* 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] Journal of Organic Chemistry, 2017, vol. 82, # 10, p. 5080 - 5095
3
[ 15226-74-1 ]
[ 696-62-8 ]
[ 6148-64-7 ]
[ 2881-83-6 ]
Yield
Reaction Conditions
Operation in experiment
89%
With 1H-imidazole; palladium diacetate; triethylamine; [5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphane; magnesium chloride In tetrahydrofuran at 90℃; for 0.5 h; Microwave irradiation
To a stirred mixture of aryl or heteroaryl halide(Br, I) (0.5 mmol), potassium mono ethyl malonate (0.75 mmol) in THF (10 mL) taken in a 30 mL microwave vial, was added Pd(OAc)2(5 molpercent), Xantphos (5 mol percent), MgCl2 (0.75), Et3N ( 0.75mmol), imidazole (1 mmol) followed by Co2(CO)8 (0.15mmol). The vial was sealed immediately and microwave irradiated at 90°C for 30min. The reaction mixture was concentrated and diluted with ethyl acetate and water. The ethyl acetate layer was separated, dried over sodium sulphate and concentrated. The crude product obtained was purified by column chromatography to get the pure compound.
Reference:
[1] Journal of the Chemical Society, 1916, vol. 109, p. 1087
17
[ 696-62-8 ]
[ 5399-03-1 ]
[ 52692-09-8 ]
Reference:
[1] Chemische Berichte, 1896, vol. 29, p. 1000,2595[2] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641
18
[ 696-62-8 ]
[ 7697-37-2 ]
[ 5399-03-1 ]
Reference:
[1] Journal of the Chemical Society, 1946, p. 406
19
[ 696-62-8 ]
[ 7697-37-2 ]
[ 5399-03-1 ]
[ 52692-09-8 ]
Reference:
[1] Chemische Berichte, 1896, vol. 29, p. 1000,2595[2] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641
[3] Bulletin de la Societe Chimique de France, 1897, vol. <3> 17, p. 115
20
[ 696-62-8 ]
[ 52692-09-8 ]
Yield
Reaction Conditions
Operation in experiment
88%
With N-Bromosuccinimide; silver nitrate In acetonitrile for 5 h; Reflux
General procedure: To a stirred mixture of CH3CN (5 mL) and NBS (1.0 mmol, 0.177 g) at reflux, was added AgNO3 (1.0 mmol, 0.169 g). N,N-Dimethylaniline (1 mmol, 0.126 mL) was then added to the mixture. After 3 h, the mixture was filtered to remove AgBr. The solvent was evaporated and the residue dissolved in CH2Cl2 (10 mL) and washed with aqueous 4percent NaHCO3 (2 .x. 5 mL) to remove N-hydroxysuccinimide from the organic phase. The aqueous phase was separated and the organic phase dried and concentrated. The residue was subjected to column chromatography over silica gel using n-hexane/EtOAc (4:1) as eluent to give 4-nitro- and 2-nitro-N,N-dimethylaniline in 69percent and 16percent yields, respectively.
75%
With iodine; silver nitrate; chloro-diphenylphosphine In dichloromethane at 20℃; for 4 h;
In a typical experiment: to a flask containing a stirred mixture of Ph2PCl (1.1 mmol, 0.202 mL) and I2 (1.1 mmol, 0.279 g) in CH2Cl2 (5 mL), was added silver nitrate (2.2 mmol, 0.373 g) at room temperature. N,N-Dimethylaniline (2.0 mmol, 0.252 mL) was then added to the reaction mixture. After 10 min, the mixture was filtered to remove precipitated AgCl and AgI. The residue was washed with saturated aqueous Na2CO3 (3 .x. 5 mL) until all the diphenylphosphinic acid was removed from the organic phase. The aqueous phase was separated and the organic phase washed with aqueous Na2S2O3 (2 .x. 5 mL) to remove the excess I2 and then H2O (5 mL), dried, and concentrated. Column chromatography of the residue was performed on silica gel using n-hexane/EtOAc (4:1) as eluent to give pure 2-nitro- and 4-nitro-N,N-dimethylanilines in 15percent and 77percent yields, respectively.
Reference:
[1] Journal of Chemical Research, Synopses, 1995, # 7, p. 284 - 285
22
[ 696-62-8 ]
[ 5399-03-1 ]
[ 52692-09-8 ]
Reference:
[1] Chemische Berichte, 1896, vol. 29, p. 1000,2595[2] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641
23
[ 696-62-8 ]
[ 7697-37-2 ]
[ 5399-03-1 ]
[ 52692-09-8 ]
Reference:
[1] Chemische Berichte, 1896, vol. 29, p. 1000,2595[2] Bulletin de la Societe Chimique de France, 1896, vol. <3> 15, p. 641
[3] Bulletin de la Societe Chimique de France, 1897, vol. <3> 17, p. 115
24
[ 547-63-7 ]
[ 696-62-8 ]
[ 6274-50-6 ]
Yield
Reaction Conditions
Operation in experiment
80%
Stage #1: With 2,2,6,6-tetramethylpiperidinyl-lithium In toluene at 20℃; for 0.25 h; Glovebox Stage #2: With palladium(l) tri-tert-butylphosphine iodide dimer In toluene at 20℃; Glovebox
General procedure: Inside the glovebox, lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 70.7 mg, 0.48 mmol, 1.2 eq.) was dissolved in toluene (1.5 mL) and carbonyl compound (3, 0.48 mmol, 1.2 eq.) was added. After 15 min of stirring at ambient temperature a solution of Pd(I) iodo dimer (2, 3.5 mg, 0.004 mmol, 1 molpercent for aryl iodides; 17.4 mg, 0.02 mmol, 5 molpercent for aryl bromides) and aryl halide (4, X = I or Br, 0.4 mmol, 1.0 eq.) in toluene (0.5 mL) was added. After 4-18 h of further stirring at ambient temperature (reaction progress was monitored by GCMS), the crude was directly adsorbed onto silica (washing with diethyl ether) and purified by flash column chromatography.
With potassium <i>tert</i>-butylate In toluene at 115℃; for 3.5 h;
EXAMPLE 5; Amination reaction was carried out in a 50 ml capacity two neck round bottom flask. In a typical experiment, Toluene (23 ml) was charged to the round bottom flask followed by CuI (0.28 mmol), 1,6-bis(diphenylphosphino)hexane (0.28 mmol), aniline (7.85 mmol), p-methoxy iodobenzene (16.48 mmols), and KOt-Bu (23.5 mmol). Reflux condenser was attached to the flask and the round bottom flask was flushed twice with nitrogen to ensure removal of air. Nitrogen balloon was attached to the condenser, to maintain nitrogen atmosphere during the reaction. The round bottom flask was then stirred by magnetic needle and heated to 115° C. in oil bath and the reaction was continued for 3.5 hours. After cooling to room temperature, the reaction solution was filtered to remove the precipitated base and washed with solvent. The product was separated by column chromatography. The isolated yield of N,N-bis(4-methoxyphenyl)aniline was 87percent.
87%
With 1,6-bis(diphenylphosphino)hexane; potassium <i>tert</i>-butylate In toluene at 115℃; for 3.5 h;
Amination reaction was carried out in a 50 ml capacity two neck round bottom flask. In a typical experiment, Toluene (23 ml) was charged to the round bottom flask followed by CuI (0. 28mmol), 1, 6-bis (diphenylphosphino) hexane (0.28mmol), aniline (7. 85mmol), p- methoxy iodobenzene (16.48mmols), and KOt-Bu (23. 5mmol). Reflux condenser was attached to the flask and the round bottom flask was flushed twice with nitrogen to ensure removal of air. Nitrogen balloon was attached to the condenser, to maintain nitrogen atmosphere during the reaction. The round bottom flask was then stirred by magnetic needle and heated to 115°C in oil bath and the reaction was continued for 3 : 5 hours. After cooling to room temperature, the reaction solution was filtered to remove the precipitated base and washed with solvent. The product was separated by column chromatography. The isolated yield of N, N-bis (4-methoxyphenyl) aniline was 87percent.
74%
With potassium <i>tert</i>-butylate In toluene at 115℃; for 3.5 h;
EXAMPLE 2; Amination reaction was carried out in a 50 ml capacity two neck round bottom flask. In a typical experiment, Toluene (23 ml) was charged to the round bottom flask followed by CuI (0.28 mmol), Bis(diphenylphosphino)methane (0.28 mmol), aniline (7.85 mmol), p-methoxy iodobenzene (16.48 mmols), and KOt-Bu (23.5 mmol). Reflux condenser was attached to the flask and the round bottom flask was flushed twice with nitrogen to ensure removal of air. Nitrogen balloon was attached to the condenser, to maintain nitrogen atmosphere during the reaction. The round bottom flask was then stirred by magnetic needle and heated to 115° C. in oil bath and the reaction was continued for 3.5 hours. After cooling to room temperature, the reaction solution was filtered to remove the precipitated base and washed with solvent. The product was separated by column chromatography. The isolated yield of N,N-bis(4-methoxyphenyl)aniline was 74percent.
