* 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.
Stage #1: With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In acetonitrile at 20℃; for 0.5 h; Inert atmosphere Stage #2: at 20℃; Inert atmosphere
General procedure: 2-iodoaniline (500.2 mg, 2.28 mmol, 1.0 equiv) was dissolved in Et3N (4.5 mL). The resulting solution was added with PdCl2(PPh3)2 (32.1 mg, 0.046 mol, 0.02 equiv) and CuI (17.4 mg, 0.091mmol, 0.04 equiv). The orange-yellow solution was degassed by bubbling with a stream of argon into the solution at room temperature for 30 min. After degassing, phenylacetylene (0.30 mL,279.0 mg, 2.73 mmol, 1.2 equiv) was added as a neat liquid into the solution via syringe. The resulting dark brown solution was allowed to stir at room temperature under argon atmosphere overnight. The reaction was quenched by addition of sat. aq. NH4Cl. The separated aqueousphase was extracted with EtOAc (3x times). The combined organic phases were washed with sat. aq. NaCl, dried over anh. Na2SO4, filtered and concentrated to a crude product. The crudeproduct was purified by SiO2 column chromatography eluting with 0-10percent EtOAc-hexane to give 398.2 mg (90percent) of 2-(phenylethynyl)aniline as an orange solid.
Reference：
[1] Angewandte Chemie - International Edition, 2013, vol. 52, # 45, p. 11835 - 11839[2] Angew. Chem., 2013, vol. 125, # 45, p. 12051 - 12055,5
[3] Tetrahedron Letters, 2018, p. 675 - 680
[4] Journal of Organic Chemistry, 2010, vol. 75, # 10, p. 3412 - 3419
[5] Beilstein Journal of Organic Chemistry, 2011, vol. 7, p. 565 - 569
[6] Tetrahedron Letters, 2013, vol. 54, # 19, p. 2357 - 2361
[7] Journal of Organic Chemistry, 2013, vol. 78, # 20, p. 10319 - 10328
[8] Organic Letters, 2013, vol. 15, # 23, p. 5940 - 5943
[9] Chemical Communications, 2014, vol. 50, # 23, p. 3024 - 3026
[10] European Journal of Organic Chemistry, 2014, vol. 2014, # 8, p. 1622 - 1629
[11] European Journal of Organic Chemistry, 2014, vol. 2014, # 8, p. 1622 - 1629
[12] RSC Advances, 2014, vol. 40, # 78, p. 41561 - 41564
[13] RSC Advances, 2014, vol. 4, # 78, p. 41561 - 41564
[14] Organic Letters, 2014, vol. 16, # 18, p. 4924 - 4927
[15] Journal of Organic Chemistry, 2016, vol. 81, # 10, p. 4412 - 4420
[16] Journal of Organic Chemistry, 2016, vol. 81, # 10, p. 3994 - 4001
[17] Advanced Synthesis and Catalysis, 2017, vol. 359, # 8, p. 1373 - 1378
[18] Chemical Communications, 2017, vol. 53, # 61, p. 8533 - 8536
[19] Organic Letters, 2017, vol. 19, # 15, p. 3982 - 3985
[20] Journal of Organic Chemistry, 2017, vol. 82, # 16, p. 8455 - 8463
[21] Organic and Biomolecular Chemistry, 2017, vol. 15, # 33, p. 6997 - 7007
[22] Organic Letters, 2017, vol. 19, # 22, p. 6128 - 6131
[23] Advanced Synthesis and Catalysis, 2018, vol. 360, # 18, p. 3460 - 3465
[24] Journal of Organic Chemistry, 2018, vol. 83, # 17, p. 10453 - 10464
2
[ 52670-38-9 ]
[ 352-34-1 ]
[ 1173153-20-2 ]
Yield
Reaction Conditions
Operation in experiment
89%
at 20℃; for 16 h; Schlenk technique; Sealed tube; Inert atmosphere
General procedure: The syntheses of alkyne-substituted aromatic amines (15–18) followed the general Scheme 1. A 50 mL Schlenk flask was charged with aryl iodide (2mmol, 1.0 eq.), bis-(triphenylphosphine) palladium dichloride (70mg, 0.05 eq.), cuprous iodide (10mg, 0.05 eq.), triphenylphosphine (13mg, 0.025 eq.), and a stir bar and sealed with rubber septum [33]. The flask was evacuated and refilled three times with Argon. Ethynylaniline (1.1 eq.) was added to 10mL of distilled dry iPr2NH and degassed together in a separated round bottom flask for 15min and then transferred to the Schlenk flask through cannula. The mixture was stirred for 16hat room temperature (65°C in the case of aryl bromide). After completion of the reaction, the mixture was diluted with ethyl acetate (50mL) and the slurry was filtered through a pad of Celite in a sintered glass funnel (medium frit). The tan solids were additionally washed with ethyl acetate until the filtrate was nearly colorless. The filtrate was washed with H2O and brine and dried over magnesium sulfate. The combined organic fraction filtrates were concentrated in vacuum, yielding a black solid. The residue was further purified by flash column chromatography on silica gel using ethyl acetate/hexane mixture as eluent.
