* 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.
With cobalt(II) chloride; lithium iodide; isoprene In tetrahydrofuran at -78 - 50℃; for 5 h; Inert atmosphere
General procedure: Coupling of Alkyl Halides with t-BuMgCl; Procedure 1 (P1)An alkyl halide (1.0 mmol), decane (63 mg as an internal standard)and LiI (5.3 mg, 0.04 mmol) were added to a dry, nitrogen-flushedtest tube equipped with a rubber septum and a magnetic stir bar.THF (0.8 mL) was added and the solution was cooled to –78 °C usinga dry ice/EtOH bath. t-BuMgCl (2a) (1.5 mL, 0.81 M in THF,1.2 mmol) was added slowly followed by isoprene (136.2 mg, 2.0mmol). To this mixture was added CoCl2 [2.6 mg, 0.02 mmol, as apowder or as a THF solution (0.5 mL, 0.04 M)]. (Note 1: CoCl2should be added after isoprene, otherwise the catalytic performancedecreases significantly). The cold bath was removed and the mixturewas warmed to r.t. (ca. over 10 min), and then heated for 5 h bysuspending the reaction vessel in an oil bath kept at 50 °C. (Note 2:when the reaction mixture was heated at 30 °C during this stage, unidentifiedside reactions occurred resulting in low yields of couplingproducts). The resulting mixture was cooled to 0 °C in an ice bathand the reaction was quenched with aq HCl (5 mL, 1 M). The productwas extracted with Et2O (3 × 20 mL). The combined organiclayer dried over Na2SO4, concentrated and analyzed by gas chromatographyto determine the GC yield. The residue was purified by silicagel column chromatography or by GPC. 1.0 mmol) and n-BuMgCl (2j) (1.0 M in THF, 1.2 mmol) were reactedunder standard conditions.Yield: 94percent (determined by GC using decane as an internal standard).
Reference：
[1] Journal of the American Chemical Society, 2002, vol. 124, # 16, p. 4222 - 4223
[2] Journal of the American Chemical Society, 2013, vol. 135, # 26, p. 9604 - 9607
[3] Synthesis (Germany), 2014, vol. 46, # 12, p. 1583 - 1592
[4] Journal of Organic Chemistry, 2014, vol. 79, # 18, p. 8522 - 8532
2
[ 7295-46-7 ]
[ 23703-22-2 ]
Yield
Reaction Conditions
Operation in experiment
45%
With potassium hydroxide; hydrazine In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol for 2 h; Heating / reflux
Compound (1) (159 g, 0.51 mol) , hydrazine hydrate (70 mL) and KOH (114.46 g, 2.04 mol) were dissolved in triethylene glycol (700 mL) , and the solution was heated under reflux for 2 hours . The reaction temperature was lowered to room temperature, and water and HCl were added to the reaction mixture. After extraction with CH2Cl2, the organic layer was washed with water and dried over anhydrous MgSO4. After filtering off MgSO4 by using a filter paper, the filtrate was evaporated by using a rotary evaporator to remove the solvent. Purification by column chromatography (eluent: n-hexane) gave colorless liquid.4-Bromohexylbenzene (2a): 1H NMR (CDCl3, 300 MHz): δ 7.45- 7.42 (d, 2H, J=8.33 Hz), 7.11-7.08 ppm (d, 2H, J=8.32 Hz), 2.63-2.58 ppm (t, 2H, J=I.69 Hz), 1.67-1.62 ppm (m, 2H), 1.40- 1.35 ppm (m, 6H), 0.97-0.93 ppm (t, 3H, J=6.60 Hz).