74%
With potassium <i>tert</i>-butylate; bis-diphenylphosphinomethane In toluene at 115℃; for 3.5 h;
Amination reaction was carried out in a 50 ml capacity two neck round bottom flask. In a typical experiment, Toluene (23 ml) was charged to the round bottom flask followed by Cul (0. 28mmol), Bis (diphenylphosphino) methane (0.28mmol), aniline (7.85mmol), p- methoxy iodobenzene (16.48mmols), and KOt-Bu (23. 5mmol). Reflux condenser was attached to the flask and the round bottom flask was flushed twice with nitrogen to ensure removal of air. Nitrogen balloon was attached to the condenser, to maintain nitrogen atmosphere during the reaction. The round bottom flask was then stirred by magnetic needle and heated to 115°C in oil bath and the reaction was continued for 3.5 hours. After cooling to room temperature, the reaction solution was filtered to remove the precipitated base and washed with solvent. The product was separated by column chromatography. The isolated yield of N, N-bis (4-methoxyphenyl) aniline was 74percent.
70.1%
With 18-crown-6 ether; copper; potassium carbonate In 1,2-dichloro-benzeneInert atmosphere; Reflux
Synthesis of N,N-bis(4-methoxyphenyl)aniline. Freshly distilled aniline (4.84 g, 52.0 mmol), />;-iodoanisole (30.4 g, 130.0 mmol), powdered anhydrous potassium carbonate (57.5 g, 416.0 mmol), electrolytic copper powder (13.3 g, 208.0 mmol), and 18-crown-6 (2.75 g, 10.4 mmol) were added to a dry, three necked round bottom flask under nitrogen. The mixture was refluxed in 100 mL o- dichlorobenzene 18 h (during which time some solvent evaporated).. Ethyl acetate (250 mL) was added to the reaction flask. The resulting mixture was filtered to remove copper and organic salts and the solvent was removed under reduced pressure. The product was purified by washing with methanol to yield a tan solid (11.2 g, 70.10Zo)-1H NMR (300 MHz, CDCl3) δ 7.16 (m, 2H), 7.01 (d, J = 9.0 Hz, 4H), 6.78 (d, J = 9.0 Hz, 4H), 6.83 (t, J = 1.5 Hz, 2H), 6.81 (t, J = 1.5 Hz, IH), 3.55 (s, 6H).
70%
at 135℃; for 6 h;
To a mixture of 4-iodoanisole (0.70 g, 3.00 mmol), t-BuOK (0.34 g, 3.00 mmol), 2,2′-bipyridine (3 mg, 0.02 mmol) and CuI(I) (4 mg, 0.02 mmol) was added toluene (6 mL) and aniline (0.09 mL, 1.00 mmol). The solution was heated and reacted for 6 hours at 135° C. After the reaction was cooled to room temperature, the solid product was filtered off and washed with toluene. The filtrates were combined, and the solvent was removed therefrom to obtain a residue. The residue was purified by Silica Gel Column Chromatography using n-hexane, to give an intermediate product as a yellow solid (0.21 g, 70percent). The intermediate product was identified and assayed, and the result was shown as follows: 1H NMR (400 MHz, CdCl3) δH=7.15 (t, J=7.6 Hz, 2H), 7.03 (d, J=7.6 Hz, 4H), 6.91 (d, J=7.6 Hz, 2H), 6.72-6.88 (m, 5H), 3.77 (s, 12H).
70.1%
With 18-crown-6 ether; copper; potassium carbonate In 1,2-dichloro-benzene for 18 h; Inert atmosphere; Reflux
Freshly distilled aniline (4.84 g, 52.0 mmol), p-iodoanisole (30.4 g, 130.0 mmol), powdered anhydrous potassium carbonate (57.5 g, 416.0 mmol), electrolytic copper powder (13.3 g, 208.0 mmol), and 18-crown-6 (2.75 g, 10.4 mmol) were added to a dry, three necked round bottom flask under nitrogen. The mixture was refluxed in 100 mL o-dichlorobenzene 18 h (during which time some solvent evaporated). Ethyl acetate (250 mL) was added to the reaction flask. The resulting mixture was filtered to remove copper and organic salts and the solvent was removed under reduced pressure. The product was purified by washing with methanol to yield a tan solid (11.2 g, 70.1percent).
65.6%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide In toluene for 12 h; Inert atmosphere; Reflux
4-iodoanisole (7.20 g, 30.76 mmol) and aniline (1.14 mL, 12.49 mmol) were dissolved in a round-bottom flask in 50 mL toluene, and o-phenanthroline (0.45 g, 2.30 mmol), cuprous iodide (0.48 g, 2.52 mmol) and potassium hydroxide (5.60 g, 100.00 mmol) were added to the solution. The mixture was refluxed under N2 atmosphere for 12 h and then treated according to previous literature to obtain the compound 1 as a white solid (2.50 g). Yield: 65.6percent. 17
49.2%
With copper(l) iodide; 1,10-Phenanthroline; potassium <i>tert</i>-butylate In 5,5-dimethyl-1,3-cyclohexadiene at 130℃; for 24 h; Inert atmosphere
Use a 50 mL two-port bottle as the reaction vessel.The reaction device is subjected to anhydrous treatment,The reflux reaction was protected by argon.Add p-iodoanisole (5.149 g, 22 mmol, 2.0 eq) to a two-necked vial.Potassium tert-butoxide (about 6 g, 60 mmol, 6.0 eq),CuI (400 mg, 2.1 mmol, 0.21 eq),1,10-phenanthroline (400 mg, 2.0 mmol, 0.2 eq), ventilated,Add xylene (25 ml) with a syringe under stirring.Add with a syringeAniline (931 mg, 0.93 mL, 10 mmol, 1.0 eq).The mixture was stirred at 130 ° C for 24 h in an oil bath.The reaction was monitored by TLC.Extract a small amount of ethyl acetate and water for 5 times with a separatory funnel.Pour the organic phase into a round bottom flask and spin dry.Add silica gel and mix.After being stirred evenly, it was separated by column chromatography (petroleum ether/ethyl acetate = 50/1: v/v).The product obtained has a mass of 1.5 g.The theoretical yield is 3.05g,The yield was 49.2percent.
32%
Stage #1: With 1,10-Phenanthroline; copper(l) chloride In o-xylene for 0.583333 h; Inert atmosphere; Schlenk technique; Reflux Stage #2: With potassium hydroxide In o-xylene for 28 h; Inert atmosphere; Schlenk technique; Reflux
An oven dried Schlenk flask was charged with o-xylene (30 mL) and the solvent degassed. To this solution, 4-iodoanisole (15.00 g, 64.1 mmol), CuCl (0.201 g, 2.03 mmol), 1,10-phenanthroline (0.274 g, 1.5 mmol) and aniline (2.78 mL, 30.5 mmol) were added, the mixture was heated at reflux for 35 min, KOH (13.70 g, 244 mmol) was added and the mixture heated at reflux for 28 h, cooled, poured into H2O (150 mL) and extracted with CH2Cl2 (3 * 60 mL). The organic layers were combined and dried over MgSO4, filtered and the solvent removed in vacuo. The residue was suspended in hexane and purified by silica column chromatography eluting with hexane increasing to hexane:CH2Cl2 (50:50), removal of the solvent and crystallisation from hot hexane gives the title compound as a white solid. Yield 3.29 g, 32percent. 1H NMR (400 MHz, CDCl3) δ 7.16 (d, J = 7 Hz, 2H), 7.05 (d, J = 9 Hz, 4H), 6.94 (d, J = 7 Hz, 2H), 6.90-6.85 (m, 1H), 6.82 (d, J = 9 Hz, 4H), 3.80 (s, 6H). Literature: [47] 1H NMR (CDCl3): δ = 7.25-6.79 (m, 13H, Ar), 3.79 ppm (s, 6H, OCH3). ESI-MS: 305.6 [M]+.
