207.274): C, 86.92; H, 6.32; N, 6.76. Found: C,
85.89; H, 6.64; N, 6.90.
1-Phenyl-1H-benzimidazole (3ae)2b
Brown oil; yield: 160 mg (82%).
10-Phenyl-10H-phenothiazine (3ag)2i
IR (KBr): 694 (s), 748 (s), 887 (w), 972 (w), 1010 (w), 1080 (w), 1149
(w), 1223 (s), 1288 (s), 1373 (w), 1458 (s), 1496 (s), 1596 (s), 1712
(m), 2954 (w), 3062 cm–1 (s).
1H NMR (250 MHz, CDCl3): δ = 7.30–7.38 (m, 2 H), 7.44–7.61 (m, 6 H),
Dark brown solid; yield: 100 mg (37%); mp 78–81 °C.
IR (KBr): 432 (w), 524 (w), 624 (m), 702 (m), 743 (s), 933 (w), 1041
(w), 1126 (w), 1242 (s), 1303 (s), 1458 (s), 1581 (m), 2923 (w), 3055
cm–1 (w).
7.89–7.90 (m, 1 H), 8.17 (s, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 110.50, 120.59, 122.78, 123.69,
123.98, 128.01, 130.04, 136.32, 142.79, 144.23.
MS: m/z (%) = 195 (M+ + 1, 81.7), 194 (M+, 100.0), 166 (13.8), 77 (64.2),
1H NMR (250 MHz, CDCl3): δ = 6.12 (d, J = 6.75 Hz, 2 H), 6.70–6.80 (m,
4 H), 6.94 (d, J = 6.50 Hz, 2 H), 7.32 (d, J = 7.00 Hz, 2 H), 7.36–7.43 (m,
1 H), 7.53 (t, J = 7 Hz, 2 H).
51 (69.7).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1131–1146

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Synthesis
13C NMR (62.9 MHz, CDCl3): δ = 116.0, 120.2, 122.4, 126.7, 126.8,
13C NMR (62.9 MHz, CDCl3): δ = 111.32, 111.39, 118.09, 120.18,
128.2, 130.7, 130.8, 141.0, 144.3.
138.51, 148.66, 151.32.
MS: m/z (%) = 277 (M+ + 2, 2.6), 276 (M+ + 1, 20.9), 275 (M+, 55.9), 149
MS: m/z (%) = 144 (M+, 8.1), 137 (9.2), 111 (16.2), 95 (30.5), 69 (100),
(22.2), 129 (10.3), 97 (20.6), 73 (49.5), 57 (100.0).
57 (89.2).
Anal. Calcd for C18H13NS (275.367): C, 78.51; H, 5.09; N, 5.09. Found:
C, 78.79; H, 5.28; N, 5.55.
Anal. Calcd for C9H8N2 (144.176): C, 74.98; H, 5.59; N, 19.43. Found: C,
75.61; H, 5.92; N, 19.08.
1-p-Tolyl-1H-indole (3ba)2d
1-Pyridin-2-yl-1H-indole (3ca)
Dark brown oil; yield: 160 mg (80%).
Dark brown oil; yield: 150 mg (81%).
1H NMR (250 MHz, CDCl3): δ = 2.35 (s, 3 H), 6.58 (dd, J = 6.58 Hz, 1 H),
7.04–7.32 (m, 7 H), 7.43–7.46 (m, 1 H), 7.58–7.62 (m, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 21.1, 103.2, 110.5, 120.2, 121.1, 122.2,
124.3, 128.1, 129.2, 130.1, 136.3, 137.3.
MS: m/z (%) = 207 (M+ + 1, 100.0), 167 (M+, 86.3), 97 (62.7), 77 (58.8),
57 (92.2).
IR (KBr): 740 (s), 879 (m), 964 (m), 1018 (m), 1095 (m), 1141 (m),
1211 (s), 1242 (s), 1280 (m), 1342 (s), 1473 (s), 1519 (s), 1589 (s),
1689 (w), 3055 cm–1 (m).
1H NMR (250 MHz, CDCl3): δ = 6.56 (d, J = 3.5 Hz, 1 H), 6.91 (t, J = 6.0
Hz, 1 H), 7.00–7.25 (m, 3 H), 7.49–7.56 (m, 3 H), 8.09 (d, J = 8.25 Hz, 1
H), 8.36–8.39 (m, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 105.7, 113.3, 114.6, 120.2, 121.2,
121.4, 123.3, 126.1, 130.6, 135.2, 138.5, 149.0, 152.5.
MS: m/z (%) = 196 (M+ + 2, 39.5), 195 (M+ + 1, 17.1), 194 (M+, 48.8),
Anal. Calcd for C15H13N (207.274): C, 86.92; H, 6.32; N, 6.76. Found: C,
86.07; H, 6.83; N, 6.96.
169 (64.4), 149 (22.4), 97 (35.5), 78 (47.3), 57 (100.0).
1-Pyridin-2-yl-1H-benzimidazole (3ce)
Anal. Calcd for C13H10N2 (194.235): C, 80.39; H, 5.19; N, 14.42. Found:
C, 80.88; H, 4.85; N, 14.76.
Brown oil; yield: 160 mg (81%).
1H NMR (250 MHz, CDCl3): δ = 7.26–7.42 (m, 3 H), 7.58 (d, J = 8.25 Hz,
1 H), 7.86–7.93 (m, 2 H), 8.06 (d, J = 7.75 Hz, 1 H), 8.58 (s, 1 H), 8.60–
8.62 (m, 1 H).
1-(4-Methoxyphenyl)-1H-pyrrole (3dd)2j
Brown solid; yield: 98 mg (57%); mp 107.0–109.0 °C.
13C NMR (62.9 MHz, CDCl3): δ = 112.6, 114.3, 120.6, 121.8, 123.3,
124.2, 132.1, 138.9, 141.3, 144.7, 149.4, 149.8.
