Synthesis of 3,5-disubstituted pyrazoles via cope-type hydroamination of 1,3-dialkynes

Article abstract of DOI:10.1021/jo302732v

An efficient method for the synthesis of 3,5-disubstituted pyrazoles is described. The reactions of 1,3-dialkynes with hydrazine proceeded smoothly in dimethyl sulfoxide under mild reaction conditions to produce 3,5-disubstituted pyrazoles in satisfactory to excellent yields. A one-pot procedure of the transformation has been developed.

Full text of DOI:10.1021/jo302732v

Note
pubs.acs.org/joc
Synthesis of 3,5-Disubstituted Pyrazoles via Cope-Type
Hydroamination of 1,3-Dialkynes
Liangguang Wang, Xiaoqiang Yu,* Xiujuan Feng, and Ming Bao*
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, China
S
* Supporting Information
ABSTRACT: An efficient method for the synthesis of 3,5-disubstituted
pyrazoles is described. The reactions of 1,3-dialkynes with hydrazine
proceeded smoothly in dimethyl sulfoxide under mild reaction conditions
to produce 3,5-disubstituted pyrazoles in satisfactory to excellent yields. A
one-pot procedure of the transformation has been developed.
yrazoles represent an interesting structural motif found
frequently in various bioactive molecules.1 Over the past
Scheme 1. Synthesis of 3,5-Disubstituted Pyrazoles via
Cope-Type Hydroamination of 1,3-Dialkynes
P
years, many methods have been developed for the construction
of the pyrazole nucleus, including the [3 + 2] cycloaddition of
alkenes/alkynes with 1,3-dipoles (diazoalkanes and nitrile
imines),2 the reaction of hydrazine with a three-carbon atom
component (such as 1,3-dicarbonyl compound, α,β-unsaturated
carbonyl compound),3 the gold-catalyzed addition of phenyl-
hydrazine to a 1,3-dialkyne,4 and others.5 Although mono- and
polysubstituted-pyrazoles can be obtained using these methods,
the synthesis frequently suffers from drawbacks, such as
multistep reactions, harsh reaction conditions (strong bases
or strong mineral acids are often required, or prolonged heating
to high temperature is necessary), and the use of transition-
metal catalysts or special starting materials.
a
Table 1. Reaction Conditions Screening
Beauchemin and co-workers have reported the uncatalyzed
intermolecular Cope-type hydroamination reaction of alkynes
(or alkenes) with hydroxylamine (or hydrazine) in 2008.6
Recently, we have reported that 3,5-disubstituted isoxazoles can
be readily obtained from the reaction of 1,3-dialkynes with
hydroxylamine (NH2OH); this reaction proceeded smoothly in
dimethyl sulfoxide (DMSO) under transition metal-, strong
base-, and strong acid-free conditions.7 The success in achieving
cycloaddition of 1,3-dialkynes with hydroxylamine encouraged
us to examine the cycloaddition of 1,3-dialkynes with hydrazine
(NH2NH2) under the same reaction conditions. As expected,
the cycloaddition of 1,3-dialkynes with hydrazine took place to
offer 3,5-disubstituted pyrazoles (Scheme 1). The intermolec-
ular Cope-type hydroamination reaction of 1,3-dialkynes 1 with
hydrazine occurred during heating to produce intermediate A
upon a proton-transfer process.8 The isomerization of A
subsequently took place to produce an allenyl oxime
intermediate B, which then transformed into a 3,5-disubstituted
pyrazoles 2 via intramolecular electrophilic addition. The
results are reported in the current work.
entry
temp (°C)
NH2NH2 (equiv)
yield (%)
1
110
100
90
4.0
4.0
4.0
4.0
4.0
4.0
4.0
3.5
3.0
2.5
83
84
83
83
82
83
68
82
83
74
2
3
4
80
5
70
6
60
7
50
8
60
9
60
10
60
a
Reaction conditions: 1,4-diphenylbuta-1,3-diyne (1a, 0.4 mmol, 81.0
mg) and aqueous hydrazine solution (50 wt %, 2.5−4.0 equiv), and
DMSO (3.0 mL) in sealed tube for 20 h.
3,5-disubstituted pyrazole, 5-benzyl-3-phenylpyrazole (2a), was
obtained in 83% yield (entry 1). The results obtained from the
subsequent investigations on the reaction temperature
indicated that the reaction temperature can be reduced to 60
In our initial studies, the reaction of 1,4-diphenylbuta-1,3-
diyne (1a) with hydrazine was chosen as a model to optimize
the reaction conditions. The results are shown in Table 1. The
reaction of 1a with hydrazine was initially performed under the
same reaction conditions as employed in the reaction of 1a with
hydroxylamine (in DMSO at 110 °C for 20 h).7 The desired
Received: December 20, 2012
Published: January 28, 2013
© 2013 American Chemical Society
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Note
°C (entries 2−7). To facilitate the complete transformation of
the 1,3-dialkyne substrate 1a to product, an excess of hydrazine
was used. The results indicated that the use of 3.0 equiv of
hydrazine is necessary to obtain product 2a in good yield (83%;
entry 9 vs entries 6, 8, and 10). Therefore, the subsequent
reactions of the symmetric (1a−1h) and unsymmetric (3a−3j)
1,3-dialkynes with hydrazine (3.0 equiv) were performed in
DMSO at 60 °C for 20 h.
The reactions of symmetric 1,3-dialkynes 1a−1h with
hydrazine were performed under optimized conditions, and
the results are summarized in Table 2. 3,5-Disubstituted
pyrazole 2a−2f were obtained from the reactions of aromatic
1,3-dialkynes 1a−1f in good to excellent yields (entries 1−6,
76−93%). The formation of 3,5-disubstituted pyrazole in
relatively higher yield from a 1,3-dialkyne bearing an electron-
withdrawing group on benzene ring than those from a 1,3-
dialkyne bearing an electron-donating group on benzene ring
was observed (entries 5 and 6 vs entries 1−4). This result
suggests that 1,3-dialkynes can be activated by decreasing their
electron density. The aliphatic 1,3-dialkynes 1g and 1h were
also employed successfully in the synthesis of 3,5-disubstituted
pyrazoles. The corresponding products 2g and 2h were
obtained in 60 and 76% yields, respectively (entries 7 and 8).