Reference：
[1] Bulletin of the Korean Chemical Society, 2012, vol. 33, # 2, p. 541 - 548
[2] Patent: WO2008/120839, 2008, A1, . Location in patent: Page/Page column 34
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 2233 - 2237
5
[ 693-25-4 ]
[ 23703-22-2 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 2233 - 2237
6
[ 71434-62-3 ]
[ 23703-22-2 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 2233 - 2237
7
[ 1122-91-4 ]
[ 23703-22-2 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 2233 - 2237
8
[ 108-86-1 ]
[ 23703-22-2 ]
Reference：
[1] Bulletin of the Korean Chemical Society, 2012, vol. 33, # 2, p. 541 - 548
[2] Patent: WO2008/120839, 2008, A1,
9
[ 142-61-0 ]
[ 23703-22-2 ]
Reference：
[1] Bulletin of the Korean Chemical Society, 2012, vol. 33, # 2, p. 541 - 548
[2] Patent: WO2008/120839, 2008, A1,
10
[ 111-25-1 ]
[ 23703-22-2 ]
Reference：
[1] Journal of Materials Chemistry, 2001, vol. 11, # 4, p. 1063 - 1071
11
[ 108-90-7 ]
[ 23703-22-2 ]
Reference：
[1] Journal of Materials Chemistry, 2001, vol. 11, # 4, p. 1063 - 1071
12
[ 111-25-1 ]
[ 106-37-6 ]
[ 23703-22-2 ]
Reference：
[1] Journal of Materials Chemistry, 2005, vol. 15, # 31, p. 3208 - 3213
13
[ 1077-16-3 ]
[ 23703-22-2 ]
[ 38409-58-4 ]
Reference：
[1] Chemistry - A European Journal, 2001, vol. 7, # 23, p. 5118 - 5134
14
[ 1077-16-3 ]
[ 23703-22-2 ]
Reference：
[1] Journal of Materials Chemistry, 2001, vol. 11, # 4, p. 1063 - 1071
15
[ 23703-22-2 ]
[ 105365-50-2 ]
Yield
Reaction Conditions
Operation in experiment
99%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 2 h; Inert atmosphere Stage #2: With hydrogenchloride; Trimethyl borate In tetrahydrofuran; hexane for 2.5 h;
[0378] In a nitrogen atmosphere, an n-hexane solution of n-butyllithium (1.67 M, 131 mL, 218 mmol) was added dropwise to a solution in dry THF (300 mL) of 4-bromohexylbenzene (50.0 g, 207 mmol) at -75°C, and this mixture was stirred. After 2 hours, trimethoxyborane (64.6 g, 622 mmol) was added dropwise thereto. This mixture was stirred for further two hours. Thereafter, 1 N dilute hydrochloric acid (300 mL) was added dropwise thereto, and the resultant mixture was stirred for 30 minutes. This mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride solution, dried with sodium sulfate, and then concentrated under reduced pressure. Thus, intermediate 40 (42.5 g; yield, 99percent) was obtained as a colorless solid.
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 2 h; Inert atmosphere Stage #2: for 2 h; Inert atmosphere Stage #3: With hydrogenchloride In tetrahydrofuran; hexane for 0.5 h; Inert atmosphere
In a nitrogen atmosphere, an n-hexane solution of n-butyllithium (1.67 M, 131 mL, 218 mmol) was added dropwise at −75° C. to a solution in dry THF (300 mL) of 4-bromohexylbenzene (50.0 g, 207 mmol), and the mixture was stirred. After 2 hours, trimethoxyborane (64.6 g, 622 mmol) was added dropwise thereto. This mixture was stirred for further 2 hours. Thereafter, 1-N diluted hydrochloric acid (300 mL) was added dropwise thereto, and this mixture was stirred for 30 minutes. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried with sodium sulfate, and then concentrated under reduced pressure. Thus, intermediate 26 (42.5 g; yield, 99percent) was obtained as a colorless solid.
68%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2 h; Inert atmosphere Stage #2: at -78 - 20℃; for 1 h; Inert atmosphere
The interior of the reaction vessel was repeatedly heated under reduced pressure and purged with nitrogen,The inside of the system was made a nitrogen atmosphere.12.06 g (0.05 mol) of p-Br omohexylbenzene was dissolved in 100 ml of dry THF and cooled to -78 ° C.To this was added dropwise 38 ml of Butyl litium (1.6 mol / l in Hexane)And reacted for 2 hours.To this was slowly added dropwise 2.86 g (0.05 mol) of Trimethyl boronic acid, and after 1 hour, the temperature was raised to room temperature.Water was added to this, neutralized with 1 N HCl, extraction was performed with ethyl acetate,Concentrated to give a white waxy crystal, 4-n-hexylphenylboronic acid6.98 g (yield 68percent) was obtained.
With buta-1,3-diene In tetrahydrofuran at 0℃; for 0.5h;
94 %Chromat.
With cobalt(II) chloride; lithium iodide; isoprene In tetrahydrofuran at -78 - 50℃; for 5h; Inert atmosphere;
94 %Chromat.
With cobalt(II) chloride; lithium iodide; isoprene In tetrahydrofuran at -78 - 50℃; for 5h; Inert atmosphere;
1-Bromo-4-hexylbenzene (5rj)
General procedure: Coupling of Alkyl Halides with t-BuMgCl; Procedure 1 (P1)An alkyl halide (1.0 mmol), decane (63 mg as an internal standard)and LiI (5.3 mg, 0.04 mmol) were added to a dry, nitrogen-flushedtest tube equipped with a rubber septum and a magnetic stir bar.THF (0.8 mL) was added and the solution was cooled to -78 °C usinga dry ice/EtOH bath. t-BuMgCl (2a) (1.5 mL, 0.81 M in THF,1.2 mmol) was added slowly followed by isoprene (136.2 mg, 2.0mmol). To this mixture was added CoCl2 [2.6 mg, 0.02 mmol, as apowder or as a THF solution (0.5 mL, 0.04 M)]. (Note 1: CoCl2should be added after isoprene, otherwise the catalytic performancedecreases significantly). The cold bath was removed and the mixturewas warmed to r.t. (ca. over 10 min), and then heated for 5 h bysuspending the reaction vessel in an oil bath kept at 50 °C. (Note 2:when the reaction mixture was heated at 30 °C during this stage, unidentifiedside reactions occurred resulting in low yields of couplingproducts). The resulting mixture was cooled to 0 °C in an ice bathand the reaction was quenched with aq HCl (5 mL, 1 M). The productwas extracted with Et2O (3 × 20 mL). The combined organiclayer dried over Na2SO4, concentrated and analyzed by gas chromatographyto determine the GC yield. The residue was purified by silicagel column chromatography or by GPC. 1.0 mmol) and n-BuMgCl (2j) (1.0 M in THF, 1.2 mmol) were reactedunder standard conditions.Yield: 94% (determined by GC using decane as an internal standard).