MS: m/z (%) = 197 (M++2, 6.1), 196 (M+ + 1, 15.1), 195 (M+, 100.0), 169
(59.4), 78 (47.6), 51 (37.3).
IR (KBr): 717 (m), 825 (m), 1033 (w), 1126 (w), 1218 (m), 1365 (m),
1427 (w), 1643 (w), 1712 cm–1 (s).
1H NMR (250 MHz, CDCl3): δ = 3.75 (s, 3 H), 6.25 (t, J = 2.25 Hz, 2 H),
6.87 (d, J = 9.00 Hz, 2 H), 6.92 (t, J = 1.75 Hz, 2 H), 7.23 (d, J = 8.75 Hz, 2
H).
13C NMR (62.9 MHz, CDCl3): δ = 55.6, 109.8, 114.6, 119.7, 122.2, 134.5,
Anal. Calcd for C12H9N3 (195.223): C, 73.83; H, 4.65; N, 21.52. Found:
C, 73.08; H, 4.53; N, 21.92.
2-Imidazol-1-ylpyridine (3cb)8n
157.6.
MS: m/z (%) = 176 (M+ + 3, 2.3), 175 (M+ + 2, 9.8), 149 (27.6), 124
Dark brown oil; yield: 120 mg (83%).
(33.3), 91 (59.8), 57 (100.0).
IR (KBr): 655 (s), 740 (m), 779 (s), 833 (m), 902 (m), 972 (m), 1059 (s),
1103 (s), 1157 (m), 1257 (m), 1303 (s), 1442 (s), 1488 (s), 1596 (s),
1697 (m), 3116 cm–1 (w).
Anal. Calcd for C11H11NO (173.214): C, 76.28; H, 6.40; N, 8.09. Found:
C, 75.67; H, 6.93; N, 8.74.
1H NMR (250 MHz, CDCl3): δ = 7.14 (s, 1 H), 7.17–7.20 (m, 1 H), 7.25–
7.34 (m, 1 H), 7.58 (s, 1 H), 7.70–7.80 (m, 1 H), 8.25 (s, 1 H), 8.41–8.43
(m, 1 H).
4-Phenylmorpholine (3ah)2e
Dark brown oil; yield: 84 mg (51%).
13C NMR (62.9 MHz, CDCl3): δ = 112.31, 116.14, 122.00, 130.62,
1H NMR (250 MHz, CDCl3): δ = 3.08–3.13 (m, 4 H), 3.80–3.82 (m, 4 H),
132.25, 134.900, 139.00, 149.12.
6.80–6.89 (m, 3 H), 7.20–7.27 (m, 2 H).
MS: m/z (%) = 147 (M+ + 2, 8.1), 146 (M+ + 1, 59.5), 145 (M+, 83.8), 91
13C NMR (62.9 MHz, CDCl3): δ = 48.3, 56.9, 118.7, 128.2, 150.6.
(83.8), 78 (100), 55 (70.3).
MS: m/z (%) = 203 (M+ + 2, 1.1), 202 (M+ + 1, 8.1), 201 (M+, 11.4), 145
Anal. Calcd for C8H7N3 (145.163): C, 66.19; H, 4.86; N, 28.95. Found: C,
65.56; H, 4.36; N, 28.39.
(11.0), 117 (100), 90 (26.6), 57 (18.2).
Anal. Calcd for C10H13NO (163.218): C, 73.59; H, 8.03; N, 8.58. Found:
C, 73.06; H, 8.66; N, 8.02.
2-Pyrrol-1-ylpyridine (3cd)
N,N-Diethylaniline (3ai)2e
Black oil; yield: 110 mg (80%).
IR (KBr): 609 (s), 740 (s), 779 (s), 871 (m), 925 (s), 987 (m), 1013 (s),
1064 (s), 1157 (s), 1249 (m), 1334 (s), 1396 (s), 1442 (s), 1488 (s),
1589 (s), 1712 (s), 1859 (m), 3016 (m), 3062 (w), 3101 (w), 3141 cm–1
(w).
1H NMR (250 MHz, CDCl3): δ = 6.39 (t, J = 2.5 Hz, 2 H), 7.06–7.11 (m, 1
H), 7.30 (d, J = 8.25 Hz, 1 H), 7.54 (t, J = 2.25 Hz, 2 H), 7.68–7.75 (m, 1
H), 8.41–8.44 (m, 1 H).
Dark brown oil; yield: 37 mg (25%).
1H NMR (250 MHz, CDCl3): δ = 1.19 (t, 6 H), 3.37 (q, 4 H), 6.63–6.73
(m, 3 H), 7.20–7.27 (m, 2 H).
13C NMR (62.9 MHz, CDCl3): δ = 12.6, 44.3, 111.8, 115.3, 129.3, 147.8.
Anal. Calcd for C10H15N (149.235): C, 80.48; H, 10.13; N, 9.39. Found:
C, 81.01; H, 10.59; N, 9.01.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1131–1146

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N,N-Dibutylaniline (3aj)2k
1-Benzyl-4-phenyl-1H-1,2,3-triazole (6aa)
Black oil; yield: 111 mg (54%).
White solid; yield: 172 mg (73% from 4a), 160 mg (68% from 4a′); mp
129.0–129.5 °C (Lit.4a 129.0–129.5 °C).
IR (KBr): 694 (m), 748 (m), 879 (w), 1234 (m), 1288 (w), 1458 (w),
1496 (m), 1596 (m), 2923 cm–1 (m).
1H NMR (250 MHz, CDCl3): δ = 0.87 (t, J = 7.5 Hz, 6 H), 1.21–1.35 (m, 4
H), 1.43–1.55 (m, 4 H), 3.18 (t, J = 7.5 Hz, 4 H), 6.53–6.58 (m, 3 H),
7.09–7.17 (m, 2 H).
IR (KBr): 694 (s), 729 (s), 768 (s), 1049 (m), 1076 (m), 1223 (m), 1358
(w), 1466 (m), 3121 cm–1 (w).
