NOTE

pubs.acs.org/joc

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 reflux is detrimental. Under
reflux 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 efficiency 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-deficient substrates gave better yields. Aromatic halides
are tolerated, and no amination was observed, so that this offers
additional opportunity for further functionalization. It is worth
noting that the olefins 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 olefins provided the corresponding N-alkynylimidazoles as well but needed a longer

N

-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 significant
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
triflates,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 suffer
from either limited substrate scope or formation of direct
nucleophilic addition side products.8b Therefore, the development of a general and efficient method for the preparation of Nalkynylheteroarenes is still highly desirable.
gem-Dibromoolefins 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 olefination10 or the more practical modified
methods.9d,11 Drawing from recent experiences in the field 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:

A

February 26, 2011

dx.doi.org/10.1021/jo2004346 | J. Org. Chem. XXXX, XXX, 000–000

1-dibromo-4-methylpenta-1. Optimization of Copper-Catalyzed N-Alkynylation of Imidazole with (2. The coupling of imidazoles bearing different substituents with various 1. We found. Subsequent oxidative addition of the alkynyl bromide onto B presumably gives a fourcoordinated copper(III) complex D. d Reaction run at 80 °C for 48 h. that vinyl 1. DMEDA = N.1-dibromo-1-alkene 2.1 mmol) in 2 mL of solvent for 24 h under N2.1dibromo-1-alkenes is a well-known and easy transformation. In path 2.5) TMEDA Cs2CO3 (4) Cs2CO3 (4) dioxane dioxane 80 80 45 0 0 0 8 CuI (10) TMEDA Cs2CO3 (4) dioxane 80 77 2 9 CuI (5) TMEDA Cs2CO3 (6) dioxane 80 79 trace 10 CuI (5) TMEDA Cs2CO3 (3) dioxane 80 65 0 11d CuI (5) TMEDA Cs2CO3 (2) dioxane 80 29 3 12 CuI (5) TMEDA Cs2CO3 (4) DMF 80 50 12 13 CuI (5) TMEDA Cs2CO3 (4) toluene 80 27 0 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 0 0 17 CuO (5) TMEDA Cs2CO3 (4) dioxane 80 trace 9 18 CuCl (5) TMEDA Cs2CO3 (4) dioxane 80 19 23 a Reactions were carried out using imidazole (1 mmol). when 2-methylimidazole was used. In the case of 4-methylimidazole (entry 20. Table 3). Table 2). The reaction was. The plausible mechanism for this transformation is depicted in Scheme 1. it is reasonable to suppose that this N-alkynylation of imidazoles with reaction time (entry 10. however. XXXX.doi. c Yields of isolated products after chromatographic purification.2-Dibromovinyl)benzenea yield (%)c entry catalyst (%) ligandb base (equiv) solvent T (°C) 3a 4 1 CuI (5) DMEDA Cs2CO3 (4) dioxane 60 41 0 2 CuI (5) DMEDA Cs2CO3 (4) dioxane 80 66 3 3 CuI (5) TMEDA Cs2CO3 (4) dioxane 80 82 0 4 CuI (5) TMEDA Cs2CO3 (4) dioxane 102 (reflux) 67 14 5 CuI (5) TMEDA Cs2CO3 (4) dioxane 60 40 0 6 7 CuI (2. the formation of 1-bromoalkynes in the presence of base from 1. Plausible Mechanism B dx. However. For example. The sequence begins with the deprotonation of the imidazole by Cs2CO3 followed by cesiumcopper transmetalation to generate a copper(I)(imidazolate) intermediate B. Dehydrobromination takes place at the late stage to generate Scheme 1. Table 2).2-dibromovinyl)benzene (1. In general. were not suitable substrates (entry 11. good yields of the N-alkynylheteroarenes derived from the coupling of the 1. the expected compound 5. (2. Table 3). found to be rather general and allowed for the synthesis of a wide range of N-alkynylimidazoles possessing ethyl.4 by NMR. and ligand (0. however. 2b. Chem. 000–000 . coupling with 2a gave a 7:1 mixture of regioisomeric N-alkynylimidazoles 5ta and 5tb.5 mmol). the first step involves the preliminary formation of alkynyl bromide F by dehydrobromination of the 1.1-dibromoalkenes 2a. b TMEDA = N.1-dibromoalkenes such as 1.13 Path 1 involves the Nalkenylation of imidazole on the more reactive trans CBr bond of the gem-dibromoolefin to furnish the trisubstituted alkene E.N0 . and 2d were observed (entries 68. Then. The regiochemistry of the major isomer 5ta was established as 1. A subsequent reductive elimination leads to the expected compound 5 and regenerates the catalytic copper(I) species A in the process. propyl. XXX.The Journal of Organic Chemistry NOTE Table 1. which are definitely not the best reaction partners in copper-catalyzed cross-coupling reactions.N0 -tetramethylethylenediamine.1-dibromo-1-alkenes 2 was investigated next under the optimized reaction conditions (Table 3).org/10.3diene.14 Taking into account that these compounds have been identified in the crude reaction mixture15 and E was never isolated. Org.N. and benzo[d] substituting groups.N0 -dimethylethanediamine.1021/jo2004346 |J. isopropyl. two hypotheses both involving the formation of a copper(III) complex C or D could be considered. the substituted imidazoles could be successfully used in this coppermediated cross-coupling reaction to give the desired products in moderate to good yields.