Reference:
[1] Tetrahedron Letters, 2002, vol. 43, # 40, p. 7143 - 7146
[2] Patent: US6894191, 2005, B1, . Location in patent: Page/Page column 8-9
[3] Patent: WO2005/63680, 2005, A1, . Location in patent: Page/Page column 9
[4] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1997, # 7, p. 1405 - 1414
[5] Patent: US6894191, 2005, B1, . Location in patent: Page/Page column 7
[6] Patent: WO2005/63680, 2005, A1, . Location in patent: Page/Page column 7; 8
[7] Tetrahedron Letters, 2004, vol. 45, # 16, p. 3253 - 3256
[8] Patent: WO2010/115854, 2010, A1, . Location in patent: Page/Page column 28
[9] Inorganic Chemistry Communications, 2011, vol. 14, # 9, p. 1352 - 1357
[10] Patent: US2013/90469, 2013, A1, . Location in patent: Paragraph 0164-0165
[11] Patent: JP5670329, 2015, B2, . Location in patent: Paragraph 0063
[12] Journal of the American Chemical Society, 2008, vol. 130, # 19, p. 6259 - 6266
[13] Dyes and Pigments, 2011, vol. 88, # 3, p. 333 - 343
[14] New Journal of Chemistry, 2015, vol. 39, # 5, p. 3736 - 3746
[15] Tetrahedron Letters, 2005, vol. 46, # 22, p. 3913 - 3916
[16] Tetrahedron, 2016, vol. 72, # 36, p. 5620 - 5625
[17] Science China Chemistry, 2013, vol. 56, # 4, p. 505 - 513
[18] Journal of the American Chemical Society, 2015, vol. 137, # 51, p. 16172 - 16178
[19] Journal of Organic Chemistry, 2005, vol. 70, # 18, p. 7397 - 7407
[20] Patent: CN108314625, 2018, A, . Location in patent: Paragraph 0092; 0093; 0094
[21] Polyhedron, 2015, vol. 86, p. 31 - 42
[22] Journal of Materials Chemistry, 2008, vol. 18, # 18, p. 2141 - 2149
[23] Chinese Journal of Chemistry, 2012, vol. 30, # 10, p. 2315 - 2321,7
[24] Journal of Polymer Science, Part A: Polymer Chemistry, 2013, vol. 51, # 13, p. 2925 - 2938
[25] Journal of Polymer Science, Part A: Polymer Chemistry, 2014, vol. 52, # 6, p. 825 - 838
[26] Ultrasonics Sonochemistry, 2015, vol. 22, p. 365 - 370
[27] Dyes and Pigments, 2015, vol. 121, p. 204 - 210
[28] Dyes and Pigments, 2017, vol. 140, p. 431 - 440
26
[ 696-62-8 ]
[ 101-70-2 ]
[ 20440-94-2 ]
Reference:
[1] Angewandte Chemie - International Edition, 2014, vol. 53, # 11, p. 2941 - 2944[2] Angew. Chem., 2014, vol. 53-126, # 11, p. 3093
27
[ 696-62-8 ]
[ 369-57-3 ]
[ 613-37-6 ]
[ 28896-47-1 ]
[ 2974-94-9 ]
[ 87441-18-7 ]
[ 75581-11-2 ]
[ 87441-17-6 ]
Reference:
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1983, p. 803 - 808
28
[ 696-62-8 ]
[ 77770-09-3 ]
Reference:
[1] Journal of the American Chemical Society, 2013, vol. 135, # 13, p. 5000 - 5003
29
[ 696-62-8 ]
[ 182056-39-9 ]
Reference:
[1] Chemical Communications, 2012, vol. 48, # 39, p. 4674 - 4676
[2] Journal of Chemical Research - Part S, 1996, # 7, p. 334 - 335
[3] Chemische Berichte, 1896, vol. 29, p. 1410
[4] Angewandte Chemie - International Edition, 2018, vol. 57, # 43, p. 14129 - 14133[5] Angew. Chem., 2018, vol. 130, # 43, p. 14325 - 14329,5
To a solution of 4-iodo-anisole (2.76 g, 11.8 mmol, 1.0 equiv.), PdCl2(PPh)2 (166 mg, 236 Mmol, 2 molpercent) and Cul (89.0 mg, 472 Mmol, 4 molpercent) in degassed NEt3 (100 mL), was added 2-ethynylbenzaldehyde (2.00 g, 15.4 mmol, 1.3 equiv.). After the reaction was stirred at room temperature over night the solvent was removed under reduced pressure. The crude material was purified by flash column chromatography (S1O2; petrolether : ethylacetate = 40:1 to 35:1 ) followed by recrystallization in ChbC /pen- tane to afford the title compound 1f as colorless solid (2.49 g, 0.5 mmol, 89percent).
Reference:
[1] Chemistry - A European Journal, 2015, vol. 21, # 41, p. 14401 - 14409
[2] Angewandte Chemie - International Edition, 2016, vol. 55, # 3, p. 1196 - 1199[3] Angew. Chem., 2016, vol. 55, # 128, p. 1212 - 1216,5
[4] Patent: WO2017/16653, 2017, A1, . Location in patent: Page/Page column 23
[5] Angewandte Chemie - International Edition, 2017, vol. 56, # 36, p. 10928 - 10932[6] Angew. Chem., 2017, vol. 129, # 36, p. 11068 - 11072,5
[7] Dalton Transactions, 2018, vol. 47, # 36, p. 12656 - 12660
39
[ 696-62-8 ]
[ 142623-90-3 ]
[ 188817-13-2 ]
Reference:
[1] European Journal of Organic Chemistry, 2017, vol. 2017, # 44, p. 6566 - 6574
40
[ 696-62-8 ]
[ 106-40-1 ]
[ 194416-45-0 ]
Yield
Reaction Conditions
Operation in experiment
78%
With 1,10-Phenanthroline; copper(l) chloride; potassium hydroxide In toluene for 20 h; Inert atmosphere; Reflux
To a 100 mL three-necked flask was added p-iodoanisole (1.1 g, 4.8 mmol) in this order,P-bromoaniline (0.34 g, 2.0 mmol),Potassium hydroxide (0.56 g, 10 mmol),1,10-phenanthroline (0.03 g, 0.16 mmol) and 60 mL of toluene,Fitted with a reflux condenser,Vacuum,Replace argon protection.Under argon flow,A catalytic amount of cuprous chloride was quickly added,The reaction was heated to reflux for 20 h.After TLC detection of raw materials reaction finished,The reaction was stopped,The solvent was distilled off under reduced pressure,The reaction mixture was dissolved in 100 mL of dichloromethane,And further washed three times with saturated brine (80 mL x 3)The organic phase was dried over anhydrous sodium sulfate overnight.The filtrate was collected by filtration,The solvent was removed under reduced pressure,The crude product was purified by column chromatography on silica gel (200-300 mesh [eluent,V (petroleum ether): V (ethyl acetate) = 8: 1] to give Intermediate 6 (0.60 g) as a pale yellow solid,Yield 78percent.
70.4%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide In toluene at 110 - 135℃; for 12 h; Inert atmosphere
A mixture of 1-iodo-4-methoxybenzene (10.00 g, 42.74 mmol), 4-bromobenzenamine (2.95 g, 17.15 mmol) and 1,10-phenanthroline anhydrous (0.62 g, 3.42 mmol) in toluene (60 mL) was heated and stirred under nitrogen atmosphere. When the temperature reached to 110 °C, the CuI (0.65 g, 3.42 mmol) and KOH (7.66 g, 136.79 mmol) were added quickly, and then the mixture was stirred at 135 °C for 12 h. After cooled to RT, the mixture was poured into distilled water (50 mL) and extracted with dichloromethane (DCM) (3 * 30 mL). The combined organic layer was dried over MgSO4 for 2 h and filtrated. The filtrate was concentrated by rotary evaporator under reduced pressure. The residue was purified by silica gel column chromatography using DCM/petroleum ether (PE) (1/5, V/V) as eluent to gain lyard powder (4.63 g, 70.4percent). 1H NMR (400 MHz, CDCl3, ppm): 7.25 (d, J = 4.0 Hz, 2H), 7.04 (d, J = 8.4 Hz, 4H), 6.83 (d, J = 8.2 Hz, 6H), 3.79 (s, 6H).
70.4%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide In toluene at 110 - 135℃; for 12 h; Inert atmosphere
In a 100 mL three-necked flask, 4-methoxyiodobenzene (10.0 g, 42.74 mmol) and p-bromoaniline (2.9 g,17.15 mmol), anhydrous 1,10-phenanthroline (0.6 g, 3.42 mmol) and 60 mL of toluene were added and the temperature was raised to 110 ° C under the protection of nitrogen.Copper iodide (0.7 g, 3.42 mmol) and potassium hydroxide (7.7 g, 136.79 mmol) were added rapidly and the reaction was further allowed to warm to 135 ° C and the reaction was stirred for 12 h. After cooling to room temperature, the reaction mixture was poured into 50 mL of distilled water and extracted with CH 2 Cl 2 (3 × 30 mL). The extract was washed with water, dried over anhydrous MgSO 4 and the solvent was removed under reduced pressure. The crude product was washed with CH 2 Cl 2: PE = 1: 5 V) as eluent, and separated by column chromatography to give 4.63 g of an off-white solid in a yield of 70.4percent.
62.2%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide In toluene at 125℃; for 24 h; Inert atmosphere
To a stirred solution of 4-iodoanisole (5.85 g, 25 mmol), 4-bromoaniline (1.72 g, 10 mmol), and 1,10-phenanthroline (0.18 g, 1 mmol) in toluene (100 mL) were added potassium hydroxide (5.61 g, 100 mmol) and copper(I) iodide (0.19 g, 1 mmol). The reaction mixture was heated under reflux for 24 h at 125 °C. The crude product was extracted into dichloromethane, and the organic layer was washed with 1 N HCl solution, brine, and water. The organic layer was dried with anhydrous MgSO4 and then the solvent was removed in vacuo. The residue was purified by column chromatography using silica gel and dichloromethane-hexane (1:1; v/v) as the eluent to give 3 (2.39 g, 62.2percent). 1H NMR (500 MHz, d6-DMSO, ppm): δ 7.31 (d, J = 9.0 Hz, 2H), 7.04-7.02 (m, 4H), 6.93-6.91 (m, 4H), 6.67 (d, J = 9.0 Hz, 2H), 3.74 (s, -OCH3 * 2, 6H). 13C NMR (126 MHz, CDCl3, ppm): δ 156.0, 147.9, 140.6, 131.7, 127.7, 126.5, 121.9, 114.8, 114.2, 112.4, 55.5. HRMS (m/z): calcd. for (C20H18BrNO2): 383.0520, found: 383.0516 [EI+]. Anal. Cald for (C20H18BrNO2): C, 62.51; H, 4.72; N, 3.65. Found: C, 62.39; H, 4.70; N, 3.52.
53.8%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide In toluene at 110℃; for 48 h; Inert atmosphere
Add 5.00 g of p-bromoaniline, 14.4 g of p-iodoanisole, 0.28 g of CuI, 12.8 g of KOH, and 0.26 g of 1,10-phenanthroline to a 250 mL two-necked flask. Nitrogen was three times, then 60 mL of anhydrous oxygen-free toluene was added and stirred at 110° C. for 48 hours. After the reaction is completed, it is cooled to room temperature, filtered directly, and the filter residue is washed three times with dichloromethane.The filtrate was then spin-dried under reduced pressure. The resulting crude product was subjected to column chromatography using petroleum ether and dichloromethane in a volume ratio of 3:1 as eluent to obtain 6.02 g of a yellow solid 3 with a yield of 53.8percent.
