* 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] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2572 - 2584
[2] New Journal of Chemistry, 2010, vol. 34, # 4, p. 723 - 731
[3] Organic Process Research and Development, 2006, vol. 10, # 1, p. 94 - 102
2
[ 123324-71-0 ]
[ 35779-04-5 ]
Yield
Reaction Conditions
Operation in experiment
86%
With perfluoroisopropyl iodide; copper; hydroquinone In N,N-dimethyl-formamide at 20℃; for 24 h;
General procedure: (4-Nitrophenyl)boronic acid (0.067 g, 0.4 mmol), copper powder (0.0052 g, 0.08 mmol,), (CF3)2CFI (0.178 g, 0.6 mmol), and DMF (2 mL) were placed in a closed tube with a rubber stopper. The mixture was reacted at room temperature equipped with an air balloon for 24 h. The resulting suspension was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and concentrated to dryness. The crude product was purified by flash column chromatography on silica gel using petroleum ether/ethyl acetate = 20: 1 (v/v) as eluent to give 0.086 g of 2j as a light yellow solid (0.35 mmol, 87percent).
85%
With copper(II) nitrate trihydrate; iodine In acetonitrile at 20℃; for 6 h; Sealed tube
General procedure: 0.05 mmol Cu(NO3)2·3H2O, 1 mmol I2, 1 mmol arylboronic acids and 0.8 mL acetonitrile were added into an about 15 mL tube. Subsequently, the reaction tube was sealed to perform the reaction for 6 h without inert gas protection. Once the reaction time was reached, 10 mL water was added. The mixture was then extracted with dichloromethane (3 x 15 mL). The combined organic layers were washed with aqueous sodium hyposulfite, distilled water, dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography and identified by 1H NMR, 13C NMR or GC-MS data.
82%
With potassium fluoride; iodine In 1,4-dioxane at 80℃; for 1 h;
General procedure: A mixture of the arylboronic acid (0.55mmol), KF (96mg, 1.65mmol) and I2 (127mg, 0.50mmol) in 1,4-dioxane (5mL) was stirred at 80°C for 1h. Then it was filtered through silica gel, eluting with Et2O (10mL) and the solvent was removed by rotary evaporation. When necessary, the product was purified by chromatography on silica gel (petroleum ether/Et2O 98:2).
Reference：
[1] Journal of Fluorine Chemistry, 2016, vol. 189, p. 59 - 67
[2] Catalysis Communications, 2013, vol. 32, p. 15 - 17
[3] Tetrahedron Letters, 2015, vol. 56, # 9, p. 1122 - 1123
3
[ 253185-03-4 ]
[ 35779-04-5 ]
Yield
Reaction Conditions
Operation in experiment
83%
With iodine In acetonitrile at 40℃; for 1.25 h;
General procedure: Typical procedure. To a solution of 1,2-dimethylbenzene (0.106 g, 1 mmol) in acetonitrile (10 mL), iodine (1 mmol. 0.126 g) and polymer-supported periodic acid (0.6 g, 1.05 mmol) were added and the mixture was stirred for 1 hour at 40 °C. The reaction progress was monitored by thin layer chromatography (TLC) using a mixture of ethyl acetate and n-hexane (1:9 v/v) as solvent. After completion of the reaction, the mixture was cooled to room temperature and filtered. The excess of iodine was removed from the filtrate by drop wise addition of sodium bisulfite solution (1 M). The organic layers were separated, dried over magnesium sulfate, filtered, and the solvent was removed by evaporation. The residue was purified by column chromatography on silica gel using n-hexane and ethyl acetate. The related product was obtained with 95percent isolated yield, b.p.: 235 °C (lit. [18] b.p.: 234 °C).
