* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Organic and Biomolecular Chemistry, 2011, vol. 9, # 7, p. 2185 - 2191
2
[ 1945-84-2 ]
[ 272-67-3 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 18, p. 2753 - 2758
3
[ 86521-05-3 ]
[ 1945-84-2 ]
Yield
Reaction Conditions
Operation in experiment
80%
With methanol; potassium hydroxide In dichloromethane at 0℃; for 0.5 h;
2-((Trimethylsilyl)ethynyl)pyridine (175mg, 1.0 mmol) was dissolved in MeOH/Dichloromethane (2mL/lmL). The solution was cooled to 0 °C and KOH (112mg, 2.0 mmol) was added. The reaction mixture stirred for 0.5 h, and then quenched with H2O, extracted with Dichloromethane (2x3 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give 2-ethynylpyridine (80 mg, 80percent yield).
75%
Stage #1: With potassium hydroxide In methanol at 20℃; for 1 h; Stage #2: With hydrogenchloride In methanol; water
a) 2-Ethynyl-pyridine A solution of 2-trimethylsilanylethynyl-pyridine (3.05 g, 14 mmol) in MeOH (8.5 mL) was added dropwise to potassium hydroxide solution (1 N, 14 mL) and the reaction mixture was stirred at room temperature for 1 h and then acidified with HCl (3 N, 8.5 mL) and the mixture concentrated. The residue was then diluted with water and make alkaline with solid sodium carbonate, extracted with diethyl ether and the combined organic extracts washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, diethylether) afforded the title compound (1.3 g, 75percent) as a brown liquid. MS: m/e=176.0 [M+H]+.
75%
Stage #1: With potassium hydroxide In methanol at 20℃; for 1 h; Stage #2: With hydrogenchloride In methanol; water Stage #3: With sodium carbonate In water
2-Ethynyl-pyridineA solution of 2-trimethylsilanylethynyl-pyridine (3.05 g, 14 mmol) in MeOH (8.5 mL) was added dropwise to potassium hydroxide solution (1 N, 14 mL) and the reaction mixture was stirred at room temperature for 1 h and then acidified with HC1 (3 N, 8.5 mL) and the mixture concentrated. The residue was then diluted with water and make alkaline with solid sodium carbonate, extracted with diethyl ether and the combined organic extracts washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, diethylether) afforded the title compound (1.3 g, 75percent) as a brown liquid. MS: m/e = 176.0[M+H]+.
Reference：
[1] Angewandte Chemie - International Edition, 2015, vol. 54, # 27, p. 7949 - 7953[2] Angew. Chem., 2015, vol. 127, # 27, p. 8060 - 8064,5
[3] Canadian Journal of Chemistry, 2005, vol. 83, # 6-7, p. 716 - 727
[4] Dalton Transactions, 2016, vol. 45, # 25, p. 10209 - 10221
[5] Phosphorus, Sulfur and Silicon and Related Elements, 2002, vol. 177, # 5, p. 1041 - 1045
[6] Synthetic Communications, 2003, vol. 33, # 14, p. 2447 - 2461
[7] Journal of Organometallic Chemistry, 2001, vol. 629, # 1-2, p. 131 - 144
[8] Patent: WO2014/124560, 2014, A1, . Location in patent: Page/Page column 35
[9] Chemistry Letters, 2011, vol. 40, # 9, p. 925 - 927
[10] Patent: US2012/115844, 2012, A1, . Location in patent: Page/Page column 20
[11] Patent: WO2012/62687, 2012, A1, . Location in patent: Page/Page column 45
[12] Research on Chemical Intermediates, 2013, vol. 39, # 1, p. 359 - 370
[13] Synthesis, 1983, # 4, p. 312 - 314
[14] Tetrahedron Letters, 2003, vol. 44, # 41, p. 7611 - 7612
[15] Chemistry - A European Journal, 2001, vol. 7, # 23, p. 5118 - 5134
[16] Chemical Communications, 2008, # 19, p. 2203 - 2205
[17] Journal of Organometallic Chemistry, 2009, vol. 694, # 9-10, p. 1317 - 1324
[18] Chemical Communications, 2012, vol. 48, # 15, p. 2080 - 2082
[19] Journal of Medicinal Chemistry, 2013, vol. 56, # 7, p. 3033 - 3047
[20] Synlett, 2013, vol. 24, # 9, p. 1101 - 1104
[21] RSC Advances, 2015, vol. 5, # 92, p. 75263 - 75267
[22] Organic and Biomolecular Chemistry, 2016, vol. 14, # 6, p. 2127 - 2133
[23] Tetrahedron, 2016, vol. 72, # 39, p. 5831 - 5842
4
[ 1121-60-4 ]
[ 90965-06-3 ]
[ 1945-84-2 ]
Yield
Reaction Conditions
Operation in experiment
71%
With potassium carbonate In methanol at 20℃; for 1.5 h;
Example 104-Methyl-2-[(E)-2-(3-methyl-5-pyridin-2-yl-3H-[1,2,3]triazol-4-yl)-vinyl]-thiazole-5-carboxylic acid isopropylamide a) 2-Ethynyl-pyridine; To a mixture of 2-pyridinecarbaldehyde (0.96 mL, 10 mmol) in MeOH (43 mL) was added potassium carbonate (2.76 g, 20 mmol) followed by a solution of (1-diazo-2-oxo-propyl)-phosphonic acid dimethyl ester (2.14 g, 11 mmol) in MeOH (14 mL) at room temperature and the resulting mixture stirred for 1.5 h. The mixture was then poured into sodium carbonate solution (1 M) and extracted with ethyl acetate and the combined organic extracts washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, diethylether) afforded the title compound (728 mg, 71percent) as a yellow liquid. MS: m/e=103.0 [M]+.
71%
With potassium carbonate In methanol at 20℃; for 1.5 h;
To a mixture of 2-pyridinecarbaldehyde (0.96 mL, 10 mmol) in MeOH (43 mL) was added potassium carbonate (2.76 g, 20 mmol) followed by a solution of (l-diazo-2-oxo-propyl)- phosphonic acid dimethyl ester (2.14 g, 11 mmol) in MeOH (14 mL) at room temperature and the resulting mixture stirred for 1.5 h. The mixture was then poured into sodium carbonate solution (1 M) and extracted with ethyl acetate and the combined organic extracts washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, diethylether) afforded the title compound (728 mg, 71percent) as a yellow liquid. MS: m/e = 103.0 [M]+.
Reference：
[1] Journal of Organic Chemistry, 2010, vol. 75, # 10, p. 3518 - 3521
17
[ 1121-60-4 ]
[ 1945-84-2 ]
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 5, p. 709 - 714
[2] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 5, p. 709 - 714
With C20H14AuN2O2(1+)*Cl(1-); water; trifluoroacetic acid In methanol at 80℃; for 5h; Sealed tube;
2.3 Typical procedure for the hydration of alkynes
General procedure: Alkyne (0.5 mmol), catalyst (2.0 mol%), H2O (4.0 equiv., 0.04 mL) and CF3COOH (2.0 mol%) were dissolvedin MeOH (0.4 mL) and the homogeneous solution was stirred in a sealed tube at 80°C for 5 h. After the completion of the reaction, the mixture was cooled to room temperature, and then CH2Cl2 and H2O were added to it. The organic layer was separated and washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified over silica gel by column chromatography (25% EtOAc in hexane).
88%
With Ag3STA; water at 100℃; for 6h; neat (no solvent); regioselective reaction;
88%
With formic acid; water; CoH6Mo6O24(3-)*3H3N*3H(1+)*7H2O at 60℃; for 1h; Green chemistry; chemoselective reaction;
82%
With water; silver trifluoromethanesulfonate for 10h; Heating;
75%
With morpholine; Au-TiO2; water In 1,4-dioxane at 120℃; for 1h; Microwave irradiation;
60%
With sulfuric acid; water; mercury(II) sulfate In acetone for 2h; Heating;
(1-(pyridin-2-yl)ethane-1,2-diyl)bis(diphenylphosphine oxide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With tetrakis(triphenylphosphine) palladium(0) In toluene for 24h; Heating;
75%
Stage #1: Diphenylphosphine oxide With lithium tert-butoxide In tetrahydrofuran for 1h; Schlenk technique; Inert atmosphere;
Stage #2: 2-ethynylpyridine In tetrahydrofuran at 70℃; for 4h; Schlenk technique; Inert atmosphere;
2 Experimental procedures for the base-catalyzed double addition of phosphine oxidesto alkyn
General procedure: In a Schlenk flask wereplaced diphenylphosphine oxide (0.2 mmol), and tBuOLi of THF solution (5 mol%, 0.01 mmol) in THF (0.15mL) under nitrogen. The mixture was stirred at ambient temperature for 1 h. Etynylbenzene(0.1 mmol) was added to the solution under nitrogen and the mixture was heatedat 70 °C for 4 h.