98 %Chromat.
With buta-1,3-diene; copper dichloride In tetrahydrofuran at 25℃; for 24h; Schlenk technique; Inert atmosphere; chemoselective reaction;
[0378] In a nitrogen atmosphere, an n-hexane solution of n-butyllithium (1.67 M, 131 mL, 218 mmol) was added dropwise to a solution in dry THF (300 mL) of 4-bromohexylbenzene (50.0 g, 207 mmol) at -75C, and this mixture was stirred. After 2 hours, trimethoxyborane (64.6 g, 622 mmol) was added dropwise thereto. This mixture was stirred for further two hours. Thereafter, 1 N dilute hydrochloric acid (300 mL) was added dropwise thereto, and the resultant mixture was stirred for 30 minutes. This mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride solution, dried with sodium sulfate, and then concentrated under reduced pressure. Thus, intermediate 40 (42.5 g; yield, 99%) was obtained as a colorless solid.
Example 3Intermediate 3Methyl 4-hexyl-1,1':2',1-terphenyl-4'-carboxylate; To a solution of aryl bromide (2.8 g, 11.6 mmol) in THF (100 mL) at -78 C. was added t-butyllithium (1.7 M in pentane, 13.8 mL) slowly dropwise. After stirring at -78 C. for 1 h, trimethyl borate (2.63 mL, 23.56 mmol) was added. The reaction mixture was warmed to RT over 2 h. After stirring at RT for 15 min, the reaction mixture was quenched with saturated solution of ammonium chloride and extracted with ethyl acetate. The combined organic layers were washed with HCl (10% solution), brine, and dried (MgSO4), filtered, and concentrated under reduce pressure to give 2.22 g boronic acid. A solution of the resulting boronic acid (2.22 g) and Intermediate 2 (3.8 g, 10.7 mmol) in toluene (200 mL) were added potassium carbonate (2.95 g, 21.4 mmol) and LiCl (454 mg) with stirring. After bubbling with Ar for 10 min, tetrakis(triphenylphosphine) palladium(0) (370 mg) was added and heated to 95 C. for 16 h. After the reaction mixture was cooled to RT, it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, and dried (MgSO4), filtered, and concentrated under reduce pressure. The residue was purified by MPLC (0-10% ethyl acetate in hexanes) gave 2.32 g of ester as a colorless oil.1H NMR (300 MHz, CDCl3) delta 8.09 (d, J=1.76 Hz, 1H), 8.05 (dd, J=1.76, 7.91 Hz, 1H), 7.50 (d, J=7.91 Hz, 1H), 7.20-7.24 (m, 3H), 7.13-7.17 (m, 2H), 7.04 (s, 4H), 3.94 (s, 3H), 2.56 (t, J=7.62 Hz, 2H), 1.53-1.63 (m, 2H), 1.25-1.33 (m, 6H), 0.88 (t, J=6.45 Hz, 3H)
With hydrazine hydrate; potassium hydroxide In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol for 20h; Reflux;
48%
With hydrazine hydrate; potassium hydroxide In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol at 210℃;
45%
With potassium hydroxide; hydrazine In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol for 2h; Heating / reflux;
1
Compound (1) (159 g, 0.51 mol) , hydrazine hydrate (70 mL) and KOH (114.46 g, 2.04 mol) were dissolved in triethylene glycol (700 mL) , and the solution was heated under reflux for 2 hours . The reaction temperature was lowered to room temperature, and water and HCl were added to the reaction mixture. After extraction with CH2Cl2, the organic layer was washed with water and dried over anhydrous MgSO4. After filtering off MgSO4 by using a filter paper, the filtrate was evaporated by using a rotary evaporator to remove the solvent. Purification by column chromatography (eluent: n-hexane) gave colorless liquid.4-Bromohexylbenzene (2a): 1H NMR (CDCl3, 300 MHz): δ 7.45- 7.42 (d, 2H, J=8.33 Hz), 7.11-7.08 ppm (d, 2H, J=8.32 Hz), 2.63-2.58 ppm (t, 2H, J=I.69 Hz), 1.67-1.62 ppm (m, 2H), 1.40- 1.35 ppm (m, 6H), 0.97-0.93 ppm (t, 3H, J=6.60 Hz).