The reaction of 1a with phenylhydrazine was finally tested
under optimized conditions. No reaction was observed.
The successful acquisition of 3,5-disubstituted pyrazoles from
the reaction of symmetric 1,3-dialkynes with hydrazine
encouraged the current authors to examine the reaction of
unsymmetric 1,3-dialkynes with hydrazine. The results are
summarized in Table 3. The reactions of unsymmetric 1,3-
Table 2. Synthesis of 3,5-Disubstituted Pyrazoles from
Symmetric 1,3-Dialkynes
a
Table 3. Synthesis of 3,5-Disubstituted Pyrazoles from
a
Unsymmetric 1,3-Dialkynes
entry
1
alkyne 3
3a, R1 = Ph
yield of 4 (%)
4a, 41
yield of 5 (%)
5a, 32
R2 = 4-MeOC6H4
3b, R1 = 4-FC6H4
R2 = 4-MeOC6H4
3c, R1 = 4-MeC6H4
R2 = n-Hexyl
3d, R1 = 4-MeC6H4
R2 = c-Hexyl
3e, R1 = 4-NO2C6H4
R2 = 4-MeOC6H4
3f, R1 = 4-NO2C6H4
R2 = Ph
3g, R1 = 4-NO2C6H4
R2 = n-Hexyl
2
4b, 72
4c, 61
4d, 64
4e, 87
4f, 90
4g, 89
4h, 94
4i, 78
4j, 81
5b, 9
5c, 12
5d, 12
5e, 0
5f, 0
3
4
5
6
7
5g, 0
5h, 0
5i, 0
8
3h, R1 = 4-NO2C6H4
R2 = c-Hexyl
9
3i, R1 = Ph
R2 = n-Hexyl
10
3j, R1 = Ph
5j, 0
R2 = c-Hexyl
a
Reaction conditions: unsymmetric 1,3-dialkyne (3a−3j, 0.4 mmol),
aqueous hydrazine solution (50 wt %, 3.0 equiv, 76.9 mg), and DMSO
(3.0 mL) in sealed tube at 60 °C for 20 h.
dialkynes 3a and 3b having the same 4-methoxyphenyl group
with hydrazine proceeded smoothly to produce a mixture of
two products, which can be separated with chromatography
(entry 1: 4a, 41% yield; 5a, 32% yield. entry 2: 4b, 72% yield;
5b, 9% yield). Similar results were obtained when 1,3-dialkynes
3c and 3d having the same 4-methylphenyl group were
employed as substrates. Products 4c, 5c, 4d, and 5d were
isolated in 61, 12, 64, and 12% yields, respectively (entries 3
and 4). The use of unsymmetric 1,3-dialkynes 3e−3h having
the same 4-nitrophenyl group led to the selective formation of
3,5-disubstituted pyrazoles 4e−4h in good to excellent yields
(entries 5−8, 87−94%). 3,5-Disubstituted pyrazoles 4i and 4j
a
Reaction conditions: symmetric 1,3-dialkyne (1a−1h, 0.4 mmol),
aqueous hydrazine solution (50 wt %, 3.0 equiv, 76.9 mg), and DMSO
(3.0 mL) in sealed tube at 60 °C for 20 h. 1,3-Dialkyne 1g was
recovered in 26% yield.
b
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were also obtained as a sole product from the reaction of
unsymmetric 1,3-dialkyne 3i or 3j with hydrazine (entry 9: 4i,
78% yield; entry 10: 4j, 81% yield). These results obtained
indicated that the reaction selectivity was controlled by the
electron property of substituents R1 and R2 in 1,3-dialkynes; the
Cope-type hydroamination of 1,3-dialkynes with hydrazine
facilely took place on the triplet bond bearing an electron-
donating group to produce 3,5-disubstituted pyrazoles 4.
Finally, the one-pot synthesis of 3,5-disubstituted pyrazoles
from alkynes was examined, and the results are summarized in
Table 4. After the Cu-catalyzed homocoupling reaction of
thienylacetylene (6p) were investigated under the same
conditions. The corresponding products 2n−2p were obtained
in moderate to excellent yields (entries 14−16, 60, 80, and
78%, respectively). All the new products 2b−2p, 4a−4j, and
5a−5d were identified through their NMR and HRMS data as
well as IR spectra.10
To prove the practicality of the present method in the
synthesis of 3,5-disubstituted pyrazoles, a gram-scale synthesis
of the 3,5-disubstituted pyrazole 2a was performed, and the
result is shown in Scheme 2. When 1.01 g of 1a was utilized,
1.01 g of product 2a was obtained in 86% yield.
Table 4. One-Pot Synthesis of 3,5-Disubstituted Pyazoles
from Alkynes
Scheme 2. Gram-Scale Synthesis of the 3,5-Disubstituted
Pyrazole 2a
a b
,
entry
alkyne 6
product 2
yield (%)
1
6a, R = Ph
2a
2b
2c
2d
2e
2f
82
76
78
78
91
92
2
6b, R = 4-MeOC6H4
6c, R = 4-MeC6H4
6d, R = 3-MeC6H4
6e, R = 4-CF3C6H4
6f, R = 4-NO2C6H4
6g, R = n-Hexyl
3
In summary, a novel and general method for the synthesis of
3,5-disubstituted pyrazoles was developed using simple and
readily available starting materials, namely, 1,3-dialkynes/
alkynes and aqueous hydrazine solution. The intermolecular
Cope-type hydroamination reaction of 1,3-dialkynes with
hydrazine and the subsequent electrophilic addition proceeded
smoothly under transition metal-, strong base-, and strong acid-
free conditions to produce 3,5-disubstituted pyrazoles in
satisfactory to excellent yields. The wide availability of the
starting materials, mild reaction conditions, and experimental
simplicity should make the present methodology more useful in
organic synthesis.