65%
With air In N,N-dimethyl-formamide at 150℃; for 22h;
59%
With potassium hexamethylsilazane In neat (no solvent) at 20℃; for 6h; Glovebox; Schlenk technique; Inert atmosphere; chemoselective reaction;
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 75℃; for 6h;
3-methoxy-5-(pyridin-2-ylethynyl)pyridine <strong>[50720-12-2]3-Bromo-5-methoxypyridine</strong> (Compound 1; 1.00 g, 5.32 mmol) and 2-ethynylpyridine (823 mg, 7.98 mmol) were added to a deoxygenated, 40 C. DMF (35 mL) solution of bis-triphenylphosphine palladium dichloride (300 mg, 0.43 mmol), CuI (162 mg, 0.85 mmol), and triethylamine (2.69 g, 26.6 mmol). The reaction was warmed to 75 C. and stirred under Ar for 6 hours, then cooled to ambient temperature and poured in to a separatory funnel containing 1:1 hexanes:EtOAc (250 mL) where it was washed with 50% dilute brine (4*75 mL), dried (MgSO4), filtered, and concentrated in vacuo. The crude residue was chromatographed on silica gel, eluding with 1:1 hexanes:EtOAc to afford 3-methoxy-5-(pyridin-2-ylethynyl)pyridine as a tan solid. 1H NMR (CDCl3, 300 MHz) delta 8.65 (d, 1H), 8.44 (d, 1H), 8.31 (d, 1H), 7.71 (m, 1H), 7.56 (d, 1H), 7.39 (m, 1H), 7.29 (m, 1H), 3.87 (s, 3H). MS (ESI) 211.1 (M++H).
Stage #1: tetra(n-butoxy)silane With hypophosphorous acid In acetonitrile for 2h; Heating;
Stage #2: 2-ethynylpyridine In acetonitrile for 24h; Heating;
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 50℃; for 5h;Schlenk technique; Inert atmosphere;
General procedure A: 2-ethylpyridine 13 (35 mL, 0.35 mmol) and dry diisopropylethylamine (DIPEA) (0.1 mL, 0.57 mmol) were added to a dispersion of 1,3-diiodobenzene 14a (46 mg, 0.14 mmol), copper(I) iodide (2 mg, 0.01 mmol) and bis(triphenylphosphine)palladium(II) chloride (5.4 mg, 0.01 mmol) in dry dimethyl formamide(DMF) (1 mL) in a Schlenk flask with argon atmosphere at room temperature. The mixture was stirred at 50 C for 5 h. The reaction mixture was diluted in EtOAc (15 mL) and washed with aqueous Na2CO3 1 N (10 mL), saturated NaHCO3 (10 mL), water (10 mL) and brine (10 mL), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified through flash chromatography using Biotage Isolera equipment (SNAP KP-C18-HS12 g, A H2O, B MeCN; 0%B 5CV, 0%B-1%B 2CV, 1%B-4%B 2.5 CV,4%B 1.5CV, 4%B-7%B 6CV, 7%B-9%B 0.5CV, 9%B-100%B 2 CV, 100%B 5CV). The title product 12a was obtained as brown colour solid (34 mg) with an 87% yield, mp 89.9-91.3 C. 1H NMR (400 MHz,CDCl3) delta 8.65 (br, 2H), 7.82 (t, J 1.6 Hz, 1H), 7.70 (td, J 7.7, 1.6 Hz,2H), 7.60 (dd, J 7.8 , 1.6 Hz, 2H), 7.54 (d, J 7.9 Hz, 2H), 7.37 (t,J 7.7 Hz, 1H), 7.31e7.22 (m, 2H). 13C NMR (101 MHz, CDCl3) delta 150.12, 143.22, 136.43, 135.42, 132.58, 128.76, 127.51, 123.16,122.86, 89.33, 88.37. HPLC-PDA-MS: RT = 5.91 min, 99.87% (254 nm), PDA lambdamax = 296 nm, MS (m/z) [M+H]+ 280.94.
[Au(2-pyridylacetylide)(triphenylphosphine)][ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64%
With sodium ethanolate; In ethanol; at 20℃; for 19h;
Under an argon atmosphere, Au(PPh3)Cl (297 mg, 0.60 mmol), 2-pyridylethyne (92.8 mg, 0.90 mmol) and ethanol (12 ml) were added to a 20 ml Schlenk tube, and then sodium ethoxide (250 µl, 0.63 mmol: 2.55 mol/l (liter) in ethanol solution) was added dropwise thereto and the mixture was stirred at room temperature for 19 hours. The reaction mixture was concentrated to approximately 1 ml, and then 40 ml of diethyl ether was added thereto. The resulting white precipitate was successively washed with water (12 mlxthree times) and diethyl ether (6 mlxthree,times) and dried under vacuum to give 0.21 g of the desired compound as a white powder (yield: 64%). 1H-NMR (400MHz, CDCl3) δ: 8.52 (m, 1H): 7.59-7.40 (m, 17H), 7.09 (m, 1H) (FAB-MS) (M/Z): 562 (M+H)+ Luminescence analysis: (CHCl3, 77K, Ex250nm) λ (nm): 416, 436, 443, 456 Elemental analysis: Found C: 51.58, H: 3.42, N: 2.47 Theoretical C: 53.49, H: 3.41, N: 2.50
18 Synthesis of 3,3,5,5-Tetramethyl-1-(2-pyridinylethynyl)cyclohexanol.
EXAMPLE 18 Synthesis of 3,3,5,5-Tetramethyl-1-(2-pyridinylethynyl)cyclohexanol. To a solution of 2-ethynylpyridine (1.0 g, 10 mmol) in THF at -78° C. was added a 1.0 M solution of ethyl magnesium bromide in THF (10 mL, 10 mmol). After stirring at reduced temperature for 30 minutes a solution of 3,3,5,5-tetramethyl-cyclohexanone (1.5 g, 10 mmol) in THF was added rapidly. The mixture was allowed to warm to ambient temperature over 16 hours, then partitioned between water and ethyl acetate. The organic layer was dried over anhydrous Na2SO4, and concentrated in vacuo. The resultant product was purified by flash column chromatography on silica gel eluding with 1:1 hexane:ethyl acetate to afford 3,3,5,5-tetramethyl-1-(2-pyridinylethynyl)cyclohexanol (250 mg, 10% yield) as a white solid. M.p. 126-127° C. 1H NMR (DMSO-d6, 300 MHz) δ8.57 (m, 1H), 7.64 (m, 1H), 7.39 (d, J=5 Hz, 1H), 7.22 (m, 1H), 1.91 (d, J=9 Hz, 2H), 1.71 (d, J=9 Hz, 2H), 1.26 (s, 2H), 1.14 (s, 6H), 1.09 (s, 6H).
10%
In tetrahydrofuran
18 Synthesis of 3,3,5,5-Tetramethyl-1-(2-pyridinylethynyl)cyclohexanol
EXAMPLE 18 Synthesis of 3,3,5,5-Tetramethyl-1-(2-pyridinylethynyl)cyclohexanol To a solution of 2-ethynylpyridine (1.0 g, 10 mmol) in TMF at -78° C. was added a 1.0 M solution of ethyl magnesium bromide in THF (10 mL, 10 mmol). After stirring at reduced temperature for 30 minutes a solution of 3,3,5,5-tetramethylcyclohexanone (1.5 g, 10 mmol) in THF was added rapidly. The mixture was allowed to warm to ambient temperature over 16 hours, then partitioned between water and ethyl acetate. The organic layer was dried over anhydrous Na2SO4, and concentrated in vacuo. The resultant product was purified by flash column chromatography on silica gel eluding with 1:1 hexane:ethyl acetate to afford 3,3,5,5-tetramethyl-1-(2-pyridinylethynyl)cyclohexanol (250 mg, 10% yield) as a white solid. M.p. 126-127° C. 1H NMR (DMSO-d6, 300 MHz) δ 8.57 (m, 1H), 7.64 (m, 1H), 7.39 (d, J=5 Hz, 1H), 7.22 (m, 1H), 1.91 (d, J=9 Hz, 2H), 1.71 (d, J=9 Hz, 2H), 1.26 (s, 2H), 1.14 (s, 6H), 1.09 (s, 6H).
