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Copper-Mediated Coupling of 1,1-Dibromo-1-alkenes with


Imidazoles: A General Method for the Synthesis of
N-Alkynylimidazoles
Mangang Wang, Jun Wu, and Zhicai Shang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China

bS Supporting Information
ABSTRACT: A Cu(I)-catalyzed cross-coupling reaction leading to the
synthesis of N-alkynylheteroarenes from 1,1-dibromo-1-alkenes is described.
Generally superior yields and functional group tolerance were obtained with
TMEDA as ligand using imidazole and benzimidazole substrates in dioxane.

Table 1); performing the same reaction at 80 C provided a 66%


yield of the desired product, together with a small amount of
homocoupling product 4 (entry 2, Table 1). To our delight, with
TMEDA as ligand instead of DMEDA, amination product 3a was
isolated in 82% yield, and none of the undesired byproducts was
observed (entry 3, Table 1); however, a further increase in
reaction temperature from 80 C to reux is detrimental. Under
reux conditions, fast disappearance of the (2,2-dibromovinyl)benzene is accompanied by the formation of the homocoupling product (entry 4, Table 1). After screening the amounts of
base and CuI, it was observed that 4 equiv of base and 0.5 equiv of
CuI are the best (compare entries 611, Table 1); other solvents
and bases such as DMF or K2CO3 led to a low yield or no
reaction at all (entries 1215, Table 1). CuI exhibited superior
catalytical eciency over all other examined Cu catalysts (entries
1618, Table 1). Thus, the above-mentioned reactions with CuI
and TMEDA were the best for the alkynylation of imidazoles to
furnish the desired N-alkynylimidazoles with little or no formation of the homocoupled bisalkyne byproducts.
The scope of the copper-catalyzed alkynylation was examined
by reacting 1a with a variety of 1,1-dibromo-1-alkenes. As shown
in Table 2, under the optimized conditions (5 mol % of CuI, 10
mol % N,N,N0 ,N0 -tetramethylethylenediamine), the alkynylation
of imidazole 1a with 2 appeared to be quite general with respect
to the substituents. Thus, 1,1-dibromoalkenes bearing electrondonating and -withdrawing groups were smoothly aminated to
give N-alkynylimidazoles 3ag in moderate to good yields.
Electron-decient substrates gave better yields. Aromatic halides
are tolerated, and no amination was observed, so that this oers
additional opportunity for further functionalization. It is worth
noting that the olens bearing heteroaryl groups can also be
smoothly transformed to the desired products in good yields
(entries 8 and 9, Table 2). In contrast to the aromatic alkenes, the
coupling reaction of linear aliphatic olens provided the corresponding N-alkynylimidazoles as well but needed a longer

-Alkynylheteroarenes are an interesting variation on ynamines


and share with ynamides the increased stability engendered
by delocalization of the lone pair of electrons on the nitrogen
atom,1 which are functional groups that possess signicant
potential in organic chemistry for the formation of carbon
carbon bonds yet underutilized intermediates in organic
synthesis2 and medicinal chemistry.3 The underlying reason is
the dearth of mild and general preparative methods of their
formation. Current preparative methods of N-alkynylheteroarenes have included elimination from haloenamines4 or enol
triates,5 isomerization of propargyl groups,6 and coupling with
alkynyl iodonium salts.7 More recently, a modern variant for the
synthesis of N-alkynylheteroarenes has been developed that is
based upon transition-metal-mediated coupling of N-heterocycles with bromoalkynes using conventional heating protocols
or microwave-assisted ones.8 However, all these methods suer
from either limited substrate scope or formation of direct
nucleophilic addition side products.8b Therefore, the development of a general and ecient method for the preparation of Nalkynylheteroarenes is still highly desirable.
gem-Dibromoolens have been used in a wide range of
applications in organic synthesis owing to their utility as synthetic
intermediates.9 They are easily and conveniently prepared by
using the Ramirez olenation10 or the more practical modied
methods.9d,11 Drawing from recent experiences in the eld of
copper-catalyzed cross-coupling reactions,8,12 we thought that an
attractive alternative for the preparation of N-alkynylheteroarenes could be performed using catalytic amounts of copper(I)
salts from readily available 1,1-dibromo-1-alkenes and their
further reaction with appropriate N-containing heterocycles.
Herein, we report a simple and facile method for the preparation
of N-alkynylheteroarenes incorporating the imidazole and benzimidazole heterocyclic cores.
Initially, imidazole 1a and (2,2-dibromovinyl)benzene 2a
were selected as the model substrates in search of a better
protocol. Under the reported conditions,12d the reaction of
imidazole with (2,2-dibromovinyl)benzene and CuI in dioxane
gave 1-(phenylethynyl)-1H-imidazole 3a in 41% yield (entry 1,
r XXXX American Chemical Society

Received:

February 26, 2011

dx.doi.org/10.1021/jo2004346 | J. Org. Chem. XXXX, XXX, 000000

The Journal of Organic Chemistry

NOTE

Table 1. Optimization of Copper-Catalyzed N-Alkynylation of Imidazole with (2,2-Dibromovinyl)benzenea

yield (%)c
entry

catalyst (%)

ligandb

base (equiv)

solvent

T (C)

3a

CuI (5)

DMEDA

Cs2CO3 (4)

dioxane

60

41

CuI (5)

DMEDA

Cs2CO3 (4)

dioxane

80

66

CuI (5)

TMEDA

Cs2CO3 (4)

dioxane

80

82

CuI (5)

TMEDA

Cs2CO3 (4)

dioxane

102 (reux)

67

14

CuI (5)

TMEDA

Cs2CO3 (4)

dioxane

60

40

6
7

CuI (2.5)

TMEDA

Cs2CO3 (4)
Cs2CO3 (4)

dioxane
dioxane

80
80

45
0

0
0

CuI (10)

TMEDA

Cs2CO3 (4)

dioxane

80

77

CuI (5)

TMEDA

Cs2CO3 (6)

dioxane

80

79

trace

10

CuI (5)

TMEDA

Cs2CO3 (3)

dioxane

80

65

11d

CuI (5)

TMEDA

Cs2CO3 (2)

dioxane

80

29

12

CuI (5)

TMEDA

Cs2CO3 (4)

DMF

80

50

12

13

CuI (5)

TMEDA

Cs2CO3 (4)

toluene

80

27

14
15

CuI (5)
CuI (5)

TMEDA
TMEDA

K2CO3 (4)
K3PO4 (4)

dioxane
dioxane

80
80

0
73

0
4

16

Cu (5)

TMEDA

Cs2CO3 (4)

dioxane

80

17

CuO (5)

TMEDA

Cs2CO3 (4)

dioxane

80

trace

18

CuCl (5)

TMEDA

Cs2CO3 (4)

dioxane

80

19

23

Reactions were carried out using imidazole (1 mmol), (2,2-dibromovinyl)benzene (1.5 mmol), and ligand (0.1 mmol) in 2 mL of solvent for 24 h under
N2. b TMEDA = N,N,N0 ,N0 -tetramethylethylenediamine; DMEDA = N,N0 -dimethylethanediamine. c Yields of isolated products after chromatographic
purication. d Reaction run at 80 C for 48 h.

the expected compound 5. In path 2, the rst step involves


the preliminary formation of alkynyl bromide F by dehydrobromination of the 1,1-dibromo-1-alkene 2. Subsequent oxidative
addition of the alkynyl bromide onto B presumably gives a fourcoordinated copper(III) complex D. A subsequent reductive
elimination leads to the expected compound 5 and regenerates
the catalytic copper(I) species A in the process. However, the
formation of 1-bromoalkynes in the presence of base from 1,1dibromo-1-alkenes is a well-known and easy transformation.14
Taking into account that these compounds have been identied
in the crude reaction mixture15 and E was never isolated, it is
reasonable to suppose that this N-alkynylation of imidazoles with

reaction time (entry 10, Table 2). We found, however, that vinyl
1,1-dibromoalkenes such as 1,1-dibromo-4-methylpenta-1,3diene, which are denitely not the best reaction partners in
copper-catalyzed cross-coupling reactions, were not suitable
substrates (entry 11, Table 2).
The coupling of imidazoles bearing dierent substituents with
various 1,1-dibromo-1-alkenes 2 was investigated next under the
optimized reaction conditions (Table 3). In general, the substituted imidazoles could be successfully used in this coppermediated cross-coupling reaction to give the desired products in
moderate to good yields. For example, when 2-methylimidazole
was used, good yields of the N-alkynylheteroarenes derived from
the coupling of the 1,1-dibromoalkenes 2a, 2b, and 2d were
observed (entries 68, Table 3). The reaction was, however,
found to be rather general and allowed for the synthesis of a wide
range of N-alkynylimidazoles possessing ethyl, propyl, isopropyl,
and benzo[d] substituting groups. In the case of 4-methylimidazole (entry 20, Table 3), coupling with 2a gave a 7:1 mixture of
regioisomeric N-alkynylimidazoles 5ta and 5tb. The regiochemistry of the major isomer 5ta was established as 1,4 by NMR.
The plausible mechanism for this transformation is depicted
in Scheme 1. The sequence begins with the deprotonation of the
imidazole by Cs2CO3 followed by cesiumcopper transmetalation to generate a copper(I)(imidazolate) intermediate B. Then,
two hypotheses both involving the formation of a copper(III)
complex C or D could be considered.13 Path 1 involves the Nalkenylation of imidazole on the more reactive trans CBr bond
of the gem-dibromoolen to furnish the trisubstituted alkene E.
Dehydrobromination takes place at the late stage to generate