4
5
6
c
7
2g
2h
2i
60
8
6h, R = c-Hexyl
6i, R = 4-nBu
76
78
9
d
10
11
12
13
14
15
6j, R = 2-MeC6H4
6k, R = 4-BrC6H4
6l, R = 4-FC6H4
6m, R = 3,4-F2C6H4
6n, R = 1-Naphthyl
6o, R = 3-Pyridyl
6p, R = 3-Thienyl
2j
65
2k
2l
86
88
86
2m
2n
2o
2p
e
60
80
78
16
EXPERIMENTAL SECTION
■
a
General Methods. Solvents were dried and degassed before use by
standard procedures. NMR spectra were run in CDCl3 on a 400 MHz
instrument and recorded at the following frequencies: proton (1H, 400
MHz), carbon (13C, 100 MHz). IR spectra were recorded on a FT-IR
spectrometer. High resolution mass spectra were recorded on either a
Q-TOF mass spectrometer or a GC-TOF mass spectrometer. The
starting materials 6a−6p are commercially available. The starting
materials 1a−1h and 3a−3i have appeared in the literature.7,11−17
Preparation and Characterization of Starting Material 3j. A
reaction flask was charged with a mixture of CuI (38.4 mg, 0.2 mmol),
P(o-Tol)3 (121.6 mg, 0.4 mmol), K2CO3 (552.0 mg, 4.0 mmol),
ethynylcyclohexane (216.4 mg, 2.0 mmol), and 1-(bromoethynyl)-4-
methylbenzene, prepared following literature procedure18 (507.2 mg,
2.6 mmol), and anhydrous ethanol (EtOH, 10.0 mL). The reaction
mixture was stirred at 100 °C for 12 h and then was cooled to room
temperature. The resultant mixture was diluted with water (10 mL)
and extracted with EtOAc (20 mL × 3). The combined organic layers
were washed with brine (10 mL × 2) and dried over Na2SO4. The
solvent was removed under reduced pressure, and the residue obtained
was purified via silica gel chromatography (eluent: cyclohexane) to
afford 1-(cyclohexylbuta-1,3-diyn-1-yl)-4-methylbenzene (3j). Yield:
Reaction conditions for first step: alkyne (6a−6p, 0.6 mmol) and
CuCl (5 mol %, 3.0 mg) in DMSO (3.0 mL) at 90 °C in air for 8 h.
Reaction conditions for second step: aqueous hydrazine solution (50
wt %, 1.5 equiv, 57.7 mg) in sealed tube at 60 °C for 20 h. 1,3-
Dialkyne 1g was recovered in 21% yield. 1,3-Dialkyne 1j was
b
c
d
e
recovered in 20% yield. 1,3-Dialkyne 1n was recovered in 25% yield.
alkyne was completed,9 aqueous hydrazine solution was added
to the resultant mixture. The reaction mixture was then treated
at 60 °C for 20 h. A similar yield of 2a was observed in the
reaction of phenylacetylene (6a) (entry 1, 82%). The reactions
of arylacetylenes 6b−6d and 6i bearing an electron-donating
n
group (MeO, Me, Bu) on 4- or 3-position of benzene ring
produced the desired products 2b−2d and 2i in good yields
(entries 2−4 and 9, 76−78%). However, the reaction of 2-
methyl phenylacetylene (6j) produced 3,5-disubstituted pyr-
azole 2j in low yield (entry 10, 60%). The poor reactivity of 6j
was considered to be due to the steric effect of the 2-methyl
group in alkyne substrate. The relatively high yields were also
observed in the reactions of arylacetylenes 6e, 6f, and 6k−6m
bearing an electron-withdrawing group on benzene ring. The
desired products, 3,5-disubstituted pyrazoles 2e, 2f, and 2k−
2m, were isolated in the range of 86−92% yields (entries 5, 6,
and 11−13). The aliphatic alkynes 6g and 6h were also utilized
successfully for the synthesis of 3,5-disubstituted pyrazoles.
Products 2g and 2h were obtained in 60 and 76% yields,
respectively (entries 7 and 8). Finally, the reactions of 1-
naphthylacetylene (6n), 3-pyridinylacetylene (6o), and 3-
1
80%, 355.7 mg, white solid, mp 118−120 °C; H NMR (400 MHz,
CDCl3) δ 7.36 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 2.56−2.51
(m, 1H), 2.33 (s, 3H), 1.84−1.30 (m, 10H); 13C NMR (100 MHz,
CDCl3) δ 139.2, 132.5, 129.3, 119.2, 88.3, 75.7, 73.9, 65.3, 32.4, 29.9,
25.9, 24.9, 21.7; IR (KBr) 2937, 2854, 2235, 2141, 1916, 1507, 1466,
820 cm−1; HRMS (EI) calcd for C17H18 222.1413 [M]+, found
222.1409.
General Procedure for Synthesis of 3,5-Disubstituted
Pyrazoles from Symmetric 1,3-Dialkynes. A reaction flask was
charged with a mixture of symmetric 1,3-dialkyne (1, 0.4 mmol),
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aqueous hydrazine solution (50 wt %, 3.0 equiv, 76.9 mg), and DMSO
(3.0 mL). The reaction mixture was sealed and stirred at 60 °C for 20
h and then was cooled to room temperature. Water (10 mL) was
added to the resultant mixture. The product was extracted with ethyl
acetate (10 mL × 3), and the combined organic layers were washed
with brine (10 mL × 2) and dried over Na2SO4. The solvent was
removed under reduced pressure, and the residue obtained was
purified via silica gel chromatography (eluent: petroleum ether/ethyl
acetate = 20:1) to afford 3,5-disubstituted pyrazoles 2.
3103, 3022, 2924, 2851, 1681, 1575, 1448 cm−1; HRMS (EI) calcd for
C16H26N2 246.2096 [M]+, found 246.2105.
General Procedure for Synthesis of 3,5-Disubstituted
Pyrazoles from Unsymmetric 1,3-Dialkynes. A reaction flask
was charged with a mixture of unsymmetric 1,3-dialkynes (3, 0.4
mmol), aqueous hydrazine solution (50 wt %, 3.0 equiv, 76.9 mg), and
DMSO (3.0 mL). The reaction mixture was sealed and stirred at 60 °C
for 20 h and then was cooled to room temperature. Water (10 mL)
was added to the resultant mixture. The product was extracted with
ethyl acetate (10 mL × 3), and the combined organic layers were
washed with brine (10 mL × 2) and dried over Na2SO4. The solvent
was removed under reduced pressure, and the residue obtained was
purified via silica gel chromatography (eluent: petroleum ether/ethyl
acetate = 20:1) to afford 3,5-disubstituted pyrazoles 4 and 5.