Reference：
[1] Synthetic Communications, 1997, vol. 27, # 20, p. 3631 - 3636
[2] Journal of Organic Chemistry, 1993, vol. 58, # 8, p. 2058 - 2060
[3] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 2, p. 439 - 443
[4] Synthesis, 2002, # 11, p. 1513 - 1518
[5] Synlett, 1998, # 5, p. 534 - 536
[6] Bulletin of the Chemical Society of Japan, 1999, vol. 72, # 10, p. 2351 - 2356
[7] Bulletin of the Chemical Society of Ethiopia, 2014, vol. 28, # 2, p. 305 - 308
[8] Synlett, 1998, # 3, p. 286 - 288
[9] Journal of Organic Chemistry, 1999, vol. 64, # 8, p. 2883 - 2889
[10] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1984, # 11, p. 2623 - 2624
[11] Tetrahedron Letters, 1989, vol. 30, # 13, p. 1649 - 1650
[12] Tetrahedron, 1969, vol. 25, p. 5019 - 5026
[13] Journal of Organic Chemistry, 1978, vol. 43, # 25, p. 4705 - 4708
[14] Journal of Organic Chemistry, 1990, vol. 55, # 11, p. 3552 - 3555
[15] Tetrahedron Letters, 1985, vol. 26, # 40, p. 4955 - 4956
[16] Tetrahedron Letters, 1989, vol. 30, # 13, p. 1649 - 1650
[17] Molecular Crystals and Liquid Crystals, 2006, vol. 444, p. 257 - 263
[18] Chemical Communications, 2009, # 42, p. 6433 - 6435
4
[ 3972-65-4 ]
[ 35779-04-5 ]
Reference：
[1] Angewandte Chemie - International Edition, 2015, vol. 54, # 1, p. 263 - 266[2] Angew. Chem., 2015, vol. 127, # 01, p. 265 - 268,4
[3] Journal of Chemical Research, Miniprint, 1989, # 8, p. 1745 - 1758
[4] Journal of Organic Chemistry, 2011, vol. 76, # 18, p. 7563 - 7568
5
[ 84563-54-2 ]
[ 253185-03-4 ]
[ 35779-04-5 ]
Yield
Reaction Conditions
Operation in experiment
78 %Spectr.
With bis(2-phenylpyridinato)(2,2'-bipyridine)iridium(III) hexafluorophosphate; cyclohexa-1,4-diene In acetonitrile at 20℃; for 2 h; Inert atmosphere; Irradiation
In an oven-dried 10 mL round-bottom flask equipped with a magnetic stirrer bar, di(4-(tertbutyl)phenyl)iodonium triflate (S1, 81 mg, 0.15 mmol), Ir(ppy)2bpyPF6 (1, 2.4 mg, 3.0mol), 1,4-cyclohexadiene (100 μL, 1.05 mmol) and MeCN (0.50 mL) were placed. The mixture was degassed by freeze-pump-thaw cycles and filled with nitrogen. The flask was placed 3 cm above 14W white LED (λ = 400-750 nm) and illuminated for 3 h. Dibenzofurane was added as internal standard for GC analysis, and the yield of 4-tertbutylbenzene (S2) was determined to be 78percent by GC.