With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In acetonitrile; for 72h;Heating/reflux;
(S)-5-(3-(1-(4-hexylphenyl)-5-oxopyrrolidin-2-yl)propyl)thiophene-2-carboxylic acid 2-hydroxyethyl ester (3); Step 1. Arylation of 4 to Give 5Copper (I) iodide (106 mg, 0.56 mmol) and N,N'-dimethylethylenediamine (120 μL, 1.11 mmol) were added in rapid succession to a mixture of (R)-5-(hydroxymethyl)pyrrolidin-2-one (4, 776 mg, 6.74 mmol), 1-bromo-4-n-hexylbenzene (1.34 g, 5.56 mmol) and potassium carbonate (1.53 g, 11.07 mmol) in acetonitrile (12.6 mL). The mixture was heated at reflux. After 3 days, the mixture was cooled to room temperature, diluted with EtOAc (100 mL), and filtered through celite, washing with excess EtOAc. The filtrate was concentrated in vacuo. Purification of the residue by chromatography on 120 g silica gel (hexanes→EtOAc, gradient) afforded 960 mg (63%) of compound 5.
63%
With potassium carbonate;copper(l) iodide; N,N`-dimethylethylenediamine; In acetonitrile; for 72h;Reflux;
Step 1. Arylation of 4 to give 5; Copper (I) iodide (106 mg, 0.56 mmol) and N,N'-dimethylethylenediamine (120 μL, 1.11 mmol) were added in rapid succession to a mixture of (R)-5-(hydroxymethyl)pyrrolidin-2-one (4, 776 mg, 6.74 mmol), 1-bromo-4-n-hexylbenzene (1.34 g, 5.56 mmol) and potassium carbonate (1.53 g, 11.07 mmol) in acetonitrile (12.6 mL). The mixture was heated at reflux. After 3 days, the mixture was cooled to room temperature, diluted with EtOAc (100 mL), and filtered through celite, washing with excess EtOAc. The filtrate was concentrated in vacuo. Purification of the residue by chromatography on 120 g silica gel (hexanes→EtOAc, gradient) afforded 960 mg (63%) of compound 5.
Stage #1: 1-bromo-4-n-hexylbenzene With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere;
Stage #2: diethyl 2,5-di(thiophen-2-yl)terephthalate In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Further stages;
4,4,9,9-tetrakis(4-hexylphenyl)-4,9-dihydro-s-indaceno[1,2-b:5,6-b']dithiophene (8).
n-butyllithium (2.70mmol, 2.5M) was slowly added to a stirred solution of 1-bromo-4-hexylbenzene (7) (655mg, 2.70mmol) in dry THF at -78°C under argon atmosphere. After 1h stirring at -78°C a solution of 6 (150mg, 0.39mmol) in 2mL of dry THF was added dropwise and the mixture was stirred 1h at -78°C and then allowed to cool to r.t. The reaction was quenched with water and the compound was extracted with AcOEt. The organic phase was washed with brine and dried over MgSO4. After solvent removal the crude product was dissolved in 15mL acetic acid and stirred 20minat r.t. 0.05mL of concentrated sulfuric acid was added, and the mixture was refluxed for 4h. The mixture was cooled to r.t. and water was added. The mixture was extracted with DCM, the organic phase was washed with brine and dried over MgSO4. After solvent removal the residue was chromatographed on silica gel (eluent: 8:0.5 PE/AcOEt, Rf=0.42). Compound 8 was isolated in 45% yield as a white solid (158mg). M.p. 157-158°C. 1H NMR (600MHz, CDCl3), δ (ppm): 7.43 (s, 2 H), 7.24 (d, J=4.8Hz, 2 H), 7.15 (d, J=7.2Hz, 8 H), 7.05 (d, J=7.2Hz, 8 H), 6.99 (d, J=4.8Hz, 2 H), 2.55 (t, J=7.8Hz, 8 H), 1.58 (m, 8 H), 1.34-1.28 (overlapped signals, 24 H), 0.87 (m, 12 H). 13C NMR (150MHz, CDCl3), δ (ppm): 155.9, 153.5, 142.2, 141.5, 141.4, 135.2, 128.4, 128.0, 127.5, 123.3, 117.6, 68.8, 35.7, 31.8, 31.5, 29.3, 22.7, 14.3. HRMS (ESI+): Calcd for C64H75S2 [M+H]+: 907.5305, found 907.5261.
