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With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique
General procedure: In a typical reaction, PdCl2(PPh3)2 (88 mg, 0.125 mmol), CuI (24 mg, 0.125 mmol) and THF (5 ml) were placed in an oven-dried, 2-neck RB flask. To this suspension, 2-iodoaniline (5.47 mg, 2.5 mmol) and triethylamine (702 μl, 5.0 mmol) were added. The reaction mixture was degassed by bubbling with argon for 15 min. Phenylacetylene (300 μl, 2.75 mmol) was then added, and the reaction mixture stirred at RT. After complete consumption of the 2-iodoanilines (~2 h, by TLC), the reaction mixture was filtered through celite, and the solvent rotary evaporated to obtain the crude product which was purified by silica gel (60-120 mesh) column chromatography using ethylacetate/ hexane (1:9, v/v) as eluent to give pure 2-phenylethynylaniline, 2a (400 mg, 83percent).
76%
With sodium hydroxide In toluene at 130℃; for 72 h;
General procedure: To a stirred solution of the corresponding 2-iodoaniline (6, 1 mmol) in toluene (3 mL) under argon atmosphere were added Pd/CuO-Fe3O4 (50 mg), NaOH (400 mg, 10 mmol), and the corresponding alkyne (2, 1.5 mmol). The resulting mixture was stirred at 130 °C until the end of reaction (see Table 6). 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 compounds 7. Yields are included in Table 6. Then, to a stirred solution of 7 (1 mmol) in toluene (4 mL) was added ZnBr2 (225 mg, 1 mmol). The resulting mixture was stirred at 130 °C during 24 h. The mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to give the pure products 8 in quantitative yields. Physical and spectroscopic data for compounds 7 and 8, as well as literature for known compounds, follow.
Reference：
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With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 20℃;Inert atmosphere; Schlenk technique;
General procedure: In a typical reaction, PdCl2(PPh3)2 (88 mg, 0.125 mmol), CuI (24 mg, 0.125 mmol) and THF (5 ml) were placed in an oven-dried, 2-neck RB flask. To this suspension, 2-iodoaniline (5.47 mg, 2.5 mmol) and triethylamine (702 mul, 5.0 mmol) were added. The reaction mixture was degassed by bubbling with argon for 15 min. Phenylacetylene (300 mul, 2.75 mmol) was then added, and the reaction mixture stirred at RT. After complete consumption of the 2-iodoanilines (~2 h, by TLC), the reaction mixture was filtered through celite, and the solvent rotary evaporated to obtain the crude product which was purified by silica gel (60-120 mesh) column chromatography using ethylacetate/ hexane (1:9, v/v) as eluent to give pure 2-phenylethynylaniline, 2a (400 mg, 83%).
76%
With sodium hydroxide; In toluene; at 130℃; for 72h;
General procedure: To a stirred solution of the corresponding 2-iodoaniline (6, 1 mmol) in toluene (3 mL) under argon atmosphere were added Pd/CuO-Fe3O4 (50 mg), NaOH (400 mg, 10 mmol), and the corresponding alkyne (2, 1.5 mmol). The resulting mixture was stirred at 130 C until the end of reaction (see Table 6). 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 compounds 7. Yields are included in Table 6. Then, to a stirred solution of 7 (1 mmol) in toluene (4 mL) was added ZnBr2 (225 mg, 1 mmol). The resulting mixture was stirred at 130 C during 24 h. The mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to give the pure products 8 in quantitative yields. Physical and spectroscopic data for compounds 7 and 8, as well as literature for known compounds, follow.
With palladium/copper catalyst;Inert atmosphere;
General procedure: All reagents were used as received without further purification.2-Alkynylanilines 1a-i were prepared by palladium/copper-catalysedSonogashira coupling reactions of 2-iodoanilines with terminalalkynes according to a literature method.31 The Fe3O4SiO2-bipy-AuCl3 complex was prepared according to our previous procedure.42The gold content was determined to be 0.62 mmol g-1. All reactionswere carried out under Ar in oven-dried glassware with magneticstirring. 1H NMR spectra were recorded on a Bruker Avance 400 (at400 MHz) spectrometer with TMS as an internal standard using CDCl3as the solvent. 13C NMR spectra were recorded on a Bruker Avance 400(at 100 MHz) spectrometer using CDCl3 as the solvent. HRMS spectrawere recorded on a quadrupole-time of flight Bruker MicroTOF-QII mass spectrometer equipped with an ESI and APCI source. Goldcontent was determined using ICP-AES on an Atomscan16 instrument(TJA Corporation).