1H NMR (250 MHz, CDCl3): δ = 5.53 (s, 2 H), 7.26–7.41 (m, 6 H), 7.69
(s, 1 H), 7.79–7.82 (m, 4 H).
13C NMR (62.9 MHz, CDCl3): δ = 14.0, 20.4, 29.4, 50.8, 111.6, 115.0,
13C NMR (62.9 MHz, CDCl3): δ = 54.1, 119.7, 125.7, 128.0, 128.2, 128.7,
129.2, 148.2.
128.8, 129.1, 130.6, 134.7, 148.1.
MS: m/z (%) = 208 (M+ + 3, 2.8), 207 (M+ + 2, 8.7), 151 (9.0), 109 (33.0),
MS: m/z (%) = 237 (M+ + 2, 0.2), 236 (M+ + 1, 7.3), 235 (M+, 7.7), 207
83 (53.9), 57 (100.0).
(24.7), 206 (30.8), 179 (9.7), 149 (23.1), 116 (94.8), 91 (100), 57 (56.0).
Anal. Calcd for C14H23N (205.342): C, 81.89; H, 11.29; N, 6.82. Found:
C, 81.05; H, 11.92; N, 6.06.
Anal. Calcd for C15H13N3 (235.284): C, 76.57; H, 5.57; N, 17.86. Found:
C, 76.40; H, 5.69; N, 17.76.
1,4-Diphenylpiperazine (3ak)2l
1-(4-Bromobenzyl)-4-phenyl-1H-1,2,3-triazole (6ba)
Dark brown solid; yield: 145 mg (61% from 2k), 96 mg (40% from
2m); mp 150.0–151.0 °C.
Colorless crystals; yield: 223 mg (71%); mp 152.0–153.0 °C (Lit.4a
152.0–153.0 °C).
IR (KBr): 524 (m), 694 (s), 763 (s), 941 (s), 987 (w), 1033 (w), 1157
(m), 1226 (s), 1326 (m), 1388 (m), 1450 (m), 1496 (s), 1596 (s), 2831
cm–1 (m).
1H NMR (250 MHz, CDCl3): δ = 3.36 (s, 8 H), 6.91 (t, J = 7.25 Hz, 2 H),
7.00 (d, J = 7.75 Hz, 4 H), 7.31 (t, J = 6.75 Hz, 4 H).
IR (KBr): 690 (s), 764 (s), 798 (s), 1049 (m), 1076 (s), 1219 (s), 1350
(w), 1435 (m), 1462 (m), 1485 (s), 3082 cm–1 (m).
1H NMR (250 MHz, CDCl3): δ = 5.52 (s, 2 H), 7.17 (d, J = 8.4 Hz, 2 H),
7.24–7.44 (m, 3 H), 7.51 (d, J = 8.4 Hz, 2 H), 7.67 (s, 1 H), 7.80 (d, J = 8.4
Hz, 2 H).
13C NMR (62.9 MHz, CDCl3): δ = 49.4, 116.4, 120.1, 129.2, 151.3.
13C NMR (62.9 MHz, CDCl3): δ = 53.4, 119.7, 122.8, 125.7, 127.6, 128.3,
128.7, 129.1, 129.6, 132.2, 133.8, 148.3.
MS: m/z (%) = 240 (M+ + 2, 3.7), 239 (M+ + 1, 20.0), 238 (M+, 27.0), 132
(43.5), 105 (100.0), 73 (29.8), 57 (38.7).
MS: m/z (%) = 316 (M+ + 2, 1.8), 315 (M+ + 1, 1.8), 314 (M+, 2.4), 312
(0.8), 284 (4.7), 286 (5.3), 207 (8.6), 180 (2.5), 178 (2.7), 171 (15.1),
169 (16.3), 116 (100), 89 (37.3).
Anal. Calcd for C16H18N2 (238.332): C, 80.63; H, 7.61; N, 11.75. Found:
C, 81.02; H, 7.08; N, 11.14.
Anal. Calcd for C15H12BrN3 (314.180): C, 57.34; H, 3.85; N, 13.37.
Found: C, 57.17; H, 3.98; N, 13.35.
N-Benzyl-N-phenethylaniline (3al)
Brown oil; yield: 155 mg (54%).
1-(4-Methylbenzyl)-4-phenyl-1H-1,2,3-triazole (6ca)
Colorless crystals; yield: 204 mg (82%); mp 110.0 °C (Lit.4a 110.0 °C).
IR (KBr): 694 (s), 748 (s), 864 (w), 956 (w), 995 (w), 1026 (w), 1080
(w), 1157 (m), 1218 (m), 1357 (s), 1450 (s), 1504 (s), 1596 (s), 1712
(m), 2923 (m), 3024 cm–1 (m).
1H NMR (250 MHz, CDCl3): δ = 2.87 (t, J = 6.75 Hz, 2 H), 3.57 (t, J = 6.75
Hz, 2 H), 4.41 (s, 2 H), 6.63–6.69 (m, 3 H), 7.12–7.22 (m, 12 H).
13C NMR (62.9 MHz, CDCl3): δ = 33.46, 53.02, 54.45, 112.11, 116.26,
IR (KBr): 694 (s), 764 (s), 1045 (m), 1076 (m), 1223 (s), 1350 (m),
1462 (m), 1516 (m), 3117 (w), 3445 cm–1 (br).
1H NMR (250 MHz, CDCl3): δ = 2.36 (s, 3 H), 5.52 (s, 2 H), 7.30–7.43
(m, 7 H), 7.64 (s, 1 H), 7.79 (dd, J1 = 8.1 Hz, J2 = 1.5 Hz, 2 H).
126.53, 126.79, 128.55, 128.77, 129.32.
13C NMR (62.9 MHz, CDCl3): δ = 21.2, 53.9, 119.6, 126.0, 128.1, 128.8,
130.2, 130.6, 131.7, 138.6, 148.1.