45%
Stage #1: diethyl 2,5-di(thiophen-2-yl)terephthalate; 1-bromo-4-n-hexylbenzene With n-butyllithium In tetrahydrofuran at -78℃; for 15h;
Stage #2: With sulfuric acid; acetic acid In tetrahydrofuran for 4h; Reflux;
Multi-step reaction with 2 steps
1.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C
1.2: -78 - 20 °C
2.1: sulfuric acid; acetic acid / Reflux
bis(acetonitrile)palladium(II) dichloride[ No CAS ]
[ 23703-22-2 ]
[ 1282582-98-2 ]
[ 534-17-8 ]
[ 564483-18-7 ]
4-Chloro-2-cyclohexyl-1-p-tolylethynylbenzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In 1,4-dioxane; water;
3.4) 4-Chloro-2-cyclohexyl-1-p-tolylethynylbenzene 10 6.6 g (30.17 mmol) of 9, 7.28 g (30.17 mmol) of 1-bromo-4-hexylbenzene, 21.63 g (66.39 mmol) of caesium carbonate, 78 mg (0.3 mmol) of bis-(acetonitrile)palladium(II) chloride and 431 mg (0.9 mmol) of 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl are dissolved in 90 ml of dioxane under nitrogen and heated at 100 C. overnight. 100 ml of water are added to the cooled solution, and the mixture is extracted twice with methyl t-butyl ether (100 ml). The combined organic phases are washed with water, dried over sodium sulfate and evaporated in vacuo. The residue is purified by column chromatography.
To a solution of 1-bromo-4-hexylbenzene (CAS 237033-22-2) (500 mg, 1.7 mmol) in THF (15 mL) at -78 C. was added t-butyllithium (1.7 M in pentane, 2.0 mL) slowly dropwise. After stirring at -78 C. for 1 h, trimethyl borate (0.39 mL, 3.46 mmol) was added. The reaction mixture was warmed at RT over 2 h. After stirring at RT for 15 min, the reaction mixture was quenched with saturated solution of ammonium chloride and extracted with ethyl acetate. The combined organic layers were washed with HCl (10% solution), brine, and dried (MgSO4), filtered, and concentrated under reduced pressure and gave 415 mg of the corresponding boronic acid as colorless solid.
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate In toluene at 120℃; for 6h; Inert atmosphere;
1 2.2.1 Synthesis of 10-(4-hexyl-phenyl)-10H-phenothiazine (1)
Phenothiazine (1.57 g, 7.87 mmol), 1-bromo-4-n-hexylbenzene (1.86 g, 6.57 mmol), sodium tert-butoxide (1.75 g, 9.2 mmol), tri-tert butyl phosphine (0.208 g, 0.78 mmol), and Pd2(dba)3 (0.2 g, 0.22 mmol) were dissolved in toluene (20 mL). The mixture was heated to 120 °C for 6 h under a nitrogen atmosphere. The reaction mixture was extracted using methylene chloride and water. The organic layer was separated and dried over anhydrous magnesium sulfate. The product was purified by recrystallization using ethyl acetate and methanol. The product was obtained as a pale yellow solid. Yield: (1.5 g, 64%). mp : 100-103 °C. 1H NMR (300 MHz, CDCl3): δ 7.40-7.26 (m, 4H), 7.01-6.83 (m, 6H), 6.19 (m, 2H) 2.73-2.68 (t, J = 7.8 Hz, 2H), 1.71-1.65 (t, J = 6.3 Hz, 2H), 1.36-1.26 (m, 4H), 0.93-0.83(m, 5H). HR-MS: Calcd. for C24H25NS m/z: 359.17; found m/z: 359.1 [M + H]+; anal. calcd. for C: 80.18; N: 3.90; S: 8.92; H: 7.01; found, C: 80.43; N: 3.78; S: 8.72; H: 7.29%.
64%
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate In toluene at 20 - 120℃; Inert atmosphere; Reflux;
1 10-(4-hexylphenyl)-10H-phenothiazine synthesis
Phenothiazine (1.57g, 7.87mmol), 1- bromo -4-n- hexyl-benzene (1.86g, 6.57mmol) and sodium tert-butoxide (1.75g, 9.2mmol) then sufficiently dissolved in toluene 20 mL .tri tert-butylphosphine (0.208 g, 0.78mmol) and Pd2 (dba) 3 (0.2g, 0.22mmol) to After the addition of a nitrogen atmosphere at room temperature for sufficiently meltingThen, the mixture was stirred under reflux at 120 .After the reaction was completed, water and chloroform 1: 1 mixed solvent in the work-up process proceeds. Work-up process after the separation with the organic phase extraction for the coarse, to remove the solvent under reduced pressure. After removing the solvent several times to obtain a solid product of a pale yellow (1.5g, 64%) through a process of re-crystallization with methanol.
48%
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate In toluene at 120℃; Inert atmosphere;
1 Synthesis of 10-(4-hexyl-phenyl)-10H-phenothiazine
Phenothiazine(3.29 g, 13.75 mmol), 1-bromo-4-hexylbenzene (3 g, 16.5 mmol) and sodium tertbutoxide (1.04 g, 5.5 mmol) are thoroughly dissolved in 100 mL of toluene.Trityl butylphosphine(8g, 20.63mmol) and Pd2 (dba) 3 (0.5g, 0.55mmol) were added and sufficiently dissolved at room temperature under nitrogen atmosphere, followed by reflux stirring at 120 ° C.When the reaction is complete, work-up is carried out with a 1: 1 mixture of water and CHCl3. The work-up organic layer is separated by extraction and the solvent is removed under reduced pressure.After removing the solvent, several times with methanolThrough recrystallization, a pale yellow solid product (2.2 g, 48%) was obtained.The chemical properties of the obtained compound are as follows.