Reference:
[1] Organic Letters, 2016, vol. 18, # 14, p. 3386 - 3389
[2] RSC Advances, 2015, vol. 5, # 37, p. 28879 - 28884
[3] New Journal of Chemistry, 2015, vol. 39, # 3, p. 1840 - 1851
[4] RSC Advances, 2014, vol. 4, # 32, p. 16385 - 16390
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[1] Chemical Communications, 2017, vol. 53, # 1, p. 180 - 183
With potassium tert-butylate;copper(l) iodide; 1,6-bis(diphenylphosphino)hexane; In toluene; at 115℃; for 3.5h;Product distribution / selectivity;
EXAMPLE 5; Amination reaction was carried out in a 50 ml capacity two neck round bottom flask. In a typical experiment, Toluene (23 ml) was charged to the round bottom flask followed by CuI (0.28 mmol), 1,6-bis(diphenylphosphino)hexane (0.28 mmol), aniline (7.85 mmol), p-methoxy iodobenzene (16.48 mmols), and KOt-Bu (23.5 mmol). Reflux condenser was attached to the flask and the round bottom flask was flushed twice with nitrogen to ensure removal of air. Nitrogen balloon was attached to the condenser, to maintain nitrogen atmosphere during the reaction. The round bottom flask was then stirred by magnetic needle and heated to 115 C. in oil bath and the reaction was continued for 3.5 hours. After cooling to room temperature, the reaction solution was filtered to remove the precipitated base and washed with solvent. The product was separated by column chromatography. The isolated yield of N,N-bis(4-methoxyphenyl)aniline was 87%.
87%
With 1,6-bis(diphenylphosphino)hexane; potassium tert-butylate;copper(l) iodide; In toluene; at 115℃; for 3.5h;Product distribution / selectivity;
Amination reaction was carried out in a 50 ml capacity two neck round bottom flask. In a typical experiment, Toluene (23 ml) was charged to the round bottom flask followed by CuI (0. 28mmol), 1, 6-bis (diphenylphosphino) hexane (0.28mmol), aniline (7. 85mmol), p- methoxy iodobenzene (16.48mmols), and KOt-Bu (23. 5mmol). Reflux condenser was attached to the flask and the round bottom flask was flushed twice with nitrogen to ensure removal of air. Nitrogen balloon was attached to the condenser, to maintain nitrogen atmosphere during the reaction. The round bottom flask was then stirred by magnetic needle and heated to 115C in oil bath and the reaction was continued for 3 : 5 hours. After cooling to room temperature, the reaction solution was filtered to remove the precipitated base and washed with solvent. The product was separated by column chromatography. The isolated yield of N, N-bis (4-methoxyphenyl) aniline was 87%.
74%
With potassium tert-butylate;copper(l) iodide; bis-diphenylphosphinomethane; In toluene; at 115℃; for 3.5h;Product distribution / selectivity;
EXAMPLE 2; Amination reaction was carried out in a 50 ml capacity two neck round bottom flask. In a typical experiment, Toluene (23 ml) was charged to the round bottom flask followed by CuI (0.28 mmol), Bis(diphenylphosphino)methane (0.28 mmol), aniline (7.85 mmol), p-methoxy iodobenzene (16.48 mmols), and KOt-Bu (23.5 mmol). Reflux condenser was attached to the flask and the round bottom flask was flushed twice with nitrogen to ensure removal of air. Nitrogen balloon was attached to the condenser, to maintain nitrogen atmosphere during the reaction. The round bottom flask was then stirred by magnetic needle and heated to 115 C. in oil bath and the reaction was continued for 3.5 hours. After cooling to room temperature, the reaction solution was filtered to remove the precipitated base and washed with solvent. The product was separated by column chromatography. The isolated yield of N,N-bis(4-methoxyphenyl)aniline was 74%.
74%
With potassium tert-butylate; bis-diphenylphosphinomethane;copper(l) iodide; In toluene; at 115℃; for 3.5h;Product distribution / selectivity;
Amination reaction was carried out in a 50 ml capacity two neck round bottom flask. In a typical experiment, Toluene (23 ml) was charged to the round bottom flask followed by Cul (0. 28mmol), Bis (diphenylphosphino) methane (0.28mmol), aniline (7.85mmol), p- methoxy iodobenzene (16.48mmols), and KOt-Bu (23. 5mmol). Reflux condenser was attached to the flask and the round bottom flask was flushed twice with nitrogen to ensure removal of air. Nitrogen balloon was attached to the condenser, to maintain nitrogen atmosphere during the reaction. The round bottom flask was then stirred by magnetic needle and heated to 115C in oil bath and the reaction was continued for 3.5 hours. After cooling to room temperature, the reaction solution was filtered to remove the precipitated base and washed with solvent. The product was separated by column chromatography. The isolated yield of N, N-bis (4-methoxyphenyl) aniline was 74%.
70.1%
With 18-crown-6 ether; copper; potassium carbonate; In 1,2-dichloro-benzene;Inert atmosphere; Reflux;
Synthesis of N,N-bis(4-methoxyphenyl)aniline. Freshly distilled aniline (4.84 g, 52.0 mmol), />;-iodoanisole (30.4 g, 130.0 mmol), powdered anhydrous potassium carbonate (57.5 g, 416.0 mmol), electrolytic copper powder (13.3 g, 208.0 mmol), and 18-crown-6 (2.75 g, 10.4 mmol) were added to a dry, three necked round bottom flask under nitrogen. The mixture was refluxed in 100 mL o- dichlorobenzene 18 h (during which time some solvent evaporated).. Ethyl acetate (250 mL) was added to the reaction flask. The resulting mixture was filtered to remove copper and organic salts and the solvent was removed under reduced pressure. The product was purified by washing with methanol to yield a tan solid (11.2 g, 70.10Zo)-1H NMR (300 MHz, CDCl3) delta 7.16 (m, 2H), 7.01 (d, J = 9.0 Hz, 4H), 6.78 (d, J = 9.0 Hz, 4H), 6.83 (t, J = 1.5 Hz, 2H), 6.81 (t, J = 1.5 Hz, IH), 3.55 (s, 6H).
70%
With [2,2]bipyridinyl; copper(l) iodide; potassium tert-butylate; at 135℃; for 6h;
To a mixture of 4-iodoanisole (0.70 g, 3.00 mmol), t-BuOK (0.34 g, 3.00 mmol), 2,2?-bipyridine (3 mg, 0.02 mmol) and CuI(I) (4 mg, 0.02 mmol) was added toluene (6 mL) and aniline (0.09 mL, 1.00 mmol). The solution was heated and reacted for 6 hours at 135 C. After the reaction was cooled to room temperature, the solid product was filtered off and washed with toluene. The filtrates were combined, and the solvent was removed therefrom to obtain a residue. The residue was purified by Silica Gel Column Chromatography using n-hexane, to give an intermediate product as a yellow solid (0.21 g, 70%). The intermediate product was identified and assayed, and the result was shown as follows: 1H NMR (400 MHz, CdCl3) deltaH=7.15 (t, J=7.6 Hz, 2H), 7.03 (d, J=7.6 Hz, 4H), 6.91 (d, J=7.6 Hz, 2H), 6.72-6.88 (m, 5H), 3.77 (s, 12H).
70.1%
With 18-crown-6 ether; copper; potassium carbonate; In 1,2-dichloro-benzene; for 18h;Inert atmosphere; Reflux;
Freshly distilled aniline (4.84 g, 52.0 mmol), p-iodoanisole (30.4 g, 130.0 mmol), powdered anhydrous potassium carbonate (57.5 g, 416.0 mmol), electrolytic copper powder (13.3 g, 208.0 mmol), and 18-crown-6 (2.75 g, 10.4 mmol) were added to a dry, three necked round bottom flask under nitrogen. The mixture was refluxed in 100 mL o-dichlorobenzene 18 h (during which time some solvent evaporated). Ethyl acetate (250 mL) was added to the reaction flask. The resulting mixture was filtered to remove copper and organic salts and the solvent was removed under reduced pressure. The product was purified by washing with methanol to yield a tan solid (11.2 g, 70.1%).
65.6%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide; In toluene; for 12h;Inert atmosphere; Reflux;
4-iodoanisole (7.20 g, 30.76 mmol) and aniline (1.14 mL, 12.49 mmol) were dissolved in a round-bottom flask in 50 mL toluene, and o-phenanthroline (0.45 g, 2.30 mmol), cuprous iodide (0.48 g, 2.52 mmol) and potassium hydroxide (5.60 g, 100.00 mmol) were added to the solution. The mixture was refluxed under N2 atmosphere for 12 h and then treated according to previous literature to obtain the compound 1 as a white solid (2.50 g). Yield: 65.6%. 17
49.2%
With copper(l) iodide; 1,10-Phenanthroline; potassium tert-butylate; In 5,5-dimethyl-1,3-cyclohexadiene; at 130℃; for 24h;Inert atmosphere;
Use a 50 mL two-port bottle as the reaction vessel.The reaction device is subjected to anhydrous treatment,The reflux reaction was protected by argon.Add p-iodoanisole (5.149 g, 22 mmol, 2.0 eq) to a two-necked vial.Potassium tert-butoxide (about 6 g, 60 mmol, 6.0 eq),CuI (400 mg, 2.1 mmol, 0.21 eq),1,10-phenanthroline (400 mg, 2.0 mmol, 0.2 eq), ventilated,Add xylene (25 ml) with a syringe under stirring.Add with a syringeAniline (931 mg, 0.93 mL, 10 mmol, 1.0 eq).The mixture was stirred at 130 C for 24 h in an oil bath.The reaction was monitored by TLC.Extract a small amount of ethyl acetate and water for 5 times with a separatory funnel.Pour the organic phase into a round bottom flask and spin dry.Add silica gel and mix.After being stirred evenly, it was separated by column chromatography (petroleum ether/ethyl acetate = 50/1: v/v).The product obtained has a mass of 1.5 g.The theoretical yield is 3.05g,The yield was 49.2%.