3. 132.427. 1H NMR (500 MHz. 121. multiplet (m). A vessel with a magnetic stir bar was charged with imidazole derivative (1 mmol). 1H). 139.1-dibromo-1-alkenes proceeds through path 2.18 (s. and N. 129.67 (d.08 (s.3. triplet (t). CDCl3) δ 7.7.4.9. J = 7. 7. 1-((3-Bromophenyl)ethynyl)-1H-imidazole (3d): yellow liquid. 13C NMR (125 MHz.N0 -tetramethylethylenediamine (TMEDA) (12 mg. 69.9.6. J = 7.7. 1H NMR (400 MHz. 121. 13C NMR (125 MHz. MS (ESI) m/z 182. under N2. 121. 1H). 3H). a 1a (1. 7.1-dibromo-1-alkenes.3 g.0844. 2H).7 ([M þ H]þ).4.32 (m.3.80 (s.07 (s. DMF was dried over 4 Å molecular sieves overnight prior to use. 128. 7. 6. 69. 7.79 (s.6.0.4-Dioxane was freshly distilled from sodium/benzophenone under nitrogen prior to use. Org.1.55  7.83 (s.31 (m.5. 000–000 .8.1021/jo2004346 |J. 7.7.17 (d. mp 7577 °C.7 ([M þ H]þ).5. 7. found. 1H). 1. 1H NMR (500 MHz.11c All solvents were reagent grade. 1H). HRMS (EI) calcd for C12H10N2 (Mþ) 182. 2H).4.6. 1H). 129.1-dibromo-1alkenes (1. 131. 7. 128.2 ([M þ H]þ).6. 1-(p-Tolylethynyl)-1H-imidazole (3b): white solid. Cs2CO3 (1. 77. HRMS (ESI) calcd for C11H7ClN2 ([M þ H]þ) 202. 13C NMR (100 MHz.2. 130.24 (m. Chem.45 (d.0 mmol) and 2 (1.9. and concentrated with a rotary evaporator (2030 mmHg). 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.4 Hz.88 (s. 2H). CuI (10 mg. MS (ESI) m/z 248. 117. organic extracts were dried with Na2SO4.66 (t. CDCl3) δ 139. 129. 4 mmol). Unless otherwise noted. 129. 78.20 (s. 135. 7.1 Hz.9793. e No reaction. J = 8. XXX. 1H). 78.9. 2H).82 (s. a solution of dry dioxane (2 mL) containing the 1.2.9. J = 1.7 ([M þ H]þ). 2H).10 (s. 1H).6 Hz. mp 54 56 °C.0. 70. 7. broad resonances (br).1 mmol) under a nitrogen atmosphere. and the reaction mixture was heated to 80 °C for 24 h. 77. J = 1. 7. d Reaction run at 80 °C for 48 h. MS (ESI) m/z 202.1 Hz. CDCl3) δ 7.05 mmol). 13C NMR (100 MHz. c Reaction run at 60 °C. The gas chromatography analysis was performed on a GC instrument with nitrogen gas as a carrier. 3. 129. 3H). 70.8. 1H).0298. 4-((1H-Imidazol-1-yl)ethynyl)benzonitrile (3e): yellow solid. CDCl3) δ 140.39 (m. 1H).19 (s. CDCl3) δ 7.3. Copper-Catalyzed Alkynylation of Imidazole with 1. mp 108110 °C. 140.0.N. Dichloromethane and toluene were freshly distilled from CaH2 prior to use. 1-(Phenylethynyl)-1H-imidazole (3a):8.The Journal of Organic Chemistry NOTE Table 2.20 (d.0.5. 7.doi. 122. The dioxane solution was then added to the reaction flask with a syringe. CDCl3) δ 140. 13C NMR (125 MHz. The residue was purified by flash column chromatography with ethyl acetate (EA) and petroleum ether (Pet) as eluent to afford the corresponding products.1. 1-((4-Chlorophenyl)ethynyl)-1H-imidazole (3c): white solid. 1H). 