Scheme 1. Plausible Mechanism

dx.doi.org/10.1021/jo2004346 |J. Org. Chem. XXXX, XXX, 000000

The Journal of Organic Chemistry

NOTE

Table 2. Copper-Catalyzed Alkynylation of Imidazole with


1,1-Dibromo-1-alkenesa

through a fritted glass funnel, and concentrated with a rotary evaporator


(2030 mmHg). Flash chromatography was performed with silica gel
(200300 mesh) using the mobile phase indicated. Unless otherwise
noted, NMR spectra were recorded for 1H NMR at 400 or 500 MHz and
13
C NMR at 100 or 125 MHz using TMS as internal standard. The
following abbreviations were used to describe peak patterns where
appropriate: singlet (s), doublet (d), triplet (t), multiplet (m), broad
resonances (br). Mass spectroscopy data of the products were collected on
an HRMS-APCI instrument or a low-resolution MS instrument using EI or
ESI ionization. The gas chromatography analysis was performed on a GC
instrument with nitrogen gas as a carrier. Melting points were measured
with a micro melting point apparatus.

General Procedure for the N-Alkynylation Reaction of


Imidazoles. A vessel with a magnetic stir bar was charged with
imidazole derivative (1 mmol), CuI (10 mg, 0.05 mmol), Cs2CO3
(1.3 g, 4 mmol), and N,N,N0 ,N0 -tetramethylethylenediamine (TMEDA)
(12 mg, 0.1 mmol) under a nitrogen atmosphere. The reaction vessel
was evacuated and backfilled with nitrogen three times. In a separate
flask, a solution of dry dioxane (2 mL) containing the 1,1-dibromo-1alkenes (1.5 mmol) was evacuated and backfilled with nitrogen gas
three times. The dioxane solution was then added to the reaction flask
with a syringe, and the reaction mixture was heated to 80 C for 24 h.
The reaction mixture was cooled to room temperature, quenched
with 5 mL of a saturated NH4Cl solution, and extracted with ethyl
acetate (3  20 mL). The combined organic phases were dried over
anhydrous sodium sulfate, filtered, and concentrated. The residue
was purified by flash column chromatography with ethyl acetate (EA)
and petroleum ether (Pet) as eluent to afford the corresponding
products.
1-(Phenylethynyl)-1H-imidazole (3a):8,16 yellow oil; 1H NMR
(500 MHz, CDCl3) 7.82 (s, 1H), 7.617.45 (m, 2H), 7.427.32 (m,
3H), 7.20 (d, J = 1.1 Hz, 1H), 7.09 (s, 1H); 13C NMR (125 MHz,
CDCl3) 140.2, 131.9, 129.4, 129.2, 128.7, 121.9, 78.2, 70.6; MS (ESI)
m/z 169.1 ([M H]).
1-(p-Tolylethynyl)-1H-imidazole (3b): white solid; mp 54
56 C; 1H NMR (400 MHz, CDCl3) 7.79 (s, 1H), 7.40 (d, J = 8.1 Hz,
2H), 7.17 (d, J = 7.6 Hz, 3H), 7.07 (s, 1H), 2.37 (s, 3H); 13C NMR (100
MHz, CDCl3) 140.0, 139.2, 131.6, 129.3, 129.1, 121.7, 117.9, 77.5, 70.4,
21.5; MS (ESI) m/z 182.7 ([M H]); HRMS (EI) calcd for C12H10N2
(M) 182.0844, found, 182.0848.
1-((4-Chlorophenyl)ethynyl)-1H-imidazole (3c): white solid;
mp 7577 C; 1H NMR (400 MHz, CDCl3) 7.80 (s, 1H), 7.46  7.39
(m, 2H), 7.37  7.31 (m, 2H), 7.18 (s, 1H), 7.08 (s, 1H); 13C NMR
(100 MHz, CDCl3) 139.9, 135.1, 132.8, 129.3, 128.8, 121.6, 119.5,
78.8, 69.3; MS (ESI) m/z 202.7 ([M H]); HRMS (ESI) calcd for
C11H7ClN2 ([M H]) 202.0298, found 202.0294.
1-((3-Bromophenyl)ethynyl)-1H-imidazole (3d): yellow liquid; 1H NMR (500 MHz, CDCl3) 7.82 (s, 1H), 7.66 (t, J = 1.7
Hz, 1H), 7.55  7.49 (m, 1H), 7.43 (dd, J = 7.7, 1.1 Hz, 1H), 7.29  7.24
(m, 1H), 7.20 (s, 1H), 7.10 (s, 1H); 13C NMR (125 MHz, CDCl3)
140.3, 134.6, 132.4, 130.4, 130.2, 129.7, 123.3, 122.6, 121.9, 79.3, 77.5,
77.3, 77.0, 69.4; MS (ESI) m/z 248.7 ([M H]); HRMS (EI) calcd
for C11H7BrN2 (M) 245.9793, found 245.9800.
4-((1H-Imidazol-1-yl)ethynyl)benzonitrile (3e): yellow solid;
mp 108110 C; 1H NMR (500 MHz, CDCl3) 7.88 (s, 1H), 7.67 (d, J
= 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.24 (s, 1H), 7.14 (s, 1H); 13C
NMR (125 MHz, CDCl3) 140.2, 132.5, 132.1, 129.9, 126.2, 121.9,
118.4, 112.4, 82.0, 69.5; MS (ESI) m/z 194.2 ([M H]); HRMS (EI)
calcd for C12H7N3 (M) 193.0640, found 193.0647.
1-((4-Methoxyphenyl)ethynyl)-1H-imidazole (3f): white solid; mp 7577 C; 1H NMR (500 MHz, CDCl3) 7.80 (s, 1H), 7.45
(d, J = 8.6 Hz, 2H), 7.19 (s, 1H), 7.08 (s, 1H), 6.89 (d, J = 8.6 Hz, 2H), 3.83
(s, 3H); 13C NMR (125 MHz, CDCl3) 160.4, 140.2, 133.6, 129.3, 122.0,

