Inorganic base-mediated stereoselective hydroamination of arylalkynes with imidazole: An efficient access to N-vinylimidazoles

Article abstract of DOI:10.1016/j.tet.2018.07.022

A metal-free inorganic base-mediated highly stereoselective hydroamination of arylalkynes with imidazoles has been developed, and the corresponding N-vinylimidazoles were obtained in good yields and with moderate to excellent stereoselectivities (up to 99

Full text of DOI:10.1016/j.tet.2018.07.022

Accepted Manuscript
Inorganic base-mediated stereoselective hydroamination of arylalkynes with
imidazole: An efficient access to N-Vinylimidazoles
Lin-Dong Liu, Zhong-Liang Lei, Hong Wang, Ming Bian, Zhen-Jiang Liu, Jin-Tao Liu,
Xiao-Jun Hu
PII:
S0040-4020(18)30843-3
10.1016/j.tet.2018.07.022
TET 29682
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 15 May 2018
Revised Date: 8 July 2018
Accepted Date: 9 July 2018
Please cite this article as: Liu L-D, Lei Z-L, Wang H, Bian M, Liu Z-J, Liu J-T, Hu X-J, Inorganic base-
mediated stereoselective hydroamination of arylalkynes with imidazole: An efficient access to N-
Vinylimidazoles, Tetrahedron (2018), doi: 10.1016/j.tet.2018.07.022.
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ACCEPTED MANUSCRIPT
Inorganic Base-Mediated Stereoselective Hydroamination of Arylalkynes with
Imidazole: An Efficient Access to N-Vinylimidazoles
Lin-Dong Liu,a,† Zhong-Liang Lei,a,† Hong Wang,a Ming Bian,a Zhen-Jiang Liu,a,b,*
Jin-Tao Liu,b Xiao-Jun Hua,*
a School of Chemical and Environmental Engineering, Shanghai Institute of
Technology, 100 Haiquan Road, Shanghai 201418, P. R. China
Fax: (+86)-21- 60877231; Tel: (+86)-21- 60877227; E-mail: zjliu@sit.edu.cn;
hxjsit@sina.com
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R.
China
Graphical abstract
† Contributed equally to this work.

ACCEPTED MANUSCRIPT
Inorganic Base-Mediated Stereoselective Hydroamination of Arylalkynes with
Imidazole: An Efficient Access to N-Vinylimidazoles
Lin-Dong Liu,a,† Zhong-Liang Lei,a,† Hong Wang,a Ming Bian,a Zhen-Jiang Liu,a,b,*
Jin-Tao Liu,b Xiao-Jun Hua,*
a School of Chemical and Environmental Engineering, Shanghai Institute of
Technology, 100 Haiquan Road, Shanghai 201418, P. R. China
Fax: (+86)-21- 60877231; Tel: (+86)-21- 60877227; E-mail: zjliu@sit.edu.cn;
hxjsit@sina.com
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R.
China
Abstract
A metal-free inorganic base-mediated highly stereoselective hydroamination of
arylalkynes with imidazoles has been developed, and the corresponding
N-vinylimidazoles were obtained in good yields and with moderate to excellent
stereoselectivities (up to 99:1). For the electron rich alkynes, the reaction system of
CsOH·H2O/NMP/140 oC led to the predominant formation of E-addition products,
while the reaction system of KOH/NMP/90 oC afforded the Z-isomers as the major
product. The electron deficient alkynes furnished predominantly the E-addition
products in both reaction systems. This study essentially provides a general and an
efficient protocol for the synthesis of E-isomer of the N-vinylimidazoles.
Keywords: hydroamination; alkynes; imidazole; N-vinylimidazole; inorganic base
† Contributed equally to this work.