1H).16 yellow oil.2. 121. 1H). found 245. doublet (d). 1H).6. In a separate flask. 7. CDCl3) δ 140. 1-((4-Methoxyphenyl)ethynyl)-1H-imidazole (3f): white solid. 1H). 1.617. 1H). 122. Unless otherwise noted. 2H). 21. This reaction has been shown to be general and provides a straightforward entry to N-alkynylheteroarenes from readily available 1. 134. 77. found 193. 82. 2H). J = 8. Melting points were measured with a micro melting point apparatus. 1H NMR (500 MHz. HRMS (EI) calcd for C12H7N3 (Mþ) 193.5.60 (d. 1H NMR (400 MHz. 7.4 Hz. 3H).1 ([M þ H]þ).0647. filtered.3. J = 8. 0. 1H). filtered C dx.09 (s. XXXX.1.9800.1-Dibromo-1-alkenes 2al were prepared according to the reported procedures. 129. 1H NMR (500 MHz. CDCl3) δ 7. and extracted with ethyl acetate (3  20 mL). MS (ESI) m/z 194. CDCl3) δ 7. 7. 1H). 7. 0. 7. MS (ESI) m/z 169.89 (d. All reactions were carried out under nitrogen in oven-dried glassware with magnetic stirring. 132. The reaction vessel was evacuated and backfilled with nitrogen three times.4.N0 . 2. 123.4.6 Hz.4.9.1 Hz. 1.2.2. 129.7. 7. 132.5. HRMS (EI) calcd for C11H7BrN2 (Mþ) 245. 1H).4. J = 8. Mass spectroscopy data of the products were collected on an HRMS-APCI instrument or a low-resolution MS instrument using EI or ESI ionization. ’ EXPERIMENTAL SECTION General Methods.5 mmol) at 80 °C for 24 h.2. 7. 77. CDCl3) δ 7. found 202. 112. 130.0640.29  7. 1H).9. 7.5. CDCl3) δ 140. 1H). 129. 182.3. 119.2. and concentrated.0294. 118. b Yields of isolated products after chromatographic purification. General Procedure for the N-Alkynylation Reaction of Imidazoles. J = 8.6 Hz.org/10.24 (s. 126.40 (d.37  7. CDCl3) δ 160.46  7. all materials were obtained from commercial suppliers and were used without further purification.5 mmol) was evacuated and backfilled with nitrogen gas three times. 7.49 (m.14 (s. The reaction mixture was cooled to room temperature. In summary.0848. 13C NMR (125 MHz.3.2. 3H). The following abbreviations were used to describe peak patterns where appropriate: singlet (s). quenched with 5 mL of a saturated NH4Cl solution. Unless otherwise noted. The combined organic phases were dried over anhydrous sodium sulfate. 2H).1-Dibromo-1-alkenesa through a fritted glass funnel. 7. 7. Flash chromatography was performed with silica gel (200300 mesh) using the mobile phase indicated.45 (m.37 (s. 7.80 (s. 69. 7. 133.7 Hz.8.4. mp 7577 °C. 131. 79. 1.3. 132.08 (s. a copper-mediated synthesis of N-alkynylimidazoles has been described. 1H).82 (s. 121.43 (dd.6.

000–000 .org/10. Copper-Catalyzed Alkynylation of Imidazole and Benzimidazole with 1.The Journal of Organic Chemistry NOTE Table 3.doi. Chem. XXX. XXXX.1-Dibromo-1-alkenesa D dx. Org.1021/jo2004346 |J.