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; potassium <i>tert</i>-butylate In 1,2-dimethoxyethane
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 110 - 120℃; for 0.333333h;Inert atmosphere; Microwave irradiation;
General procedure: K3PO4 (0:33 g, 1:54 mmol) was dissolved in 5 mL dmf and 5 mL water, and the solution was saturated with argon. A mixture of Pd(PPh3)4 (0:06 g, 0:05 mmol), 3a(THP) (0:14 g, 0:51 mmol), and 4-pentylbromobenzene (0:12 g, 92 mL, 0:51 mmol) was added to the K3PO4 solution. Theresulting suspension was saturated with argon. After microwave irradiation at 120 C for 20 min, the reaction mixture was treated with a saturated aqueous NaHCO3 solution (30 mL). The product was extracted into ethyl acetate (3 x 30 mL). The combined organic layers were washed three times with 30 mL of a saturated aqueous NaCl solution and dried over anhydrous MgSO4. After removal of the solvent in vacuo, the THP-protected product remained as a pale-yellow oil (0:12 g, 82%). Treatment with a solution of HCl in MeOH (10 mL, AcCl in MeOH) and stirring for 30 min yielded the hydrochloride of 6(pentyl) [13]. When the hydrochloride was treated with NEt3 (1 mL), the pyrazole 6(pentyl) [13] was obtained quantitatively. After evaporation of the solvent, the crude product was purified by column chromatography (hexane/ethyl acetate 2 : 1). Colorless solid (yield: 0:07 g, 68%).
Stage #1: 1-bromo-4-n-hexylbenzene With iodine; magnesium In tetrahydrofuran for 2h; Reflux;
Stage #2: 5H-dithieno[3,2-b:2',3'-d]pyran-5-one In tetrahydrofuran at -25 - 80℃; Inert atmosphere;
(4-Hexylphenyl)magnesium bromide was prepared by the following procedure. To a suspension of magnesium powder (2.64g, 110mmol) and iodine tablets in dry tetrahydrofuran (THF) (100mL) was slowly added 1-bromo-4-hexylbenzene (24.1g, 100mmol) dropwise, and the mixture was refluxed for 2h. 5H-dithieno[3,2-b:2',3'-d]pyran-5-one (2.7g, 13.0mmol) was dissolved in THF (70mL) under argon protection in a 250mL three-neck round-bottom flask. The flask was kept at-25°C and (4-hexylphenyl)magnesium bromide (45mL) was added slowly. Then, the temperature was raised to room temperature and kept stirring for 30min. The mixture was refluxed for 16h at 80°C. The reaction was stopped by adding water (50mL) into the solution, and the organic part was extracted by dichloromethane. The dichloromethane solution was dehydrated with magnesium sulfate. The solvent was removed to give yellow oil. The crude product was dissolved in toluene (120mL) under argon protection in a 250mL three-neck round-bottom flask. p-Toluenesulfonic acid monohydrate (p-TSA) (500mg) was added into the solution and stirred for 12h at 110°C. The solution was cooled down to room temperature, and water (100mL) was added and the organic part was extracted by toluene. The toluene solution was dried with magnesium sulfate, and then the solvent was removed. The compound was purified by silica gel chromatography using petroleum ether as the eluent to obtain a yellow oil. Yield, 72%. FTIR (KBr, cm-1) 3108, 3086, 3053, 3026, 3001 (aromatic C-H), 2960, 2927, 2871, 2856 (alkyl C-H), 1465 (CH3), 1455 (CH2), 1377 (CH3), 1576, 1530, 1510, 1412 (aromatic C=C), 722 ((CH2)5). 1H NMR (400MHz, CDCl3) δ 7.27 (d, 4H, J=6.76 Hz), 7.17 (d, 3H, J=7.73Hz), 7.04 (d, 1H, J=4.83Hz), 6.98 (d, 1H, J=4.83Hz), 6.83 (d, 1H, J=5.31Hz), 6.55 (d, 1H, J=5.31Hz), 2.65 (t, 4H, J=7.73Hz), 1.65 (t, 4H, J=8.62Hz), 1.38 (s, 12H), 0.96 (s, 6H). HRMS (m/z): cacld for (M+) C33H38OS2 (514.2364), found 514.2377.