10%
In tetrahydrofuran
18 Synthesis of 3,3,5,5-Tetramethyl-1-(2-pyridinylethynyl)cyclohexanol
EXAMPLE 18 Synthesis of 3,3,5,5-Tetramethyl-1-(2-pyridinylethynyl)cyclohexanol To a solution of 2-ethynylpyridine (1.0 g, 10 mmol) in TBF at -78° C. was added a 1.0 M solution of ethyl magnesium bromide in THF (10 mL, 10 mmol). After stirring at reduced temperature for 30 minutes a solution of 3,3,5,5-tetramethyl-cyclohexanone (1.5 g, 10 mmol) in THF was added rapidly. The mixture was allowed to warm to ambient temperature over 16 hours, then partitioned between water and ethyl acetate. The organic layer was dried over anhydrous Na2SO4, and concentrated in vacuo. The resultant product was purified by flash column chromatography on silica gel eluding with 1:1 hexane:ethyl acetate to afford 3,3,5,5-tetramethyl-1-(2-pyridinylethynyl)cyclohexanol (250 mg, 10% yield) as a white solid. M.p. 126-127° C. 1H NMR (DMSO-d6, 300 MHz) Δ8.57 (m, 1H), 7.64 (m, 1H), 7.39 (d, J=5 Hz, 1H), 7.22 (m, 1H), 1.91 (d, J=9 Hz, 2H), 1.71 (d, J=9 Hz, 2H), 1.26 (s, 2H), 1.14 (s, 6H), 1.09 (s, 6H).
10%
In tetrahydrofuran
18 Synthesis of 3,3,5,5-Tetramethyl-1-(2-pyridinylethynyl)cyclohexanol
EXAMPLE 18 Synthesis of 3,3,5,5-Tetramethyl-1-(2-pyridinylethynyl)cyclohexanol To a solution of 2-ethynylpyridine (1.0 g, 10 mmol) in THF at -78° C. was added a 1.0 M solution of ethyl magnesium bromide in THF (10 mL, 10 mmol). After stirring at reduced temperature for 30 minutes a solution of 3,3,5,5-tetramethyl-cyclohexanone (1.5 g, 10 mmol) in THF was added rapidly. The mixture was allowed to warm to ambient temperature over 16 hours, then partitioned between water and ethyl acetate. The organic layer was dried over anhydrous Na2SO4, and concentrated in vacuo. The resultant product was purified by flash column chromatography on silica gel eluding with 1:1 hexane:ethyl acetate to afford 3,3,5,5-tetramethyl-1-(2-pyridinylethynyl)cyclohexanol (250 mg, 10% yield) as a white solid. M.p. 126-127° C. 1H NMR (DMSO-d6, 300 MHz) Δ8.57 (m, 1H), 7.64 (m, 1H), 7.39 (d, J=5 Hz, 1H), 7.22 (m, 1H), 1.91 (d, J=9 Hz, 2H), 1.71 (d, J=9 Hz, 2H), 1.26 (s, 2H), 1.14 (s, 6H), 1.09 (s, 6H).
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In N,N-dimethyl-formamide; at 60℃; for 12h;
To the solution of <strong>[6293-83-0]2-iodo-4-nitroaniline</strong> (3.0 g, 11 mmol) in DMF (60 mL) and Et3N (60 mL) was added 2-ethynylpyridine (3.0 g, 45 mmol), Pd(PPh3)2Cl2 (600 mg) and CuI (200 mg) under N2. The reaction mixture was stirred at 60 C. for 12 h. The mixture was diluted with water and extracted with dichloromethane (3×100 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuum. The residue was purified by chromatography on silica gel (5-10% ethyl acetate/petroleum ether) to afford 4-nitro-2-(pyridin-2-ylethynyl)aniline (1.5 g, 60%). 1H NMR (300 MHz, CDCl3) delta 8.60 (s, 1H), 8.13 (d, J=2.1 Hz, 1H), 7.98 (d, J=1.8, 6.9 Hz, 1H), 7.87-7.80 (m, 2H), 7.42-7.39 (m, 1H), 7.05 (brs, 2H), 6.80 (d, J=6.9 Hz, 1H).
60%
With CuI; triethylamine;Pd(PPh3)2Cl2; In N,N-dimethyl-formamide;
4-Nitro-2-(pyridin-2-ylethynyl)aniline To the solution of <strong>[6293-83-0]2-iodo-4-nitroaniline</strong> (3.0 g, 11 mmol) in DMF (60 mL) and Et3N (60 mL) was added 2-ethynylpyridine (3.0 g, 45 mmol), Pd(PPh3)2Cl2 (600 mg) and CuI (200 mg) under N2. The reaction mixture was stirred at 60 C. for 12 h. The mixture was diluted with water and extracted with dichloromethane (3*100 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuum. The residue was purified by chromatography on silica gel (5-10% ethyl acetate/petroleum ether) to afford 4-nitro-2-(pyridin-2-ylethynyl)aniline (1.5 g, 60%). 1H NMR (300 MHz, CDCl3) delta 8.60 (s, 1H), 8.13 (d, J=2.1 Hz, 1H), 7.98 (d, J=1.8, 6.9 Hz, 1H), 7.87-7.80 (m, 2H), 7.42-7.39 (m, 1H), 7.05 (brs, 2H), 6.80 (d, J=6.9 Hz, 1H).
60%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 60℃; for 12h;
To the solution of <strong>[6293-83-0]2-iodo-4-nitroaniline</strong> (3.0 g, 11 mmol) in DMF (60 mL) and Et3N (60 mL) was added 2-ethynylpyridine (3.0 g, 45 mmol), Pd(PPh3)2Cl2 (600 mg) and CuI (200 mg) under N2. The reaction mixture was stirred at 60 C. for 12 h. The mixture was diluted with water and extracted with dichloromethane (3*100 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuum. The residue was purified by chromatography on silica gel (5-10% ethyl acetate/petroleum ether) to afford 4-nitro-2-(pyridin-2-ylethynyl)aniline (1.5 g, 60%). 1H NMR (300 MHz, CDCl3) delta 8.60 (s, 1H), 8.13 (d, J=2.1 Hz, 1H), 7.98 (d, J=1.8, 6.9 Hz, 1H), 7.87-7.80 (m, 2H), 7.42-7.39 (m, 1H), 7.05 (brs, 2H), 6.80 (d, J=6.9 Hz, 1H).
With copper(l) iodide; bis(triphenylylphosphine)palladium(II) dichloride; triethylamine; In N,N-dimethyl-formamide; at 25℃; for 2h;Inert atmosphere;
Step 1 (= reaction 1): 750 mg 3-Acetyl-2-bromopyridin, 550 2-ethynyl-pyridine, 765 triethylamin, 255 mg triphenylphosphinpalladium(II) chlorid, 17 mg Cu(I)I were suspended in 10 mL DMF under argon atmosphere and stirred for 2 h at 25C. The mixture was diluted with DCM and extracted with diluted aq. N¾ and saturated NH4C1 solution. The organic phase was concentrated and the mixture separated via FCC (100 g Si02, cyclohexane cyclohexane /ethylacetate 35:65) to yield 455 mg l-(2-(pyridin-2-ylethynyl)pyridin-3- yl)ethanone as solid. Analysis: HPLC-MS: Rt = 0.88 min (methode E) M+H = 223.
455 mg
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 25℃; for 2h;Inert atmosphere;
Alternatively 6.3 can be synthesized as described in: Godet, Thomas; Belmont, Philippe Synlett, 2008,16, 2513-2517 3-Acetyl-2-bromopyridin, 550 muL 2-ethynyl-pyridine, 765 muL triethylamin, 255 mg triphenylphosphinpalladium(II) chlorid, 17 mg Cu(I)I were suspended in 10 mL DMF under argon atmosphere and stirred for 2 h at 25 C. The mixture was diluted with DCM and extracted with diluted aq. NH3 and saturated NH4Cl solution. The organic phase was concentrated and the mixture separated via FCC (100 g SiO2, cyclohexane?cyclohexane/ethylacetate 35:65) to yield 455 mg 1-(2-(pyridin-2-ylethynyl)pyridin-3-yl)ethanone as solid. Analysis: HPLC-MS: Rt=0.88 min (method E) M+H=223.
With diethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; at 20℃; for 12h;
Step 1: ethyl 5-(pyridine-2-ylethynyl)thiophene-2-carboxylateA solution of <strong>[5751-83-7]ethyl 5-bromothiophene-2-carboxylate</strong> (2.00 g, 8.51 mmol) and 2-ethynylpyridine (0.99 mL, 9.80 mmol) in diethylamine (30 mL) and THF (60 mL) was degassed with argon. To the reaction mixture was added bis(triphenylphosphine)palladium(II) chloride (0.422 g, 0.601 mmol) and copper iodide (0.154 g, 0.809 mmol). The reaction mixture was allowed to stir at rt for 12 h. The reaction mixture was diluted with water and EtOAc, and then extracted with more EtOAc. The organic solutions were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography to give ethyl 5-(.yridine-2-ylethynyl)thiophene-2-carboxylate (1.43 grams, 5.54 mmol) as an oil. LCMS: (FA) ES+258.2.