With pyridine; In dichloromethane; at 20℃; for 8h;
General procedure: Therequisite 2-alkynylaniline derivatives were prepared from 2-iodoanilines or2-bromoanilines reacted with alkynes following the modified method reported byZhao and co-workers.1To a solution of 2-alkynylaniline (1.00 mmol) inCH2Cl2 (8 mL) were added pyridine (5.00 mmol) and TsCl (1.20mmol) respectively. The resulting reaction mixture was stirred at rt for 8 h.After which the reaction mixture was quenched by H2O (10 mL), andthe aqueous layer was extracted with CH2Cl2 (3×15 mL).The combined organic layers were dried over Na2SO4,filtered, and concentrated under reduced pressure. The crude product waspurified by silica gel flash column chromatography to obtain corresponding product.
With zinc dibromide; In toluene; at 130℃; for 24h;
General procedure: To a stirred solution of the corresponding 2-iodoaniline (6, 1 mmol) in toluene (3 mL) under argon atmosphere were added Pd/CuO-Fe3O4 (50 mg), NaOH (400 mg, 10 mmol), and the corresponding alkyne (2, 1.5 mmol). The resulting mixture was stirred at 130 C until the end of reaction (see Table 6). 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 compounds 7. Yields are included in Table 6. Then, to a stirred solution of 7 (1 mmol) in toluene (4 mL) was added ZnBr2 (225 mg, 1 mmol). The resulting mixture was stirred at 130 C during 24 h. The mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to give the pure products 8 in quantitative yields. Physical and spectroscopic data for compounds 7 and 8, as well as literature for known compounds, follow.
91%
With sodium tetrafluoroborate; bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In acetonitrile; at 40℃; for 8h;Inert atmosphere; Schlenk technique;
General procedure: In a typical reaction [Cp*IrCl2]2 (8 mg, 0.01 mmol), NaBF4 (2 mg, 0.02 mol) and 2-(phenylethynyl)aniline (97 mg, 0.5 mmol) were dissolved in dry acetonitrile (3 mL) in a Carius tube. The mixture was subjected to three cycles of freeze-pump-thaw and was then stirred at 40oC for 8 h, after which the reaction solvent was removed by rotary evaporation to give the crude product. Purification of the crude product by silica gel (60-120 mesh) column chromatography using ethylacetate/hexane (1:9, v/v) as eluent gave pure 2-phenylindole, 3a. Similar procedures were used with the other alkynylanilines to obtain 3b-s. The amount of reagents used, product formed (with yield) and HRMS for the products, are given in the Table 2.
With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 80℃;
A mixture of 2-alkynylaniline 1a-1e (0.2 mmol), dichalcogenide 2a-2e (0.15 mmol), CuI (0.02 mmol), and Cs2CO3 (0.2 mmol) in DMSO (2 mL) was stirred at 80 C under an air atmosphere. After completion of the reaction that was monitored by GC-MS or TLC, 25 mL water was added, and the mixture was extracted with ethyl acetate, the combined organic layers were washed with water (10 mL x 3), dried over anhydrous Na2SO4. After filtration and removal of solvents in vacuum, the residue was purified by silica gel column chromatography to afford the corresponding products.
With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 80℃;
A mixture of 2-alkynylaniline 1a-1e (0.2 mmol), dichalcogenide 2a-2e (0.15 mmol), CuI (0.02 mmol), and Cs2CO3 (0.2 mmol) in DMSO (2 mL) was stirred at 80 C under an air atmosphere. After completion of the reaction that was monitored by GC-MS or TLC, 25 mL water was added, and the mixture was extracted with ethyl acetate, the combined organic layers were washed with water (10 mL x 3), dried over anhydrous Na2SO4. After filtration and removal of solvents in vacuum, the residue was purified by silica gel column chromatography to afford the corresponding products.