5-Benzyl-3-(4-methoxyphenyl)-1H-pyrazole (4a). Yield: 41%,
43.3 mg, white solid, mp 105−107 °C; 1H NMR (400 MHz, CDCl3) δ
7.56 (d, J = 8.4 Hz, 2H), 7.29−7.20 (m, 5H), 6.84 (d, J = 8.0 Hz, 2H),
6.23 (s, 1H), 3.96 (s, 2H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 159.6, 148.8, 147.9, 138.9, 128.9, 128.8, 127.1, 126.7, 124.8, 114.2,
101.6, 55.4, 33.4; IR (KBr) 3186, 2926,1615, 1509, 1495, 1250, 1030,
835, 719 cm−1; HRMS (EI) calcd for C17H16N2O 264.1263 [M]+,
found 264.1260.
5-Benzyl-3-phenyl-1H-pyrazole (2a).19 Yield: 83%, 77.9 mg,
white solid, mp 88−90 °C; 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J =
7.2 Hz, 2H), 7.38−7.24 (m, 8H), 6.35 (s, 1H), 4.01 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 138.6, 132.1, 128.9, 128.8, 128.1, 126.8, 125.8,
102.2, 33.3; IR (KBr) 3185, 3131, 3046, 3025, 2912, 1949, 1604, 1570,
1494, 1464, 1453, 764, 721 cm−1; HRMS (EI) calcd for C16H14N2
234.1157 [M]+, found 234.1164.
5-(4-Methoxybenzyl)-3-(4-methoxyphenyl)-1H-pyrazole
1
(2b). Yield: 76%, 89.5 mg, white solid, mp 120−122 °C; H NMR
(400 MHz, CDCl3) δ 7.57 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.4 Hz,
2H), 6.87−6.82 (m, 4H), 6.23 (s, 1H), 3.92 (s, 2H), 3.80 (s, 3H), 3.77
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.6, 158.4, 149.1, 148.0,
130.8, 129.9, 127.0, 124.9, 114.25, 114.19, 101.4, 55.4, 32.5; IR (KBr)
3445, 3246, 3009, 2957, 2838, 1895, 1613, 1525, 1513, 1438, 1282,
1250, 1030, 838, 796 cm−1; HRMS (EI) calcd for C18H18N2O2
294.1368 [M]+, found 294.1363.
5-(4-Fluorobenzyl)-3-(4-methoxyphenyl)-1H-pyrazole (4b).
1
Yield: 72%, 81.3 mg, white solid, mp 118−120 °C; H NMR (400
MHz, CDCl3) δ 9.42 (s, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.2 (dd, J = 5.6,
8.0 Hz, 2H), 6.93 (dd, J = 8.8, 8.8 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H),
6.19 (s, 1H), 3.89 (s, 2H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 161.7 (d, 1J = 242.7 Hz), 159.6, 148.4, 148.2, 134.6, 130.3 (d, 3J = 7.8
Hz), 127.1, 124.4, 115.5 (d, 2J = 21.2 Hz), 114.3, 101.5, 55.4, 32.6; IR
(KBr) 3189, 3133, 3084, 3006, 2933, 2836, 1890, 1614, 1529, 1508,
1455, 1251, 1222, 1031, 835 cm−1; HRMS (EI) calcd for C17H15N2OF
282.1168 [M]+, found 282.1168.
5-(4-Methylbenzyl)-3-(p-tolyl)-1H-pyrazole (2c). Yield: 78%,
1
81.9 mg, white solid, mp 95−97 °C; H NMR (400 MHz, CDCl3) δ
9.49 (s, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.13−7.07 (m, 6H), 6.29 (s,
1H), 3.92 (s, 2H), 2.33 (s, 3H), 2.30 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 137.7, 136.09, 136.08, 135.6, 135.5, 129.4, 129.3, 128.7,
125.6, 32.8, 21.3, 21.1; IR (KBr) 3227, 3018, 2917, 2859, 1900, 1639,
1580, 1566, 1513, 1445, 1112, 961, 787 cm−1; HRMS (EI) calcd for
C18H18N2 262.1470 [M]+, found 262.1461.
3-Hexyl-5-(4-methylbenzyl)-1H-pyrazole (4c). Yield: 61%, 62.6
1
mg, colorless oil; H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 7.10
5-(3-Methylbenzyl)-3-(m-tolyl)-1H-pyrazole (2d). Yield: 78%,
1
(d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 5.79 (s, 1H), 3.90 (s,
2H), 2.55 (t, J = 8.0 Hz, 2H), 2.30 (s, 3H), 1.61−1.54 (m, 2H), 1.32−
1.26 (m, 6H), 0.86 (t, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 149.0, 148.6, 136.5, 135,9, 129.3, 128.8, 102.8, 33.5, 31.8, 29.5, 29.2,
27.0, 22.7, 21.2, 14.3; IR (neat) 3190, 3132, 3100, 3021, 2927, 2857,
1900, 1578, 1514, 1495, 1433, 1023, 1005, 790 cm−1; HRMS (EI)
calcd for C17H24N2 256.1939 [M]+, found 256.1939.
81.9 mg, colorless oil; H NMR (400 MHz, CDCl3) δ 9.74 (s, 1H),
7.48 (s, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.21−7.13 (m, 2H), 7.07−7.00
(m, 4H), 6.23 (s, 1H), 3.90 (s, 2H), 2.29 (s, 3H), 2.27 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 138.6, 138.34, 138.26, 129.6, 128.7, 128.6,
128.5, 127.3, 126.4, 125.8, 122.8, 33.2, 21.41, 21.40; IR (neat) 3175,
3102, 3018, 2918, 1608, 1589, 1573, 1476, 1025, 758 cm−1; HRMS
(EI) calcd for C18H18N2 262.1470 [M]+, found 262.1473.