(5Z)-5-[(pyridin-2-yl)methylene]-5H-furan-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
With copper(l) iodide; palladium 10% on activated carbon; triethylamine; triphenylphosphine; In 1,4-dioxane; at 25 - 80℃; for 3.5h;Inert atmosphere;
General procedure: (a) The reaction was performed in a bigger scale using 100 mg of 10% Pd/C (0.092 mmol), PPh3 (0.37 mmol), CuI (0.184 mmol), Et3N (10.68 mmol), compound 1a (3.56 mmol), and acetylenic compound 2a (5.32 mmol) in 1,4-dioxane (20.0 mL). After stirring at 80 C for 3 h under nitrogen the mixture was cooled to room temperature. The Pd/C was filtered off and washed with water (2 10 mL), acetone (2 10 mL), and EtOAc (2 10 mL). Then the catalyst was collected, dried at 100 C in an oven, and reused for the next run. The co-catalyst CuI along with PPh3 was added in every repeated run. (b) General method for the preparation of 3: A mixture of compound 1 (0.89 mmol), 10% Pd/C (0.023 mmol), PPh3 (0.092 mmol), CuI (0.046 mmol), and Et3N (2.67 mmol) in 1,4-dioxane (5.0 mL) was stirred at 25 C for 30 min under nitrogen. The acetylenic compound 2 (1.33 mmol) was added slowly with stirring. The mixture was then stirred at 80 C for 3 h, cooled to room temperature, diluted with EtOAc (30 mL), and filtered through celite. The filtrate was collected and concentrated. The residue was purified by column chromatography (2-15% EtOAc/hexane) to afford the desired product
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In toluene; at 100℃; for 6.0h;
Methyl 3-bromo-4-chlorobenzoate (1.758 g, 7.089 mmol), 2-ethynyl pyridine (1.40 mL, 13.9 mmol), and triethylamine (2.20 mL, 15.8 mmol) were dissolved <n="150"/>in 34 ml. dry toluene. Nitrogen gas was bubbled through the mixture for 10 minutes, and then dichlorobis(triphenylphosphine)-palladium(ll) (1.00 g, 1.42 mmol) and copper(l) iodide (0.268 g, 1.41 mmol) were added to the mixture. Nitrogen was bubbled through the mixture for another 5 minutes, and then the mixture was then heated to 100 0C for 6 hours. The mixture was cooled, and then filtered through a pad of Celite. The Celite pad was washed with ethyl acetate (2X) and then -5% methanol/methylene chloride (2X). The combined filtrate was evaporated and the residue was chromatographed on silica gel using a gradient elution of ethyl acetate in methylene chloride. Methyl 4-chloro-3-(pyridin-2-ylethynyl)benzoate is obtained (0.843 g, 3.11 mmol; 44% yield) as a light brown-gray solid.
44%
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In toluene; at 100℃; for 6.0h;Inert atmosphere;
Methyl 3-bromo-4-chlorobenzoate (1.758 g, 7.089 mmol), 2-ethynyl pyridine (1.40 ml_, 13.9 mmol), and triethylamine (2.20 ml_, 15.8 mmol) were dissolved in 34 ml. dry toluene. Nitrogen gas was bubbled through the mixture for 10 minutes, and then dichlorobis(triphenylphosphine)- palladium(ll) (LOO g, 1.42 mmol) and copper(l) iodide (0.268 g, 1.41 mmol) was added to the mixture. Nitrogen was bubbled through the mixture for another 5 minutes, and then the mixture was then heated to 1000C for 6 hours. The mixture was cooled, and then filtered through a pad of Celite. The Celite pad was washed with ethyl acetate (2X) and then -5% methanol/methylene chloride 2X). The combined filtrate was evaporated and the residue was chromatographed on silica gel using a gradient elution of ethyl acetate in methylene chloride. Methyl 4-chloro-3-(pyridin-2- ylethynyl)benzoate was obtained (0.843 g, 3.11 mmol; 44% yield) as a light brown-gray solid. MS (+ESI): m/z 272.0 [M+H]+.
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In toluene; at 100℃; for 6h;Inert atmosphere;
<strong>[90347-66-3]Methyl 3-iodo-4-methylbenzoate</strong> (5.52 g, 20 mmol), 2-ethynylpyridine (3.2 ml_, 31 mmol), and triethylamine (6.2 ml_, 44.7 mmol) were dissolved in 100 ml. of toluene and purged with nitrogen. Then CuI (0.78 g, 3.9 mmol) and Pd(Ph3P)2CI2 (2.9 g, 4.1 mmol) were added and the <n="109"/>resulting suspension was stirred at 100 0C for 6 hours. The reaction was concentrated at reduced pressure and purified by flash chromatography on silica (40:1 CH2CI2/Et0Ac) to yield 2.63 g (52%) of the product as a greenish solid.
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In toluene; at 100℃; for 6h;Inert atmosphere;
<strong>[82702-31-6]Methyl 3-bromo-4-fluorobenzoate</strong> (4.66 g, 20 mmol), 2-ethynylpyridine (3.2 mL, 31 mmol), and triethylamine (6.2 mL, 44.7 mmol) were dissolved in 100 mL of toluene and purged with nitrogen. Then CuI (0.78 g, 3.9 mmol) and Pd(Ph3P)2CI2 (2.9 g, 4.1 mmol) were added and the <n="113"/>resulting suspension was stirred at 100 0C for 6 hours. The reaction was concentrated at reduced pressure and purified by flash chromatography on silica (40:1 CH2CI2/Et0Ac) to yield 2.0 g (39%) of the product as a brown solid.
39%
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In toluene; at 100℃; for 6h;Inert atmosphere;
<strong>[82702-31-6]Methyl 3-bromo-4-fluorobenzoate</strong> (4.66 g, 20 mmol), 2-ethynylpyridine (3.2 ml_, 31 mmol), and triethylamine (6.2 ml_, 44.7 mmol) were dissolved in 100 ml. of toluene and purged with nitrogen. The CuI (0.78 g, 3.9 mmol) and Pd(Ph3P)2CI2 (2.9 g, 4.1 mmol) were added and the resulting suspension was stirred at 1000C for 6 hours. The reaction was concentrated at reduced pressure and purified by flash chromatography on silica (40:1 CH2CI2/Et0Ac) to yield 2.0 g (39%) of the product as a brown solid. HRMS (+ESI): m/z 256.0769 [M+H]+.
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In toluene; at 100℃; for 6.0h;Inert atmosphere;
A mixture of <strong>[1131614-23-7]methyl 4-(difluoromethoxy)-3-iodobenzoate</strong> (2 g, 6.1 mmol) from step 1 , 2-ethynylpyridine (0.94 ml_, 9.2 mmol), dichlorobistriphenylphosphine palladium(ll) (0.86 g, 1.2 mmol), copper iodide (0.23 g, 1.2 mmol) and triethylamine(1.7 ml_, 12.2 mmol) in toluene (30 ml.) was stirred at 100 0C under an atmosphere of nitrogen for six hours. After the reaction was complete, the reaction mixture was <n="147"/>concentrated to yield a semi-solid residue. This residue was purified by flash chromatography on SiO2 (gradient elution using EtOAc/hexane 20/80) to yield the title compound as a white solid (1.47 g, 80% yield).
80%
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In toluene; at 100℃; for 6.0h;Inert atmosphere;
mixture of <strong>[1131614-23-7]methyl 4-(difluoromethoxy)-3-iodobenzoate</strong> (2 g, 6.1 mmol) from step 1 , 2- ethynylpyridine (0.94 ml_, 9.2 mmol), dichlorobistriphenylphosphine palladium(ll) (0.86 g, 1.2 mmol), copper iodide (0.23 g, 1.2 mmol) and triethylamine (1.7 ml_, 12.2 mmol) in toluene (30 ml.) was stirred at 100 0C under an atmosphere of nitrogen for six hours. After the reaction was complete, the reaction mixture was concentrated to yield a semi-solid residue. This residue was purified by flash chromatography on SiO2 (gradient elution using EtOAc/hexane 20/80) to yield the title compound as a white solid (1.47 g, 80% yield).