Reference：
[1] Journal of Organic Chemistry, 1990, vol. 55, # 11, p. 3552 - 3555
11
[ 154318-75-9 ]
[ 35779-04-5 ]
Reference：
[1] Journal of the American Chemical Society, 2012, vol. 134, # 36, p. 14760 - 14763
[2] Journal of the American Chemical Society, 2017, vol. 139, # 25, p. 8621 - 8627
Reference：
[1] Bulletin de la Societe Chimique de France, 1906, vol. <3> 35, p. 826
30
[ 129333-82-0 ]
[ 7553-56-2 ]
[ 35779-04-5 ]
Reference：
[1] Russian Chemical Bulletin, 1999, vol. 48, # 3, p. 448 - 452
31
[ 5421-53-4 ]
[ 107-94-8 ]
[ 253185-03-4 ]
[ 35779-04-5 ]
[ 3972-56-3 ]
Reference：
[1] Journal of Organic Chemistry, 1994, vol. 59, # 6, p. 1381 - 1388
32
[ 96274-08-7 ]
[ 7553-56-2 ]
[ 35779-04-5 ]
[ 13121-86-3 ]
Reference：
[1] Journal of the Chemical Society, 1963, p. 681 - 689
[2] Poc. Chem. Soc., 1963, p. 51 - 51
[3] , Gmelin Handbook: Sn: Org.Verb.2, 1.1.2.11, page 339 - 345,
33
[ 98-73-7 ]
[ 35779-04-5 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1971, vol. 751, p. 17 - 26
34
[ 370-69-4 ]
[ 61358-25-6 ]
[ 603-35-0 ]
[ 35779-04-5 ]
[ 1428647-08-8 ]
Reference：
[1] Journal of Organic Chemistry, 2013, vol. 78, # 8, p. 3561 - 3569
[2] Journal of Organic Chemistry, 2013, vol. 78, # 8, p. 3561 - 3569
35
[ 35779-04-5 ]
[ 3282-56-2 ]
Yield
Reaction Conditions
Operation in experiment
66%
With potassium nitrite; copper(II) bis(trifluoromethanesulfonate) In dimethyl sulfoxide at 130℃; for 48 h; Inert atmosphere; Sealed tube
General procedure: An oven dried pressure tube was charged with haloarenes (0.5 mmol), copper(II) triflate (45 mg, 0.125 mmol), KNO2 (128 mg, 1.5 mmol) and anhydrous DMSO (0.6 mL) under nitrogen atmosphere. The tube was sealed with a teflon screw cap having mininert valve and nitrogen is purged through it for 5 min. It is stirred at room temperature for 10 min and then the temperature was gradually increased to 130 oC and is maintained at the same for 48 h. The reaction mixture was then cooled to room temperature, washed with excess ice cold water and extracted with ethyl acetate (3 x 10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product which was purified by column chromatography using silica gel (Table 2, entries 1-18) or basic alumina (Table 2, entries 19-23) and a mixture of ethyl acetate and hexane as the eluent to afford the desired products in good yields.
With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine In 1,4-dioxane at 110℃; for 12h;
1.3
Methyl 4-(3-(4-tert-butylphenyl)-2-oxoimidazolidin-l-yl)benzoate (step 3 in Scheme 1): Methyl 4-(2-oxoimidazolidin-l-yl)benzoate (220 mg, 1.0 mmole) was mixed with iodo- l-tert-butyl-4-iodobenzene (260 mg, 1.0 mmol), CuI (38 mg, 0.2 mmol), K3PO4 (426 mg, 2 mmol), N,N'-dimethyl ethylenediamine (17 mg, 0.2 mmol) and 1,4-dioxane (5 ml). The mixture was heated at 110 0C with stirring for 12 hours, and the solvent was removed in vacuum. The residue was suspended in dichloromethane and purified on ISCO system (5% methanol in dichloromethane) to give a pure product as a white crystalline (275 mg, 78%): 1H NMR (400 MHz, CDCl3) δ 8.05 (dd, 2H), 7.70 (dd, 2H), 7.36 (dd, 2H), 7.20 (dd, 2H), 4.02 (s, 4H), 3.90 (s, 3H)5 1.30 (s, 9H). MS (ESI) m/z: Calculated: 352.18; Observed: 353.10 (M++1).
With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 24h;
General procedure: CuI (0.05 equiv), 1,10-phenanthroline (0.1 equiv) and K2CO3 (2 equiv) were placed in an oven-dried screw-capped test tube with Teflon-lined septum that was filled with nitrogen. About 2.5 mL of dry DMF was then added at room temperature. Now the corresponding aryl iodide (1.0 mmol) was added followed by MBI or FMBI (1.0 equiv) and the tube was placed in the preheated oil bath at 140 C and the reaction mixture was magnetically stirred for 22 h. After complete disappearance of iodobenzene (the progress of the reaction was followed by TLC), the reaction mixture was allowed to cool to room temperature. Then water was added and the reaction mixture was extracted with ethyl acetate. After removal of the solvent in vacuum, the crude residue was purified by column chromatography.5- (or 6-) (Difluoromethoxy)-2-(phenylsulfanyl)-1H-benzimidazole (1).