MS (ESI) m/z 253. J = 1.org/10.47 (d.84. 76. 1H NMR (500 MHz. 1H). 1H). 7. 1H).5 mmol) at 80 °C for 24 h.65 (d.8. HRMS (EI) calcd for C16H26N2 (Mþ) 246.3.81 (s. 0. 1H).32 (dd. 1H NMR (400 MHz. 2. MS (ESI) m/z 199. 1H). 1H).7 Hz.9.8.6.8.2.1 ([M þ H]þ). 5H).42 (dt.02 (m. 70. 125.0.28 (d. 128. 13 C NMR (125 MHz. 7. 2H).0. 14.66 (d.9 Hz. 7.5.4. found 198.8. 1H).2.36 (dd. 1H). 18. CDCl3) δ 140. 1H NMR (500 MHz. 134. 21. 1H).0 ([M þ H]þ). 116.2.4. 7. mp 8890 °C. J = 7. 1-(Phenylethynyl)-1H-benzo[d]imidazole (5a):8.5.2. 113. 7.09 (dd. 3H). 134. 1H). CDCl3) δ 7. 124. 111. yellow oil.3. 13C NMR (125 MHz. 129. mp 5052 °C. HRMS (EI) calcd for C12H10N2 (Mþ) 174. 1H).7. 1H NMR (500 MHz. 7.35 (m.0598.1.85 (d. 0.4. XXX. CDCl3) δ 7. 78. 6. 13C NMR (125 MHz. 64.2.0793.1. 14H).2. 7. 29.837. 1H). 1-(p-Tolylethynyl)-1H-benzo[d]imidazole (5b): yellow solid. 129. 77.1 ([M þ H]þ). found 246.9 Hz. J = 3.4 Hz. MS (ESI) m/z 187.1. c GC yield. CDCl3) δ 7.537.36 (m. CDCl3) δ 8. Org.3 Hz.0454. HRMS (EI) calcd for C16H12N2 (Mþ) 232.7.8.9 ([M þ H]þ).8 ([M þ H]þ). 1H). 7.8.68 (s.0. HRMS (EI) calcd for C11H7FN2 (Mþ) 186. J = 8.4.7 Hz. J = 25.9. 29.0480. 121. 1H).4. 29. 13C E dx. J = 1. J = 8.8 Hz.78 (m. 129. 7.4. 69. 7. 118.83 (d.1. 1-(Furan-2-ylethynyl)-1H-imidazole (3h). 1H NMR (500 MHz.9 Hz. 28.40 (s. 72. 13C NMR (125 MHz.0456.6. 134.8.2. 73. found 186. CDCl3) δ 7.8.7 Hz.9 Hz.9 Hz.9.8.0 Hz.0. 1H).4.1. 117. 1H). 1H). CDCl3) δ 8.28 (d. 2H). 73. J = 5.57 (dd.0. 122. 1H). 134. 121. Continued 1 (1. 1H). CDCl3) δ 8. 128. d The ratio of the isomeric products was determined by GC. HRMS (EI) calcd for C9H6N2O (Mþ) 158.8 Hz.5 Hz. 129. 7. J = 1.0 ([M þ H]þ). 1. 7.The Journal of Organic Chemistry NOTE Table 3.0 Hz.0.1002. 135. 7. 121.9.46 (dd.3.84 (d. 2H).48 (dd.2. 134.0 mmol) and 2 (1. 129.2096.6.9 Hz. 2H). 29. 121. J = 14. 81.4 Hz. 13C NMR (125 MHz. white solid. 1-((4-Chlorophenyl)ethynyl)-1H-benzo[d]imidazole (5c): white solid. 2H).88 (t.8 ([M þ H]þ). Chem. 13C NMR (125 MHz. 1H). mp 4648 °C.3. found 232.73 (s. J = 6. 1H NMR (500 MHz. 1H).9 Hz.09 (s. 0. 125. 2.8. 1. 7. 7. CDCl3) δ 143.1000.04 (dd. 1H).2102. 121.37 (m. e Reaction run at 80 °C for 48 h.74 (dd. 1H).6.1 Hz.6. HRMS (EI) calcd for C15H9ClN2 (Mþ) 252. J = 5. 7. 125.18 (t. 120.67 (d.5.1. 134. 1. 2H). J = 8.9 Hz. with 1-methyl1H-imidazole as the internal standard. 7.3. 13C NMR (125 MHz. 127.8.0257. CDCl3) δ 143.6. 61. 162. 7.5. 122. J = 14. 