1

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Introduction
N-Vinylimidazoles are versatile intermediates in organic synthesis.1 They are also
found to have wide application in the preparation of biologically active molecules,2
pharmaceuticals,3 and polymeric materials.4 In addition, the vinyl group can also act
as an efficient protecting group for these imidazole derivatives.5 A variety of methods
have been developed for the synthesis of these compounds. The most straightforward
protocol amongst them involves transition-metal mediated cross-coupling reactions of
different vinyl sources with imidazoles.6 This protocol is relatively simpler because
the coupling reaction can proceed in a comparatively milder condition. However, it
suffers from certain drawbacks. For example, the use of prefunctionalized vinyl
halides or vinyl boronic acids renders the reaction process more tedious. Furthermore,
the use of the transition-metal catalysts and ligands results not only in a high
economic cost but also increases the possibilities of concomitant metal contamination
of the product. These aspects greatly restrict their applications in the industry. Another
alternate methodology commonly used to synthesize N-vinylimidazoles is the direct
hydroamination of alkynes with imidazoles, which is entirely (100%) an
atom-economical and waste-free process.7 However, the stereocontrol of the double
bond geometry remains the biggest challenge in this addition reaction. During the past
few years, significant progress has been made on the base-mediated hydroamination
of alkynes with various N-heterocycles.7,8 Nonetheless, only a few methods are
available for the hydroamination of alkynes with imidazoles.8g-l In contrast to the
electron-rich N-heterocycles such as indoles and pyrroles, imidazoles are
electron-deficient and less reactive.8h The higher activation energy barrier between
imidazole and alkyne makes the addition process more challenging.7, 8g-h In 1999,
Knochel and co-workers reported the first and the only example for the addition of
imidazole to alkynes using CsOH·H2O in NMP.8g Recently, Verma and co-workers8h
and Mao and co-workers8i independently reported the hydroamination of alkynes with
imidazoles using two different reaction systems, viz. KOH/DMSO and K3PO4/DMSO.
Nevertheless, all the above reports produced predominantly the Z-isomer of the
N-vinylimidazoles.8g-m The synthesis of the E-isomer of the N-vinylimidazoles was
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carried out only by the addition of imidazoles to activated alkynes.8h Therefore, there
still exists a need to develop a general method for the efficient synthesis of either of
the isomers of N-vinylimidazoles, and more specifically, its E-isomer. Herein, we
report an inorganic base-mediated highly stereoselective hydroamination of
arylalkynes with imidazoles, which provides a practical method for the efficient
synthesis of either isomer of N-vinylimidazoles. Our study essentially presents an
efficient protocol for the synthesis of E-isomer of the N-vinylimidazoles.
Results and discussion
Scheme 1. Unexpected inorganic base-mediated addition of imidazole to alkynes
In one of our previous study on the copper-catalyzed oxidative C-N coupling of
terminal alkynes with imidazoles,9 phenylacetylene 1a and imidazole 2a were
o
selected as the model substrates. CsOH·H2O was used as the base in NMP at 100 C
for 24 hours in this reaction. However, the expected product A was not obtained
(Scheme 1). Instead, the direct hydroamination product 3a/4a, with a yield of 77%
was obtained with moderate stereoselectivity (E:Z = 77:23) (Scheme 1). E-addition
product was obtained as the major product (Scheme 1). An extensive literature survey
revealed that Knochel had reported a sole example of the addition of imidazole to
phenylacetylene using CsOH·H2O as the base in NMP.8g However, the reaction gave
exclusively the Z-addition product.
To further investigate this intriguing formation of the exclusive E-addition product,
a number of reaction conditions were screened considering the addition of imidazole
2a to phenylacetylene 1a as the model reaction. The results are summarized in Table 1.
The effect of temperature on the reaction was examined first. Elevating the
o
o
temperature of the reaction from 100 C to 150 C resulted predominantly in the
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formation of the thermodynamically favored E-addition product (Table 1, entries 3-8).
o
When the same was carried out at 140 C, the E-addition product (E:Z = 99:1) was
obtained almost exclusively with 82% yield (Table 1, entry 7). Gratifyingly, lowering
o
the reaction temperature to 90 C led to a reversal in the stereoselectivity of the
addition product, affording predominantly the kinetically favored Z-isomer in high
yield and with excellent stereoselectivity (Table 1, entry 2). The results are very
similar to those reported by Knochel (83% yield, Z:E = 100:0). Further decrease in the
reaction temperature to 80 oC resulted in a dramatic reduction of the yield albeit with
high stereoselectivity, predominantly forming the Z isomer (Z:E = 98:2) (Table 1,
entry 1). The above results revealed that when the reaction was carried out at two
o
o
different temperatures (140 C versus 90 C), either of the stereoisomers of
N-vinylimidazole was obtained. Since the choice of base has often been found to be
critical in the addition of N-heterocycles to alkynes,7,8 commonly used bases such as
KOH, NaOH, K3PO4, K2CO3, and Cs2CO3 were subsequently investigated at two
o
reaction temperatures (140 oC and 90 C) (Table 1, entries 9-13, 15-19). When the
reaction was carried out at 140 oC, both KOH and K2CO3 gave high stereoselectivities
with E configuration while the use of NaOH, K3PO4, and Cs2CO3 resulted in a
mixture of E and Z stereoisomers (Table 1, entries 9-13). Surprisingly, when the
o
reaction was carried out at 90 C, all the tested bases except K2CO3 gave high
stereoselectivities with Z configuration, although the yields observed for K3PO4 and
Cs2CO3 as the bases were low (Table 1, entries 2 and 15-19). Control experiments
confirmed that the absence of base did not result in the formation of any
hydroamination product (Table 1, entries 14 and 20). On the basis of the above results,
the optimized reaction conditions for the hydroamination reaction to produce either of
the isomers of N-vinylimidazole were chosen to be (A) CsOH·H2O/NMP/140 oC for
E-selective product and (B) KOH/NMP/90 oC for Z-selective product.