MS: m/z (%) = 251 (M+ + 2, 3.0), 250 (M+ + 1, 15.9), 249 (M+, 16.2), 220
MS: m/z (%) = 240 (M+ + 2, 3.7), 239 (M+ + 1, 20), 238 (M+, 27.0), 132
(43.5), 105 (100.0), 73 (29.8), 57 (38.7).
(41.4), 206 (14.2), 179 (16.3), 130 (7.0), 116 (100), 89 (25.9), 77 (27.4).
Anal. Calcd for C21H21N (287.404): C, 87.76; H, 7.36; N, 4.87. Found: C,
87.17; H, 7.75; N, 4.01.
Anal. Calcd for C16H15N3 (249.311): C, 77.08; H, 6.06; N, 16.85. Found:
C, 76.92; H, 5.94; N, 16.77.
1-Phenyl-4-pyridin-2-ylpiperazine (3ck)
1-(4-Nitrobenzyl)-4-phenyl-1H-1,2,3-triazole (6da)
Pale yellow crystals; yield: 179 mg (64%); mp 156.0–157.0 °C (Lit.4a
156.0–157.0 °C).
Light brown solid; yield: 174 mg (73%); mp 101.0–102.0 °C.
IR (KBr): 516 (m), 686 (m), 748 (s), 871 (w), 948 (m), 1033 (w), 1157
(s), 1234 (s), 1380 (m), 1434 (s), 1473 (m), 1596 (s), 2839 cm–1 (m).
IR (KBr): 690 (s), 733 (s), 764 (s), 1045 (m), 1076 (m), 1223 (m), 1350
(s), 1520 (s), 1605 (m), 3082 cm–1 (m).
1H NMR (250 MHz, CDCl3): δ = 5.68 (s, 2 H), 7.32–7.38 (m, 3 H), 7.42
(d, J = 8.5 Hz, 2 H), 7.78 (s, 1 H), 7.79 (d, J = 7.9 Hz, 2 H), 8.19 (dd, J1 =
9.1 Hz, J2 = 2.2 Hz, 2 H).
13C NMR (62.9 MHz, CDCl3): δ = 53.1, 119.8, 124.3, 125.7, 128.5, 128.9,
130.1, 141.8, 148.6.
1H NMR (250 MHz, CDCl3): δ = 3.24 (t, J = 5.50 Hz, 4 H), 3.64 (t, J = 5.25
Hz, 4 H), 6.56–6.65 (m, 2 H), 6.82 (t, J = 7.50 Hz, 1 H), 6.91 (d, J = 7.75
Hz, 2 H), 7.18–7.25 (m, 2 H), 7.41–7.47 (m, 1 H), 8.14–8.16 (m, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 33.46, 53.02, 54.45, 112.11, 116.26,
126.53, 126.79, 128.55, 128.77, 129.32.
Anal. Calcd for C15H17N3 (239.319): C, 75.28; H, 7.16; N, 17.56. Found:
C, 75.75; H, 7.62; N, 17.92
MS: m/z (%) = 281 (M+ + 1, 4.1), 280 (M+, 5.6), 252 (3.3), 206 (7.0), 136
(5.0), 116 (100.0), 89 (41.0), 63 (18.8).
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Anal. Calcd for C15H12N4O2 (280.282): C, 64.28; H, 4.32; N, 19.99.
Found: C, 64.38; H, 4.12; N, 19.86.
Anal. Calcd for C13H17N3 (215.294): C, 72.52; H, 7.96; N, 19.52. Found:
C, 72.37; H, 7.79; N, 19.58.
2-Hydroxy-5-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]benzalde-
(1-Benzyl-1H-1,2,3-triazol-4-yl)methanol (6ad)
Colorless crystals; yield: 130 mg (69%); mp 78.0–79.0 °C (Lit.4a 78–
78.5 °C).
hyde (6ea)
White solid; yield: 210 mg (75%); mp 165.0–170.0 °C (Lit.3b 165.0–
170.0 °C).
IR (KBr): 690 (s), 721 (s), 769 (m), 841 (s), 1014 (s), 1038 (s), 1130
(m), 1223 (m), 1458 (m), 3263 cm–1 (br).
1H NMR (250 MHz, CDCl3): δ = 4.65 (s, 2 H), 5.40 (s, 2 H), 7.17–7.29
(m, 5 H), 7.45 (s, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 4.0, 55.8, 122.0, 128.1, 128.7, 129.0,
IR (KBr): 455 (w), 506 (w), 555 (w), 686 (m), 763 (s), 1087 (m), 1157
(m), 1311 (s), 1365 (w), 1442 (m), 1612 (m), 1674 (s), 2846 (w), 2931
cm–1 (w).
1H NMR (250 MHz, DMSO-d6): δ = 5.36 (s, 2 H), 6.80 (d, J = 8.5 Hz, 1
H), 7.09–7.22 (m, 3 H), 7.31 (d, J = 8.5 Hz, 1 H), 7.43 (s, 1 H), 7.60 (d, J =
8.0 Hz, 2 H), 7.71 (s, 1 H), 9.76 (s, 1 H), 10.75 (s, 1 H).
13C NMR (62.9 MHz, DMSO-d6): δ = 57.50, 122.92, 126.18, 127.00,
130.30, 131.86, 133.06, 133.90, 134.65, 135.41, 141.45, 152.01,
165.88, 197.22.
134.6, 148.3.
MS: m/z (%) = 191 (M+ + 2, 0.1), 190 (M+ + 1, 0.8), 189 (M+, 1.1), 160
(3.3), 149 (3.4), 143 (5.2), 130 (6.6), 91 (100), 65 (21.5).
Anal. Calcd for C10H11N3O (189.214): C, 63.48; H, 5.86; N, 22.21.
Found: C, 63.62; H, 5.73; N, 22.35.
MS: m/z (%) = 281 (M+ + 2, 0.2), 280 (M+ + 1, 0.6), 279 (M+, 9.3), 250
(12.2), 135 (35.2), 116 (100.0), 85 (30.0), 57 (90.2).