a
1a (1.0 mmol) and 2 (1.5 mmol) at 80 C for 24 h, under N2. b Yields of
isolated products after chromatographic purication. c Reaction run at
60 C. d Reaction run at 80 C for 48 h. e No reaction.

1,1-dibromo-1-alkenes proceeds through path 2.


In summary, a copper-mediated synthesis of N-alkynylimidazoles has been described. This reaction has been shown to be
general and provides a straightforward entry to N-alkynylheteroarenes from readily available 1,1-dibromo-1-alkenes.

EXPERIMENTAL SECTION
General Methods. All reactions were carried out under nitrogen in
oven-dried glassware with magnetic stirring. Unless otherwise noted, all
materials were obtained from commercial suppliers and were used without
further purification. 1,1-Dibromo-1-alkenes 2al were prepared according
to the reported procedures.11c All solvents were reagent grade. 1,4-Dioxane
was freshly distilled from sodium/benzophenone under nitrogen prior to
use. Dichloromethane and toluene were freshly distilled from CaH2 prior
to use. DMF was dried over 4 molecular sieves overnight prior to use.
Unless otherwise noted, organic extracts were dried with Na2SO4, filtered
C

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NOTE

Table 3. Copper-Catalyzed Alkynylation of Imidazole and Benzimidazole with 1,1-Dibromo-1-alkenesa

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NOTE

Table 3. Continued

1 (1.0 mmol) and 2 (1.5 mmol) at 80 C for 24 h, under N2. b Yields of isolated products after chromatographic purication. c GC yield, with 1-methyl1H-imidazole as the internal standard. d The ratio of the isomeric products was determined by GC. e Reaction run at 80 C for 48 h.
a

114.4, 113.0, 77.1, 70.4, 55.5; MS (ESI) m/z 199.0 ([M H]); HRMS
(EI) calcd for C12H10N2O (M) 198.0793, found 198.0792.
1-((4-Fluorophenyl)ethynyl)-1H-imidazole (3g): yellow oil;
1
H NMR (500 MHz, CDCl3) 7.81 (s, 1H), 7.537.44 (m, 2H), 7.19
(s, 1H), 7.117.02 (m, 3H); 13C NMR (125 MHz, CDCl3) 164.1,
162.1, 140.2, 134.03, 134.0, 129.5, 121.9, 117.3, 116.2, 116.1, 78.0, 69.6;
MS (ESI) m/z 187.0 ([M H]); HRMS (EI) calcd for C11H7FN2
(M) 186.0593, found 186.0598.
1-(Furan-2-ylethynyl)-1H-imidazole (3h). yellow oil; 1H NMR
(500 MHz, CDCl3) 7.837.78 (m, 1H), 7.48 (dd, J = 1.9, 0.7 Hz, 1H),
7.19 (t, J = 1.3 Hz, 1H), 7.09 (dd, J = 1.4, 0.8 Hz, 1H), 6.74 (dd, J = 3.4,
0.7 Hz, 1H), 6.46 (dd, J = 3.4, 1.9 Hz, 1H); 13C NMR (125 MHz,
CDCl3) 144.9, 140.6, 135.5, 129.8, 122.1, 117.7, 111.5, 82.0, 61.8; MS
(ESI) m/z 158.9 ([M H]); HRMS (EI) calcd for C9H6N2O (M)
158.0480, found 158.0469.
1-(Thiophen-2-ylethynyl)-1H-imidazole (3i). white solid; mp
4648 C; 1H NMR (500 MHz, CDCl3) 7.80 (s, 1H), 7.36 (dd,
J = 5.2, 1.0 Hz, 1H), 7.32 (dd, J = 3.6, 1.0 Hz, 1H), 7.18 (t, J = 1.2 Hz, 1H), 7.09
(s, 1H), 7.04 (dd, J = 5.1, 3.7 Hz, 1H); 13C NMR (125 MHz, CDCl3) 140.4,
133.7, 129.6, 128.8, 127.5, 122.0, 121.0, 81.6, 64.5; MS (ESI) m/z 174.9 ([M
H]); HRMS (EI) calcd for C12H10N2 (M) 174.0252, found 174.0257.
1-(Tridec-1-ynyl)-1H-imidazole (3j). yellow oil; 1H NMR (500
MHz, CDCl3) 7.68 (s, 1H), 7.07 (s, 1H), 7.01 (s, 1H), 2.36 (t, J = 7.1
Hz, 2H), 1.57 (dd, J = 14.9, 7.3 Hz, 2H), 1.48  1.37 (m, 2H), 1.28 (d,
J = 14.4 Hz, 14H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR (125 MHz,
CDCl3) 140.2, 128.9, 122.0, 70.8, 70.0, 32.1, 29.8, 29.7, 29.5, 29.3,