2H).0. 135.6. 1. 142. CDCl3) δ 8.21 (d. CDCl3) δ 143. 129. J = 7. J = 15. 1-(Thiophen-2-ylethynyl)-1H-imidazole (3i).55 (m. 140. 132.7.1. 7.2. 7.50 (d. CDCl3) δ 144. 1-((4-Fluorophenyl)ethynyl)-1H-imidazole (3g): yellow oil.9 Hz. 140. 122. mp 7476 °C.15 (s.0. 2H). 3. 7.9.9 ([M þ H]þ). J = 7.1. 7.0469.117. 1H).9.6. 77.07 (s. 1H). 1H). 1H). J = 3.2. MS (ESI) m/z 232. 128. MS (ESI) m/z 218. 133.1.48  1.03. 1-((3-Bromophenyl)ethynyl)-1H-benzo[d]imidazole (5d): white solid.4. 111. 7. CDCl3) δ 164.44 (m.5.13 (s. 132. 7.63 (d. 121. found 158. 111. b Yields of isolated products after chromatographic purification.6. 116.62  7. J = 1. 133.36 (t. 55.0 Hz. 1H NMR (500 MHz. HRMS (EI) calcd for C12H10N2O (Mþ) 198. 7. 131.33 (m. J = 7. 1H).2.5. found 252.2.16a yellow oil.0. 7. 142.1. J = 7. 142.9.0252. J = 7. 82. 1. 128. under N2. XXXX. 1. 70.4. 7. 7.1 Hz.0. 139. 7.2 Hz.5.1.0. 124. a 114. 7.5. 3H). CDCl3) δ 140.8.3 Hz.7. yellow oil. 1H).7.doi. 124.9. MS (ESI) m/z 247.1. 2H).15 (s. found 174. 111. 1 H NMR (500 MHz.3. 22. 2H). J = 7.6.8. 32.7.52 (dd. 1-(Tridec-1-ynyl)-1H-imidazole (3j).0.01 (s.48  7. 0.17 (s.0792.80 (s. MS (ESI) m/z 158.0. 6. 1H). 7. 2H). J = 7.0593. 7.467.8 Hz. 3H).1. 29.19 (t.2. 7. 7. 1H). 000–000 .5. 76.19 (s. 7.45  7. J = 7. J = 3. 4H).1021/jo2004346 |J.9 Hz. 70.2. MS (ESI) m/z 174. 117.85 (d. J = 7.

129.5.0 ([M þ H]þ). 125.3. J = 6. 21. 6.6 Hz.1. 3H). 133. J = 20. 1H). J = 8.1000. 131.33 (m.1 ([M þ H]þ).1. 80. 124. J = 1. 123.0 Hz.6.0.2. CDCl3) δ 7.0. CDCl3) δ 7. 7.1 Hz.0800. 130. J = 7.35 (m. HRMS (EI) calcd for C12H9BrN2 (Mþ) 259.7.79 (s.0.36 (ddd. 7.6 Hz. 2H). 1H). CDCl3) δ 149. 2H).5. J = 1.3. 1H).2252.0874.6.6.1.2256. 2H).4.03 (t. 122. 11. J = 7. 1H NMR (500 MHz. 3H). CDCl3) δ 153. found 278.9. 27.5. 132. J = 1. 122.47  7. 128. MS (ESI) m/z 211. 127. 1H).45 (m.39 (m. J = 6.8. CDCl3) δ 7. 132. CDCl3) δ 7.2. 11.4 Hz. 1. 1H).3. 3. 2. 1. HRMS (EI) calcd for C16H9N3 (Mþ) 243.1.7 ([M þ H]þ). 121. 121. 128. 7. 110. 76. 130. J = 6.0767.1. J = 7. 111.6.89 (s. found 196. J = 1. 110.2.09 (d. 1H). 4H).73.90 (q.1.0 Hz. 135.4.0.4 Hz. found 266.5. 1-((4-Chlorophenyl)ethynyl)-2-ethyl-1H-imidazole (5l): yellow oil.387. 123. 21.0109.6 Hz. 7. 129. 6. 1. CDCl3) δ 8.90 (d.16b yellow oil. 72. 2H).6.3. 2. mp 7577 °C. CDCl3) δ 149. J = 1. 131.75 (s. 1H).1 Hz.0 Hz. 130.2.8. CDCl3) δ 7.44 (dt. 132.5. 121. J = 7. 1.92 (d.47 (m. 7.8. 2H).0. 3H).33 (m. 1H). J = 15. J = 8.5. 