«Synthesis Example 24» Synthesis of tetramethylammonium triphenyl(2-pyridinylethynyl)borate according to the reaction represented by the following formula: [Show Image] [Show Image] In an argon atmosphere, a tetrahydrofuran (20 ml) solution containing 2-ethynylpyridine (613 mg, 6.0 mmol) dissolved therein was cooled to -78C, and 1.6 M n-butyl lithium (3.4 ml, 5.5 mmol) was added dropwise thereto, followed by stirring for 30 minutes. Then, triphenylborane pyridine complex was added at once, and the mixture was warmed to room temperature while stirring. The mixture was stirred at room temperature for 1 hour, and the reaction was then terminated by adding several drops of methanol. The solvent was removed using a rotary evaporator. The residue was dissolved in methanol, and tetramethylammonium chloride was added to the solution. The solid formed was collected by filtration and then dried under a reduced pressure. Thus, tetramethylammonium triphenyl(2-pyridinylethynyl)borate (1.86 g, 4.45 mmol) was obtained in a yield of 89%. The physical and chemical properties thereof were as follows: 1H-NMR (CD3CN): delta 3.0 (s, 12H), 6.89-6.95 (m, 3H), 7.03-7.11 (m, 7H), 7.35 (ddd, J = 10.4, 1.2, 0.9 Hz, 1H), 7.41 (d, J = 6.9 Hz, 6H), 7.59 (dt, J = 1.8, 2.1, 7.5, 7.7 Hz, 1H), 8.44 (ddd, J = 4.8, 1.8, 1.2 Hz, 1H).
With silver trifluoromethanesulfonate; aniline In tetrahydrofuran; 1,2-dichloro-ethane at 80℃; for 3h;
A typical procedure for the AgOTf-catalyzed one-pot synthesis of 2-quinolines from the reactions of Alkynes with 2-aminobenzaldehydes
General procedure: A solution of 2-aminobenzaldehyde (1a) (61 mg, 0.5 mmol) in DCE (2 ml) was added Phenylacetylene (2a) (0.083 ML, 0.75 mmol), aniline (0.091ML, 1.0 mmol) and AgOTf (3.2 mg, 5 mol %, 0.05 M in THF), and the resulted reaction mixture was stirred at 80 oC for 3 h under air. After cooling to room temperature, the solvent was evaporated under vacuo and the residue was purified by chromatography on silica gel(eluent: petroleum ether/ethyl acetate=10:1). A yellow solid of product (84%) 3a was obtained.
With CuO-Fe3O4; potassium hydroxide In toluene at 130℃; for 24h; Inert atmosphere;
4.3. General procedure for the synthesis of benzofurans
General procedure: To a stirred solution of 2-iodophenol (1, 1 mmol) in toluene (3 mL) under argon atmosphere were added CuO-Fe3O4 (50 mg), KOH (67 mg, 1.2 mmol) and the corresponding alkyne (2, 1.2 mmol). The resulting mixture was stirred at 130 °C until the end of reaction. The catalyst was removed by a magnet and the resulting mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to remove the solvent. The product was purified by chromatography on silica gel (hexane/ethyl acetate) to give the corresponding products 3 and 5. Yields are included in Table 3 and Scheme 1. Physical and spectroscopic data, as well as literature data for known compounds, follow.
69%
With potassium phosphate; diethylzinc; N,N`-dimethylethylenediamine In acetonitrile at 125℃; for 12h; Sealed tube; Inert atmosphere;
Synthesis of 2-Phenylbenzofuran (3a)
General procedure: A dry sealed tube was charged with 1.1 mmol (271 mg) of 2-iodophenol and 2 equiv. of K3PO4 (424 mg). To the above mixture was added 1 mmol of phenylacetylene (102 mg, 0.109 ml), 5 mol % of Et2Zn (0.05 ml), 10 mol % of DMEDA (0.01 ml) and 3 ml of acetonitrile under nitrogen. The sealed tube was heated in an oil bath which was preheated to 125 °C and the reaction mixture was stirred under the same conditions for 12 hours. The reaction mixture was then cooled and extracted with ethyl acetate (3 x 15 ml) and the ethyl acetate layer was washed with distilled water. The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure in a rotary evaporator. The crude residue was purified by column chromatography using hexane as the eluent to get 180 mg (93 %) of the product as a colourless solid. All other benzofuran derivatives were synthesized by similar procedure.
33 %Chromat.
With C53H43IN3P2Pd(1+)*I(1-); potassium carbonate In dimethyl sulfoxide at 90℃; for 2h;
With 2,2'-bis(2-oxazoline); acetic acid; copper(l) chloride In 1,3-dimethyl-2-imidazolidinone; water at 60℃; for 18h; Air;
79%
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 110℃; for 0.0833333h; Microwave irradiation; diastereoselective reaction;
General procedure: Phenylacetylene (102 mg, 1mmol), sodium benzene sulfinate (164 mg, 1 mmol), andCu(OTf)2 (16 mg, 2.5 mol%) were added to a 10-mLmicrowave tube containing AcOH (2 mL) and a magneticstirrer bar. The reaction mixture was placed in a CEMDiscover BenchMate. The reaction parameters were set to200 W, 250 psi, 110 °C for 5 min with stirring. Aftercompletion of the reaction, the reaction mixture was dilutedwith H2O (10 mL) and extracted with EtOAc (2 × 10 mL).The organic layer was dried with anhyd Na2SO4, filtered andthe solvent evaporated on a rotary evaporator to give thecrude product which was purified by passing through a silicacolumn to give pure 3a (200 mg, 82%) as a white solid.
67%
With Cu2+(25% mol)-doped nanoparticles supported on zeolitic imidazolate framework-8 In acetonitrile at 20℃; for 12h; stereoselective reaction;
2.3 Synthesis of (E)-Vinyl sulfones
General procedure: Phenyl acetylene 1a (0.5 mmol, 1 equiv.), sodium 4-methylbenzenesulfinate 2a (0.6 mmol, 1.2 equiv.), Cu25%/ZIF-8(0.05 mmol, 0.1 equiv.) and acetonitrile (2 mL) were added to a 5 mL glass tube at room temperature and stirred for 3 h and monitored periodically by TLC. Then the reaction mixture was extracted with ethyl acetate (3 × 5 mL) and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, and the crude product was purified by silica gelcolumn chromatography using petroleum ether and ethyl acetate (9:1 v/v) as eluent to give the pure product 3a.
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 100℃; for 2h;
General procedure: In a dry Schlenk tube, the dihalopyridine, CuI (6 mol %), and PdCl2(PPh3)2 (3 mol %) were added in Et3N (2 mL per mmol of pyridine). After stirring for 10 min, the (hetero)arylacetylene (1.0 or 1.1 equiv) was added, and the solution was heated to 100 C in a silicone bath for 2 h. The reactions were monitored by TLC, following the disappearance of the starting materials. After completion, the mixture was allowed to cool to room temperature. Then ethyl acetate and water were added and the organic phase was separated, dried (MgSO4), and filtered. Removal of the solvent under reduced pressure gave either oils, which were submitted to column chromatography or pure products corresponding to the expected (hetero)arylethynylpyridines.
With sodium azide; sodium L-ascorbate In water at 70℃; for 2.5h;
General procedure for the one-pot CuAAC reaction
General procedure: A mixture of benzyl halides (1.0 mmol), terminal alkynes (1.0 mmol), NaN3(1.2 mmol), sodium ascorbate (10 mol%), a catalytic amount of CuIICMC/CaCO3catalyst (2.0 mol% of Cu), and 3.0 mL H2O were charged into a flask. The reactionmixture was heated at 70 °C for a specific time with constant stirring. The progresswas tracked by TLC. After completion of the reaction, ethyl acetate was added tothe flask and the catalyst was filtered by suction, washed with enough ethyl acetate,and dried in vacuum for the next run. The resulting mixture was washed with brineand dried over anhydrous Na2SO4 and evaporated in vacuum using a rotary evapora-tor to obtain the crude product. The desired pure products were further purified byrecrystallization with ethanol/H2O mixed solvent.
85%
With sodium azide; sodium L-ascorbate In water at 70℃; for 2.66667h; regioselective reaction;
General procedure for the catalytic CuAAC reactions
General procedure: A mixture of sodium azide (1.2 mmol), sodium ascorbate (0.1 mmol), alkyne (1.1 mmol), benzyl compound (1.0 mmol), PVC-EDA-Cu(II) (0.015 g, mol%), and water (3 mL) was vigorously stirred at 70 °C under for specific time under aerobic condition. The reaction process was monitored by TLC. Upon completion of the reaction, the mixture was filtered to recover the catalyst. The catalyst was washed with water and ethanol, dried, and stored for subsequent runs. The filtrate was extracted with ethyl acetate (10 mL x 3) and washed with brine. After removing the organic solvent using a rotary evaporator, the crude product was further purified by recrystalization using ethanol as the solvent to afford the pure product.