(1-Benzyl-1H-1,2,3-triazol-4-yl)propan-2-ol (6ab)
Colorless crystals; yield: 139 mg (64%); mp 76.0–77.0 °C (Lit.4a
77.0 °C).
Anal. Calcd for C16H13N3O2 (279.297): C, 68.81; H, 4.69; N, 15.04.
Found: C, 68.38; H, 4.50; N, 14.96.
IR (KBr): 698 (w), 733 (s), 795 (m), 960 (m), 1057 (m), 1173 (s), 1219
(m), 1369 (m), 1458 (m), 1500 (w), 2978 (s), 3310 cm–1 (br).
1H NMR (250 MHz, CDCl3): δ = 1.57 (s, 6 H), 3.18 (s, 1 H), 5.42 (s, 2 H),
7.21–7.36 (m, 5 H), 7.39 (s, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 30.4, 54.1, 68.4, 119.2, 128.1, 128.7,
129.1, 134.6, 152.1.
MS: m/z (%) = 217 (M+, 0.5), 204 (0.4), 203 (2.3), 202 (16.0), 201 (3.2),
130 (1.6), 91 (100), 90 (30.3), 65 (18.5).
1-Allyl-4-phenyl-1H-1,2,3-triazole (6fa)
White solid; yield: 148 mg (80% from 4f), 143 mg (77% from 4f′); mp
59.0–61.0 °C (Lit.4a 58.0–62.0 °C).
IR (KBr): 698 (s), 764 (s), 933 (w), 991 (w), 1045 (w), 1076 (w), 1443
(m), 1608 (w), 1720 (m), 2928 (m), 3074 cm–1 (w).
1H NMR (250 MHz, CDCl3): δ = 4.96 (d, J = 6.1 Hz, 2 H), 5.29 (dd, J1 =
16.9 Hz, J2 = 10.2 Hz, 2 H), 5.86–6.08 (m, 1 H), 7.23–7.42 (m, 3 H), 7.69
(s, 1 H), 7.76 (dd, J1 = 8.5 Hz, J2 = 1.1 Hz, 2 H).
Anal. Calcd for C12H15N3O (217.267): C, 66.34; H, 6.96; N, 19.34.
Found: C, 66.49; H, 7.11; N, 19.52.
13C NMR (62.9 MHz, CDCl3): δ = 52.8, 118.7, 119.4, 120.2, 125.7, 128.2,
128.8, 129.0, 129.5, 131.3.
Anal. Calcd for C11H11N3 (185.225): C, 71.33; H, 5.99; N, 22.69. Found:
C, 71.19; H, 5.79; N, 22.61.
{4-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-2-hydroxyphe-
nyl](phenyl)methanone (6ae)
White solid; yield: 231 mg (60%); mp 102.0–104.0 °C (Lit.3b 102.0–
104.0 °C).
2-(1-Allyl-1H-1,2,3-triazol-4-yl)propan-2-ol (6fb)3b
Brown oil; yield: 127 mg (76%).
IR (KBr): 948 (w), 1064 (w), 1164 (br), 1527 (m), 1697 (br), 2977 cm–1
(w).
1H NMR (250 MHz, CDCl3): δ = 1.44 (s, 6 H), 4.26 (s, 1 H), 4.76 (d, J =
6.2 Hz, 2 H), 5.02–5.16 (m, 2 H), 5.74–5.90 (m, 1 H), 7.41 (s, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 30.3, 52.4, 68.2, 119.6, 119.8, 131.3,
156.0.
MS: m/z (%) = 168 (M+ + 1, 0.6), 167 (M+, 2.8), 152 (100.0), 124 (12.0),
IR (KBr): 702 (s), 818 (m), 925 (m), 1010 (m), 1118 (s), 1195 (s), 1257
(s), 1342 (s), 1458 (m), 1504 (m), 1620 (s), 3124 cm–1 (m).
1H NMR (250 MHz, CDCl3): δ = 5.10 (s, 2 H), 5.42 (s, 2 H), 6.36 (dd, J1 =
8.9 Hz, J2 = 2.5 Hz, 1 H), 6.49 (d, J = 2.4 Hz, 1 H), 7.10–7.52 (m, 11 H),
12.55 (s, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 54.2, 62.1, 102.1, 107.5, 113.5, 123.0,
128.1, 128.3, 128.8, 129.2, 131.6, 134.4, 135.4, 138.1, 143.3, 164.7,
166.1, 200.1.
98 (14.7), 82 (35.1), 55 (44.2).
MS: m/z (%) = 387 (M2+, 1.3), 386 (M+ + 1, 6.4), 385 (M + , 18.2), 213
Anal. Calcd for C8H13N3O (167.210): C, 57.47; H, 7.84; N, 25.13. Found:
C, 57.50; H, 7.91; N, 25.39.
(9.5), 172 (3.5), 144 (43.1), 91 (100), 57 (23.1).
Anal. Calcd for C23H19N3O3 (385.420): C, 71.68; H, 4.97; N, 10.9.
Found: C, 71.57; H, 5.05; N, 10.21.
1-Benzyl-4-butyl-1H-1,2,3-triazole (6ac)4a
Oil; yield: 155 mg (72%).
4-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]benzaldehyde (6af)
IR (KBr): 698 (s), 737 (s), 1018 (s), 1207 (m), 1454 (s), 1497 (m), 2338
(w), 2816 (m), 2874 (m), 3028 cm–1 (s).
White solid; yield: 226 mg (77%); mp 101.0–102.0 °C (Lit.3b 101.0–
102.0 °C).
1H NMR (250 MHz, CDCl3): δ = 0.81 (t, J = 7.0 Hz, 3 H), 1.17–1.56 (m, 4
H), 2.35–2.62 (m, 2 H), 5.38 (s, 2 H), 7.03–7.26 (m, 5 H), 7.38 (s, 1 H).
IR (KBr): 709 (m), 1033 (m), 1249 (m), 1519 (m), 1643 (m), 1712 (m),
2885 (w), 2923 cm–1 (w).