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 100℃; for 18h;Inert atmosphere;
Under a nitrogen atmosphere, hexyl aniline (A-8) 8.8g, hexyl bromobenzene (A-9) 12.0g, tetrafluoroborate tri -t- butylphosphine (PtBu3BF4) 0.29 g, tris (dibenzylideneacetone) dipalladium (0) (Pd2(dba)3) 0.46 g, and toluene 100mL were stirred at room temperature.Further sodium -t- butoxide (tadded BuONa) 6.21 g, was reacted for 18 hours at 100 C..After allowed to cool and filtered through celite.The filtrate was washed with dilute hydrochloric acid.The organic layer was dried over sodium sulfate, the solvent was distilled off under reduced pressure.The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 50: 1) to give diphenylamine (A-10) 14.4 g, was obtained in 85% yield.
73%
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In toluene; for 24h;Reflux;
Round bottom flask 4-hexylbenzenamine(2.7 g, 11.25 mmol), 1-bromo-4-hexylbenzene(1.33 g, 7.5 mmol), sodium tert-butoxide(1.075 g, 11.25 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.14 g, 0.15 mmol) And 50 mL of toluene tri-tert-butylphosphine(0.03 g, 0.15 mmol) was added thereto, and the mixture was refluxed for 24 hours and stirred. After confirming with HPLC and LC-MASS, the reaction is terminated and the solvent is removed and extracted with MC / H2O. Column (EA: HEX = 1: 4), reprecipitated in MC / hexane and vacuum dried to give 1.85 g of bis<strong>[33228-45-4](4-hexylphenyl)amine</strong> (Yield: 73%).
69%
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; sodium t-butanolate; In toluene; for 24h;Schlenk technique; Inert atmosphere;
4-n-hexyl bromobenzene (2.5 g, 10.37 mmol), 4-n-hexyl aniline (3.43 g, 11.40 mmol), Pd(OAc) 2 (116 mg, 0.52 mmol), 1,1'-bis(diphenylphosphino)ferrocene (575 mg, 1.04 mmol) and sodium t-butoxide (2.98 g, 31.10 mmol) were added to a 100 ml Schlenk flask with a large length and 70 ml of anhydrous toluene was added under an argon atmosphere, and stirred for 24 hours.The solvent was removed from the resulting solution under reduced pressure, the product was separated by silica column chromatography eluted with toluene to obtain 2.4 g of the product. The yield is 69%.
38%
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; 10,11-dimethoxy-3-hydroxy-5,6,13,13a-tetrahydro-8H-dibenzo<a,g>quinolizine; In toluene; for 24h;
4-Hexyl aniline (20 g, 112.81 mmol)And 1-bromo-4-hexylbenzene (40.81 g, 169.21 mmol)Pd (OAc) 2 (2.53 g, 11.28 mmol),DPPF (6.25 g, 11.28 mmol),STB (32.20 g, 335.04 mmol) and Was added with 200 ml of toluene and stirred at 80 DEG C for 24 hours.After completion of the reaction, the solvent was removed, and the mixture was extracted with water and ethyl acetate, dried over MgSO4 and then subjected to column chromatography (n-hexane / EtOAc = 2/1) to obtain the title compound. The yield was 38% (15 g).
2,6-dibromo-9,10-bis(4-hexylphenyl)-9,10-dihydroxyanthracene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
To a solution of 1-bromo-4-hexylbenzene (0.47 mL, 2.30 mmol) in dry THF (7 mL) was added to a n-BuLi hexane solution (1.64 M, 1.28 mL, 2.10mmol) under Ar. The resulting mixture was stirred at -78 C for 1 h. To the resulting 4-hexylphenyllithium solution at -78 C was added a solution of <strong>[633-70-5]2,6-dibromoanthraquinone</strong> (366 mg,1.00 mmol) in dry THF (7 mL). The reaction mixture was allowed to warm to room temperature with stirring overnight and then quenched with H2O. The resulting mixture was extracted with CH2Cl2. The organic layer was washed with H2O and brine, dried over Na2SO4. After evaporation of solvents, the residue was purified by column chromatography on silica gel eluted with CH2Cl2-AcOEt (1:1) to give 2,6-dibromo-9,10-bis(4-hexylphenyl)-9,10-dihydroxyanthracene (741 mg) as a crude product. Next, to a mixture of the crude diol (741 mg), KI (1.49 g, 9.00 mmol), and NaH2PO2·H2O (1.27 g,12.0 mmol) was added AcOH (10 mL). The resulting mixture was stirred at 120 C for 4 h under Ar andlight shielding. After cooling to room temperature, the mixture was poured into H2O, filtrated, andwashed with H2O and MeOH. The filtered solid was purified by column chromatography on silica geleluted with hexane-CH2Cl2 (4:1) followed by recycle preparative HPLC to give 10 (252 mg, 38% yieldfor 2 steps) as a white solid.