29.1, 28.6, 22.9, 18.3, 14.3; MS (ESI) m/z 247.1 ([M H]); HRMS
(EI) calcd for C16H26N2 (M) 246.2096, found 246.2102.
1-(Phenylethynyl)-1H-benzo[d]imidazole (5a):8,16a yellow
oil; 1H NMR (500 MHz, CDCl3) 8.17 (s, 1H), 7.85 (d, J = 7.9 Hz,
1H), 7.67 (d, J = 7.9 Hz, 1H), 7.62  7.55 (m, 2H), 7.48  7.36 (m, 5H);
13
C NMR (125 MHz, CDCl3) 143.9, 142.2, 134.8, 134.1, 132.0, 131.5,
129.2, 128.84, 128.8, 125.0, 124.3, 121.6, 121.1, 111.2, 76.7, 73.8; MS
(ESI) m/z 218.8 ([M H]).
1-(p-Tolylethynyl)-1H-benzo[d]imidazole (5b): yellow solid;
mp 7476 C; 1H NMR (500 MHz, CDCl3) 8.15 (s, 1H), 7.84
(d, J = 7.9 Hz, 1H), 7.66 (d, J = 7.9 Hz, 1H), 7.47 (d, J = 8.1 Hz, 2H),
7.45  7.35 (m, 2H), 7.21 (d, J = 7.9 Hz, 2H), 2.40 (s, 3H); 13C NMR
(125 MHz, CDCl3) 143.9, 142.2, 139.6, 134.8, 132.0, 129.6, 125.0, 124.2,
121.0, 118.4, 111.3, 76.1, 73.8, 21.8; MS (ESI) m/z 232.8 ([M H]);
HRMS (EI) calcd for C16H12N2 (M) 232.1000, found 232.1002.

1-((4-Chlorophenyl)ethynyl)-1H-benzo[d]imidazole (5c):
white solid; mp 8890 C; 1H NMR (400 MHz, CDCl3) 8.13 (s,
1H), 7.83 (d, J = 7.8 Hz, 1H), 7.63 (d, J = 7.9 Hz, 1H), 7.50 (d, J = 8.5 Hz,
2H), 7.467.33 (m, 4H); 13C NMR (125 MHz, CDCl3) 143.7, 142.2,
135.4, 134.7, 133.2, 129.2, 125.1, 124.4, 121.2, 120.1, 111.2, 77.5, 72.8;
MS (ESI) m/z 253.1 ([M H]); HRMS (EI) calcd for C15H9ClN2
(M) 252.0454, found 252.0456.

1-((3-Bromophenyl)ethynyl)-1H-benzo[d]imidazole (5d):
white solid; mp 5052 C; 1H NMR (500 MHz, CDCl3) 8.15 (s, 1H),
7.85 (d, J = 8.0 Hz, 1H), 7.73 (s, 1H), 7.65 (d, J = 7.9 Hz, 1H), 7.52 (dd, J =
15.8, 7.8 Hz, 2H), 7.42 (dt, J = 25.6, 7.4 Hz, 2H), 7.28 (d, J = 7.9 Hz, 1H); 13C
E

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NOTE

NMR (125 MHz, CDCl3) 143.7, 142.2, 134.6, 132.3, 130.4, 130.3, 125.2,
124.5, 123.6, 122.6, 121.1, 111.2, 77.8, 72.5; MS (ESI) m/z 296.9 ([M
H]); HRMS (EI) calcd for C15H9BrN2 (M), 295.9949, found 295.9940.

4-((1H-Benzo[d]imidazol-1-yl)ethynyl)benzonitrile

2-Ethyl-1-((4-(trifluoromethyl)phenyl)ethynyl)-1H-imidazole (5n): yellow oil; 1H NMR (500 MHz, CDCl3) 7.61 (q, J = 8.4
Hz, 4H), 7.12 (d, J = 1.4 Hz, 1H), 6.95 (d, J = 1.4 Hz, 1H), 2.92 (q, J = 7.6
Hz, 2H), 1.41 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) 153.8,
131.8, 130.8, 130.6, 128.3, 125.73, 125.7, 125.1, 122.9, 121.4, 80.4, 71.9,
21.0, 11.8; MS (ESI) m/z 265.0 ([M H]); HRMS (EI) calcd for
C14H11F3N2 (M) 264.0874, found 264.0873.