Table 1: Optimization of the reaction conditionsa
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Entry
1
Base
CsOH·H2O
CsOH·H2O
CsOH·H2O
CsOH·H2O
CsOH·H2O
CsOH·H2O
CsOH·H2O
CsOH·H2O
KOH
Temp. (oC)
80
Yield (%)b
E:Z (3a/4a)c
2:98
8:92
77:23
64:36
94:6
91:9
99:1
98:2
94:6
85:15
43:57
37:63
94:6
-
10
77
77
75
72
69
82
64
80
77
94
97
57
0
2
90
3
100
110
120
130
140
150
140
140
140
140
140
140
90
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
NaOH
K3PO4
Cs2CO3
K2CO3
-
KOH
83
79
15
38
-
2:98
8:92
2:98
5:95
-
NaOH
90
K3PO4
90
Cs2CO3
K2CO3
90
90
-
90
0
-
a
Reaction conditions: phenylacetylene 1a (2.0 mmol), imidazole 2a (2.4 mmol) and base (1.0
mmol) in 3.0 mL NMP under N2. b Isolated yields. c The E/Z (3a/4a) ratio was determined by GC
chromatography.
With the two aforesaid optimized reaction conditions, a variety of arylalkynes were
employed as the substrate to explore the scope of the stereoselective hydroamination
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reaction. The results are summarized in Table 2. It was evident that the electronic
properties of the substituents attached to the aryl group of the triple bond and the
nature of the N-heterocycles had a significant influence on the stereoselectivity of the
reaction.7,8h,l Phenylacetylene 1a and alkynes 1b-c containing electron-donating
substituents on the phenyl ring proved to be excellent substrates in both the reaction
systems, giving the corresponding hydroamination products in moderate to excellent
stereoselectivities (Table 2, entries 1-6). However, the addition to 3-methyl substituted
phenylacetylene 1c resulted in only a moderate yield (Table 2, entry 6). Interestingly,
when alkynes containing the electron-withdrawing groups 1d-f were subjected to
either reaction system, E-addition products were predominantly formed in moderate
to good yields (Table 2, entries 7-12). Other N-heterocycles, such as pyrazole 2b and
pyrrole 2c, were also tested in the hydroamination reaction (Table 2, entries 13-20).
To our delight, the electron-deficient pyrazole 2b was also found to be compatible in
both the reaction systems, affording the corresponding hydroamination products in
high yields and with excellent stereoselectivities (Table 2, entries 13-18). However,
the addition of electron-rich pyrrole resulted only in the E-isomer in good yields,
irrespective of the reaction system that was used (Table 2, entries 19-20). Aliphatic
alkynes and internal alkynes were also evaluated under both the optimized reaction
systems, but only traces of the desired hydroamination products were found. It is
worth noting that a general and efficient protocol for the synthesis of E-isomer of the
N-vinylimidazoles could be established (Table 2, entries 1, 3, 5, 7, 9, 11, 13, 15, 17,
19), in contrast to the previous reports.8g-l
Table 2: Scope of the inorganic base-mediated addition reaction of N-heterocycles to
alkynes
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Entry
1
R
N-heterocycles Conditionsa Product Yield (%)b E/Z (3/4)c
H (1a)
H (1a)
Imidazole (2a)
Imidazole (2a)
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
3a+4a
3a+4a
3b+4b
3b+4b
3c+4c
3c+4c
3d+4d
3d+4d
3e+4e
3e+4e
3f+4f
82
83
77
81
92
38
44
86
73
77
42
61
89
86
93
89
79
86
88
72
99:1
2:98
2
3
4-Me (1b) Imidazole (2a)
4-Me (1b) Imidazole (2a)
3-Me (1c) Imidazole (2a)
3-Me (1c) Imidazole (2a)
3-F (1d) Imidazole (2a)
3-F (1d) Imidazole (2a)
4-Cl (1e) Imidazole (2a)
4-Cl (1e) Imidazole (2a)
4-Br (1f) Imidazole (2a)
4-Br (1f) Imidazole (2a)
83:17
1:99
4
5
85:15d
6
2:98
7
99:1
8
98:2
9
97:3