13C NMR (62.9 MHz, CDCl3): δ = 13.8, 22.7, 25.3, 31.5, 53.9, 120.5,
126.8, 127.9, 128.9, 134.6, 149.1.
1H NMR (250 MHz, CDCl3): δ = 5.03 (s, 2 H), 5.32 (s, 2 H), 6.86 (d, J =
8.75 Hz, 2 H), 7.04–7.17 (m, 5 H), 7.38 (s, 1 H), 7.59 (d, J = 8.75 Hz, 2
H), 9.64 (s, 1 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1131–1146

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13C NMR (62.9 MHz, CDCl3): δ = 54.1, 62.0, 115.0, 123.2, 128.1, 128.8,
129.1, 130.2, 132.0, 134.5, 143.4, 163.1, 190.7.
MS: m/z (%) = 293 (M+, 2.1), 172 (23.5), 144 (54.1), 91 (100.0).
1H NMR (250 MHz, CDCl3): δ = 5.49 (s, 2 H), 5.54 (s, 2 H), 7.23–7.41
(m, 5 H), 7.63 (s, 1 H), 7.96 (d, J = 8.5 Hz, 1 H), 8.13 (dd, J1 = 8.13 Hz,
J2 = 2.25 Hz, 1 H), 8.29 (d, J = 2.25 Hz, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 54.2, 59.2, 121.4, 124.1, 125.9, 128.1,
128.9, 129.1, 132.2, 134.3, 134.9, 135.1, 142.2, 149.5, 163.8.
Anal. Calcd for C17H15N3O2 (293.324): C, 69.61; H, 5.15; N, 14.33.
Found: C, 69.30; H, 5.07; N, 14.39.
MS: m/z (%) = 373 (M+ + 1, 0.3), 372 (M+, 0.9), 337 (0.9), 281 (0.9), 184
(23.1), 160 (10.2), 91 (100.0).
(1-Allyl-1H-1,2,3-triazol-4-yl)methyl 3-Chlorobenzoate (6fg)
White solid; yield: 219 mg (79%); mp 51.0–53.0 °C (Lit.3b 51.0–
53.0 °C).
Anal. Calcd for C17H13ClN4O4 (372.766): C, 54.78; H, 3.51; N, 15.03.
Found: C, 54.79; H, 3.45; N, 15.24.
IR (KBr): 671 (s), 740 (s), 794 (s), 840 (s), 933 (s), 1118 (s), 1280 (s),
1427 (s), 1573 (m), 1643 (m), 1720 (s), 2970 (m), 3078 (m), 3139 (m),
3440 cm–1 (w).
(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl 3-Nitrobenzoate (6ak)
White solid; yield: 233 mg (69%); mp 116.5–118.0 °C (Lit.3b 116.0–
118.0 °C).
1H NMR (250 MHz, CDCl3): δ = 4.97 (d, J = 6.50 Hz, 2 H), 5.28–5.38 (m,
2 H), 5.45 (s, 2 H), 5.92–6.10 (m, 1 H), 7.32–7.38 (m, 1 H), 7.48–7.52
(m, 1 H), 7.69 (s, 1 H), 7.90 (d, J = 7.5 Hz, 1 H), 7.99 (s, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 52.8, 58.3, 120.5, 123.8, 127.8, 129.7,
130.9, 131.4, 133.2, 134.5, 142.7, 165.2.
IR (KBr): 578 (w), 663 (w), 717 (s), 771 (m), 840 (m), 935 (m), 1064
(s), 1126 (s), 1257 (s), 1296 (s), 1350 (s), 1473 (m), 1527 (s), 1620 (m),
1720 (s), 1959 (w), 2862 (w), 2962 (w), 3085 (w), 3139 cm–1 (m).
1H NMR (250 MHz, CDCl3): δ = 5.49 (s, 2 H), 5.55 (s, 2 H), 7.26–7.40 (m
5 H), 7.60–7.66 (m 2 H), 8.33–8.43 (m 2 H), 8.83 (s 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 54.2, 58.7, 127.1, 124.6, 127.6, 128.2,
MS: m/z (%) = 279 (M+ + 2, 1.7), 278 (M+ + 1, 2.5), 277 (M+, 3.8), 206
(1.6), 167 (2.0), 139 (100.0), 111 (31.7), 73 (12.4), 57 (27.7).
128.8, 129.1, 129.7, 131.4, 134.3, 135.4, 142.5, 148.1, 164.2.
MS: m/z (%) = 340 (M+ + 2, 0.3), 339 (M+ + 1, 1.2), 338 (M+, 3.0), 187
Anal. Calcd for C13H12ClN3O2 (277.709): C, 56.23; H, 4.36; N, 15.13.
Found: C, 56.30; H, 4.27; N, 15.22.
(16.8), 150 (32.9), 91 (100.0).
(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl 4-Bromobenzoate (6ah)
White solid; yield: 257 mg (69%); mp 123.0–124.5 °C (Lit.3b 123.0–
Anal. Calcd for C17H14N4O4 (338.320): C, 60.35; H, 4.17; N, 16.56.
Found: C, 60.27; H, 4.22; N, 16.59.
124.0 °C).
(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl 4-Methoxybenzoate (6al)
White solid; yield: 210 mg (65%); mp 111.0–113.0 °C (Lit.3b 111.0–
113.0 °C).
IR (KBr): 570 (m), 717 (s), 763 (s), 840 (m), 925 (s), 1010 (s), 1095 (s),
1172 (m), 1262 (s), 1388 (m), 1458 (m), 1589 (s), 1720 (s), 2962 (m),
3070 (m), 3124 cm–1 (m).
1H NMR (250 MHz, CDCl3): δ = 5.43 (s, 2 H), 5.52 (s, 2 H), 7.26–7.42
(m, 5 H), 7.55 (d, J = 8.5 Hz, 2 H), 7.60 (s, 1 H), 7.87 (d, J = 8.5 Hz, 2 H).