3-Cyclohexyl-5-(4-methylbenzyl)-1H-pyrazole (4d). Yield:
5-(4-(Trifluoromethyl)benzyl)-3-(4-(trifluoromethyl)phenyl)-
1H-pyrazole (2e). Yield: 93%, 137.7 mg, white solid, mp 174−176
°C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.4 Hz, 2H), 7.62 (d, J
= 8.0 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 7.6 Hz, 2H), 6.40
(s, 1H), 4.09 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 142.2, 135.7,
1
64%, 65.1 mg, colorless oil; H NMR (400 MHz, CDCl3) δ 9.96 (s,
1H), 7.11 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 5.78 (s, 1H),
3.91 (s, 2H), 2.61−2.55 (m, 1H), 2.31 (s, 3H), 1.95−1.66 (m, 5H),
1.40−1.18 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 153.4, 149.1,
136.6, 135.9, 129.3, 128.9, 101.1, 36.3, 33.7, 33.1, 26.4, 26.2, 21.2; IR
(neat) 3186, 3097, 3019, 2926, 2852, 1901, 1575, 1514, 1448, 1007,
987, 809 cm−1; HRMS (EI) calcd for C17H22N2 254.1783 [M]+, found
254.1778.
2
2
130.7 (q, J = 32.6 Hz), 130.1 (q, J = 32.6 Hz), 129.6, 129.2, 128.4,
1
126.2, 126.0, 124.3 (q, J = 270.1 Hz), 103.1, 33.0; IR (KBr) 2918,
1619, 1508, 1459, 1436, 1417, 1331, 1160, 1111, 1069, 841 cm−1;
HRMS (EI) calcd for C18H12N2F6 370.0905 [M]+, found 370.0896.
5-(4-Nitrobenzyl)-3-(4-nitrophenyl)-1H-pyrazole (2f). Yield:
3-(4-Methoxyphenyl)-5-(4-nitrobenzyl)-1H-pyrazole (4e).
1
1
93%, 120.6 mg, pale yellow solid, mp 212−214 °C; H NMR (400
Yield: 87%, 107.6 mg, pale yellow solid, mp 140−142 °C; H NMR
MHz, CDCl3) δ 13.2 (s, 1H), 8.25 (d, J = 8.4 Hz, 2H), 8.21 (d, J = 8.4
Hz, 2H), 8.03 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 6.74 (s,
1H), 4.20 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 154.1, 152.2,
151.7, 148.0, 145.5, 135.2, 135.1, 131.1, 129.5, 129.1, 108.2, 36.2; IR
(KBr) 3113, 3074, 3010, 1636, 1602, 1512, 1349, 1109, 963, 855 cm−1;
HRMS (EI) calcd for C16H12N4O4 324.0859 [M]+, found 324.0867.
5-Heptyl-3-hexyl-1H-pyrazole (2g). Yield: 60%, 60.1 mg,
(400 MHz, CDCl3) δ 8.01 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz,
2H), 7.25 (d, J = 8.8 Hz, 2H), 6.81 (d, J = 8.4 Hz, 2H), 6.20 (s, 1H),
3.97 (s, 2H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.8,
148.2, 147.1, 146.9, 146.7, 129.5, 127.0, 123.8, 123.3, 114.3, 101.7,
55.4, 33.7; IR (KBr) 3134, 3012, 2934, 2837, 1606, 1572, 1513, 1346,
1251, 1029, 835, 729 cm−1; HRMS (EI) calcd for C17H15N3O3
309.1113 [M]+, found 309.1107.
5-(4-Nitrobenzyl)-3-phenyl-1H-pyrazole (4f). Yield: 90%, 100.5
mg, pale yellow solid, mp 138−140 °C; 1H NMR (400 MHz, CDCl3)
δ 11.58 (s, 1H), 8.08 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 6.4 Hz, 2H),
7.37−7.30 (m, 5H), 6.31 (s, 1H), 4.03 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 146.8, 146.7, 130.7, 129.6, 129.1, 128.6, 125.7, 123.9, 102.5,
33.7; IR (KBr) 3104, 3011, 2930, 1604, 1516, 1345, 1013, 856, 729
cm−1; HRMS (EI) calcd for C16H13N3O2 279.1008 [M]+, found
279.1007.
1
colorless oil; H NMR (400 MHz, CDCl3) δ 9.30 (s, 1H), 5.85 (s,
1H), 2.60 (t, J = 7.6 Hz, 4H), 1.62−1.59 (m, 4H), 1.30−1.27 (m,
14H), 0.88 (t, J = 6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 149.4,
102.0, 31.9, 31.8, 29.64, 29.60, 29.5, 29.3, 27.3, 22.8, 22.7, 14.2; IR
(neat) 3191, 3132, 3102, 3027, 2955, 2927, 2856, 1580, 1466 cm−1;
HRMS (EI) calcd for C16H30N2 250.2409 [M]+, found 250.2405.
3-Cyclohexyl-5-(cyclohexylmethyl)-1H-pyrazole (2h). Yield:
1
76%, 74.9 mg, colorless oil; H NMR (400 MHz, CDCl3) δ 8.54 (s,
1H), 5.81 (s, 1H), 2.63−2.59 (m, 1H), 2.47 (d, J = 7.2 Hz, 2H), 1.99−
0.88 (m, 21H); 13C NMR (100 MHz, CDCl3) δ 154.2, 147.7, 101.1,
38.4, 36.6, 35.2, 33.4, 33.2, 26.6, 26.42, 26.36, 26.2; IR (neat) 3196,
3-Hexyl-5-(4-nitrobenzyl)-1H-pyrazole (4g). Yield: 89%, 102.3
mg, white solid, mp 48−50 °C; H NMR (400 MHz, CDCl3) δ 9.25
(s, 1H), 8.07 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 8.8 Hz, 2H), 5.80 (s,
1
1696
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The Journal of Organic Chemistry
Note
1H), 4.01 (s, 2H), 2.54 (t, J = 8.0 Hz, 2H), 1.59−1.51 (m, 2H), 1.30−
1.23 (m, 6H), 0.84 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 148.7, 147.6, 147.2, 146.6, 129.6, 123.8, 103.0, 34.2, 31.6, 29.2, 29.0,
26.3, 22.6, 14.1; IR (KBr) 3192, 3104, 2929, 2857, 1927, 1605, 1578,
1519, 1346, 857, 732 cm−1; HRMS (EI) calcd for C16H21N3O2
287.1634 [M]+, found 287.1640.
h under air atmosphere and then was cooled to room temperature.