10
11
12
13
14
15
16
17
18
19
20
88:12
94:6
96:4
3f+4f
H (1a)
H (1a)
Pyrazole (2b)
Pyrazole (2b)
3g+4g
3g+4g
3h+4h
3h+4h
3i+4i
93:7
5:95
4-Me (1b) Pyrazole (2b)
4-Me (1b) Pyrazole (2b)
4-Cl (1e) Pyrazole (2b)
4-Cl (1e) Pyrazole (2b)
73:27d
5:95
98:2
84:16
95:5
3i+4i
H (1a)
H (1a)
Pyrrole (2c)
Pyrrole (2c)
3j+4j
98:2
3j+4j
a Conditions A: alkynes 1 (2.0 mmol), N-heterocycles 2 (2.4 mmol) and CsOH·H2O (1.0 mmol) in
3.0 mL NMP at 140 oC for 24 h under N2. Conditions B: alkynes 1 (2.0 mmol), N-heterocycles 2
b
c
(2.4 mmol) and KOH (1.0 mmol) in 3.0 mL NMP at 90 oC for 24 h under N2. Isolated yields.
The E/Z (3/4) ratio was determined by GC chromatography. d The stereoisomers can’t be isolated
by silica gel column chromatography.
In order to verify whether the kinetically favored Z-addition product was initially
formed or not, the product of the hydroamination of phenylacetylene 1a with
imidazole 2a under the reaction condition of CsOH·H2O/NMP/140 oC was monitored
as a function of time (Scheme 2, eq. a). When the reaction was run for 6 h, an
7

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isomeric ratio of E:Z = 75:25 was observed. Prolonging the reaction time to 12 and 18
h led to a dramatic increment of the E-isomer. Extending the reaction time to 24 h led
to the exclusive formation of E-addition product 3a. The transformation experiments
showed that the inorganic base played an important role in the reaction (Scheme 2, eq.
b). From the above results, it can be deduced that the kinetically favored Z-isomers of
N-vinylimidazoles are initially formed, which later undergo slow isomerization to the
thermodynamically stable E-isomers under the specified reaction conditions. However,
the exact underlying reaction pathway is still unclear at present.10
Scheme 2.
Conclusions
In summary, we have developed an inorganic base-mediated highly stereoselective
hydroamination of arylalkynes with imidazoles under metal-free conditions. The
electron rich alkynes are compatible in both the reaction systems, affording either
stereoisomer of the corresponding N-vinylimidazoles in good yields and with
moderate to excellent stereoselectivities. The electron deficient alkynes furnished
predominantly the E-isomer of N-vinylimidazoles in both the reaction systems.
Importantly, the current hydroamination reaction provided a general and efficient
protocol for the synthesis of E-isomer of the N-vinylimidazoles, which is
complementary to the previous reports. Further studies to clarify the reaction
mechanism and expand the substrate scope of this methodology are currently in
progress in our laboratory.
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Experimental
General experimental methods
Unless otherwise mentioned, solvents and reagents were purchased from commercial
sources and used as received. NMP were freshly distilled over CaH2 prior to use. The
NMR chemical shifts are reported in ppm. 1H NMR spectra were recorded on Bruker
Bruker AM-500 (500 MHz) or Agilent 400 (400 MHz) spectrometers with TMS as
internal standard. 13C NMR spectra were recorded on Agilent 400 (101 MHz) or
Bruker AM-400 (101 MHz) spectrometers. IR spectra were obtained with a Shimadzu
IR-440 spectrophotometer. EI-MS (LR) was recorded on a Agilent 5973N
spectrometer. ESI-MS (LR) was recorded on a 1100 LCMSD SL spectrometer. HRMS
data were obtained on a Waters Micromass GCT mass spectrometer. All reactions
were monitored by TLC with Huanghai GF254 silica gel coated plates. Flash column
chromatography was carried out using 300-400 mesh silica gels.