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; CyJohnPhos In toluene at 100℃; for 12h;
General Procedure:
General procedure: The substrates were prepared by following a modified reportedprocedure.5 A mixture of Pd2(dba)3 (3 mol %), ligand (2-(dicyclohexylphosphino)biphenyl) (8mol %) and 15 mL of dry toluene were placed in an oven-dried tube. The tube was sealed andthe solution was degassed with bubbling argon for 1 h. Aryl halide (1.0 equiv), 1,2,3,4-tetrahydroisoquinolines (1.2 equiv), and t-BuONa (1.4 equiv) were added sequentially. Thenthe reaction mixture was heated at 100 °C for 12 h. The reaction mixture was cooled to roomtemperature, quenched by adding water, and extracted with ethyl acetate. The organic layer wasdried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product waspurified by column chromatography on silica gel using hexanes/ethyl acetate as the eluent toafford the desired products.
71%
With potassium phosphate; copper(l) iodide In ethylene glycol; isopropyl alcohol at 85℃; for 24h; Inert atmosphere;
35%
With potassium phosphate; copper(l) iodide; ethylene glycol In isopropyl alcohol at 85 - 90℃; for 24h; Schlenk technique; Inert atmosphere;
With potassium phosphate; copper(l) iodide In ethylene glycol; isopropyl alcohol at 90℃; for 24h; Inert atmosphere;
With potassium phosphate; copper(l) iodide In ethylene glycol; isopropyl alcohol at 85 - 90℃; for 36h; Schlenk technique; Inert atmosphere;
With potassium phosphate; copper(l) iodide In isopropyl alcohol at 85℃; for 36h; Reflux; Inert atmosphere;
2.1 Synthesis of 1a-1m, 1o
General procedure: Copper(I) iodide (1.0 mmol, 0.1 equiv, 200 mg) and potassium phosphate (20.0 mmol, 2.0 equiv,4.25 g) were added to a well dried bottom flasks with two necks and then evacuated and backfilled with Argon. 2-Propanol (30 mL), ethylene glycol (20.0 mmol, 2.0 equiv, 1.2 mL), 1,2,3,4-tetrahydroisoquinoline (15 mmol, 1.5 equiv, 2 mL) and an aryl iodide (10 mmol, 1 equiv) wereadded at room temperature. The reaction mixture was heated at 85 and refluxed for 36 h.After complete the reaction, it was quenched with water and extracted with ethyl acetate. Thenpurification the crude by column chromatography using petroleum / ethyl acetate to afford pureproduct of 1a-1m, 1o.
With potassium phosphate; copper(l) iodide In ethylene glycol; isopropyl alcohol at 90℃; for 24h; Schlenk technique; Inert atmosphere;
With potassium phosphate; rac-diaminocyclohexane In 1,4-dioxane at 110℃; for 6h;
6
Synthesi s of N-tert-butylphenyl-tri scarbazoleIn a one liter flask is introduced K3P04 (7 eq) in dioxane, Cul (10 % mol), 4-t-butyl-l-iodobenzene (1.25 eq) and triscarbazole (1 eq) are then added to the medium. After the final addition of 1,2-diaminocyclohexane (0.16 eq) the temperature is raised to 110 °C for 6 h. After cooling, the reaction medium is filtered on a celite pad and washed with THF. The solid recovered by solvent evaporation is flash chromatography (Yield 90 %).
With copper; potassium carbonate In nitrobenzene at 180℃; for 24h; Inert atmosphere;
2 9-(4-tert-butylphenyl)-9H-carbazole:
Under a nitrogen atmosphere, 9H-carbazole (4.0 g, 23.9 mmol), 1-tert-butyl-4-iodobenzene (7.0 g, 26.9 mmol), Cu (0.5 g, 7.5 mmol), K2CO3 (10.2 g, 60 mmol) 60 mL of nitrobenzene was added to the reaction tube, and the mixture was reacted at 180 ° C for 24 hours under a nitrogen atmosphere.After completion of the reaction, the nitrobenzene was distilled off with an oil pump, and the substrate was extracted three times with dichloromethane, and the solvent was evaporated. Separation by column (with petroleum ether / dichloromethane = 20:1) 4.6 g of a white solid were obtained in a yield of 64%.