Aqueous hydrazine solution (50 wt %, 1.5 equiv, 57.7 mg) was added
to the resultant mixture, and then the mixture was sealed and stirred at
60 °C for 20 h. Water (10 mL) was added to the resultant mixture at
room temperature. The product was extracted with ethyl acetate (10
mL × 3), and the combined organic layers were washed with brine (10
mL × 2) and dried over Na2SO4. The solvent was removed under
reduced pressure, and the residue obtained was purified via silica gel
chromatography (eluent: petroleum ether/ethyl acetate = 3:1) to
afford 3,5-disubstituted pyrazoles 2.
5-(4-Butylbenzyl)-3-(4-butylphenyl)-1H-pyrazole (2i). Yield:
78%, 81.1 mg, white solid, mp 96−98 °C; 1H NMR (400 MHz,
CDCl3) δ 10.14 (s, 1H), 7.55 (d, J = 7.6 Hz, 2H), 7.13−7.06 (m, 6H),
6.30 (s, 1H), 3.90 (s, 2H), 2.60−2.54 (m, 4H), 1.61−1.52 (m, 4H),
1.38−1.29 (m, 4H), 0.91 (t, J = 7.6 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ 142.8, 141.2, 136.0, 129.5, 128.9, 128.7, 125.7, 35.5, 35.4,
33.8, 33.7, 32.9, 22.54, 22.49, 14.1; IR (KBr) 2956, 2925, 2856, 1903,
1583, 1566, 1511, 1453, 963, 834 cm−1; HRMS (EI) calcd for
C24H30N2 346.2409 [M]+, found 346.2418.
5-(2-Methylbenzyl)-3-(o-tolyl)-1H-pyrazole (2j). Yield: 65%,
51.2 mg, colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 7.6
Hz, 1H), 7.23−7.15 (m, 7H), 6.11 (s, 1H), 3.95 (s, 2H), 2.39 (s, 3H),
2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 137.3, 136.6, 136.1,
131.5, 130.9, 130.5, 129.6, 129.1, 128.2, 126.9, 126.3, 126.0, 105.0,
31.4, 21.0, 19.7; IR (neat) 3184, 3103, 3016, 2953, 2923, 1605, 1570,
1492, 1463, 762, 737 cm−1; HRMS (EI) calcd for C18H18N2 262.1470
[M]+, found 262.1481.
3-Cyclohexyl-5-(4-nitrobenzyl)-1H-pyrazole (4h). Yield: 94%,
1
107.3 mg, colorless oil; H NMR (400 MHz, CDCl3) δ 9.36 (s, 1H),
8.06 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 5.79 (s, 1H), 4.01
(s, 2H), 2.58−2.53 (m, 1H), 1.91−1.64 (m, 5H), 1.37−1.13 (m, 5H);
13C NMR (100 MHz, CDCl3) δ 152.1, 148.6, 147.6, 146.6, 129.6,
123.7, 101.3, 35.8, 34.3, 32.9, 26.1, 25.9; IR (neat) 3190, 3103, 2928,
2852, 1923, 1599, 1573, 1518, 1346, 858, 729 cm−1; HRMS (EI) calcd
for C16H19N3O2 285.1477 [M]+, found 285.1475.
5-Benzyl-3-hexyl-1H-pyrazole (4i). Yield: 78%, 75.6 mg, color-
1
less oil; H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 7.29−7.20 (m,
5H), 5.82 (s, 1H), 3.97 (s, 2H), 2.58 (t, J = 8.0 Hz, 2H), 1.64−1.56
(m, 2H), 1.36−1.28 (m, 6H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 149.0, 148.5, 139.6, 128.9, 128.7, 126.5, 102.9, 34.0,
31.8, 29.5, 29.2, 26.9, 22.7, 14.3; IR (neat) 3189, 3102, 3027, 2954,
2928, 2857, 1726, 1603, 1578, 1495, 1466, 1454, 722 cm−1; HRMS
(EI) calcd for C16H22N2 242.1783 [M]+, found 242.1791.
5-Benzyl-3-cyclohexyl-1H-pyrazole (4j). Yield: 81%, 77.9 mg,
1
colorless oil; H NMR (400 MHz, CDCl3) δ 9.15 (s, 1H), 7.28−7.17
(m, 5H), 5.78 (s, 1H), 3.94 (s, 2H), 2.60−2.54 (m, 1H), 1.94−1.65
(m, 5H), 1.40−1.17 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 153.3,
149.1, 139.8, 129.1, 128.8, 126.5, 101.3, 36.4, 34.3, 33.2, 26.5, 26.3; IR
(neat) 3185, 3100, 3025, 2926, 2851, 1603, 1576, 1494, 1449, 1029,
1008, 718 cm−1; HRMS (EI) calcd for C16H20N2 240.1626 [M]+,
found 240.1630.
5-(4-Bromobenzyl)-3-(4-bromophenyl)-1H-pyrazole (2k).
1
Yield: 86%, 101.2 mg, white solid, mp 142−144 °C; H NMR (400
MHz, CDCl3) δ 7.50 (d, J = 8.8 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H),
7.40 (d, J = 8.4 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.29 (s, 1H), 3.90
(s, 2H); 13C NMR (100 MHz, CDCl3) δ 137.4, 132.2, 132.1, 131.1,
130.7, 129.1, 129.0, 127.4, 122.3, 121.0, 102.6, 32.7; IR (KBr) 3126,
3101, 3004, 2920, 2854, 1894, 1636, 1487, 1072, 1007, 826, 802 cm−1;
HRMS (EI) calcd for C16H12N2Br2 389.9367, 391.9347 [M]+, found
389.9375, 391.9350.