General procedure for the hydroamination of alkynes 1 with N-heterocycles 2
under CsOH·H2O.
An oven-dried tube was cooled to room temperature under N2 atmosphere and
charged with N-heterocycles 2 (2.4 mmol), CsOH·H2O (168 mg, 1.0 mmol). Under an
N2 atmosphere alkynes 1 (2.0 mmol) was added followed by dry NMP (3 mL). The
o
tube was sealed and the mixture was heated to 140 C. After stirring at this
temperature for 24 h, the mixture was cooled to room temperature and quenched with
saturated sodium bicarbonate (10 mL). The resulting mixture was extracted with ethyl
acetate (10 mL x 3). The combined organic solution was washed with saturated brine
(10 mL) and dried over Na2SO4. After the removal of volatile solvents under vacuum,
the residue was further purified by silica gel column chromatography (PE:EA = 2:1)
to give product 3.
(E)-1-styryl-1H-imidazole (3a)6b-c, i
1
White solid; 280 mg, yield 82%; E:Z = 99:1; H NMR (400 MHz, CDCl3) δ 7.71 (s,
9

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1H), 7.37-7.23 (m, 7H), 7.11 (s, 1H), 6.69 (d, J = 14.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 136.47, 134.42, 130.42, 128.93, 128.02, 126.17, 122.69, 118.57, 116.25;
FT-IR (KBr, cm-1): ν 3110, 1655, 1485, 1291, 1019, 937, 655, 509; EI-MS (m/z, %):
170 (M+, 98), 169 (100), 115 (41.79), 142 (29.36), 143 (25.31); HR-MS calcd. for
C11H10N2 [M+]: 170.0844; Found: 170.0847.
(E)-1-(4-methylstyryl)-1H-imidazole (3b)6i
White solid; 284 mg, yield 77%; E:Z = 83:17; 1H NMR (400 MHz, CDCl3) δ 7.74 (s,
1H), 7.34-7.24 (m, 4H), 7.20-7.13 (m, 3H), 6.72 (d, J = 14.4 Hz, 1H), 2.36 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 138.37, 130.68, 129.63, 129.45, 129.37, 128.46,
126.10, 123.95, 121.73, 21.25; FT-IR (KBr, cm-1): ν 3111, 3026, 1656, 1491, 1321,
1226, 1073, 820, 656, 602; EI-MS (m/z, %): 184 (M+,100), 183 (88.84), 156 (43.17),
115 (32.67), 157 (19.63); HR-MS calcd. for C12H12N2 [M+]: 184.1000; Found:
184.0996.
(E)-1-(3-methylstyryl)-1H-imidazole (3c)
Yellow oil; 338.5 mg, yield 92%; E:Z = 85:15; 1H NMR (400 MHz, CDCl3): δ 7.73 (s,
1H), 7.31 (d, J = 14.6 Hz, 1H), 7.27-7.18 (m, 4H), 7.13 (s, 1H), 7.10 (d, J = 7.2 Hz,
13
1H), 6.69 (d, J = 14.6 Hz, 1H), 2.36 (s, 3H); C NMR (100 MHz, CDCl3) δ 138.53,
136.40, 134.32, 130.31, 128.86, 128.81, 126.87, 123.34, 122.50, 118.83, 116.26,
21.41; FT-IR (KBr, cm-1): ν 3111, 3031, 1661, 1494, 1230, 1026, 936, 776, 656, 621;
EI-MS (m/z, %): 184 (M+, 100), 183 (94.86), 115 (43.72), 156(37.55), 157(20.15);
HR-MS calcd. for C12H12N2 [M+]: 184.1000; Found: 184.1003.
(E)-1-(3-fluorostyryl)-1H-imidazole (3d)6i
1
Yellow oil; 166 mg, yield 44%; E:Z = 99:1; H NMR (400 MHz, CDCl3) δ 7.75 (s,
1H), 7.35-7.29 (m, 2H), 7.26 (s, 1H), 7.18-7.13 (m, 2H), 7.09 (d, J = 10.0 Hz, 1H),
13
7.01-6.93 (m, 1H), 6.68 (d, J = 14.8 Hz, 1H); C NMR (100 MHz, CDCl3) δ 163.08
(d, J = 244.0 Hz), 136.78 (d, J = 7.5 Hz), 136.56, 130.62, 130.45 (d, J = 7.5 Hz),
123.75, 122.11 (d, J = 3.0 Hz), 117.29 (d, J = 3.0 Hz), 116.18, 114.78 (d, J = 22.0 Hz),
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112.60 (d, J = 22.0 Hz); FT-IR (KBr, cm-1): ν 3112, 3072, 1664, 1512, 1294, 1148,
1026, 935, 779, 684; EI-MS (m/z, %): 188 (M+, 100), 187 (94.56), 133 (56.74), 160
(37.31), 161 (28.71); HR-MS calcd. for C11H9N2F [M+]: 188.0750; Found: 188.0751.