64%
With copper; potassium carbonate In nitrobenzene at 180℃; for 24h; Inert atmosphere;
With 18-crown-6 ether; copper; potassium carbonate In 1,2-dichloro-benzene at 190℃; for 20h;
With perfluoroisopropyl iodide; copper; hydroquinone; In N,N-dimethyl-formamide; at 20℃; for 24h;
General procedure: (4-Nitrophenyl)boronic acid (0.067 g, 0.4 mmol), copper powder (0.0052 g, 0.08 mmol,), (CF3)2CFI (0.178 g, 0.6 mmol), and DMF (2 mL) were placed in a closed tube with a rubber stopper. The mixture was reacted at room temperature equipped with an air balloon for 24 h. The resulting suspension was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and concentrated to dryness. The crude product was purified by flash column chromatography on silica gel using petroleum ether/ethyl acetate = 20: 1 (v/v) as eluent to give 0.086 g of 2j as a light yellow solid (0.35 mmol, 87%).
85%
With copper(II) nitrate trihydrate; iodine; In acetonitrile; at 20℃; for 6h;Sealed tube;
General procedure: 0.05 mmol Cu(NO3)2·3H2O, 1 mmol I2, 1 mmol arylboronic acids and 0.8 mL acetonitrile were added into an about 15 mL tube. Subsequently, the reaction tube was sealed to perform the reaction for 6 h without inert gas protection. Once the reaction time was reached, 10 mL water was added. The mixture was then extracted with dichloromethane (3 x 15 mL). The combined organic layers were washed with aqueous sodium hyposulfite, distilled water, dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography and identified by 1H NMR, 13C NMR or GC-MS data.
82%
With potassium fluoride; iodine; In 1,4-dioxane; at 80℃; for 1h;
General procedure: A mixture of the arylboronic acid (0.55mmol), KF (96mg, 1.65mmol) and I2 (127mg, 0.50mmol) in 1,4-dioxane (5mL) was stirred at 80C for 1h. Then it was filtered through silica gel, eluting with Et2O (10mL) and the solvent was removed by rotary evaporation. When necessary, the product was purified by chromatography on silica gel (petroleum ether/Et2O 98:2).
With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; tetrabutylammomium bromide; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; zinc In tetrahydrofuran at 60℃; for 12h; Inert atmosphere;
47%
With copper In dimethyl sulfoxide at 60℃; for 12h; Inert atmosphere;
43%
With copper In dimethyl sulfoxide at 60℃; for 12h; Inert atmosphere;
General Procedure A (Synthesis of ethyl α,α-difluoroarylacetates or ethyl α-fluoroarylacetates from aryl iodides)
General procedure: To a suspension of activated Cu powder (2.6 eq.) in DMSO (0.38 M) was added the appropriate aryl iodide (1.0 eq.) and ethyl bromodifluoroacetate (1.0 eq.) or ethyl bromofluoroacetate (1.0 eq.) under nitrogen atmosphere. The reaction mixture was stirred at 60°C for 12 h. The reaction mixture was filtered through a pad of Celite and washed with Et2O. The mixture was washed with aq. NH4Cl (sat., 2x) and brine (2x), then dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography.