Reference：
[1] European Journal of Medicinal Chemistry, 2016, vol. 118, p. 266 - 275
3
[ 1314806-83-1 ]
[ 1173153-20-2 ]
Reference：
[1] Organic and Biomolecular Chemistry, 2011, vol. 9, # 13, p. 4983 - 4986
General procedure: 2-iodoaniline (500.2 mg, 2.28 mmol, 1.0 equiv) was dissolved in Et3N (4.5 mL). The resulting solution was added with PdCl2(PPh3)2 (32.1 mg, 0.046 mol, 0.02 equiv) and CuI (17.4 mg, 0.091mmol, 0.04 equiv). The orange-yellow solution was degassed by bubbling with a stream of argon into the solution at room temperature for 30 min. After degassing, phenylacetylene (0.30 mL,279.0 mg, 2.73 mmol, 1.2 equiv) was added as a neat liquid into the solution via syringe. The resulting dark brown solution was allowed to stir at room temperature under argon atmosphere overnight. The reaction was quenched by addition of sat. aq. NH4Cl. The separated aqueousphase was extracted with EtOAc (3x times). The combined organic phases were washed with sat. aq. NaCl, dried over anh. Na2SO4, filtered and concentrated to a crude product. The crudeproduct was purified by SiO2 column chromatography eluting with 0-10% EtOAc-hexane to give 398.2 mg (90%) of 2-(phenylethynyl)aniline as an orange solid.
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 sulfuric acid; 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 25℃; for 24h;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.
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 bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine; triphenylphosphine; at 20℃; for 16h;Schlenk technique; Sealed tube; Inert atmosphere;
General procedure: The syntheses of alkyne-substituted aromatic amines (15-18) followed the general Scheme 1. A 50 mL Schlenk flask was charged with aryl iodide (2mmol, 1.0 eq.), bis-(triphenylphosphine) palladium dichloride (70mg, 0.05 eq.), cuprous iodide (10mg, 0.05 eq.), triphenylphosphine (13mg, 0.025 eq.), and a stir bar and sealed with rubber septum [33]. The flask was evacuated and refilled three times with Argon. Ethynylaniline (1.1 eq.) was added to 10mL of distilled dry iPr2NH and degassed together in a separated round bottom flask for 15min and then transferred to the Schlenk flask through cannula. The mixture was stirred for 16hat room temperature (65C in the case of aryl bromide). After completion of the reaction, the mixture was diluted with ethyl acetate (50mL) and the slurry was filtered through a pad of Celite in a sintered glass funnel (medium frit). The tan solids were additionally washed with ethyl acetate until the filtrate was nearly colorless. The filtrate was washed with H2O and brine and dried over magnesium sulfate. The combined organic fraction filtrates were concentrated in vacuum, yielding a black solid. The residue was further purified by flash column chromatography on silica gel using ethyl acetate/hexane mixture as eluent.
(E)-4-(3-(2-((4-fluorophenyl)ethynyl)phenyl)triaz-1-enyl)benzimidamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
49%
General procedure: The synthesis of DMZ analogues followed previously reported procedure [19a], see Scheme 2. <strong>[2498-50-2]4-Aminobenzamidine dihydrochloride</strong> (212mg, 1.0mmol) was added to a stirred solution of 12N HCl (0.27mL) and water (1.5mL) in a 10mL flask at 0C and stirring was continued for 15min. To the mixture was added (dropwise) cold (?0C) NaNO2 solution (76mg in 0.27mL water, 1.1 eq.) and stirring was continued for 15min before cold (?0C) NaOAc solution (328mg in 1.5mL water, 4.0 eq.) was added dropwise over 15min to adjust the pH to 6.0. Cold (?0C) aromatic amine solution (1.0mmol in 1.0mL methanol) was added dropwise to the above solution and stirring was continued for another 1-12hat 0C. After the reaction was completed, the solvent was removed under reduced pressure. Water (100mL) was added to the residue and the aqueous mixture was washed with dichloromethane (2×15mL). The aqueous layer was then basified with 2.5% NaOH solution to make the pH>10.0. The desired compound was then extracted from the aqueous layer with ethyl acetate (2×100mL). The organic layer was washed with brine and dried with sodium sulfate. Finally, the solvent was removed under reduced pressure and the final product was obtained with purity >95%.
(E)-N-(1-(tert-butyl)-3-(4-fluorophenyl)pyrrolo[2,3-b]indol-2(1H)-ylidene)-4-methylaniline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
General procedure: Under a nitrogen atmosphere, 2-(phenylethynyl)aniline (1b, 96.5 mg, 0.5 mmol), p-toluidine (3a, 64.2 mg, 0.6 mmol, 1.2 equiv), Co(acac)2 (12.8 mg, 0.05 mmol, 10 mol %) and AgOTf (12.8 mg, 0.05 mmol, 10 mol %) were introduced into a 25-mL Schlenk reaction flask, tert-butyl isocyanide (2, 99.6 mg, 1.2 mmol, 2.4 equiv) and 1,4-dioxane (4.0 mL) were then successively added into this reaction mixture. The reaction system was stirred at 120 C for 24 h. After the completion of the reaction (monitored by TLC), the reaction mixture was continuously stirred at room temperature under air conditions for 5 h until the reaction solution turned red. Next, the solvent was removed under vacuum. The residue was separated by column chromatography on silica gel (eluent, petroleum ether/ethylacetate) to afford the pure red solid 4b.