32%
An oven dried Schlenk flask was charged with o-xylene (30 mL) and the solvent degassed. To this solution, 4-iodoanisole (15.00 g, 64.1 mmol), CuCl (0.201 g, 2.03 mmol), 1,10-phenanthroline (0.274 g, 1.5 mmol) and aniline (2.78 mL, 30.5 mmol) were added, the mixture was heated at reflux for 35 min, KOH (13.70 g, 244 mmol) was added and the mixture heated at reflux for 28 h, cooled, poured into H2O (150 mL) and extracted with CH2Cl2 (3 * 60 mL). The organic layers were combined and dried over MgSO4, filtered and the solvent removed in vacuo. The residue was suspended in hexane and purified by silica column chromatography eluting with hexane increasing to hexane:CH2Cl2 (50:50), removal of the solvent and crystallisation from hot hexane gives the title compound as a white solid. Yield 3.29 g, 32%. 1H NMR (400 MHz, CDCl3) delta 7.16 (d, J = 7 Hz, 2H), 7.05 (d, J = 9 Hz, 4H), 6.94 (d, J = 7 Hz, 2H), 6.90-6.85 (m, 1H), 6.82 (d, J = 9 Hz, 4H), 3.80 (s, 6H). Literature: [47] 1H NMR (CDCl3): delta = 7.25-6.79 (m, 13H, Ar), 3.79 ppm (s, 6H, OCH3). ESI-MS: 305.6 [M]+.
25%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide; In toluene; at 90℃; for 60h;Inert atmosphere;
4-iodoanisole 6 (14.4 g, 62.5 mmol), 1,10-phenanthroline (0.7 g, 3.75 mmol), aniline (1.71 mL, 18.75 mmol) and dry toluene (50 mL). ) were sequentially added to a 250 mL two-necked flask. After the reaction liquid was heated to 90 C, cuprous chloride (0.371 g, 3.75 mmol) and potassium hydroxide (7 g, 0.125 mol) were rapidly added under a nitrogen atmosphere. The reaction solution was heated to reflux for 60 hours. After the reaction was stopped, acetic acid (6.8 mL, 0.12 mol) dissolved in 20 mL of toluene was added to the reaction mixture and stirred for 15 min. Subsequently, the reaction solution was extracted with dichloromethane, and washed three times with 300 mL of water and 100 mL of saturated brine. The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and then evaporated. The obtained crude product was separated on a chromatographic column using petroleum ether/ethyl acetate (50:1, v/v).Finally a yellow solid 7 was obtained with a yield of 25%.The molar ratio of 4-iodoanisole to 1,10-phenanthroline, aniline, cuprous chloride and potassium hydroxide is 1:0.06:0.3:0.06:0.002.
With copper(I) iodide; 1,7-phenanthroline; potassium hydroxide; In toluene;Inert atmosphere; Reflux;
General procedure: In a two-necked flask a mixture of aniline (3mmol), iodobenzene (7.5mmol), CuI nanoparticles (3%mol), 1,10-phenanthroline (3%mol), potassium hydroxide (1.29g, 0.024mmol) and 20mL of toluene was stirred under nitrogen atmosphere at reflux for a suitable time. The completion of the reaction was monitored by TLC with hexane as the eluent. At the end of reaction, the mixture was then cooled to room temperature and poured into distilled water. The products were extracted by CH2Cl2 and the organic layer was dried over anhydrous sodium sulfate (Na2SO4). Then the solvent was evaporated in vacuo, the products were purified by silica column chromatography using normal hexane as an eluent.
With copper phthalocyanine; sodium hydroxide; In dimethyl sulfoxide; at 100℃;
General procedure: In a 50mL RB, N-H heterocycles (1.0mmol), aryl halide (1mmol), Cu(II)Pc (0.01mmol), NaOH (1.5mmol) and DMSO (2mL) was added. This reaction mixture was stirred to a preheated oil bath at 100C for 8-12h. After completion of the reaction, it was cooled to room temperature and 20mL ethyl acetate was added. It was filtered; solid catalyst was separated and washed with 2×5mL ethyl acetate. The washing and filtrate were combined and washed with water. Ethyl acetate was removed under reduced pressure and product was purified with column chromatography.
94%
With copper(II) acetate monohydrate; caesium carbonate; In N,N-dimethyl-formamide; at 110℃; for 24h;Inert atmosphere;
General procedure: To a solution of Cu(OAc)2·H2O (0.01 mmol) in DMF (2 mL) were added aryl iodide (1.2 mmol), nitrogen-containing heterocycle (1.0 mmol), and Cs2CO3 (2 mmol) under nitrogen atmosphere. The mixture was stirred at 110 C for 24 h. After cooling to ambient temperature, the mixture was partitioned between water and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel.
93%
With copper(I) oxide; 1-(2-methylhydrazine-1-carbonyl)isoquinoline 2-oxide; tetrabutylammomium bromide; sodium hydroxide; In ethanol; water; at 120℃; for 12h;Schlenk technique;
General procedure: A 25 mL Schlenk tube was charged with Cu2O (0.05 mmol), ArX (0.5 mmol), NHR1R2 (0.75 mmol), NaOH (1 mmol), TBAB (0.1 mmol), L2 (0.1 mmol) and H2O/EtOH (1 mL, 1/1, v/v). The mixture was stirred at 120 C for 12 h. The reaction mixture was extracted with ethyl acetate (3 10 mL), washed with water and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatograph on silica gel(ethyl acetate/petroleum ether as the eluent) to provide the target products 3a-3w and 6.
84%
With copper(ll) sulfate pentahydrate; sodium hydroxide; In dimethyl sulfoxide; at 110℃; for 12h;Sealed tube;
General procedure: CuSO4·5H2O (12.50 mg, 0.05 mmol), the aryl iodide or bromide(1.0 mmol), pyrrole (1.5 mmol), NaOH (80 mg, 2 mmol), and DMSO(2 mL) were placed in a 10 mL sealed tube. The mixture was heatedat 110 C in a preheated oil bath for 12 h. It was then cooled to roomtemperature, diluted with 20 mL H2O, and the mixture was extractedwith ethyl acetate (3 × 20 mL). The combined organic phases waswashed with water and brine, dried over anhydrous Na2SO4, andconcentrated in vacuo. The residue was purified by flash columnchromatography on silica gel (ethyl acetate/petroleum ether, 1 : 100)to afford the target products. All C-N coupling products reported hereare known products and were characterised by GC-MS and 1H NMR,which were compared with the previously reported dates.
75%
With copper(I) oxide; caesium carbonate; N-phenyl-2-pyridincarboxamide-1-oxide; In dimethyl sulfoxide; at 120℃; for 20h;Inert atmosphere;
General procedure: In 50 mL round bottom flask, aryl halide (1.0 mmol), pyrazole (1.2 mmol), ligand (0.04 mmol), Cu2O (0.10 mmol), cesium carbonate (2.0 mmol), and dry solvent (20 mL) were placed under nitrogen atmosphere. The reaction mixture was heated in oil bath up to specified temperature under constant stirring for 20 h and then allowed to cool to room temperature. The reaction mixture was filtered through a plug of Celite in a fritted filter funnel and washed with ethyl acetate. If DMSO is used as solvent, it is extracted by washing the filtrate with 25 mL water for three times. The organic phase was dried over anhydrous MgSO4 and was removed under reduced pressure to provide the crude product which was purified by column chromatography on silica gel, using hexane and ethyl acetate in 3:1 ratio, respectively, as an eluent.
74%
With 2-(2-tert-butylhydrazinecarbonyl)pyridine-1-oxide; tetrabutylammomium bromide; copper; potassium hydroxide; In water; at 120℃; for 12h;Sealed tube; Green chemistry;
Cu (0.05 mmol), L4 (0.1 mmol), aryl halides(0.5 mmol), imidazoles (0.75 mmol), KOH (1 mmol), TBAB (0.15 mol), and H2O(1 mL) were added to a 10 mL sealed tube. The reaction mixture was reacted at120 C in a pre-heated oil bath for 12 h. The reaction mixture was cooled to room temperature, diluted with 10 mL H2O, and then the mixture was extracted with ethyl acetate (3 20 mL). The combined organic phases were washed withwater and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatograph on silica gel (ethyl acetate/petroleum ether, 2:1 to pure ethyl acetate) to afford the target products.
73%
With caesium carbonate; at 135℃; for 4h;
General procedure: A mixture of pyrrole (3 ml), Cs2CO3 (1.96 g, 6 mmol), Cu0/4A or Cu2+/4A (0.3 g) and the appropriate aryl halide (3 mmol) were stirred at 135 C (bath temperature) for 4-36 h. Before adding to the mixture, Cu2+/4A was preheated at ca. 150 C for 1 h. The mixture was filtered, the solid was washed with dichloromethane. The filtrate was extracted with deionised water (2 x 40 ml). The organic phase was dried over Na2SO4 and concentrated in vacuum. The residue was distilled and clarified. Certain products (3c, 3f) were purified by recrystallization from MeOH.