With copper In dimethyl sulfoxide at 60℃; for 12h; Inert atmosphere;
With copper In dimethyl sulfoxide at 60℃; for 12h; Inert atmosphere;
1.2 Preparation of N-(2,2-difluoro-2-phenylethyl) picolinamide
General procedure: General Procedure A: In a 50 mL round bottom flask under an atmosphere of N2, the appropriate aryl iodide (10 mmol, 1.0 equiv) and ethyl bromodifluoroacetate (1.3 mL, 10 mmol, 1.0 equiv) were added to a suspension of activated Cu powder (1.7 g, 26 mmol, 2.6 equiv) in DMSO (26 mL, 0.4 M). The reaction mixture was stirred at 60 °C for 12 h, after which time it was poured into a mixture of ice and sat. aq. NH4Cl, the aqueous phase was extracted with EA (3 × 50 mL). The combined organic phases were washed with sat. aq. NH4Cl (2 × 50 mL) and brine (2 × 50 mL), then dried over MgSO4, filtered, and concentrated in vacuo. The crude mixture was purified by flash column chromatography. A solution of the above ethyl α, α-difluoroaryl acetate and NH3 in MeOH (7 M, 10 mL) were stirred at room temperature for 2 h and concentrated to afford α, α-difluoroaryl acetamide. To a s solution of α, α-difluoroaryl acetamide (4 mmol, 1.0equiv) in THF (5 mL) was added borane in THF (1 M, 20 mL, 20 mmol, 5.0 equiv) at 0 °C. After refluxed 70°C for 12 h, then cooled to 0 °C. The reaction mixture was quenched by 4 M HCl in MeOH, after refluxed at 70 °C for 2 h, concentrated to afford α, α-difluoroaryl ethylamine. A mixture of α, α-difluoroaryl ethylamine (6 mmol, 1.0 equiv), picolinic acid (11mmol, 1.1 equiv), HATU (2.1 g, 11 mmol, 1.1 equiv), Et3N (5.2 mL, 30 mmol, 4.0 equiv) in anhydrous CH2Cl2 (20 mL) were stirred at room temperature overnight. Water was added and the mixture was extracted with CH2Cl2. The combined organic layer was washed with water and brine, dried over anhydrous Mg2SO4, and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography to give the desired picolinamide product. Compound 1a-1o was isolated (Rf =0.30, 20% EtOAc in hexanes)
6 EXAMPLE 6
To an aryl iodide substrate (0.2 mmol) were added a CuC2F5 solution prepared as described in Example 5(0.35 mL; 1.2 equiv) and 1,3-bis(trifluoromethyl)benzene (internal standard; 15.5 mL). This mixture was kept at 23°C or50°C or first at 23°C and then at 50°C for a certain period of time. The conversions of the CuC2F5 and yields of thecorresponding pentafluoroethylated products were determined by quantitative 19F NMR analysis. Conversion of thestarting aryl iodide was determined by GC-MS. See Table 1 for specifics.
89%
In N,N-dimethyl-formamide at 80℃; for 36h; Inert atmosphere; Sealed tube; Glovebox;
96 %Spectr.
With triethylamine tris(hydrogen fluoride) at 23 - 50℃; for 40h; Inert atmosphere; Sealed tube;
With bis(2-phenylpyridinato)(2,2'-bipyridine)iridium(III) hexafluorophosphate; cyclohexa-1,4-diene; In acetonitrile; at 20℃; for 2h;Inert atmosphere; Irradiation;
In an oven-dried 10 mL round-bottom flask equipped with a magnetic stirrer bar, di(4-(tertbutyl)phenyl)iodonium triflate (S1, 81 mg, 0.15 mmol), Ir(ppy)2bpyPF6 (1, 2.4 mg, 3.0mol), 1,4-cyclohexadiene (100 muL, 1.05 mmol) and MeCN (0.50 mL) were placed. The mixture was degassed by freeze-pump-thaw cycles and filled with nitrogen. The flask was placed 3 cm above 14W white LED (lambda = 400-750 nm) and illuminated for 3 h. Dibenzofurane was added as internal standard for GC analysis, and the yield of 4-tertbutylbenzene (S2) was determined to be 78% by GC.