82%
With sodium azide; copper(II) ferrite In water at 70℃; for 4h;
General Procedure for the Synthesis of 1,4-Disubstituted 1, 2, 3-triazoles:
General procedure: Benzyl bromide (1 mmol), phenyl acetylene (1 mmol) and NaN3 (72 mg, 1.1 mmol) were placed in a 10 ml round-bottomed flask in H2O (2 mL). Sequentially CuFe2O4 (5 mol %, 12 mg) was added. The reaction mixture was warmed to 70 °C and monitored by TLC until conversion of the starting materials is satisfactory. After completion of the reaction, the reaction mixture was magnetically concentrated with the aid of a magnet to separate the catalyst. Catalyst was separated and washed several times with ether followed by water, dried under vacuum. Water (30 mL) was added to the resulting reaction mixture followed by extraction with EtOAc (4 × 10 mL). The collected organic phases were dried with Na2SO4 and the solvent was removed under vacuum to give the corresponding triazole, which did not require any further purification (except compounds 3ga, 3ha and 3ii).
80%
With sodium azide; copper(II) sulfate; sodium L-ascorbate In tetrahydrofuran; water at 50℃; for 48h;
4-Chloro-3-iodobenzenetrifluoride (306 mg) was dissolved in toluene (3 ml), and thereto were added 2-ethynylpyridine (155 mg), copper iodide (19.0 mg), 1,3-bis-(2,6-diisopropylphenyl)-imidazolium chloride (42.5 mg), acetic acid palladium (II) (22.5 mg) and cesium carbonate (489 mg), and the mixture was heated to 100 C. After the mixture was stirred for 3 h, the mixture was kept standing to cool to room temperature, and thereto were added 3-amino-6-methoxypyridine (149 mg) and potassium-t-butoxide (168 mg), and the reaction mixture was heated to 100 C. After the reaction mixture was stirred all day and all night, it was kept standing to cool to room temperature, and to the reaction solution were added ethyl acetate and water. After an insoluble material was filtrated, the organic layer was separated. The organic layer was washed with a saturated saline and dried with anhydrous sodium sulfate. After the organic layer was filtrated and concentrated, the residue was purified by the silica gel column chromatography affording the compound 2 (77.0 mg).MS m/z 370 [M+H]+, APCI(+)
With diethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triphenylphosphine; In N,N-dimethyl-formamide; at 80℃; for 16h;Inert atmosphere;
V-2 was dissolved in DMF (15 mL) and purged with N2 on an oil bath at 80C for 10 minutes. Then bis(triphenylphosphine)palladium(ll) dichloride (69 mg, 0.098 mmol), triphenylphosphine (57.6 mg, 0.22 mmol) and copper iodide (42.5 mg, 0.22 mmol) were added. After 5 minutes of purging with N2, diethylamine (3.15 mL, 30.31 mmol) was added followed by the addition of 2-pyridylethyne (168 mg, 1 .63 mmol). The vessel was closed and the reaction stirred at 80C for 16 hours. The reaction mixture was poured into ice water, and the precipitate was isolated by filtration, washed with water and dried under vacuum. The product was stirred in dichloromethane for 30 minutes. The precipitate was isolated by filtration, washed with dichloromethane and diisopropyl ether and dried under vacuo at 50C to obtain V-12.LC-MS m/z = 263 (M-H)
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 80℃; for 16h;Inert atmosphere;
Step 1. V-2 was dissolved in DMF (15 mL) and purged with N2 on an oil bath at 80 C. for 10 minutes. Then bis(triphenylphosphine)palladium(II)dichloride (69 mg, 0.098 mmol), triphenylphosphine (57.6 mg, 0.22 mmol) and copper iodide (42.5 mg, 0.22 mmol) were added. After 5 minutes of purging with N2, diethylamine (3.15 mL, 30.31 mmol) was added followed by the addition of 2-pyridylethyne (168 mg, 1.63 mmol). The vessel was closed and the reaction stirred at 80 C. for 16 hours. The reaction mixture was poured into ice water, and the precipitate was isolated by filtration, washed with water and dried under vacuum. The product was stirred in dichloromethane for 30 minutes. The precipitate was isolated by filtration, washed with dichloromethane and diisopropyl ether and dried under vacuo at 50 C. to obtain V-12.LC-MS m/z=263 (M-H)
3-lodo-2-aminopyridine (1.00 g, 99%, 4.54 mmol), lithium chloride (289 mg, 6.81 mmol) and sodium carbonate (1.93 g, 18.2 mmol) were dried 1 h in a vacuum oven at 100C. The Reaction vessel was spilled with Argon and cooled to RT. To the mixture dry degassed N,N-dimethylformamide (25 ml), 2-ethynylpyridine (563 mg, 5.45 mmol) and the catalyst Pd(dppf)Cl2*CH2Cl2 (371 mg, 0.54 mmol) were added and stirring was continued for 18 h at 100C. After cooling to RT water was added and the mixture was extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulphate, filtered and the solvent was evaporated to dryness in vacuo. The residue was purified by flash chromatography on silica gel using a gradient from cyclohexane.ethyl acetate 1 :1 to 100% ethyl acetate as eluent system to yield in a colorless solid identified as compound 16 (555 mg, 2.85 mmol, 63%)
63%
n. 3-Iodo2-aminopyridine (1 .00 g, 99%, 4.54 mmol), lithium chloride (289 mg, 6.81 mmol) and sodium carbonate (1.93 g, 18.2 mmol) were dried 1 hin a vacuum oven at tOO C.. The Reaction vessel was spilled with Argon and cooled to RT. To the mixture dry degassed N,N-dimethylformamide (25 mL), 2-ethynylpyridine (563 mg, 5.45 mmol) and the catalyst Pd(dppOCl2*CH2CI2 (371 mg, 0.54 mmol) were added and stirring was continued for 18 h at 1 00 C.. After cooling to RT water was added and the mixture was extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulphate, filtered and the solvent was evaporated to dryness in vacuo. The residue was purified by flash chromatography on silica gel using a gradient from cyclohexane:ethyl acetate 1:1 to 100% ethyl acetate as eluent system to yield in a colorless solid identified as compound 16 (555 mg, 2.85 mmol, 63%).
With [2,2]bipyridinyl; copper(l) iodide; potassium bromide; In acetic acid; at 80℃; for 18h;
General procedure: 4.3 Typical procedure for copper-catalyzed synthesis of beta-haloalkenyl sulfone (Table 4): To a mixture of CuI (4.6 mg, 0.024 mmol), bpy (3.7 mg, 0.024 mmol), PhSO2Na (54.2 mg, 0.33 mmol), and KBr (107.1 mg, 0.9 mmol) in AcOH (0.3 mL) were added phenylacetylene (30.6 mg, 0.3 mmol), and the mixture was stirred at 80 C for 18 h in air. After the residue was dissolved in Et2O, the solution was washed with saturated sodium hydrogencarbonate, H2O, and saturated sodium chloride and dried over anhydrous magnesium sulfate. Chromatography on silica gel (40% diethyl ether/hexane) gave (E)-2-bromo-1-phenylsulfonyl-2-phenylethene (71.5 mg, 74%):
With 1,3-dimethyl-2-imidazolidinone; copper(l) chloride; (S,S)-N,N'-bis(p-tolylsulfonyl)-trans-cyclohexane-1,2-diamine; In water; acetic acid; at 60℃; for 18h;
General procedure: 4.2. Typical procedure hydrosulfonylation of alkynes (Table 2 ): To a mixture of CuCl (1.5 mg, 0.015 mmol), 2,2'-bis(2-oxazoline) (2.1 mg, 0.015 mmol), and PhSO2Na (54.2 mg, 0.33 mmol), in DMI (0.1 mL), H2O (0.1 mL), and AcOH (0.1 mL) were added phenylacetylene (30.6 mg, 0.3 mmol), and the mixture was stirred at 60 C for 18 h in air. After the residue was dissolved in Et2O, the solution was washed with H2O and saturated sodium chloride and dried over anhydrous magnesium sulfate. Chromatography on silica gel (40% diethyl ether/hexane) gave (E)-1-phenylsulfonyl-2-phenylethene (61.8 mg, 85%):1
With palladium dichloride In dimethyl sulfoxide at 50℃; for 8h; chemoselective reaction;
74%
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 110℃; for 0.0833333h; Microwave irradiation; diastereoselective reaction;
General procedure: Phenylacetylene (102 mg, 1mmol), sodium benzene sulfinate (164 mg, 1 mmol), andCu(OTf)2 (16 mg, 2.5 mol%) were added to a 10-mLmicrowave tube containing AcOH (2 mL) and a magneticstirrer bar. The reaction mixture was placed in a CEMDiscover BenchMate. The reaction parameters were set to200 W, 250 psi, 110 °C for 5 min with stirring. Aftercompletion of the reaction, the reaction mixture was dilutedwith H2O (10 mL) and extracted with EtOAc (2 × 10 mL).The organic layer was dried with anhyd Na2SO4, filtered andthe solvent evaporated on a rotary evaporator to give thecrude product which was purified by passing through a silicacolumn to give pure 3a (200 mg, 82%) as a white solid.