With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 80℃;
A mixture of 2-alkynylaniline 1a-1e (0.2 mmol), dichalcogenide 2a-2e (0.15 mmol), CuI (0.02 mmol), and Cs2CO3 (0.2 mmol) in DMSO (2 mL) was stirred at 80 C under an air atmosphere. After completion of the reaction that was monitored by GC-MS or TLC, 25 mL water was added, and the mixture was extracted with ethyl acetate, the combined organic layers were washed with water (10 mL x 3), dried over anhydrous Na2SO4. After filtration and removal of solvents in vacuum, the residue was purified by silica gel column chromatography to afford the corresponding products.
With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 80℃;
A mixture of 2-alkynylaniline 1a-1e (0.2 mmol), dichalcogenide 2a-2e (0.15 mmol), CuI (0.02 mmol), and Cs2CO3 (0.2 mmol) in DMSO (2 mL) was stirred at 80 C under an air atmosphere. After completion of the reaction that was monitored by GC-MS or TLC, 25 mL water was added, and the mixture was extracted with ethyl acetate, the combined organic layers were washed with water (10 mL x 3), dried over anhydrous Na2SO4. After filtration and removal of solvents in vacuum, the residue was purified by silica gel column chromatography to afford the corresponding products.
With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 80℃;
A mixture of 2-alkynylaniline 1a-1e (0.2 mmol), dichalcogenide 2a-2e (0.15 mmol), CuI (0.02 mmol), and Cs2CO3 (0.2 mmol) in DMSO (2 mL) was stirred at 80 C under an air atmosphere. After completion of the reaction that was monitored by GC-MS or TLC, 25 mL water was added, and the mixture was extracted with ethyl acetate, the combined organic layers were washed with water (10 mL x 3), dried over anhydrous Na2SO4. After filtration and removal of solvents in vacuum, the residue was purified by silica gel column chromatography to afford the corresponding products.
With 1,4-diaza-bicyclo[2.2.2]octane; silver nitrate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;
General experimental procedure for tandem addition-cyclization of 2-alkynylbenzenamines (1) with CS2: A solution of 2-alkynylbenzenamines 1 (0.30 mmol), CS2 (3.0 mmol, 10 equiv), AgNO3 (5 mol %), DABCO (1.2 equiv) in DMF (2.0 mL) was stirred at room temperature. After completion of reaction as indicated by TLC, the reaction was quenched with water (10 mL), extracted with EtOAc (2×10 mL), and dried by anhydrous Na2SO4. Evaporation of the solvent followed by purification on silica gel provided the corresponding 4-benzylidene-4H-benzo[d][1,3]thiazine 2a.
With palladium dichloride; In acetonitrile; at 60℃; for 2h;Inert atmosphere;
General procedure: The substituted 2-alkynylaniline (1.0 mmol) was dissolved in acetonitrile (5.0 mL) and stirred until the solution became homogeneous. To this solution, methyl vinyl ketone (1.5 mmol) followed by 20 mol % of PdCl2 (59-60%, 35 mg) was added under a nitrogen atmosphere, then heated to 60 C and monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature and the acetonitrile was removed by vacuum evaporation. The resulting crude product was purified by column chromatography to afford the desired 2,3-disubstituted indoles. 4-(5-Chloro-2-phenyl-1H-indol-3-yl)butan-2-one (3d) Yield: (193 mg, 65%); White solid; mp: 170-171 C. FT-IR (KBr) (nu/cm-1): 3345, 1702. 1H NMR (400 MHz, CDCl3) deltaH (ppm): 8.13 (br s, 1H), 6.95 (s, 1H), 7.54-7.45 (m, 5H), 7.41-7.36 (m, 1H), 7.28-7.26 (m, 1H), 7.15 (dd, J=8.5, 1.96 Hz, 1H), 3.14-3.10 (m, 2H), 2.79-2.75 (m, 2H), 2.11 (s, 3H). 13C NMR (100 MHz, CDCl3) deltaC (ppm): 208.5, 136.1, 134.4, 132.7, 130.1, 129.2, 128.3, 128.1, 125.5, 122.7, 118.5, 112.1, 111.6, 44.5, 30.1, 18.7. LRMS (EI) (m/z) (relative intensity): 297 (M+, 42), 240 (100), 204 (40); HRMS calcd for C18H16Cl1 O1N1 (M+): 297.0920, found 297.0912.