13C NMR (62.9 MHz, CDCl3): δ = 54.3, 58.2, 123.9, 128.1, 128.3, 128.6,
IR (KBr): 1110 (w), 1265 (m), 1527 (m), 1705 (br), 3618 cm–1 (w).
1H NMR (250 MHz, CDCl3): δ = 3.83 (s, 3 H), 5.40 (s, 2 H), 5.51 (s, 2 H),
6.88 (d, J = 9.0 Hz, 2 H), 7.25–7.37 (m, 5 H), 7.60 (s, 1 H), 7.93 (d, J = 9.0
Hz, 2 H).
128.9, 129.2, 131.2, 131.7, 134.3, 165.7.
MS: m/z (%) = 374 (M+ + 2, 0.1), 373 (M+ + 1, 1.5), 372 (M+, 0.5), 183
13C NMR (62.9 MHz, CDCl3): δ = 54.2, 55.4, 57.8, 113.6, 122.0, 123.8,
(41.9), 91 (100.0).
128.1, 128.8, 129.1, 131.8, 134.4, 143.5, 163.5, 166.1.
Anal. Calcd for C17H14BrN3O2 (372.22): C, 54.86; H, 3.79; N, 11.29.
Found: C, 54.96; H, 3.84; N, 11.41.
MS: m/z (%) = 325 (M+ + 2, 0.3), 324 (M+ + 1, 2.2), 323 (M+, 5.3), 188
(18.6), 135 (100.0), 91 (63.3).
Anal. Calcd for C18H17N3O3 (323.349): C, 66.86; H, 5.30; N, 13.00.
Found: C, 66.91; H, 5.25; N, 13.09.
(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl 2-Bromobenzoate (6ai)
White solid; yield: 242 mg (65%); mp 68.0–69.5 °C (Lit.3b 68.0–
69.0 °C).
N,N-Bis[(1-allyl-1H-1,2,3-triazol-4-yl)methyl]aniline (6fm)
IR (KBr): 709 (w), 1033 (m), 1249 (m), 1458 (m), 1519 (m), 1643 (m),
1712 (m), 2923 cm–1 (w).
1H NMR (250 MHz, CDCl3): δ = 5.38 (s, 2 H), 5.45 (s, 2 H), 7.18–7.28
(m, 7 H), 7.50–7.55 (m, 1 H), 7.65–7.71 (m, 2 H).
13C NMR (62.9 MHz, CDCl3): δ = 54.0, 58.6, 121.6, 124.2, 127.2, 128.0,
White solid; yield: 178 mg (53%); mp 92.0–97.0 °C.
IR (KBr): 509.0 (m), 694 (s), 748 (s), 786 (s), 856 (m), 941 (s), 995 (m),
1049 (s), 1134 (m), 1164 (m), 1211 (s), 1272 (w), 1326 (s), 1373 (s),
1411 (m), 1504 (s), 1542 (w), 1596 (s), 2885 (w), 2923 (w), 3062 (m),
3116 cm–1 (m).
128.7, 129.0, 131.4, 132.8, 134.2, 134.5, 142.7, 165.7.
1H NMR (250 MHz, CDCl3): δ = 4.61 (s, 4 H), 4.86 (s, 4 H), 5.13–5.27
(m, 4 H), 5.82–5.96 (m, 2 H), 6.65–7.19 (m, 5 H), 7.29 (s, 2 H).
13C NMR (62.9 MHz, CDCl3): δ = 46.8, 52.7, 113.4, 117.7, 120.0, 121.8,
MS: m/z (%) = 374 (M+ + 2, 0.3), 373 (M+ + 1, 1.1), 372 (M+, 0.4), 185
(44.8), 91 (100.0).
129.3, 131.2, 145.6, 147.9.
Anal. Calcd for C17H14BrN3O2 (372.22): C, 54.86; H, 3.79; N, 11.29.
Found: C, 54.93; H, 3.85; N, 11.41.
Anal. Calcd for C18H21N7 (335.411): C, 64.46; H, 6.31; N, 29.23. Found:
C, 70.08; H, 5.25; N, 29.75.
(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl 2-Chloro-4-nitrobenzoate
(6aj)
1-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol (6ga)4b
White solid; yield: 235 mg (63%); mp 91.0–93 °C (Lit.3b 91.0–93.0 °C).
White solid; yield: 212 mg (80%); mp 125–127 °C (Lit.4b 125.5–126.58
°C).
IR (KBr): 578 (m), 732 (s), 856 (m), 941 (s), 1049 (s), 1134 (s), 1242
(s), 1280 (s), 1350 (s), 1458 (m), 1519 (s), 1743 (s), 3078 cm–1 (m).
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1H NMR (250 MHz, CDCl3): δ = 3.62 (s, 1 H), 4.15 (dd, J1 = 12.7 Hz, J2 =
3.8 Hz, 1 H), 4.56 (dd, J1 = 12.4 Hz, J2 = 8.2 Hz, 1 H), 5.60 (dd, J1 = 8.2
Hz, J2 = 3.7 Hz, 1 H), 7.17–7.26 (m, 5 H), 7.28 (s, 1 H), 7.29–7.34 (m, 2
H), 7.62–7.69 (m, 3 H).
13C NMR (62.9 MHz, CDCl3): δ = 64.7, 67.3, 120.7, 126.0, 127.2, 128.2,
128.8, 129.0, 130.2, 136.2, 147.4.
Klein, B.; Hamelin, J. Synthesis 1986, 409. (h) Xiao, R.; Zhao, H.;
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Basaveswara Rao, M. V. Am. J. Mater. Sci. 2011, 1, 98.
(k) Watanabe, Y.; Suzuki, N.; Tsuji, Y.; Shim, S. C.; Mitsudo, T.-a.
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Chem. 1977, 14, 535.