130. 7.4 Hz.7. 13C NMR (125 MHz. 124. 129. 1H).1.9. CDCl3) δ 157.6. CDCl3) δ 139. 7. 2H). HRMS (EI) calcd for C14H13ClN2 (Mþ) 244. MS (ESI) m/z 275. 1H).4.41 (d. 2H). 71.9. 128. 141.0. 7. CDCl3) δ 144.7. 1H NMR (500 MHz.4. 1H). 3. 8.1. 120. 7.3 Hz.6. 129. 1H).3. 2H). CDCl3) δ 153. 121. 1H NMR (500 MHz.8. J = 8.5. 14. 21.5 Hz.8. 13C NMR (125 MHz.09 (d. 1H).53  7.1 Hz.52 (ddd.4.0998.9. 3H).8. CDCl3) δ 7.1 Hz. J = 1.1. CDCl3) δ 152.1.6.8. 6.12 (s. 128.32 (dt.37  7.3. 7.0. 13C NMR (125 MHz. 1.5.9 Hz. 1H). Chem.39 (t.2. J = 7.0611.4 Hz. J = 1. 1.9 ([M þ H]þ). 130. 1H).3. 71. 0.8. J = 7.0262.1. J = 1. 6. J = 6.09 (d. mp 4951 °C.6.0.45  7.5. 130. 2H).6.29 (m.1.7.1. 7.427. 7.0 Hz. 77. 1. MS (ESI) m/z 183. 7. 7. J = 1. CDCl3) δ 7. 129.2.1 ([M þ H]þ). 129. 6. 70. 6. J = 7. 7.40 (t.89 (q.1 ([M þ H]þ).1. 3H).7. tR = 10.0262. 75. CDCl3) δ 153. J = 14.3. MS (ESI) m/z 261.51 (m.2 Hz. J = 1.7. 14.4 Hz. CDCl3) δ 152. 132. 138. 7.4 Hz. 2H). 120. 2-Isopropyl-1-((4-(trifluoromethyl)phenyl)ethynyl)-1Himidazole (5q): yellow solid. 111.5. 121. 124.9.3 Hz. 7.2. 1H).7. 1H). 127. J = 14. HRMS (EI) calcd for C13H12N2 (Mþ) 196. J = 1.81 (d. 120.37 (m. 32. 2H).2.61 (q. 1-((4-Chlorophenyl)ethynyl)-2-methyl-1H-benzo[d]imidazole (5j): yellow oil. 122.3. 4H). 1H NMR (500 MHz.7. 135.1027.70 (dd.2. 3H).12 (d. 73.9 Hz. 121.36 (m. 132.2.8. 21.4 Hz.9.4 Hz.51 (dd. 6.1. MS (ESI) m/z 182.55 (s.09 (d.2.3. XXXX.50 (ddd. J = 1.57 (d. 134. 3H). 7.0998. MS (ESI) m/z 231.467.3. 2-Ethyl-1-(p-tolylethynyl)-1H-imidazole (5k): yellow oil. 112. 1H).5 Hz.7. 2.25 (dd.10 (d. 1H).8.91 (d. found 264.76 (s. 1H). 1H).0796. MS (ESI) m/z 267. 124. 1H).5.64 (t.2. 2H). 28.8. 118. 2H). MS (ESI) m/z 244.4. 79. 128. 132. 77. 72.41 (m. 2. 3H). 1H).48 (t. J = 6. 68.9 Hz. 6. 1. 7.92 (q. J = 7. 118. CDCl3) δ 7. 72. J = 1.63 (t. MS (ESI) m/z 279.0. J = 1. 2.2.42 (d. 78. 2H). 7. 2. 13C NMR (125 MHz.0 Hz. 130. CDCl3) δ 7. 125. 3. 129.5.17 (s. 2H). J = 7.70 (dd. 2. 13. 6. 125. 3H).25 (dd. 120. HRMS (EI) calcd for C14H13BrN2 (Mþ) 288.9949. 130. 1H). 119. 1H NMR (500 MHz. 125. 6. 13C NMR (125 MHz.9.1 ([M þ H]þ). 7.92 (d. 20. 2H). 1H).8. 121. J = 8. 5H). 2H).5 Hz. 71.0. 21. 80. 13C NMR (125 MHz. CDCl3) δ 149. 121.3. 11.72 (s. 3H).0.6 Hz. 2. 79.4.4.9951.1 Hz.4.9 Hz. 130.9 Hz. MS (ESI) m/z 289. 1H).40  7. 3H).08 (d.08 (d.9. 72.The Journal of Organic Chemistry NOTE NMR (125 MHz.51 (ddd. J = 13. CDCl3) δ 153. 127. 121.1. 1H). J = 1. 