(E)-1-(4-chlorostyryl)-1H-imidazole (3e)6c, i
White solid; 299.2 mg, yield 73%; E:Z = 97:3; 1H NMR (500 MHz, CDCl3) δ 7.68 (s,
1H), 7.27 (s, 4H), 7.25 (d, J = 14.5 Hz, 1H), 7.19 (s, 1H), 7.08 (s, 1H), 6.65 (d, J =
14.5 Hz, 1H); FT-IR (KBr, cm-1): ν 3312, 3028, 1662, 1488, 1291, 1224, 1083, 819,
654, 511; 13C NMR (100 MHz, CDCl3) δ 136.47, 133.67, 132.96, 130.65, 129.12,
127.34, 123.18, 117.46, 116.20; EI-MS (m/z, %): 204 (M+, 100), 203 (64.31), 115
(46.3), 205 (33.56), 206 (33.16); HR-MS calcd. for C11H9N2Cl [M+]: 204.0454;
Found: 204.0456.
(E)-1-(4-bromostyryl)-1H-imidazole (3f)
1
White solid; 210 mg, yield 42%; E:Z = 94:6; H NMR (400 MHz, CDCl3) δ 7.75 (s,
1H), 7.49 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 14.6 Hz, 1H), 7.27 (d, J = 8.2 Hz, 3H), 7.15
13
(s, 1H), 6.71 (d, J = 14.6 Hz, 1H); C NMR (100 MHz, CDCl3) δ 136.47, 133.42,
131.98, 130.47, 127.64, 123.22, 121.67, 117.37, 116.20; FT-IR (KBr, cm-1): ν 3102,
1656, 1510, 1484, 1291, 1104, 1078, 931, 695, 529; EI-MS (m/z, %): 247 (M+, 62.59),
115 (100), 248 (99.53), 250 (99.38), 249 (75.91); HR-MS calcd. for C11H9N2Br [M+]:
247.9949; Found: 247.9948.
(E)-1-styryl-1H-pyrazole (3g)6a-b
1
White solid; 303.2 mg, yield 89%; E:Z = 93:7; H NMR (400 MHz, CDCl3) δ
7.69-7.65 (m, 2H), 7.52 (d, J = 14.4 Hz, 1H), 7.43 (d, J = 7.5 Hz, 2H), 7.35 (t, J = 7.5
13
Hz, 2H), 7.28-7.24 (m, 1H), 7.06 (d, J = 14.4 Hz, 1H), 6.41-6.38 (m, 1H); C NMR
(100 MHz, CDCl3) δ 141.14, 135.04, 128.87, 128.04, 127.61, 126.43, 126.22, 116.94,
107.34; FT-IR (KBr, cm-1): ν 3121, 1656, 1413. 1227, 1046, 966, 776, 692, 609, 504;
EI-MS (m/z, %): 170 (M+, 54.46), 169 (100), 102 (41.98), 168 (11.24), 115 (11.03);
HR-MS calcd. for C11H10N2 [M+]: 170.0844; Found: 170.0839.
11

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(E)-1-(4-methylstyryl)-1H-pyrazole (3h)8b, 11
Yellow oil; 343 mg, yield 93%; E:Z = 73:27; 1H NMR (500 MHz, CDCl3) δ 7.67-7.65
(m, 1H), 7.48 (d, J = 14.5 Hz, 0.73H), 7.33 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz,
2H), 7.11-7.06 (m, 1H), 7.02 (d, J = 14.5 Hz, 0.73H), 6.96 (d, J = 9.5 Hz, 0.27H),
6.39 (t, J = 2.0 Hz, 0.73H), 6.24 (d, J = 9.5 Hz, 0.27H), 6.20 (t, J = 2.0 Hz, 0.27H),
2.35 (s, 2.19H), 2.34 (s, 0.81H); 13C NMR (125 MHz, CDCl3) δ 140.95, 137.51,
132.11, 129.54, 129.31, 128.59, 126.10, 119.50, 106.52, 21.24; EI-MS (m/z, %): 184
(M+, 78.97), 183 (100), 116 (69.67), 115 (67.66), 91 (20.91), 168 (16.91), 77 (11.92),
185 (9.98); HR-MS calcd. for C12H12N2 [M+]: 184. 1000; Found 184. 0998.