(5e):

white solid; mp 140143 C; 1H NMR (400 MHz, CDCl3) 8.17


(s, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.68 (m, 5H), 7.44 (dt, J = 19.9, 7.2 Hz,
2H); 13C NMR (125 MHz, CDCl3) 143.6, 132.5, 132.1, 126.7, 125.3,
124.7, 121.3, 118.5, 112.4, 111.1, 80.6, 72.8; MS (ESI) m/z 244.1 ([M
H]); HRMS (EI) calcd for C16H9N3 (M) 243.0796, found 243.0800.
2-Methyl-1-(phenylethynyl)-1H-imidazole (5f):8,16b yellow
oil; 1H NMR (500 MHz, CDCl3) 7.577.45 (m, 2H), 7.427.33
(m, 3H), 7.10 (d, J = 1.3 Hz, 1H), 6.91 (d, J = 1.2 Hz, 1H), 2.55 (s, 3H);
13
C NMR (125 MHz, CDCl3) 149.1, 131.8, 129.1, 128.7, 128.0, 121.6,
121.5, 78.3, 72.8, 13.5; MS (ESI) m/z 182.7 ([M H]).
2-Methyl-1-(p-tolylethynyl)-1H-imidazole (5g): yellow oil; 1H
NMR (500 MHz, CDCl3) 7.39 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 7.9 Hz,
2H), 7.09 (d, J = 1.4 Hz, 1H), 6.90 (d, J = 1.3 Hz, 1H), 2.54 (s, 3H), 2.38 (s,
3H); 13C NMR (125 MHz, CDCl3) 149.1, 139.4, 131.8, 129.5, 127.9,
121.5, 118.5, 77.8, 72.9, 21.7, 13.4; MS (ESI) m/z 197.1 ([M H]);
HRMS (EI) calcd for C13H12N2 (M) 196.1000, found 196.0998.

1-((4-Chlorophenyl)ethynyl)-2-isopropyl-1H-imidazole
(5o): yellow oil; 1H NMR (500 MHz, CDCl3) 7.467.41 (m, 2H),
7.387.34 (m, 2H), 7.09 (d, J = 1.4 Hz, 1H), 6.95 (d, J = 1.4 Hz, 1H),
3.32 (dt, J = 13.8, 6.9 Hz, 1H), 1.41 (d, J = 6.9 Hz, 6H); 13C NMR (125
MHz, CDCl3) 157.2, 135.1, 132.9, 129.1, 127.9, 121.3, 120.2, 79.1,
72.0, 27.3, 21.0; MS (ESI) m/z 245.1 ([M H]); HRMS (EI) calcd
for C14H13ClN2 (M) 244.0767, found 244.0766.

1-((3-Bromophenyl)ethynyl)-2-isopropyl-1H-imidazole
(5p): yellow oil; 1H NMR (500 MHz, CDCl3) 7.65 (t, J = 1.6 Hz, 1H),

7.52 (ddd, J = 8.0, 1.8, 0.9 Hz, 1H), 7.47  7.41 (m, 1H), 7.26 (dd, J =
15.6, 7.7 Hz, 1H), 7.09 (d, J = 1.5 Hz, 1H), 6.95 (d, J = 1.4 Hz, 1H), 3.32
(dt, J = 13.8, 6.9 Hz, 1H), 1.42 (d, J = 6.9 Hz, 6H); 13C NMR (125 MHz,
CDCl3) 157.2, 134.3, 132.1, 130.2, 128.0, 123.7, 122.6, 121.3, 79.4,
71.7, 27.3, 21.1; MS (ESI) m/z 289.1 ([M H]); HRMS (EI) calcd
for C14H13BrN2 (M) 288.0262, found 288.0268.

1-((3-Bromophenyl)ethynyl)-2-methyl-1H-imidazole (5h):
yellow oil; 1H NMR (500 MHz, CDCl3) 7.65 (t, J = 1.7 Hz, 1H), 7.51
(ddd, J = 8.1, 1.8, 1.0 Hz, 1H), 7.42 (dt, J = 7.6, 1.1 Hz, 1H), 7.25 (dd,
J = 14.8, 6.9 Hz, 1H), 7.09 (d, J = 1.5 Hz, 1H), 6.92 (d, J = 1.5 Hz, 1H), 2.55 (s,
3H); 13C NMR (125 MHz, CDCl3) 149.1, 134.4, 132.2, 130.3, 130.2, 128.2,
123.6, 122.6, 121.4, 79.4, 71.5, 13.5; MS (ESI) m/z 261.1 ([M H]);
HRMS (EI) calcd for C12H9BrN2 (M) 259.9949, found 259.9951.