In a nitrogen atmosphere, an n-hexane solution of n-butyllithium (1.67 M, 131 mL, 218 mmol) was added dropwise at -75 C. to a solution in dry THF (300 mL) of 4-bromohexylbenzene (50.0 g, 207 mmol), and the mixture was stirred. After 2 hours, trimethoxyborane (64.6 g, 622 mmol) was added dropwise thereto. This mixture was stirred for further 2 hours. Thereafter, 1-N diluted hydrochloric acid (300 mL) was added dropwise thereto, and this mixture was stirred for 30 minutes. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried with sodium sulfate, and then concentrated under reduced pressure. Thus, intermediate 26 (42.5 g; yield, 99%) was obtained as a colorless solid.
68%
The interior of the reaction vessel was repeatedly heated under reduced pressure and purged with nitrogen,The inside of the system was made a nitrogen atmosphere.12.06 g (0.05 mol) of p-Br omohexylbenzene was dissolved in 100 ml of dry THF and cooled to -78 C.To this was added dropwise 38 ml of Butyl litium (1.6 mol / l in Hexane)And reacted for 2 hours.To this was slowly added dropwise 2.86 g (0.05 mol) of Trimethyl boronic acid, and after 1 hour, the temperature was raised to room temperature.Water was added to this, neutralized with 1 N HCl, extraction was performed with ethyl acetate,Concentrated to give a white waxy crystal, 4-n-hexylphenylboronic acid6.98 g (yield 68%) was obtained.
1.16.3 g (0.67 mol) of magnesium turnings were placed under the surface of 90 ml of THF in a round bottom flask and 70 ml of 1-bromo-4-hexylbenzene (150 g, 0.622 mol) in 400 ml of THF was slowly added. The reaction was initiated by adding a drop of bromine. After the reaction has begun, the remainder of the hexyl bromide solution is added such that the reaction is maintained at reflux. After the addition was complete, the reaction was refluxed for 1 h, allowed to cool to -25 C and diluted with 100 ml THF. Next, 90 ml of THF containing 75 ml (0.67 mol) of trimethyl borate was added so that the temperature was maintained between -25C and 0C. Another 100 ml of THF was added and the reaction was stirred at 0 C to 5 C for 1 h. Water was added and the mixture was acidified with hydrochloric acid. Extraction with MTB ether followed by evaporation of the solvent gave 4-hexylbenzoic acid as a colorless solid (86% purity by HPLC).
In a argon atmosphere, a short magnesium strip 0.4g and 5mL (lmol/L) of iPr2NBH2 were added to a solution of 3.618 g of 4-hexylbromobenzene in 40 mL of anhydrous tetrahydrofuran, and the reaction was stirred at 70 C. 20 hours. The reaction solution was cooled to room temperature, and 30 mL of 3 mol/L hydrochloric acid was added to the reaction solution under ice-cooling, and stirred at room temperature for 45 minutes. Then, water and diethyl ether were added to the reaction system, and the organic phase was separated, and the aqueous phase was extracted with dichloromethane. Three times, the organic phases were combined, dried, filtered and evaporated and evaporated. The obtained oily compound was dissolved in 15 mL of diethyl ether, and 1.985 g of <strong>[83-73-8]5,7-diiodo-8-hydroxyquinoline</strong> was added to the solution, and the mixture was stirred at room temperature for 15 hours, a large amount of n-pentane was added to the solution, and a green precipitate was precipitated and filtered. Collecting the filter cake, which is a powder sample;
With bis(tri-t-butylphosphine)palladium(0); potassium carbonate In tetrahydrofuran; water at 70℃; for 0.5h; Inert atmosphere;
2 (Preparation of Intermediate Compound A-2)
2.0 g (3.52 mmol, 1.0 eq) of the intermediate compound A-1 according to Preparation Example 1,2.12 g (8.79 mmol, 2.5 eq) of 1-bromo-4-hexylbenzene was placed in a 500 mL two-neck round-bottom flask and replaced with nitrogen atmosphere. Add 250 mL of THF and 2N K2CO3 (aq.) and stir at 70°C for 30 minutes.After adding 0.09 g (0.18 mmol, 0.05 eq) of catalyst Pd(PtBu3)2, the mixture was reacted with stirring at 70°C overnight. The organic layer was separated by extraction with EA/H2O, MgSO4 and acidic clay were added and stirred for 30 minutes to pass through a silica pad.The solvent of the filtrate was dried and dissolved in hexane to obtain the compound A-2 (1.84 g, yield 82%) through MPLC.
2,5-di(thiophen-2-yl)-1,4-phenylenebis[(4-hexylphenyl)methanone][ No CAS ]
[ 1049034-67-4 ]
Yield
Reaction Conditions
Operation in experiment
42%
Stage #1: 1-bromo-4-n-hexylbenzene With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere;
Stage #2: 2,5-di(thiophen-2-yl)-1,4-phenylenebis[(4-hexylphenyl)methanone] In tetrahydrofuran Inert atmosphere;
Stage #3: With boron trifluoride diethyl etherate In dichloromethane at 20℃; for 2h; Inert atmosphere;
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