2-Methyl-1-(p-tolylethynyl)-1H-imidazole (5g): yellow oil.3.41 (t. 3H). 1H).7.doi.1159. J = 15. 122. 6. 78. found 296.0 Hz. 295.1 ([M þ H]þ).4 Hz.9.39 (t. 1.8. 128. HRMS (EI) calcd for C16H12N2 (Mþ) 232.5.7.1 Hz. 2H).9 Hz. 2H). CDCl3) δ 139. 77. J = 8. found 244. 131.4.7. 6H).16 (m. found 278.6. 71.1.65 (t. J = 6.7. 2.6 Hz. CDCl3) δ 7.0611.577. 1H). 79.6 Hz. 0.7.2.94 (d.8. found 232.8.8. 4H).3.5.9 ([M þ H]þ). J = 8.5 Hz. XXX. J = 7. 13.9. 7.9. 2. J = 19.8.09 (d.org/10. 139. found 288.09 (d. J = 1.87 (t.4 Hz. 29.1 ([M þ H]þ).2. 126. 13. 7. 13C NMR (125 MHz.1 ([M þ H]þ).4 Hz.0. 6.6 Hz. 125.0611. 13C NMR (125 MHz. 1. 29.1000. 72.0.8.9. 121.45 (m. 3H).4. 18.9.4 Hz. 13C NMR (125 MHz.2. 135. 2H). 6. 131.95 (d. CDCl3) δ 153.6.1.7.8.33 (dt. 122. 1. 13C NMR (125 MHz.3. CDCl3) δ 157. J = 6. 126.9 Hz.35 (s. 133. 80.9. 123.3. 3H). 2-Methyl-1-(phenylethynyl)-1H-imidazole (5f):8.41 (m.4. 125.6 Hz.3. CDCl3) δ 143. 130.2.65 (t.0608. J = 7.5.6.4 Hz. HRMS (EI) calcd for C13H11ClN2 (Mþ) 230. 132.5 Hz.1. 1H).0766. 9. J = 19. J = 13. 1H).63  7. 139. 77. 2H).3. J = 7.4 Hz. 128.0.1.9. 21.8. 72.7. 21.95 (d. 79. 121. 7. 3H). 21. 74. 7.9949. CDCl3) δ 7. 1H). 7. 2.0.70  1.95 (d. J = 1.3 Hz.0873. 6. 1H NMR (500 MHz. 130.5 Hz. 1H). 13C NMR (125 MHz. found 274. 2. J = 7.3 ([M þ H]þ). 1H). 2H). J = 7. J = 1. 7.1.38 (s. 121. CDCl3) δ 157. 11. 14. 1H NMR (500 MHz. 2H).1 ([M þ H]þ). 1H). 4-((1H-Benzo[d]imidazol-1-yl)ethynyl)benzonitrile 2-Ethyl-1-((4-(trifluoromethyl)phenyl)ethynyl)-1H-imidazole (5n): yellow oil. 13C NMR (125 MHz.8. 121.2. J = 1.1. 124.1031. MS (ESI) m/z 265. MS (ESI) m/z 233.4. J = 7.5. CDCl3) δ 7. J = 7. 142.87 (dd. 1-((3-Bromophenyl)ethynyl)-2-propyl-1H-imidazole (5r): yellow oil. 1H). 118. 1.2. 76.5. 131. 71. 124. 72. 21. J = 1. J = 7.8.9.9. 6. J = 14.86 (d.68 (m. 128.6.9.05 (s. 1H NMR (400 MHz. 21.0106.5. 7. 1H).5. 2-Propyl-1-((4-(trifluoromethyl)phenyl)ethynyl)-1H-imidazole (5s): yellow oil. 119. 7. 123.4.7.9.94 (d. found 230. 13C NMR (125 MHz. 128. 1-((3-Bromophenyl)ethynyl)-2-ethyl-1H-imidazole (5m): yellow oil.39 (d. J = 13. 124.4. 6. 2H).4.7. 1H). 80.4.0.9 Hz. 128. 7. 125. 1. 1H). (5e): white solid. 79. 5-Methyl-1-(phenylethynyl)-1H-imidazole (5tb):8b yellow oil.54 (s.3. 1.417.3.1 ([M þ H]þ). 1H).6.4 Hz. 135. 128.2. 71.40  1. F dx.5. 123. J = 1.41  7.1. MS (ESI) m/z 296. J = 1.55 (s.8.41 (d.4. 13C NMR (125 MHz. HRMS (EI) calcd for C13H11BrN2 (Mþ) 274. 7. 