2-(4-Phenyl-1H-1,2,3-triazol-1-yl)cyclohexanol (6ha)4b
(3) (a) Campbell-Verduyn, L. S.; Mirfeizi, L.; Dierckx, R. A.; Elsinga,
P. H.; Feringa, B. L. Chem. Commun. 2009, 2139. (b) Sharghi, H.;
Shiri, P.; Aberi, M. Mol Divers. 2014, 18, 559. (c) Berg, R.; Straub,
J.; Schreiner, E.; Mader, S.; Rominger, F.; Straub, B. F. Adv. Synth.
Catal. 2012, 354, 3445. (d) Ozkal, E.; Llanes, P.; Bravo, F.; Ferrali,
A.; Pericàs, M. A. Adv. Synth. Catal. 2014, 356, 857. (e) Antilla, J.
C.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124,
11684. (f) Lv, X.; Bao, W. J. Org. Chem. 2007, 72, 3863. (g) Chen,
H.; Lei, M.; Hu, L. Tetrahedron 2014, 70, 5626.
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Catal. 2009, 351, 207. (b) Sharghi, H.; Beyzavi, M. H.; Safavi, A.;
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2391. (c) Sharghi, H.; Hosseini-Sarvari, M.; Moeini, F.; Khalifeh,
R.; Beni, A. S. Helv. Chim. Acta 2010, 93, 435.
White solid; yield: 187 mg (77%); mp 179–180.5 °C (Lit.4b 179–180
°C).
1H NMR (250 MHz, CDCl3): δ = 1.39–2.25 (m, 8 H), 4.09–4.17 (m, 3 H),
7.23–7.36 (m, 3 H), 7.36 (dd, J1 = 8.2 Hz, J2 = 1.7 Hz, 2 H), 7.69 (s, 1 H).
13C NMR (62.9 MHz, CDCl3): δ = 24.1, 24.8, 31.5, 33.8, 67.4, 72.5,
120.1, 125.4, 127.9, 128.7, 130.2
1-Phenoxy-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propan-2-ol (6ia)4b
White solid; yield: 242 mg (82%); mp 78–79 °C (Lit.4b 78–79 °C).
1H NMR (250 MHz, CDCl3): δ = 3.88 (s, 1 H), 4.01–4.05 (m, 2 H), 4.55
(dd, J1 = 12.7, J2 = 3.5 Hz, 2 H), 4.68–4.77 (m, 1 H), 6.90–7.02 (m, 3 H),
7.6–7.02 (m, 5 H), 7.69–7.72 (m, 2 H), 7.85 (s, 1 H).
(5) Fernandes, A. E.; Jonas, A. M.; Riant, O. Tetrahedron 2014, 70,
1709.
13C NMR (62.9 MHz, CDCl3): δ = 53.5, 68.6, 68.9, 114.5, 121.4, 121.6,
125.5, 128.1, 128.8, 129.6, 130.0, 147.2, 158.2.
(6) Huang, D.; Zhao, P.; Astruc, D. Coord. Chem. Rev. 2014, 272, 145.
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2008, 86, 1044. (b) Sharghi, H.; Khalifeh, R.; Mansouri, S. G.;
Aberi, M.; Eskandari, M. M. Catal. Lett. 2011, 141, 1845.
(c) Sharghi, H.; Ebrahimpourmoghaddam, S.; Doroodmand, M.
M. J. Organomet. Chem. 2013, 738, 41. (d) Sharghi, H.; Aberi, M.
Synlett 2014, 25, 1111. (e) Sharghi, H.; Shiri, P.; Aberi, M. Syn-
thesis 2014, 46, 2489.
Acknowledgment
We gratefully acknowledge the support of this work by the Shiraz
University Research Council.
(8) (a) Díez-González, S. Catal. Sci. Technol. 2011, 1, 166. (b) Xue, F.;
Cai, C.; Sun, H.; Shen, Q.; Rui, J. Tetrahedron Lett. 2008, 49, 4386.
(c) Haneda, S.; Adachi, Y.; Hayashi, M. Tetrahedron 2009, 65,
10459. (d) Suramwar, N. V.; Thakare, S. R.; Karade, N. N.; Khaty,
N. T. J. Mol. Catal. A: Chem. 2012, 359, 28. (e) Islam, S. M.; Salam,
N.; Mondal, P.; Roy, A. S.; Ghosh, K.; Tuhina, K. J. Mol. Catal. A:
Chem. 2014, 387, 7. (f) Rao, R. K.; Naidu, A. B.; Jaseer, E. A.; Sekar,
G. Tetrahedron 2009, 65, 4619. (g) Yang, H.; Xi, C.; Miao, Z.; Chen,
R. Eur. J. Org. Chem. 2011, 3353. (h) Sreedhar, B.; Kumar, K. B. S.;
Srinivas, P.; Balasubrahmanyam, V.; Venkanna, G. T. J. Mol.
Catal. A: Chem. 2007, 265, 183. (i) Cristau, H.-J.; Cellier, P. P.;
Spindler, J.-F.; Taillefer, M. Eur. J. Org. Chem. 2004, 695.
(j) Zhang, Q.; Wang, X.; Cheng, C.; Zhu, R.; Liu, N.; Hu, Y. Org.
Biomol. Chem. 2012, 10, 2847. (k) Jindabot, S.; Teerachanan, K.;
Thongkam, P.; Kiatisevi, S.; Khamnaen, T.; Phiriyawirut, P.;
Charoenchaidet, S.; Sooksimuang, T.; Kongsaeree, P.;
Sangtrirutnugul, P. J. Organomet. Chem. 2014, 750, 35. (l) Verma,
A. K.; Singh, J.; Sankar, V. K.; Chaudhary, R.; Chandra, R. Tetrahe-
dron Lett. 2007, 48, 4207. (m) Haneda, S.; Adachi, Y.; Hayashi, M.
Tetrahedron 2009, 65, 10459. (n) Xi, Z.; Liu, F.; Zhou, Y.; Chen,
W. Tetrahedron 2008, 64, 4254.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379951.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1131–1146