With 1,4-diaza-bicyclo[2.2.2]octane; silver(I) acetate; In dimethyl sulfoxide; at 60℃; under 7500.75 Torr; for 8h;Autoclave;
To the autoclave was added 0.20 mmol of 2 - ((4-fluorophenyl) ethynyl) aniline,0.24 mmol of bis (2,4,6-trimethylphenyl) iodonium triflate,0.04 mmol silver acetate, 0.02 mmolDiazabicyclo [2.2.2] octane (DABCO), 2 ml of DMSO,Filled with 1MPa of CO2, the reaction was stirred at 60 for 8 hours, stop heating and stirring,Cool to room temperature and allow to vent slowly to unreacted CO2. The reaction solution was washed with 10mL water,Extract three times with ethyl acetate (10 mL each)The organic phases were combined and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure,Then separated and purified by column chromatography to obtain the desired product.The column eluate used was a volume ratio of 2: 1 petroleum ether:Ethyl acetate mixed solvent, yield 84%.
N-(2-((4-fluorophenyl)ethynyl)phenyl)acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With triethylamine; In dichloromethane; at 0 - 20℃;
General procedure: 2-(phenylethynyl)aniline (302.8 mg, 1.57 mmol, 1.0 equiv) was dissolved in DCM (5.0 mL) and cooled to 0 C. The solution was then added with Et3N (0.24 mL, 174.1 mg, 1.72 mmol, 1.1equiv), followed by acetyl chloride (0.18 mL, 198.0 mg, 2.52 mmol, 1.6 equiv). The resulting reaction mixture was allowed to stir at 0 C while slowly warming to room temperature over 5 h,at which point the reaction was complete as indicated by TLC. The reaction mixture was byaddition of water. The separated aqueous phase was extracted with DCM (3x times). The combined organic phases were washed with sat. aq. NaCl, dried over anh. Na2SO4, filtered and concentrated to a crude solid. The crude solid product was purified by SiO2 column chromatography eluting with 20% EtOAc-hexane to give 354.4 mg (96%) of compound 1a as awhite solid.
6-(4-fluorophenyl)-11H-indolo[3,2-c]quinoline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; at 120℃; for 20h;Sealed tube;
1 l (0.3 mmol, 63.4 mg), [RhCp*Cl2] 2 (0.015 mmol, 9.3 mg) and hexafluoroisopropanol (2 mL) were sequentially added to a 15 mL reaction tube.The reaction tube was sealed in an air atmosphere, and the reaction was stirred at 120 C for 20 h. After the completion of the reaction, the reaction tube was cooled to room temperature, and 10 mL of water was added thereto, followed by extraction with ethyl acetate (10 mL × 3), and the organic phase was washed successively with water and brine, and dried over anhydrous sodium sulfate. filter,Spin dry, separated by silica gel column (petroleum ether / ethyl acetate = 5 / 1)The product was obtained as a white solid, 2l (33mg, 70%).
2-(4-(4-fluorobenzyl)-2-(4-fluorophenyl)quinolin-3-yl)aniline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; at 120℃; for 20h;Inert atmosphere; Sealed tube;Catalytic behavior;
In 15 ml reaction tube adding 1 m (0.3 mmol, 63.4 mg), [RhCp * Cl2 ]2 (0.015 Mmol, 9.3 mg) and hexafluoroisopropanol (2 ml), in a nitrogen atmosphere of the reaction pipe sealing, in the 120 C stirring for 20 h. After the reaction, the reaction tube to be cooled to the room temperature, adding 10 ml water, then the extraction of ethyl acetate (10 ml × 3), after the organic phase with water and saturated salt water are successively washing, drying with anhydrous sodium sulfate. Filtering, turns on lathe does, too separating by silica gel column (petroleum ether/ethyl acetate=10/1) to yellow solid product 2 m (42 mg, 66%). The compound of the characterization data are as follows
3-(2-(4-fluorophenyl)-1H-indol-1-yl)isobenzofuran-1(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With palladium diacetate; In toluene; at 100℃; for 6h;Microwave irradiation;
Preparation method of the above compound III-3 provided in this example:Add 211 mg (about 1 mmol) of 2-((4-fluorophenyl) ethynyl) aniline and 225 mg (about 1.5 mmol) of o-carboxybenzaldehyde to a microwave reaction tube.2 mg (about 1 mol%) of the catalyst palladium acetate and 1 mL of the solvent toluene, and then the reaction tube was sealed.After stirring at 100 C for 6 hours, the solvent toluene was distilled off under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate as an eluent.315 mg of product III-3 was obtained as a white solid with a yield of 92%.
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