5-(4-Methoxybenzyl)-3-phenyl-1H-pyrazole (5a). Yield: 32%,
33.8 mg, white solid, mp 114−116 °C; 1H NMR (400 MHz, CDCl3) δ
7.60 (d, J = 7.2 Hz, 2H), 7.31−7.20 (m, 3H), 7.09 (d, J = 8.4 Hz, 2H),
6.77 (d, J = 8.4 Hz, 2H), 6.26 (s, 1H), 3.88 (s, 2H), 3.71 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 158.5, 147.8, 132.2, 130.5, 129.9, 128.9,
128.1, 125.7, 114.2, 102.0, 55.4, 32.4; IR (KBr) 3189, 2927, 1610,
1511, 1463, 1246, 1033, 766 cm−1; HRMS (EI) calcd for C17H16N2O
264.1263 [M]+, found 264.1260.
5-(4-Fluorobenzyl)-3-(4-fluorophenyl)-1H-pyrazole (2l).
1
Yield: 88%, 71.4 mg, white solid, mp 128−130 °C; H NMR (400
3-(4-Fluorophenyl)-5-(4-methoxybenzyl)-1H-pyrazole (5b).
MHz, CDCl3) δ 9.56 (s, 1H), 7.59 (dd, J = 8.0, 5.6 Hz, 2H), 7.12 (dd,
J = 8.0, 5.6 Hz, 2H), 7.00 (dd, J = 8.4, 8.4 Hz, 2H), 6.95 (dd, J = 8.4,
8.4 Hz, 2H), 6.25 (s, 1H), 3.90 (s, 2H); 13C NMR (100 MHz, CDCl3)
1
Yield: 9%, 10.2 mg, white solid, mp 124−126 °C; H NMR (400
MHz, CDCl3) δ 7.61 (dd, J = 8.8, 5.2 Hz, 2H), 7.09 (d, J = 8.4 Hz,
2H), 6.99 (dd, J = 8.8, 8.8 Hz, 2H), 6.81 (d, J = 8.8 Hz, 2H), 6.24 (s,
1H), 3.87 (s, 2H), 3.76 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.7
(d, 1J = 245.2 Hz), 158.5, 149.3, 147.2, 130.3, 129.8, 128.8, 127.5 (d, 3J
1
1
δ 162.8 (d, J = 245.7 Hz), 161.9 (d, J = 243.5 Hz), 148.9, 147.2,
134.1, 130.2 (d, 3J = 7.9 Hz), 128.4, 127.5 (d, 3J = 8.1 Hz), 115.8 (d, 2J
= 20.8 Hz), 115.6 (d, 2J = 20.5 Hz), 102.1, 32.3; IR (KBr) 3259, 1604,
1525, 1508, 1448, 1432, 1220, 841, 793 cm−1; HRMS (EI) calcd for
C16H12N2F2 270.0969 [M]+, found 270.0970.
2
= 8.0 Hz), 115.7 (d, J = 21.5 Hz), 114.2, 101.8, 55.4, 32.0; IR (KBr)
3182, 3133, 3077, 3007, 2912, 2836, 1889, 1611, 1583, 1511, 1454,
1246, 839 cm−1; HRMS (EI) calcd for C17H15N2OF 282.1168 [M]+,
found 282.1170.
5-(3,4-Difluorobenzyl)-3-(3,4-difluorophenyl)-1H-pyrazole
1
(2m). Yield: 86%, 79.0 mg, white solid, mp 130−132 °C; H NMR
(400 MHz, CDCl3) δ 11.10 (s, 1H), 7.49−7.26 (m, 2H), 7.17−6.89
(m, 4H), 6.29 (s, 1H), 3.94 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
151.8, 150.8 (dd, 1,2J = 246.5, 12.6 Hz), 150.4 (dd, 1,2J = 247.8, 12.9
Hz), 149.5 (dd, 1,2J = 246.0, 12.3 Hz), 149.3, 135.0, 129.4, 124.6 (d, 3J
5-Heptyl-3-(p-tolyl)-1H-pyrazole (5c). Yield: 12%, 12.3 mg,
white solid, mp 98−100 °C; 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J
= 8.4 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.33 (s, 1H), 2.66 (t, J = 7.6
Hz, 2H), 2.37 (s, 3H), 1.71−1.64 (m, 2H), 1.39−1.25 (m, 8H), 0.88
(t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 149.8, 148.3,
137.8, 129.8, 129.6, 125.6, 101.0, 31.9, 29.4, 29.2, 26.7, 21.4, 14.3; IR
(KBr) 2950, 2926, 2850, 1900, 1580, 1566, 1464, 1425, 1041, 1017,
960, 821, 792 cm−1; HRMS (EI) calcd for C17H24N2 256.1939 [M]+,
found 256.1939.
5-(Cyclohexylmethyl)-3-(p-tolyl)-1H-pyrazole (5d). Yield:
12%, 12.2 mg, white solid, mp 45−47 °C; 1H NMR (400 MHz,
CDCl3) δ 7.62 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 6.31 (s,
1H), 2.51 (d, J = 6.8 Hz, 2H), 2.37 (s, 3H), 1.73−1.53 (m, 6H), 1.26−
0.88 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 150.1, 146.7, 137.7,
130.0, 129.5, 125.7, 101.7, 38.4, 34.5, 33.2, 26.5, 26.3, 21.4; IR (KBr)
3187, 3135, 3093, 2922, 2851, 1900, 1583, 1531, 1511, 1448, 1028,
822 cm−1; HRMS (EI) calcd for C17H22N2 254.1783 [M]+, found
254.1778.
3
2
= 3.4 Hz), 121.9 (d, J = 3.3 Hz), 117.8 (d, J = 17.8 Hz), 117.66,
2
2
117.61 (d, J = 17.8 Hz), 114.8 (d, J = 18.3 Hz), 102.6, 32.1; IR
(KBr) 3176, 1610, 1530, 1518, 1478, 1281, 773 cm−1; HRMS (EI)
calcd for C16H10N2F4 306.0780 [M]+, found 306.0782.