2-Isopropyl-1-((4-(trifluoromethyl)phenyl)ethynyl)-1Himidazole (5q): yellow solid; mp 4951 C; 1H NMR (500 MHz,

CDCl3) 7.61 (dd, J = 19.3, 8.3 Hz, 4H), 7.11 (d, J = 1.2 Hz, 1H),
6.95 (d, J = 1.1 Hz, 1H), 3.33 (dt, J = 13.8, 6.9 Hz, 1H), 1.41 (d, J = 6.9
Hz, 6H); 13C NMR (125 MHz, CDCl3) 157.3, 131.8, 130.8, 130.6,
128.1, 125.74, 125.7, 125.1, 122.9, 121.3, 80.4, 72.1, 27.4, 21.1; MS
(ESI) m/z 279.1 ([M H]); HRMS (EI) calcd for C15H13F3N2
(M) 278.1031, found 278.1028.

2-Methyl-1-(phenylethynyl)-1H-benzo[d]imidazole (5i):
yellow oil; 1H NMR (500 MHz, CDCl3) 7.70 (dd, J = 6.7, 2.0 Hz, 1H),
7.63  7.51 (m, 3H), 7.44  7.37 (m, 3H), 7.37  7.29 (m, 2H), 2.76 (s,
3H); 13C NMR (125 MHz, CDCl3) 153.6, 141.9, 135.7, 132.0, 129.1,
128.8, 124.1, 124.0, 121.8, 119.8, 110.9, 76.5, 76.0, 14.4; MS (ESI) m/z
233.1 ([M H]); HRMS (EI) calcd for C16H12N2 (M) 232.1000,
found 232.0998.

1-((3-Bromophenyl)ethynyl)-2-propyl-1H-imidazole (5r):
yellow oil; 1H NMR (500 MHz, CDCl3) 7.63 (t, J = 1.6 Hz, 1H), 7.53
 7.46 (m, 1H), 7.41 (dd, J = 7.7, 1.1 Hz, 1H), 7.23 (t, J = 7.9 Hz, 1H),
7.08 (d, J = 1.5 Hz, 1H), 6.94 (d, J = 1.4 Hz, 1H), 2.84 (t, J = 7.5 Hz, 2H),
1.85 (dd, J = 14.9, 7.4 Hz, 2H), 1.02 (t, J = 7.4 Hz, 3H); 13C NMR (125
MHz, CDCl3) 152.7, 134.3, 132.1, 130.21, 130.2, 128.2, 123.7, 122.5,
121.3, 79.4, 71.5, 29.3, 21.2, 14.0; MS (ESI) m/z 289.1 ([M H]);
HRMS (EI) calcd for C14H13BrN2 (M) 288.0262, found 288.0264.

1-((4-Chlorophenyl)ethynyl)-2-methyl-1H-benzo[d]imidazole (5j): yellow oil; 1H NMR (500 MHz, CDCl3) 7.70 (dd, J =
6.4, 2.4 Hz, 1H), 7.577.47 (m, 3H), 7.417.36 (m, 2H), 7.367.29
(m, 2H), 2.75 (s, 3H); 13C NMR (125 MHz, CDCl3) 153.5, 142.0,
135.6, 135.2, 133.1, 129.2, 124.2, 124.0, 120.3, 119.9, 110.8, 77.4, 75.0,
14.4; MS (ESI) m/z 267.1 ([M H]); HRMS (EI) calcd for
C16H11ClN2 (M) 266.0611, found 266.0608.
2-Ethyl-1-(p-tolylethynyl)-1H-imidazole (5k): yellow oil; 1H
NMR (500 MHz, CDCl3) 7.39 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.0 Hz,
2H), 7.08 (d, J = 1.4 Hz, 1H), 6.92 (d, J = 1.4 Hz, 1H), 2.89 (q, J = 7.6 Hz,
2H), 2.37 (s, 3H), 1.39 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz,
CDCl3) 153.7, 139.3, 131.7, 129.5, 127.8, 121.4, 118.5, 77.6, 72.9, 21.7,
20.9, 11.8; MS (ESI) m/z 211.3 ([M H]); HRMS (EI) calcd for
C14H14N2 (M) 210.1157, found 210.1159.