63%
With copper(II) acetate monohydrate; caesium carbonate; In N,N-dimethyl-formamide; at 20 - 110℃; for 24h;Inert atmosphere; Schlenk technique;
General procedure: An oven-dried Schlenk tube was charged with Cu(OAc)2·H2O (0.1 mmol, 0.01 equiv), Cs2CO3(20 mmol, 2 equiv), and aryl iodide (if solid, 12 mmol, 1.2 equiv). The tube was degassed with argon for three times. Then DMF (20 mL), pyrrole (10 mmol, 1 equiv), and aryl iodide (if liquid,12 mmol, 1.2 equiv) were added via syringe under room temperature. The mixture was stirred at110 C for 24 h, and then cooled down to room temperature. The reaction mixture was quenched with water (40 mL) and extracted with ethyl ether (20 mL) for three times. The combined organic layers were dried with Na2SO4, filtered and concentrated. The crude products were purified using flash column chromatography on silica gel to afford the desired product.
46%
With copper; caesium carbonate; In acetonitrile; for 72h;Inert atmosphere; Reflux;
General procedure: To azole (6.0 mmol) and aryl halide (4.0 mmol) in acetonitrile (20 mL) were successively added Cu (50 mg, 0.80 mmol), Cs2CO3 (2.6 g, 8.0 mmol) and, in the case of aryl bromides, KI (99 mg, 6.0 mmol). The mixture was stirred under argon at acetonitrile reflux temperature (the reaction time is given in the product description) before dilution with AcOEt (40 mL) and filtration. Concentration under reduced pressure and purification by chromatography on silica gel (the eluent is given in the product description) led to the expected compounds.
44%
With copper(I) oxide; potassium phosphate; tetrabutylammomium bromide; In water; at 130℃; for 24h;Closed system;
General procedure for N-arylation of amines:The N-nucleophile (1.47 mmol), Cu2O (Sigma-Aldrich, 99.99% purity, 0.147 mmol), K3PO4 (2.94 mmol), the aryl halide (1.76 mmol), phase transfer catalyst (0.147 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 130 C for 24 h, then the heterogeneous mixture was cooled to RT and diluted with dichloromethane. The resulting solution was directly filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of all products was confirmed by 1H and 13C NMR spectroscopic analysis.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 100℃;
A mixture of 1.4 g (7.13 mmol) 5-chlorobenzofuranboronic acid, 1.24 g (5.30 mmol) 4-iodoanisole, 150 mg Pd(PPh3)4, 7.1 ml 1M aqueous sodium carbonate solution, and 25 ml 1,2-dimethoxyethane were heated in a sealed tube at 100 C. under argon overnight. It was cooled to room temperature and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. 600 mg of the title benzofuran were obtained by crystallization from ethyl acetate and another 250 mg were obtained from the mother liquid after chromatography on silica gel with hexane. [0327] total yield: 850 mg (62%)
Step B: 5-Chloro-2-(4-methoxyphenyl)benzofuran (X=4-OCH3) A mixture of 1.4 g (7.13 mmol) 5-chlorobenzofuranboronic acid, 1.24 g (5.30 mmol) 4-iodoanisole, 150 mg Pd(PPh3)4, 7.1 ml 1M aqueous sodium carbonate solution, and 25 ml 1,2-dimethoxyethane were heated in a sealed tube at 100 C. under argon overnight. It was cooled to room temperature and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. 600 mg of the title benzofuran were obtained by crystallization from ethyl acetate and another 250 mg were obtained from the mother liquid after chromatography on silica gel with hexane. total yield: 850 mg (62%) The following compounds or Preparations 41-44 were prepared essentially in the same manner by Suzuki coupling reaction with the corresponding iodobenzenes:
With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 110℃; for 24h;
General procedure: to a stirred solution of iodo benzene (1.0 mmol) and trans-4-hydroxy-L-proline (2.0 equiv) in dry DMSO (3.0 mL) at rt was added CuI (20 mol percent) followed by Cs2CO3 (2.5 equiv) and heated at 110 °C for 24 h. The progress of the reaction was monitored by TLC. After the reaction was complete, the reaction mixture was allowed to cool, and a 1:1 mixture of ethyl acetate/water (20 mL) was added. The combined organic extracts were dried with anhydrous Na2SO4. The solvent and volatiles were completely removed under vacuum to give the crude product, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 9:1) to afford the corresponding coupling product.
With N-Bromosuccinimide; silver nitrate; In acetonitrile; for 5h;Reflux;
General procedure: To a stirred mixture of CH3CN (5 mL) and NBS (1.0 mmol, 0.177 g) at reflux, was added AgNO3 (1.0 mmol, 0.169 g). N,N-Dimethylaniline (1 mmol, 0.126 mL) was then added to the mixture. After 3 h, the mixture was filtered to remove AgBr. The solvent was evaporated and the residue dissolved in CH2Cl2 (10 mL) and washed with aqueous 4% NaHCO3 (2 × 5 mL) to remove N-hydroxysuccinimide from the organic phase. The aqueous phase was separated and the organic phase dried and concentrated. The residue was subjected to column chromatography over silica gel using n-hexane/EtOAc (4:1) as eluent to give 4-nitro- and 2-nitro-N,N-dimethylaniline in 69% and 16% yields, respectively.
75%
With iodine; silver nitrate; chloro-diphenylphosphine; In dichloromethane; at 20℃; for 4h;
In a typical experiment: to a flask containing a stirred mixture of Ph2PCl (1.1 mmol, 0.202 mL) and I2 (1.1 mmol, 0.279 g) in CH2Cl2 (5 mL), was added silver nitrate (2.2 mmol, 0.373 g) at room temperature. N,N-Dimethylaniline (2.0 mmol, 0.252 mL) was then added to the reaction mixture. After 10 min, the mixture was filtered to remove precipitated AgCl and AgI. The residue was washed with saturated aqueous Na2CO3 (3 × 5 mL) until all the diphenylphosphinic acid was removed from the organic phase. The aqueous phase was separated and the organic phase washed with aqueous Na2S2O3 (2 × 5 mL) to remove the excess I2 and then H2O (5 mL), dried, and concentrated. Column chromatography of the residue was performed on silica gel using n-hexane/EtOAc (4:1) as eluent to give pure 2-nitro- and 4-nitro-N,N-dimethylanilines in 15% and 77% yields, respectively.
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide; In toluene; at 110℃; for 12h;
In a 100 mL three-necked flask, 40 mL of toluene, 1.72 g of 4-bromoaniline and4.68g 4-iodoanisole is mixed,And add 1.7g of potassium hydroxide to the solution,Add 0.19g of cuprous iodide and 0.18g of 1,10-phenanthroline,The mixture was stirred at 110 C and refluxed for 12 h. After cooling to room temperature, the crude product was diluted with CH 2Cl 2, and washed with 1M HCl solution and saturated NaCl solution, and dried over anhydrous MgSO4. (3) a compound, wherein the eluent comprises petroleum ether and methylene chloride in a volume ratio of 20/1 to 5/1, the compound of the formula (3) is a white solid, the yield is 3.2 g, and the yield is 84%;
78%
With 1,10-Phenanthroline; copper(l) chloride; potassium hydroxide; In toluene; for 20h;Inert atmosphere; Reflux;
To a 100 mL three-necked flask was added p-iodoanisole (1.1 g, 4.8 mmol) in this order,P-bromoaniline (0.34 g, 2.0 mmol),Potassium hydroxide (0.56 g, 10 mmol),1,10-phenanthroline (0.03 g, 0.16 mmol) and 60 mL of toluene,Fitted with a reflux condenser,Vacuum,Replace argon protection.Under argon flow,A catalytic amount of cuprous chloride was quickly added,The reaction was heated to reflux for 20 h.After TLC detection of raw materials reaction finished,The reaction was stopped,The solvent was distilled off under reduced pressure,The reaction mixture was dissolved in 100 mL of dichloromethane,And further washed three times with saturated brine (80 mL x 3)The organic phase was dried over anhydrous sodium sulfate overnight.The filtrate was collected by filtration,The solvent was removed under reduced pressure,The crude product was purified by column chromatography on silica gel (200-300 mesh [eluent,V (petroleum ether): V (ethyl acetate) = 8: 1] to give Intermediate 6 (0.60 g) as a pale yellow solid,Yield 78%.
70.4%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide; In toluene; at 110 - 135℃; for 12h;Inert atmosphere;
A mixture of 1-iodo-4-methoxybenzene (10.00 g, 42.74 mmol), 4-bromobenzenamine (2.95 g, 17.15 mmol) and 1,10-phenanthroline anhydrous (0.62 g, 3.42 mmol) in toluene (60 mL) was heated and stirred under nitrogen atmosphere. When the temperature reached to 110 C, the CuI (0.65 g, 3.42 mmol) and KOH (7.66 g, 136.79 mmol) were added quickly, and then the mixture was stirred at 135 C for 12 h. After cooled to RT, the mixture was poured into distilled water (50 mL) and extracted with dichloromethane (DCM) (3 * 30 mL). The combined organic layer was dried over MgSO4 for 2 h and filtrated. The filtrate was concentrated by rotary evaporator under reduced pressure. The residue was purified by silica gel column chromatography using DCM/petroleum ether (PE) (1/5, V/V) as eluent to gain lyard powder (4.63 g, 70.4%). 1H NMR (400 MHz, CDCl3, ppm): 7.25 (d, J = 4.0 Hz, 2H), 7.04 (d, J = 8.4 Hz, 4H), 6.83 (d, J = 8.2 Hz, 6H), 3.79 (s, 6H).