3-(Naphthalen-1-yl)-5-(naphthalen-1-ylmethyl)-1H-pyrazole
(2n). Yield: 60%, 60.2 mg, pale yellow solid, mp 84− 86 °C; 1H NMR
(400 MHz, CDCl3) δ 10.68 (s, 1H), 8.22 (d, J = 8.0 Hz, 1H), 7.89 (d,
J = 7.6 Hz, 1H), 7.80−7.64 (m, 4H), 7.44−7.18 (m, 8H), 6.18 (s, 1H),
4.18 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 147.4, 134.8, 134.0,
133.9, 132.0, 131.4, 130.0, 128.8, 128.7, 128.4, 127.5, 127.2, 126.9,
126.5, 126.2, 126.0, 125.82, 125.75, 125.7, 125.3, 124.1, 30.7; IR (KBr)
2970, 1633, 1597, 1509, 1397, 777 cm−1; HRMS (EI) calcd for
C24H18N2 334.1470 [M]+, found 334.1464.
3-((3-(Pyridin-3-yl)-1H-pyrazol-5-yl)methyl)pyridine (2o).
1
Yield: 80%, 56.7 mg, white solid, mp 118−120 °C; H NMR (400
General Procedure for One-Pot Synthesis of 3,5-Disubsti-
tuted Pyrazoles from Alkynes. A reaction flask was charged with a
mixture of terminal alkynes (6, 0.6 mmol), CuCl (3.0 mg, 5 mol %),
and DMSO (3.0 mL). The reaction mixture was stirred at 90 °C for 8
MHz, CDCl3) δ 10.57 (s, 1H), 8.95 (d, J = 1.6 Hz, 1H), 8.50−8.43
(m, 3H), 8.02−7.99 (m, 1H),7.54 (d, J = 8.0 Hz, 1H), 7.29−7.18 (m,
2H), 6.40 (s, 1H), 4.02 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
1697
dx.doi.org/10.1021/jo302732v | J. Org. Chem. 2013, 78, 1693−1698

The Journal of Organic Chemistry
Note
149.5, 148.6, 147.8, 146.8, 136.5, 134.3, 133.0, 128.5, 123.73, 123.72,
102.4, 30.1; IR (KBr) 3195, 3113, 3084, 2844, 1727, 1577, 1444, 1435,
1422, 1029, 810, 704 cm−1; HRMS (EI) calcd for C14H12N4 236.1062
[M]+, found 236.1057.
3-(Thiophen-3-yl)-5-(thiophen-3-ylmethyl)-1H-pyrazole
(2p). Yield: 78%, 57.6 mg, white solid, mp 98−100 °C; 1H NMR (400
MHz, CDCl3) δ 9.44 (s, 1H), 7.44 (d, J = 1.6 Hz, 1H), 7.34−7.23 (m,
3H), 6.96−6.91 (m, 2H), 6.24 (s, 1H), 3.94 (s, 2H); 13C NMR (100
MHz, CDCl3) δ 147.0, 145.0, 138.8, 133.5, 128.4, 126.3, 126.0, 121.8,
121.0, 102.2, 27.8; IR (KBr) 3204, 3136, 3093, 2889, 1600, 1474,
1431, 1010, 854, 784, 737 cm−1; HRMS (EI) calcd for C12H10N2S2
246.0285 [M]+, found 246.0283.
(5) Other methods for synthesis of pyrazoles, see: (a) Panda, N.;
Jena, A. K. J. Org. Chem. 2012, 77, 940. (b) Kinjo, R.; Donnadieu, B.;
Bertrand, G. Angew. Chem., Int. Ed. 2011, 50, 5560. (c) Shan, G.; Linu,
P.; Rao, Y. Org. Lett. 2011, 13, 1746. (d) Martin, R.; Rivero, M. R.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2006, 45, 7079. (e) Vanier, C.;
Wagner, A.; Mioskowski, C. J. Comb. Chem. 2004, 6, 846. (f) Klein, J.
F.; Pommelet, J. C.; Chuche, J. Can. J. Chem. 1993, 71, 410.
(g) Khrimyan, A. P.; Karapetyan, A. V.; Badanyan, Sh. O. Chem.
Heterocycl. Compd. 1984, 20, 189. (h) Paudler, W. W.; Zeiler, A. G. J.
Org. Chem. 1969, 34, 999.
(6) For the Cope-type hydroamination reaction of alkynes, see:
(a) Moran, J.; Gorelsky, S. I.; Dimitrijevic, E.; Lebrun, M.-E.; Bedard,
A.-C.; Seguin, C.; Beauchemin, A. M. J. Am. Chem. Soc. 2008, 130,
17893. (b) Cebrowski, P. H.; Roveda, J.-G.; Moran, J.; Gorelsky, S. I.;
Beauchemin, A. M. Chem. Commun. 2008, 492. (c) Beauchemin, A.
M.; Moran, J.; Lebrun, M.-E.; Seguin, C.; Dimitrijevic, E.; Zhang, L.;
Gorelsky, S. I. Angew. Chem., Int. Ed. 2008, 47, 1410.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Characterization for compounds, including copies of H and
13C NMR spectra and crystallographic data of 4b (CIF). This
material is available free of charge via the Internet at http://
pubs.acs.org.
(7) Wang, L.; Yu, X.; Feng, X.; Bao, M. Org. Lett. 2012, 14, 2418.
(8) For the proton-transfer process, see: Cooper, N. J.; Knight, D. W.
Tetrahedron 2004, 60, 243.
(9) For the Cu-catalyzed homocoupling reaction of alkynes, see:
(a) Niu, X.; Li, C.; Li, J.; Jia, X. Tetrahedron Lett. 2012, 53, 5559.
(b) Li, Y.-N.; Wang, J.-L.; He, L.-N. Tetrahedron Lett. 2011, 52, 3485.
(c) Yin, K.; Li, C.; Li, J.; Jia, X. Green Chem. 2011, 13, 591. (d) Wang,
D.; Li, J.; Li, N.; Gao, T.; Hou, S.; Chen, B. Green Chem. 2010, 12, 45
and references therein.
AUTHOR INFORMATION
Corresponding Author
*E-mail: yuxiaoqiang@dlut.edu.cn; mingbao@dlut.edu.cn.
Notes
■
1
(10) The structural assignment was based on the analysis of the H
The authors declare no competing financial interest.
and 13C NMR spectra. The product 4b was further identified by
determining its X-ray structure; the crystallographic data are available
on Supporting Information.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (No. 21002010 and 21173032) for their financial
support.
(11) Mizunoa, N.; Kamata, K.; Nakagawa, Y.; Oishia, T.; Yamaguchi,
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