3H).8.21. 111. 121.3.11 (d. 1H NMR (500 MHz. J = 15. 33. 1-(Tridec-1-ynyl)-1H-benzo[d]imidazole (5u): yellow oil.0 Hz.1 ([M þ H]þ). 29.94 (d.0.7.477. 13.1.90 (q. 1-((3-Bromophenyl)ethynyl)-2-methyl-1H-imidazole (5h): yellow oil. 1H NMR (500 MHz.4.85 (dd. 7.9 Hz. 2.7. 14H). Org.26 (dd. 3H).25 (s.3.1.32 (dt. 118. 2H). 1H NMR (500 MHz.18 (d. 3H). 1-((3-Bromophenyl)ethynyl)-2-isopropyl-1H-imidazole (5p): yellow oil. 7. 29. 3. 1H).1028. 6. 1.4.6. 2-Methyl-1-(phenylethynyl)-1H-benzo[d]imidazole (5i): yellow oil. 2H).22.88 (t.6.5 Hz. 1H). 6H). 1H NMR (500 MHz. 8.577. 7. 7.9940. 71.0. 129. 1H NMR (500 MHz.2.4. J = 8. 1H).4.23 (t.8. HRMS (EI) calcd for C14H13BrN2 (Mþ) 288. HRMS (EI) calcd for C20H28N2 (Mþ) 296. 13C NMR (125 MHz.0.9. HRMS (EI) calcd for C15H9BrN2 (Mþ). 7. MS (ESI) m/z 182. CDCl3) δ 7.1 Hz. 1H). 121. 134.34 (m.8. found 295. 122.1.9 Hz.6 Hz. 7. 131. 14. 2H). 7.6. 14.1021/jo2004346 |J.4.62 (dd.1157. HRMS (EI) calcd for C15H13F3N2 (Mþ) 278. 134.4. 132. 125.3.1 ([M þ H]þ).9. 1H NMR (500 MHz.1. 3H). 130. 7. J = 16. 77. 135. 128.0. 7.74.5 Hz. found 210. 1H). 7.7. J = 1. 142.2. 1.3.29 (m. HRMS (EI) calcd for C15H13F3N2 (Mþ) 278. 1-((4-Chlorophenyl)ethynyl)-2-isopropyl-1H-imidazole (5o): yellow oil.1031. 1H). 7. 123. 4. 1. 8.7. 1H). 122. 7.2 Hz.8.2. MS (ESI) m/z 289. tR = 10. 4-Methyl-1-(phenylethynyl)-1H-imidazole (5ta):8b yellow solid. 3H). HRMS (EI) calcd for C16H11ClN2 (Mþ) 266.3. 13C NMR (125 MHz. MS (ESI) m/z 197.17 (d. 1H).4 Hz.9.6 Hz.7. 7. CDCl3) δ 143. 121. 128. 1H NMR (500 MHz.9.8.1.48 (dd.387. 7.5 Hz. 134. 7. J = 1.8.02 (t. 1H). 2.1.39 (m.8. CDCl3) δ 7. CDCl3) δ 153.9 Hz. 1.7 Hz.2 Hz. found 259.367. 1H).3. 6H).2 ([M þ H]þ).9. 7. 130.9. 1H NMR (500 MHz. 29.4.1 ([M þ H]þ).7 Hz.61 (dd. J = 7. 29. 000–000 . J = 8.9 Hz.1.3.5 Hz. 132.46 (m. MS (ESI) m/z 245. J = 7. CDCl3) δ 7.54  7. 121.37 (s. HRMS (EI) calcd for C14H11F3N2 (Mþ) 264. 22.60 (m. 7.0264. 29. 131. 1H). 1H).8.0.7. 1. found 243. MS (ESI) m/z 279. 121. 134.6. 11. 7. 130.3.9. 131. J = 1. J = 1.1.0268.6. 2. CDCl3) δ 8.75 (s.5. 13 C NMR (125 MHz. 1H).2 Hz.95 (d. 2. 1H NMR (500 MHz.7. 1.41 (dd. 125.1.96 (s. 27.44  7. MS (ESI) m/z 297.39 (d. 1. 2.42 (dt. 27.8. 3H).0. CDCl3) δ 7. 2. 129.1 ([M þ H]þ). 13C NMR (125 MHz. found 288. HRMS (EI) calcd for C14H14N2 (Mþ) 210.32 (m. 79.84 (t.6. 7. 1H NMR (500 MHz. 3H). 6.8.3. 1H).5.1 Hz. mp 140143 °C.0.9 Hz.

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