2-Propyl-1-((4-(trifluoromethyl)phenyl)ethynyl)-1H-imidazole (5s): yellow oil; 1H NMR (500 MHz, CDCl3) 7.62 (dd, J =
20.9, 8.1 Hz, 4H), 7.12 (s, 1H), 6.96 (s, 1H), 2.87 (t, J = 7.5 Hz, 2H), 1.87
(dd, J = 14.8, 7.4 Hz, 2H), 1.03 (t, J = 7.4 Hz, 3H); 13C NMR (125 MHz,
CDCl3) 152.8, 131.8, 128.3, 125.7, 121.3, 80.5, 71.9, 29.4, 21.3, 14.0;
MS (ESI) m/z 279.1 ([M H]); HRMS (EI) calcd for C15H13F3N2
(M) 278.1031, found 278.1027.
4-Methyl-1-(phenylethynyl)-1H-imidazole (5ta):8b yellow
solid; mp 7577 C; tR = 10.3; 1H NMR (500 MHz, CDCl3) 7.72
(s, 1H), 7.54  7.45 (m, 2H), 7.40  7.32 (m, 3H), 6.89 (s, 1H), 2.25 (s,
3H); 13C NMR (125 MHz, CDCl3) 139.7, 138.7, 131.9, 129.1, 128.8,
121.6, 118.0, 78.6, 70.0, 13.7; MS (ESI) m/z 183.2 ([M H]).
5-Methyl-1-(phenylethynyl)-1H-imidazole (5tb):8b yellow
oil; tR = 10.4; 1H NMR (500 MHz, CDCl3) 7.75 (s, 1H), 7.51 (dd,
J = 6.5, 3.0 Hz, 2H), 7.41  7.35 (m, 3H), 6.79 (s, 1H), 2.35 (s, 3H); 13C
NMR (125 MHz, CDCl3) 139.2, 131.9, 130.6, 129.1, 128.8, 126.1,
121.5, 77.0, 73.1, 9.4; MS (ESI) m/z 182.9 ([M H]).
1-(Tridec-1-ynyl)-1H-benzo[d]imidazole (5u): yellow oil; 1H
NMR (500 MHz, CDCl3) 8.05 (s, 1H), 7.81 (d, J = 7.9 Hz, 1H),
7.57 (d, J = 8.0 Hz, 1H), 7.36 (ddd, J = 16.3, 11.3, 4.1 Hz, 2H), 2.48
(t, J = 7.1 Hz, 2H), 1.70  1.60 (m, 2H), 1.48 (dd, J = 15.0, 7.2 Hz, 2H),
1.40  1.16 (m, 14H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR (125 MHz,
CDCl3) 144.2, 124.7, 123.9, 120.9, 111.1, 74.0, 68.3, 33.8, 32.2,
29.9, 29.8, 29.6, 29.4, 29.2, 28.9, 22.9, 18.6, 14.4; MS (ESI) m/z 297.1
([M H]); HRMS (EI) calcd for C20H28N2 (M) 296.2252, found
296.2256.

1-((4-Chlorophenyl)ethynyl)-2-ethyl-1H-imidazole (5l):
yellow oil; 1H NMR (500 MHz, CDCl3) 7.477.39 (m, 2H),
7.387.33 (m, 2H), 7.09 (d, J = 1.5 Hz, 1H), 6.94 (d, J = 1.5 Hz,
1H), 2.90 (q, J = 7.6 Hz, 2H), 1.39 (t, J = 7.6 Hz, 3H); 13C NMR (125
MHz, CDCl3) 153.7, 135.2, 133.0, 129.1, 128.1, 121.4, 120.1, 79.1,
71.9, 21.0, 11.9; MS (ESI) m/z 231.1 ([M H]); HRMS (EI) calcd
for C13H11ClN2 (M) 230.0611, found 230.0611.

1-((3-Bromophenyl)ethynyl)-2-ethyl-1H-imidazole (5m):
yellow oil; 1H NMR (500 MHz, CDCl3) 7.64 (t, J = 1.6 Hz, 1H), 7.50
(ddd, J = 8.0, 1.8, 1.0 Hz, 1H), 7.45  7.39 (m, 1H), 7.25 (dd, J = 15.9,
8.0 Hz, 1H), 7.09 (d, J = 1.5 Hz, 1H), 6.94 (d, J = 1.4 Hz, 1H), 2.90 (q, J =
7.6 Hz, 2H), 1.40 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz, CDCl3)
153.7, 134.4, 132.1, 130.22, 130.2, 128.2, 123.7, 122.5, 121.3, 79.3, 71.5,
21.0, 11.8; MS (ESI) m/z 275.1 ([M H]); HRMS (EI) calcd for
C13H11BrN2 (M) 274.0106, found 274.0109.
F

dx.doi.org/10.1021/jo2004346 |J. Org. Chem. XXXX, XXX, 000000

The Journal of Organic Chemistry

NOTE

ASSOCIATED CONTENT

bS

130, 1820. (d) Raw, S. A.; Reid, M.; Roman, E.; Taylor, R. J. K. Synlett
2004, 819.
(15) See the Supporting Information for details.
(16) (a) Laroche, C.; Kerwin, S. M. J. Org. Chem. 2009, 74, 9229.
(b) Laroche, C.; Kerwin, S. M. Tetrahedron Lett. 2009, 50, 5194.

Copies of 1H and 13C NMR


spectra for all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
Supporting Information.

AUTHOR INFORMATION
Corresponding Author

*E-mail: shangzc@zju.edu.cn.

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