(E)-1-(4-chlorostyryl)-1H-pyrazole (3i)
o
1
Yellow oil; 323.6 mg, yield 79%; E:Z = 98:2; m.p. 92-94 C; H NMR (500 MHz,
CDCl3 ) δ 7.67 (d, J = 2.0 Hz, 1H), 7.65 (d, J = 2.5 Hz, 1H), 7.48 (d, J = 14.4 Hz, 1H),
7.35 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 7.01 (d, J = 14.4 Hz, 1H), 6.40 (t, J
= 2.3 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 141.33, 133.57, 133.16, 129.01, 128.12,
127.33, 126.76, 115.73, 107.48; EI-MS (m/z, %): 204 (M+, 81.56), 136 (100), 203
(91), 169 (43.74), 115 (40.66), 205 (37.94), 138 (24.15), 168 (34.14); HR-MS calcd.
for C11H9N2Cl [M+]: 204.0454; Found 204.0451.
(E)-1-styryl-1H-pyrrole (3j)6b
White solid; 298 mg, yield 88%; E:Z = 95:5; 1H NMR (500 MHz, CDCl3) δ 7.31 (d, J
= 7.5 Hz, 2H), 7.26 (t, J = 7.5 Hz, 2H), 7.23 (d, J = 14.5 Hz, 1H), 7.16 (t, J = 7.5 Hz,
1H), 6.92 (t, J = 2.0 Hz, 2H), 6.53 (d, J = 14.5 Hz, 1H), 6.21 (t, J = 2.0 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 135.74, 128.80, 127.03, 126.95, 125.76, 119.14, 114.33,
110.49; FT-IR (KBr, cm-1): ν 3125, 1658, 1481, 1339, 1096, 728, 613, 583; EI-MS
(m/z, %): 169 (M+, 50.99), 168 (100), 167 (39.28), 115 (7.85), 170 (6.48); HR-MS
calcd. for C12H11N [M+]: 169.0891; Found: 169.0889.
General procedure for the hydroamination of alkynes 1 with N-heterocycles 2
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under KOH.
An oven-dried tube was cooled to room temperature under N2 atmosphere and
charged with N-heterocycles 2 (2.4 mmol), KOH (56 mg, 1.0 mmol). Under an N2
atmosphere alkynes 1 (2.0 mmol) was added followed by dry NMP (3 mL). The tube
was sealed and the mixture was heated to 90 oC. After stirring at this temperature for
24 h, the mixture was cooled to room temperature and quenched with saturated
sodium bicarbonate (10 mL). The resulting mixture was extracted with ethyl acetate
(10 mL x 3). The combined organic solution was washed with saturated brine (10 mL)
and dried over Na2SO4. After the removal of volatile solvents under vacuum, the
residue was further purified by silica gel column chromatography (PE:EA = 2:1) to
give product 4.
(Z)-1-styryl-1H-imidazole (4a)6h, 8h-i
1
Viscous yellow oil; 283 mg, yield 83%; Z:E = 98:2; H NMR (500 MHz, CDCl3) δ
7.41 (s, 1H), 7.26-7.20 (m, 3H), 7.05-7.03 (m, 2H), 6.97 (s, 1H), 6.80 (s, 1H), 6.68 (d,
J = 9.3 Hz, 1H), 6.30 (d, J = 9.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 137.01,
133.68, 129.52, 128.77, 128.54, 128.35, 123.44, 122.37, 118.56; FT-IR (KBr, cm-1): ν
3111, 1659, 1493, 1229, 1073, 1025, 775, 696, 617, 549; EI-MS (m/z, %): 170 (M+,
90.04), 169 (100), 115 (43.36), 142 (28.83), 143 (23.68); HR-MS calcd. for C11H10N2
[M+]: 170.0844; Found: 170.0845.