70.4%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide; In toluene; at 110 - 135℃; for 12h;Inert atmosphere;
In a 100 mL three-necked flask, 4-methoxyiodobenzene (10.0 g, 42.74 mmol) and p-bromoaniline (2.9 g,17.15 mmol), anhydrous 1,10-phenanthroline (0.6 g, 3.42 mmol) and 60 mL of toluene were added and the temperature was raised to 110 C under the protection of nitrogen.Copper iodide (0.7 g, 3.42 mmol) and potassium hydroxide (7.7 g, 136.79 mmol) were added rapidly and the reaction was further allowed to warm to 135 C and the reaction was stirred for 12 h. After cooling to room temperature, the reaction mixture was poured into 50 mL of distilled water and extracted with CH 2 Cl 2 (3 × 30 mL). The extract was washed with water, dried over anhydrous MgSO 4 and the solvent was removed under reduced pressure. The crude product was washed with CH 2 Cl 2: PE = 1: 5 V) as eluent, and separated by column chromatography to give 4.63 g of an off-white solid in a yield of 70.4%.
66%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide; In toluene; at 112℃; for 12h;Inert atmosphere; Schlenk technique;
KOH (2.8 g, 50 mmol) and CuI (0.1 g, 0.5 mmol) were added to a stirred toluene solutionof p-iodoaniline (2.92 g, 12.5 mmol), p-bromoaniline 3a (009 g, 0.50 mmol) and1,10-phenanthroline (18 mg, 0.1 mmol) under an argon atmosphere. The mixture wasstirred at 125 C for 12 h. Chromatography on silica gel (CH2Cl2/petroleum ether 1/1)gave 3e as a light-yellow powder. Yield: 1.27 g, 66%. 1H NMR (500 MHz, CDCl3), d(ppm): 3.79 (s, 6H, OMe), 6.79 (d, J(HH)10.0 Hz, 2 H), 6.81 (t, J(HH)5.0 Hz, 2 H), 6.83(t, J(HH)5.0 Hz, 2 H), 7.03 (d, J(HH)10.0 Hz, 4 H), 7.24 (t, J(HH) 10.0 Hz, 2 H).
62.2%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide; In toluene; at 125℃; for 24h;Inert atmosphere;
To a stirred solution of 4-iodoanisole (5.85 g, 25 mmol), 4-bromoaniline (1.72 g, 10 mmol), and 1,10-phenanthroline (0.18 g, 1 mmol) in toluene (100 mL) were added potassium hydroxide (5.61 g, 100 mmol) and copper(I) iodide (0.19 g, 1 mmol). The reaction mixture was heated under reflux for 24 h at 125 C. The crude product was extracted into dichloromethane, and the organic layer was washed with 1 N HCl solution, brine, and water. The organic layer was dried with anhydrous MgSO4 and then the solvent was removed in vacuo. The residue was purified by column chromatography using silica gel and dichloromethane-hexane (1:1; v/v) as the eluent to give 3 (2.39 g, 62.2%). 1H NMR (500 MHz, d6-DMSO, ppm): delta 7.31 (d, J = 9.0 Hz, 2H), 7.04-7.02 (m, 4H), 6.93-6.91 (m, 4H), 6.67 (d, J = 9.0 Hz, 2H), 3.74 (s, -OCH3 * 2, 6H). 13C NMR (126 MHz, CDCl3, ppm): delta 156.0, 147.9, 140.6, 131.7, 127.7, 126.5, 121.9, 114.8, 114.2, 112.4, 55.5. HRMS (m/z): calcd. for (C20H18BrNO2): 383.0520, found: 383.0516 [EI+]. Anal. Cald for (C20H18BrNO2): C, 62.51; H, 4.72; N, 3.65. Found: C, 62.39; H, 4.70; N, 3.52.
53.8%
With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide; In toluene; at 110℃; for 48h;Inert atmosphere;
Add 5.00 g of p-bromoaniline, 14.4 g of p-iodoanisole, 0.28 g of CuI, 12.8 g of KOH, and 0.26 g of 1,10-phenanthroline to a 250 mL two-necked flask. Nitrogen was three times, then 60 mL of anhydrous oxygen-free toluene was added and stirred at 110 C. for 48 hours. After the reaction is completed, it is cooled to room temperature, filtered directly, and the filter residue is washed three times with dichloromethane.The filtrate was then spin-dried under reduced pressure. The resulting crude product was subjected to column chromatography using petroleum ether and dichloromethane in a volume ratio of 3:1 as eluent to obtain 6.02 g of a yellow solid 3 with a yield of 53.8%.
With 1,10-Phenanthroline; copper(l) chloride; potassium hydroxide; In para-xylene; at 160℃; for 40h;Inert atmosphere;
The Ullmann type condensation reaction was performed under an argon atmosphere, in alarge round bottom flask (250 mL) equipped with a condenser protected from light. p-Bromoaniline (4.9 g, 28.6 mmol, 1 equiv), CuCl (280.1 mg, 10 mol%), 1,10-phenanthroline.H2O (557.0 mg,10 mol%) and KOH (8.0 g, 143.0 mmol, 2.5 equiv) were successively added to a degassed solution of piodoanisole(16.0 g, 68.4 mmol, 2.4 equiv) in p-xylene (75 mL). The reaction medium was stirred at 160 C for40 h. Water was then added at rt and a solution of concentrated HCl was used to neutralize the black reactionmedium. Extractions with CH2Cl2 were performed. The organic layers were combined and washed withwater, dried with brine and over Na2SO4. Purification on an alumina column chromatography usingpetroleum ether/CH2Cl2 (90/10) as eluent afforded a brownish ochre solid.
2-(4'-methoxybiphenyl-2-yl)-1-methyl-1H-benzoimidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
96%
With [ruthenium(II)(eta6-1-methyl-4-isopropyl-benzene)(chloride)(mu-chloride)]2; potassium carbonate; triphenylphosphine; In benzene; at 150℃; for 24h;Sealed tube;
General procedure: In a 30-mL sealed tube, <strong>[2622-63-1]1-methyl-2-phenylbenzimidazole</strong> (1, 0.25mmol), [RuCl2(p-cymene)]2 (0.0125 mmol), Ph3P (0.075 mmol),K2CO3 (0.50 mmol), and iodoarene (0.25 mmol) were combined inanhydrous benzene (2 mL) under air. The mixture was then stirredat 150 °C for 24 h. The mixture was cooled to r.t., diluted with EtOAc, and filtered through a small pad of Celite. The filtrate was concentrated in vacuo and purified by flash chromatography (silicagel, EtOAc?hexane) to give the analytically pure 2-(biphenyl-2-yl)benzimidazoles. 2-(4?-Methoxybiphenyl-2-yl)-1-methyl-1H-benzoimidazole (2a) Pale yellow oil; yield: 76 mg (96percent); Rf = 0.26 (hexane?acetone,3:1).1H NMR (400 MHz, CDCl3): delta = 7.85 (d, J = 7.8 Hz, 1 H, HAr), 7.71(d, J = 7.6 Hz, 1 H, HAr), 7.50?7.62 (m, 2 H, HAr), 7.47 (t, J = 7.3Hz, 1 H, HAr), 7.20?7.35 (m, 2 H, HAr), 7.17 (d, J = 7.6 Hz, 1 H,HAr), 7.13 (d, J = 8.8 Hz, 2 H, HAr), 6.73 (d, J = 8.8 Hz, 2 H, HAr),3.73 (s, 3 H, OMe), 3.02 (s, 3 H, NMe).13C NMR (100 Hz, CDCl3): delta = 158.8, 154.1, 143.1, 141.2, 135.5,132.5, 132.1, 130.3, 129.7 (2 CAr), 129.6, 128.7, 127.1, 122.3,122.0, 119.7, 114.0 (2 CAr), 109.5, 55.1 (OMe), 30.2 (NMe).HRMS (FAB): m/z [M + H]+ calcd for C21H19ON2: 315.1497; found: 315.1507.
2-(4'-methoxybiphenyl-2-yl)-1-methyl-1H-benzoimidazole[ No CAS ]
C28H24N2O2[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73%; 20%
With [ruthenium(II)(eta6-1-methyl-4-isopropyl-benzene)(chloride)(mu-chloride)]2; mesitylenecarboxylic acid; potassium carbonate; In toluene; at 150℃; for 24h;Sealed tube;
General procedure: In a 30-mL sealed tube, <strong>[2622-63-1]1-methyl-2-phenylbenzimidazole</strong> (1, 0.25mmol), [RuCl2(p-cymene)]2 (0.0125 mmol), Ph3P (0.075 mmol),K2CO3 (0.50 mmol), and iodoarene (0.25 mmol) were combined inanhydrous benzene (2 mL) under air. The mixture was then stirredat 150 °C for 24 h. The mixture was cooled to r.t., diluted with EtOAc, and filtered through a small pad of Celite. The filtrate was concentrated in vacuo and purified by flash chromatography (silicagel, EtOAc?hexane) to give the analytically pure 2-(biphenyl-2-yl)benzimidazoles.