With triethylamine; In ethanol; for 16h;Inert atmosphere;
General procedure: A representative synthesis for the Pt(alkynyl)2(COD) precursor complexes is described in the following modified procedure [17]. To a 100mL three-necked round-bottom flask equipped with a 25mL addition funnel and a magnetic stir bar was placed PtCl2(COD) (0.100g, 0.267mmol). Absolute ethanol (30mL) was added to the flask and the resulting suspension was stirred for 5min. Triethylamine (0.080g, 0.80mmol) was then added to the suspension followed by the dropwise addition of 4-ethynyltoluene (0.307g, 2.67mmol) over 5min with stirring. Additional absolute ethanol (5mL) was added and the solution was stirred over 16h and a white precipitate gradually formed. The resulting mixture was filtered using a sintered glass frit. The white solid obtained was washed with methanol (3×5mL) and dried in a vacuum desiccator for 6h. The solid was dissolved in a minimal amount of CH2Cl2 and filtered. The filtrate containing the product was evaporated and the resultant precipitate was washed with 5mL of diethyl ether and dried in vacuo. The product was obtained as a white solid (0.121g, 85% yield).
With copper diacetate; triethylamine; In 1,4-dioxane; at 130℃; for 18h;
A mixture of di-2-pyridinone(55 mg, 0.3 mmol), 2-pyridineacetylene (62 mg, 0.6 mmol), copper acetate (5.4 mg,0.03 mmol), and triethylamine (60 mg, 0.6 mmol) were dissolved in 1,4-dioxane (2 mL). The resulting mixture is obtainedThe reaction was heated to 130 C and the reaction was complete after 18 h of reaction. The reaction was stopped, filtered and the crude product was passed through a silica gel columnChromatography (100-200 mesh, n-hexane: ethyl acetate = 1: 2) to give 53 mg of the desired product in 61% yield.
With carbon monoxide; hydrogen; In tetrahydrofuran; at 70℃; under 7757.43 Torr; for 6h;Autoclave;
General procedure: To a 100 mL high-pressure reactor, phenylacetylene (1 mmol),Pd (0.96 mol%) in a 10 mL THF were transferred under an inertatmosphere. The reactor was flushed three times with nitrogen then pressurized with desired 150 psi of syngas, then heated at70C with constant stirring (400 rpm) for 6 h. After the comple-tion of reaction, the reactor cooled down to room temperature andthe remaining syngas was carefully depressurized. The resultantreaction mixture filtered off by simple filtration. The filtrate was then collected in sample vial and the product was extracted for fur-ther analysis such as GC, GC-MS,1H &13C NMR and matched with those of authentic data. Selective experiments were performed in triplicate and it was observed that results showed variation of ±2%.
With fac-tris(2-phenylpyridinato-N,C2')iridium(III); tert.-butylnitrite In acetonitrile at 20℃; for 15h; Sealed tube; Irradiation; regioselective reaction;
With copper(ll) sulfate pentahydrate; sodium L-ascorbate; triethylamine; In tetrahydrofuran; water; at 80℃; for 0.5h;Microwave irradiation;
General procedure: Azide 6 (3.0mmol) and alkyne (3.0 mmol) was dissolved in a mixture ofTHF and water (1:1, v/v; 10 mL). CuSO4-5H2O (0.06 mmol),sodium ascorbate (0.3 mmol) and Et3N (0.3 mmol) wasadded under rigorous stirring. The mixture was heated to 80C under microwave irradiation for 30 min. The mixture wasdiluted with water and extracted with EtOAc (3x15 mL). Thecombined organic phases was dried with Na2SO4, concentratedand purified by column chromathography (Heptane/EtOAc/Acetic acid 10:9:1) to the product.
bis(triphenylphosphine)bis[(pyridin-2-yl)ethynyl]palladium(II)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
Stage #1: 2-ethynylpyridine With n-butyllithium In tetrahydrofuran; hexane at -78℃; Inert atmosphere;
Stage #2: tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran; hexane at -78 - 20℃; for 44h; Inert atmosphere;
4.1.6 Bis(triphenylphosphine)bis[(pyridinium-2-yl)ethynyl]palladium(II) 17
A sample of 73mg (0.71mmol) in 4mL of anhydrous THF was cooled to -78°C and then treated with 0.45mL (46mg, 0.72mmol) of a 15% solution of nBuLi in hexane and 204mg (0.29mmol) of PdCl2(PPh3)2. After stirring for 4h at that temperature, the suspension was allowed to warm to rt, and stirring was continued for 1d. Then, the solvent was distilled off in vacuo and the crude reaction product was recrystallized form EtOAc/MeOH. The resulting crystals were washed with MeOH and EtOAC, and dried in vacuo. Yield: 77mg (0.10mmol, 34%) of a brown powder. 1H NMR (400MHz, DMSO-d6: δ=8.20-8.18 (m, 1H), 7.77-7.71 (m, 12H), 7.64-7.53 (m, 6H), 7.46-7.41 (m, 12H), 7.33-7.29 (m, 1H), 6.94-6.91 (m, 1H), 6.12-6.10 (m, 1H); due to the limited solubility, no 13C NMR spectrum was obtained. IR (ATR): ν ν =3333, 3050, 2920, 2196, 2109, 1580, 1554, 1516, 1479, 1458, 1432, 1421, 1329, 1307, 1236, 1182, 1147, 1118, 1092, 1071, 1046, 1026, 997, 987, 774, 742, 721, 703, 691, 629, 617, 577, 540, 519, 506, 498, 453, 445, 437, 428, 418cm-1. ESI-MS (5eV): m/z (%)=769.0 (10) [M++H+]. Due to the limited solubility, no HRMS could be obtained.
bis(triphenylphosphine)palladium(II)(pyridin-2-yl-ethynyl)chloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
34%
A sample of 73mg (0.71mmol) in 4mL of anhydrous THF was cooled to -78C and then treated with 0.45mL (46mg, 0.72mmol) of a 15% solution of nBuLi in hexane and 204mg (0.29mmol) of PdCl2(PPh3)2. After stirring for 4h at that temperature, the suspension was allowed to warm to rt, and stirring was continued for 1d. Then, the solvent was distilled off in vacuo and the crude reaction product was recrystallized form EtOAc/MeOH. The resulting crystals were washed with MeOH and EtOAC, and dried in vacuo. Yield: 77mg (0.10mmol, 34%) of a brown powder. 1H NMR (400MHz, DMSO-d6: delta=8.20-8.18 (m, 1H), 7.77-7.71 (m, 12H), 7.64-7.53 (m, 6H), 7.46-7.41 (m, 12H), 7.33-7.29 (m, 1H), 6.94-6.91 (m, 1H), 6.12-6.10 (m, 1H); due to the limited solubility, no 13C NMR spectrum was obtained. IR (ATR): nu nu =3333, 3050, 2920, 2196, 2109, 1580, 1554, 1516, 1479, 1458, 1432, 1421, 1329, 1307, 1236, 1182, 1147, 1118, 1092, 1071, 1046, 1026, 997, 987, 774, 742, 721, 703, 691, 629, 617, 577, 540, 519, 506, 498, 453, 445, 437, 428, 418cm-1. ESI-MS (5eV): m/z (%)=769.0 (10) [M++H+]. Due to the limited solubility, no HRMS could be obtained.
2-[[4-[2-(2-pyridyl)ethynyl]phenyl]sulfanylmethyl]pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
2-[[4-[2-(2-pyridyl)ethynyl]phenyl]sulfanylmethyl]pyrimidine (14c): A one dram vial equipped with a stir bar was charged with <strong>[54198-88-8]2-(chloromethyl)pyrimidine</strong> (12.mg,0.070 mmol), 4-bromothiophenol (13.06 mg, 0.070 mmol), and cesium carbonate (95.37 mg, 0.290 mmol). The solids were then dissolved in MeCN (0.145 mL) and stirred at 90 C for 20 min before the vial was removed from the heat. At this time 2-ethynylpyridine (9.55 lL, 0.095 mmol) and [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (5.34 mg, 0.010 mmol) were added to the reaction mixture followed by a thirty second purge with argon. The reaction vessel was allowed to stir at 90° C for an additional fourhours. After being allowed to cool to room temperature the crude reaction mixture was filtered over a thin celite plug in a phase separator with EtOAc (10 mL) and the resulting organics concentrated before crude product was purified using Gilson reverse phase automated system (30x50 mm column, 15-65percent MeCN in 0.1percent Aq. TFA, 5 min gradient). Fractions containing product by LC/MS were pooled and quenched with sat. sodium bicarbonate before being extracted with DCM (5 mL) and dried to afford 2-[[4-[2-(2-pyridyl)ethynyl]phenyl]sulfanylmethyl]pyrimidine (14c, 12.2 mg, 0.04 mmol, 55percent) as a brown oil. 1H NMR (400 MHz, CDCl3) d 8.72 (d, J = 4.9 Hz, 2H), 8.62 (d, J = 4.6 Hz, 1H),7.68 (t, J = 7.7 Hz, 1H), 7.51 (d, J = 8.1 Hz, 1H), 7.44 (q, J = 8.4 Hz, 4H), 7.24 (m,1H), 7.19 (t, J = 4.9 Hz, 1H), 4.44 (s, 2H).