With palladium dichloride; In acetonitrile; at 60℃; for 1.5h;Inert atmosphere;
General procedure: The substituted 2-alkynylaniline (1.0 mmol) was dissolved in acetonitrile (5.0 mL) and stirred until the solution became homogeneous. To this solution, methyl vinyl ketone (1.5 mmol) followed by 20 mol % of PdCl2 (59-60%, 35 mg) was added under a nitrogen atmosphere, then heated to 60 C and monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature and the acetonitrile was removed by vacuum evaporation. The resulting crude product was purified by column chromatography to afford the desired 2,3-disubstituted indoles. 1-(5-Chloro-2-phenyl-1H-indol-3-yl)pentan-3-one (3n) Yield: (300 mg, 96%); Colorless solid. Mp: 138-140 C. FT-IR (KBr) (nu/cm-1): 3370, 1711. 1H NMR (400 MHz, CDCl3) deltaH (ppm): 8.10 (br s, 1H), 7.55-7.53 (m, 3H), 7.47 (t, J=7.5 Hz, 2H), 7.40-7.36 (m, 1H), 7.27 (d, J=8.56 Hz, 1H), 7.15 (dd, J=8.5, 1.9 Hz, 1H), 3.15-3.11 (m, 2H), 2.77-2.73 (m, 2H), 2.39 (q, J=7.3 Hz, 2H), 1.03 (t, J=7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) deltaC (ppm): 211.1, 136.1, 134.4, 132.7, 130.1, 129.2, 128.3, 128.1, 125.5, 122.7, 118.6, 112.1, 111.9, 43.1, 36.2, 18.9, 7.9. LRMS (EI) (m/z) (relative intensity): 311 (M+, 50), 328 (100); HRMS calcd for C19H18Cl1O1N1 (M+): 311.1077, found 311.1086.
With palladium dichloride; In acetonitrile; at 60℃; for 48h;Inert atmosphere;
General procedure: The substituted 2-alkynylaniline (1.0 mmol) was dissolved in acetonitrile (5.0 mL) and stirred until the solution became homogeneous. To this solution, methyl vinyl ketone (1.5 mmol) followed by 20 mol % of PdCl2 (59-60%, 35 mg) was added under a nitrogen atmosphere, then heated to 60 C and monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature and the acetonitrile was removed by vacuum evaporation. The resulting crude product was purified by column chromatography to afford the desired 2,3-disubstituted indoles. 4-(5-Chloro-2-phenyl-1H-indol-3-yl)pentan-2-one (3q) Yield: (218 mg, 70%); Colorless solid. Mp: 170-171 C. FT-IR (KBr) (nu/cm-1): 3423, 1638. 1H NMR (400 MHz, CDCl3) deltaH (ppm): 8.08 (br s, 1H), 7.70 (d, J=1.9 Hz, 1H), 7.52-7.44 (m, 4H), 7.42-7.37 (m, 1H), 7.27-7.24 (m, 1H), 7.15-7.12 (m, 1H), 3.79-3.70 (m, 2H), 3.01-2.88 (m, 2H), 1.98 (s, 3H), 1.44 (d, J=7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) deltaC (ppm): 208.3, 135.9, 134.7, 132.8, 129.0, 128.9, 128.4, 128.3, 125.1, 122.3, 119.7, 116.3, 112.3, 50.5, 30.6, 27.0, 21.5. LRMS (EI) (m/z) (relative intensity): 311 (M+, 38), 254 (100); HRMS calcd for C19H18Cl1O1N1 (M+): 311.1077, found 311.1080.
With sulfuric acid; 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 25℃; for 32h;Sealed tube; Inert atmosphere;
General procedure: A sealed tube was charged with the mixture of 2-alkynylaniline 1 (1 mmol), carbon disulfide (1.5 mmol), then stirred in a solution of DBUH+ in CH3CN (1.5 mL) at room temperature under nitrogen atmosphere for indicated time. After completion, then H2O (5 mL) was added and the mixture was extracted with EtOAc (5 mL x 3), dried by anhydrous Na2SO4. Evaporation of the solvent followed by purification on silica gel (petroleum ether/ethylacetate = 4/1) provided the corresponding product 2.
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