(Z)-1-(4-methylstyryl)-1H-imidazole (4b)8h
1
Viscous yellow oil; 299 mg, yield 81%; Z:E = 99:1; H NMR (400 MHz,CDCl3) δ
7.46 (s, 1H), 7.07 (d, J = 8.4 Hz, 2H), 7.04 (s, 1H), 6.97 (d, J = 8.4 Hz, 2H), 6.86 (s,
1H), 6.67 (d, J = 9.4 Hz, 1H), 6.32 (d, J = 9.4 Hz, 1H), 2.31 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 138.31, 136.95, 130.69, 129.46, 129.43, 128.45, 123.82, 121.76,
118.56, 21.25; FT-IR (KBr, cm-1): ν 3112, 3030, 1655, 1511, 1491, 1228, 1104, 820,
+
657, 547; ESI-MS (m/z): 184 (M+); HR-MS(DART) calcd. For C12H13N2 [M++1]:
185.1073; Found: 185.1071.
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(Z)-1-(3-methylstyryl)-1H-imidazole (4c)8h
1
Viscous yellow oil; 140.2 mg, yield 38%; Z:E = 98:2; H NMR (400 MHz, CDCl3) δ
7.48 (s, 1H), 7.18 (t, J = 7.6 Hz, 1H), 7.08 (d, J = 7.2 Hz, 1H), 7.03 (s, 1H), 6.93-6.87
13
(m, 3H), 6.72 (d, J = 9.2 Hz, 1H), 6.33 (d, J = 9.2 Hz, 1H), 2.29 (s, 3H); C NMR
(100 MHz, CDCl3) δ 138.42, 137.00, 133.62, 129.39, 129.25, 129.09, 128.65, 125.51,
123.43, 122.19, 118.59, 21.36; FT-IR (KBr, cm-1): ν 3111, 3039, 1655, 1490, 1321,
1229, 1073, 783, 696, 622; EI-MS (m/z, %): 184 (M+, 100), 183 (95.99), 115 (41.22),
156(40.43), 157(19.69); HR-MS calcd. for C12H12N2 [M+]: 184.1000; Found:
184.1001.
(Z)-1-styryl-1H-pyrazole (4g)8i
1
Yellow oil; 292.8 mg, yield 86%; Z:E = 95:5; H NMR (400 MHz, CDCl3) δ 7.59 (s,
1H), 7.33-7.26 (m, 4H), 7.20 (d, J = 7.2 Hz, 2H), 7.01 (d, J = 9.6 Hz, 1H), 6.26 (d, J =
9.6 Hz, 1H), 6.19 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 140.31, 134.44, 129.51,
128.72, 128.66, 127.91, 127.03, 119.03, 106.68; FT-IR (KBr, cm-1): ν 3081, 1655,
1517, 1447, 1082, 882, 753, 696, 611, 547; EI-MS (m/z, %): 170 (M+, 43.64), 169
(100), 102 (39.48), 77 (14.03), 115 (13.96); HR-MS calcd. for C11H10N2 [M+]:
170.0844; Found: 170.0839.
(Z)-1-(4-methylstyryl)-1H-pyrazole (4h)8b, 11
Yellow oil; 328 mg, yield 89%; Z:E = 95:5; 1H NMR (500 MHz, CDCl3) δ 7.58 (d, J
= 1.5 Hz, 1H), 7.33 (d, J = 2.5 Hz, 1H), 7.10 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz,
2H), 6.96 (d, J = 9.8 Hz, 1H), 6.22 (d, J = 9.8 Hz, 1H), 6.19 (t, J = 2.0 Hz, 1H), 2.32
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 140.19, 137.78, 131.37, 129.54, 129.32,
128.61, 126.48, 119.50, 106.53, 21.29; EI-MS (m/z, %): 184 (M+, 74.68), 183 (100),
115 (63.76), 116 (62.33), 91 (18.61), 168 (18.33), 77 (11.83), 135 (10.04); HR-MS
calcd. for C12H12N2 [M+]: 184. 1000; Found 184. 0997.
Acknowledgements
Financial support from the National Natural Science Foundation of China (Nos.
14

ACCEPTED MANUSCRIPT
21102093,
21302204),
the
Science and Technology Commission of Shanghai Municipality (Nos. 15DZ1942203,
16090503500), the Innovation Program of Shanghai Municipal Education
Commission (Nos. 14YZ144, 17SG52), Chemical Engineering and Technology
(Perfume and Aroma Technology) of Shanghai Plateau Discipline, Shanghai
Education Development Foundation (Shuguang Program) and Shanghai Institute of
Technology (No. XTCX2016-5) is gratefully acknowledged.
Supplementary data
The supporting information for this article is available on the WWW under
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17