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; trimethylamine; In N,N-dimethyl-formamide; at 90℃; for 0.75h;Inert atmosphere;
2-Ethynylpyridine (0.57 mL, 5.6 mmol), <strong>[135050-44-1]4-iodo-3-chloroaniline</strong> (1.01 g, 4.0 mmol), PdCl2(PPh3)2 (281 mg, 0.4 mmol), copper (I) iodide (152 mg, 0.8 mmol), trimethylamine (5.6 mL, 40 mmol) and DMF (4.5 mL) were added to a vial with a stirbar and the mixture was sparged with Argon. The reaction mixture was heated in a 90 C heating block for 45 min then cooled to ambient temperature. The mixture was partitioned between water and ethyl acetate, and the organic layer was washed with brine, dried over Na2S04, filtered and evaporated under reduced pressure. The crude product was purified by gradient flash column chromatography from 0 - 100% EtOAc in hexanes to yield 660 mg (72%) of 3-chloro-4-(pyridin-2-ylethynyl)aniline (12) as a yellow solid. 1H MR (400 MHz, CDC13) delta 8.61 (s, 1H), 7.69 (t, J= 7.7 Hz, 1H), 7.54 (d, J= 7.8 Hz, 1H), 7.41 (d, J= 8.4 Hz, 1H), 7.26 - 7.21 (m, 1H), 6.72 (s, 1H), 6.53 (d, J= 8.4 Hz, 1H), 3.95 (br s, 2H).
With tris[2-phenylpyridinato-C2,N]iridium(III) In acetonitrile Irradiation; Overall yield = 77 %;
3
1a and 2c described in Table 2 were synthesized under various conditions described in Table 4 below to obtain 3ac and 3ac '. 1a and 2c was added 0.3 mol% of photocatalyst fac-Ir (ppy) 3, and the blue LED was irradiated under MeCN to synthesize 3ac and 3ac ' The ratios and the total yields were obtained and are shown together in Table 4 below. 30 and 31 show that Abs and
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In 1,4-dioxane; at 100℃; for 4h;Inert atmosphere;
To a solution of 10 (500mg, 1.Smmoi) in 5mL of dry dioxane was added 11(300mg, 2.9mmoi), CuT (30mg. 0.iSmmoi), Pd( Ph3)2C12 (70mg, 0.iSrnmoi) and TEA (400mg, 3.9mmoi). The mixture was degassed under vacuo and purged with N2 for several times. Then the mixture was stirred at 100C for 4h. TLC showed the obtaining of the product. The mixture was concentrated. The crude was washed with water (2OrnL) and extracted with EtOAc (8OmL).The organic layer was washed with water and brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by prepTLC to give product 12 (450 mg, yield: 94.3%).LCMS: m/z, 3 19.1 (M+H).
With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; tetrabutyl-ammonium chloride; benzoic acid anhydride; N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 20℃; for 16h; Irradiation; regioselective reaction;
General procedure: 3-Amino-2-bromopyridine (1a) (87 mg, 0.5 mmol) or2-bromoaniline (1b) (172 mg, 1.00 mmol), Pd(PPh3)2Cl2(9.0 mg, 13 mmol or 17.5 mg, 25.0 mmol), and(1-Ad)2PBn·HBr (12 mg, 25 mmol or 23.6 mg, 50.0 mmol)were placed into a dry screw-cap Schlenk tube with amagnetic stirring bar, and the vessel was evacuated. Afterflushing the vessel with nitrogen, dry DMSO (1.0 or 1.5 ml),the corresponding alkyne 2a-j (0.6 mmol or 1.2 mmol),and DBU (225 mg, 1.50 mmol or 457 mg, 3.00 mmol)were added. The reaction mixture was stirred at 100Cunder nitrogen for 1 h until the bromide was completelyconsumed (monitored by TLC). After cooling to roomtemperature, KOt-Bu (253 mg, 2.25 mmol or 281 mg,2.50 mmol) and DMSO (0.50 or 1.00 ml) were added to thereaction mixture, and the mixture was stirred at 100Cunder nitrogen for 0.25 h. After cooling to roomtemperature, deionized water or brine (20 ml) was added tothe mixture. The aqueous layer was extracted several timeswith EtOAc or CH2Cl2. The combined organic phases weredried over anhydrous Na2SO4 and after filtration, thesolvents were removed under reduced pressure. The residuewas purified by flash chromatography on silica gel to givethe analytically pure products 3a-j
1-(naphthalen-1-yl)-3-(pyridin-2-yl)benzo[de]phosphanaphthalene-1-oxide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
With copper(l) iodide; di-tert-butyl peroxide; In acetone; at 50℃;
Add 2-ethynylpyridine (0.052 g, 0.5 mmol) to the reaction flask.Dinaphthylphosphorus (0.30 g, 1 mmol),CuI (0.019 g, 0.1 mmol), di-tert-butyl peroxide(0.30 g, 2 mmol), and acetone (2 mL),50oC reaction;TLC tracks the reaction until it is completely over;The crude product obtained after the completion of the reaction was separated by column chromatography (ethyl acetate: petroleum ether = 1:1) to give the desired product. (Yield 63%).
With 1,4-diaza-bicyclo[2.2.2]octane; copper(II) tungstate; In water; at 60℃;Green chemistry;
General procedure: To a mixture of isatin (1 equiv.) and phenyl acetylene (1.2 equiv.) in water (3 mL), CuWO4 (10 mol%) and DABCO (40 mol%) were added at room temperature and the mixture was heated at 60 C for 2 to 5 h. After completion of reaction (monitoring by TLC) mixture was cooled to room temperature and extracted with EtOAc (2×10 mL). The organic layers were washed with brine, dried using sodium sulfate. Evaporation of the solvent gave the crude product which was purified by silica gel column chromatography to give 3-hydroxy-3-(phenylethynyl)indolin-2-ones (3a-3u).
With copper(l) iodide; caesium carbonate; In tetrahydrofuran; at 80℃; for 1.5h;Inert atmosphere; Sealed tube;
First, put a stirrer in a 35 mL sealed tube, and then add 2-ethynylpyridine (34 muL, 0.33 mmol), 0.9 mL of tetrahydrofuran (0.9 mL), and 2-chloroacetamidoquinoline (66.2 mg, 0.3 mmol). ), Dimethyl 2-fluoromalonate (70.4 mg, 0.45 mmol), and CuI (5.7 mg, 0.03 mmol) and Cs2CO3 (117.3 mg, 0.36 mmol) were added to the uniformly mixed solution in this manner. The glass tube was filled with N2 for 3 minutes, the air was fully expelled, the nozzle was sealed with a cock, and the reaction was stirred at 800C for 1.5 hours. After the reaction was completed, the system was cooled to room temperature, 2 ml of distilled water was added to the reaction system, and extracted with ethyl acetate. The organic phases were combined, the solvent of the organic phase was distilled off under reduced pressure, and 103.6 mg of product 4c was separated by silica gel column chromatography with a yield of 79%.
6-hydroxy-6-(pyridin-2-ylethynyl)indolo[2,1-b]quinazolin-12(6H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
With copper(II) choride dihydrate; potassium carbonate In 1,4-dioxane at 60℃; for 36h; Schlenk technique;
Copper-Catalyzed Addition Reaction of Tryptanthrins andAlkynes - General Procedure
General procedure: In air, a clean and dried Schlenk tube was charged with CuCl2·2H2O (0.02 mmol,10 mol%), K2CO3 (0.4 mmol, 2.0 equiv.),tryptanthrin 1a (0.2 mmol, 1.0 equiv.), alkyne 2 (1.0 mmol, 5.0 equiv.), and 1,4-dioxane or THF (2 mL). The resulting mixture was stirred at the 60 °C or 80 °C for 36 h until the reaction completed. The crude mixture was purified through flash column chromatography on a silica gel using DCM/EtOAc (100:1, v/v) as eluent to give the desired products.
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