3-(N-methyl-4-methoxyphenylamino)propane-1,2-diol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
32%
With copper; for 4h;
General procedure: Iodobenzene (1 mmol), ethanolamine (3 mmol), KOH (3.7 mmol) and Cu0 powder (1 mmol, 63 mg) werestirred for different times (15 min, 25 min, 30 min, 1 hr, 2 hrs, 3 hrs, 4 hrs, 1 day, 2 days). The crudeproduct was dissolved in CH2Cl2 (2 mL) and filtered on Buechner funnel with a sintered glass disc usingCH2Cl2. The solvent was evaporated in vacuum, the crude product was dried and analyzed by GC-MS. Themixture was purified by flash chromatography on silica gel (CH2Cl2-methanol-ammonia) to afford thedesired product. The pure product was analyzed by 1H, 13C NMR spectroscopy and MALDI-TOF massspectrometry after dissolution in an appropriate solvent. Milling was accomplished at 650 rpmfor 4 hours, without Al2O3 and KOH.1H NMR (300 MHz, CDCl3): delta 6.85 (4 H, m), 3.95 (1 H, m), 3.76(4 H, m), 3.58-3.52 (1H, dd, J=6 Hz ), 3.29-3.26 (1 H, m), 3.16 (1 H, m), 2.87 (3 H, s) ppm; 13C NMR (75MHz, CDCl3): delta 153.28, 144.64, 116.69, 114.57, 68.89, 64.20, 57.78, 55.62, 40.51 ppm. m/z (MALDI-TOFMS): calcd for C11H17NO3 [M + H]+: 212.1256, found: 212.1264.
General procedure: To a solution of the 2-Iodo-5-methoxyphenol (1mmol, 252mg) and the 4-Ethynylanisole (1.2 equiv., 166mg) in dry THF (1.6mL, 0.6M of the Iodophenol), at 0C under N2, was added CH3MgBr (THF solution, 2.3M, 2 equiv., 0.792mL) dropwise. The mixture was allowed to warm to room temperature, and Pd(Ph3P)2Cl (3mol%, 21.3mg) was added before the mixture was heated to 65C for 2h under N2. The reaction mixture was then cooled to room temperature and the THF was removed under reduced pressure. DMSO (2mL) was added to the residue followed by addition of 2-Fluoro-4-iodopyridine (1.2 equiv., 269.7mg) and the mixture was heated to 80C for 4h under N2. The mixture was cooled to room temperature and diluted with EtOAc, washed with H2O and brine. The organic phase was dried over Na2SO4, concentrated and purified on silica followed by preparative HPLC (25?100% B over 25min).
General procedure: To a solution of the 2-Iodo-5-methoxyphenol (1mmol, 252mg) and the 4-Ethynylanisole (1.2 equiv., 166mg) in dry THF (1.6mL, 0.6M of the Iodophenol), at 0C under N2, was added CH3MgBr (THF solution, 2.3M, 2 equiv., 0.792mL) dropwise. The mixture was allowed to warm to room temperature, and Pd(Ph3P)2Cl (3mol%, 21.3mg) was added before the mixture was heated to 65C for 2h under N2. The reaction mixture was then cooled to room temperature and the THF was removed under reduced pressure. DMSO (2mL) was added to the residue followed by addition of 2-Fluoro-4-iodopyridine (1.2 equiv., 269.7mg) and the mixture was heated to 80C for 4h under N2. The mixture was cooled to room temperature and diluted with EtOAc, washed with H2O and brine. The organic phase was dried over Na2SO4, concentrated and purified on silica followed by preparative HPLC (25?100% B over 25min).
6-bromo-2-N,N-bis(4-methoxyphenyl)aminonaphthalene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
With copper(l) iodide; 1,10-Phenanthroline; sodium t-butanolate; In toluene; at 120℃; for 48h;Inert atmosphere;
The reaction equation is as follows: Paraiodoanisole (15 g, 0.064 mol) and 6-bromo-2-naphthylamine (3.3 g, 0.015 mol) were dissolved in 120 ml of anhydrous toluene.Add CuI (0.89 g, 4.67 mmol) rapidly under nitrogen atmosphere.1,10-phenanthroline (1.232 g, 6.83 mmol) and sodium tert-butoxide (7 g, 75 mmol) were heated to 120C.After about 48 hours of reaction, the toluene is concentrated and removed.Simultaneously added dichloromethane and distilled water extraction (the volume ratio of dichloromethane and distilled water is 1:1),The organic layer was dried over anhydrous magnesium sulfate.filter,After decompression, concentratePurification by column chromatography (column chromatography with petroleum ether and various volumes of petroleum ether and dichloromethane,The first developing agent was petroleum ether.Subsequent developing agents are petroleum ether and dichloromethane in different volume ratios.The volume of methylene chloride increases sequentially;Finally, develop the petroleum ether in the agent:Dichloromethane = 4:1 (v:v)),A pale yellow solid, Compound 1, was obtained.The yield is about 88% (5.8g);
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 120℃; under 7500.75 Torr; for 20h;Inert atmosphere; Autoclave;
General procedure: A 12mL vial was charged with MCM-41-2P-Pd(OAc)2 (2molpercent), 2-aminobenzamide (1mmol), aryl iodide (1mmol) (if solid) and a stirring bar. Then, DMF (2mL), aryl iodide (1mmol) (if liquid) and DBU (2mmol) were injected by syringe under an argon atmosphere. The vial was placed in an alloy plate, which was transferred into a 300mL Parr Instruments 4560 series autoclave under an argon atmosphere. After flushing the autoclave three times with CO, a pressure of 10bar CO was fixed at ambient temperature. The autoclave was heated for 20hat 120°C. After completion of the reaction, the autoclave was cooled to room temperature and the pressure was released carefully. The reaction mixture was diluted with ethyl acetate (10mL) and filtered. The palladium catalyst was washed with distilled water (2×5mL) and acetone (2×5mL), and reused in the next run. The filtrate was concentrated in vacuo and the pure product was isolated by either washed with water, ethyl acetate and finally hexane or recrystallization from MeOH.
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 120℃; under 7500.75 Torr; for 20h;Inert atmosphere; Autoclave;
General procedure: A 12mL vial was charged with MCM-41-2P-Pd(OAc)2 (2molpercent), 2-aminobenzamide (1mmol), aryl iodide (1mmol) (if solid) and a stirring bar. Then, DMF (2mL), aryl iodide (1mmol) (if liquid) and DBU (2mmol) were injected by syringe under an argon atmosphere. The vial was placed in an alloy plate, which was transferred into a 300mL Parr Instruments 4560 series autoclave under an argon atmosphere. After flushing the autoclave three times with CO, a pressure of 10bar CO was fixed at ambient temperature. The autoclave was heated for 20hat 120°C. After completion of the reaction, the autoclave was cooled to room temperature and the pressure was released carefully. The reaction mixture was diluted with ethyl acetate (10mL) and filtered. The palladium catalyst was washed with distilled water (2×5mL) and acetone (2×5mL), and reused in the next run. The filtrate was concentrated in vacuo and the pure product was isolated by either washed with water, ethyl acetate and finally hexane or recrystallization from MeOH.
5-amino-2-(4-methoxyphenyl)isoindolin-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
51.54%
With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In dimethyl sulfoxide; at 20 - 120℃;
General procedure: Isoindolin-1-one (200 mg, 1.50mmol) was dissolved in super-dry DMSO (4 mL), and Cs2CO3 (1215 mg, 3.75 mmol), CuI (58 mg, 0.30mmol) and N1,N2-dimethylethane-1,2-diamine (27 mg, 33 muL, 0.30 mmol) were added to the solution.The resulting mixture was stirred at room temperature for 10 min, after which iodobenzene (2.25mmol) was added. Then the mixture was heated to 120 C. When TLC showed that isoindolin-1-onehad been fully converted, the reaction was stopped. The mixture was extracted with ethyl acetate (20mL) and H2O (10 mL). The water phase was re-extracted with ethyl acetate (20 mL). The organic layerwas combined and washed with brine (10 mL). Then the solution was dried over anhydrous MgSO4,filtered and concentrated, and the crude residue was purified by flash chromatography over silica gelusing CH2Cl2/CH3OH as the gradient elution to afford the title compounds.
9-methyl-8-(p-methoxyphenyl)-2,6-dichloropurine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With copper(l) iodide; palladium diacetate; caesium carbonate; In N,N-dimethyl-formamide; at 160℃; for 60h;Inert atmosphere;
Compound 2 (0.404 g, 2 mmol), Pd(OAc) 2 (0.022 g, 0.1 mmol),CuI (1.142 g, 6 mmol), p-iodoanisole (0.936 g, 4 mmol) and Cs2CO3 (1.630 g, 5 mmol) were added to a 100 ml two-necked flask.20 ml of DMF was added under a nitrogen atmosphere, and the reaction was carried out at 160 C for 60 hours.After the reaction was completed, the reaction system was cooled to room temperature, and then 150 ml of dichloromethane was added thereto in three portions for extraction.The organic phases were combined and the organic phase was washed with water and a saturated NaCl solution, respectively.The organic phase was dried over anhydrous MgSO Purification by column chromatography gave the brownish yellow crystalline compound 3.
With trifluorormethanesulfonic acid; palladium diacetate; silver trifluoroacetate; acetic acid; glycine; at 100℃; for 24h;Sealed tube;
General procedure: A sealed tube with magnetic stir bar was charged with substrate 1 (0.24 mmol), glycine (0.1 mmol, 7.5 mg), Pd(OAc)2 (0.02 mmol, 4.45 mg), AgTFA (0.24 mmol, 53.01 mg) and 2 (0.2 mmol) under air. After addition of AcOH (2 mL) as solvent, TfOH (0.1 mmol, 15.0 mg) was added. The reaction mixture was allowed to stir at 100 C for 24 hours. Upon completion, the reaction mixture was cooled to room temperature, diluted with DCM, and then extracted with saturated NaHCO3 aqueous solution. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The crude residue was purified by column chromatography on silica gel using PE as the eluent to afford the desired products.