With 1H-imidazole; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; ammonium chloride; N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 90℃; for 3h; Sealed tube;
General procedure for the synthesis of primary amides:
General procedure: To a stirred solution of aryl halide (Br/I) (1 mmol) in dry dioxane in a 25 mL sealed tube, was added Pd(OAc)2 (5 mol%), dppf (6 mol %), DIPEA (2 mmol), imidazole (0.25 mmol), ammonium chloride (2 mmol) and then Co2(CO)8 (0.3 mmol). The seal tube was closed immediately and stirred at 90 °C for 3h. After the reaction time the reaction mixture was cooled to room temperature. The reaction mixture was filtered through celite pad and washed with dioxane, the filtrate was concentrated under reduced pressure and the residue obtained was purified by column chromatography.
2-((4-(tert-butyl)phenyl)thio)cyclohexa-2,5-diene-1,4-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62%
Stage #1: 3-mercaptophenol; 1-tert-butyl-4-iodobenzene With copper(l) iodide; oxygen; caesium carbonate In N,N-dimethyl-formamide at 90℃; for 24h;
Stage #2: With dipotassium peroxodisulfate In N,N-dimethyl-formamide for 2h;
2.1. Typical procedure for the synthesis of 3a
2.1. Typical procedure for the synthesis of 3a: To a solution of3-hydroxybenzenethiol (1.0 mmol) in DMF (4 mL) was added iodobenzene (1.5mmol)in a Schlenk tube at room temperature under oxygen condition. Subsequently, Cs2CO3(1.5 mmol), and CuI (0.1 mmol) were added. The mixture was heated under 90 oCfor 12 h and then K2S2O8 (2.0 mmol) were addedand stirred for another 2 h. Water (10 mL) was added to the reaction mixtureand EtOAc (3x10 mL) were used to extract the crude product. After removing thesolvent, the resulting crude was purified by column chromatography withpetroleum ether/ethyl acetate (20:1) as eluent to give 3aas an orange solid.
With nickel(II) oxide; potassium tert-butylate; triphenylphosphine; In tetrahydrofuran; at 100℃; for 24h;Inert atmosphere; Sealed tube; Green chemistry;
General procedure: Under an argon atmosphere, nickel oxide (50 mumol, 5 mol%), triphenylphosphine (0.1 mmol, 10 mol%), <strong>[494-19-9]iminodibenzyl</strong> substrate (1 mmol), potassium tert-butoxide (2 mmol, 2.0 equiv), 4 were successively - Tert-butyl halide (2 mmol, 2.0 equiv) and tetrahydrofuran (2 mL) were added to a 10 mL sealed tube and placed in a 100C oil bath with heating and stirring for 24 hours. The reaction was completed and the reaction was exposed to air quenching, followed by direct The amine product was isolated by column chromatography.According to the results of column chromatographic separation, the yields of 4-tert-butylbromobenzene and 4-tert-butyl iodobenzene respectively reacted with the substrate were: 82%, 81%;
78%
With potassium tert-butylate; copper(II) oxide; In dimethyl sulfoxide; at 80℃; for 18h;Sealed tube; Inert atmosphere;
Under an argon atmosphere, copper oxide (50 mumol), <strong>[494-19-9]iminodibenzyl</strong> substrate (1 mmol), potassium tert-butoxide (2 mmol, 2.0 equiv), 4-tert-butyl-substituted aromatic hydrocarbon (2 mmol, 2.0 equiv), solvent ( 2 mL) was added to a 10 mL sealed tube and placed in an oil bath heated to 80 C. for 18 hours. After the reaction was completed, the reaction was exposed to air quenching, and then directly separated by column chromatography to obtain an amine product.According to the results of column chromatographic separation, when DMSO was used as the reaction solvent, the yields of 4-tert-butylchlorobenzene, bromobenzene, and iodobenzene respectively reacted with the substrate were: 83%, 88%, 78%; when used When DMF was used as a reaction solvent, the yields of 4-tert-butylchlorobenzene, bromobenzene, and iodobenzene respectively reacted with the substrate were: 68%, 77%, 58%
4-(tert-butyl)-N-(4H-1,2,4-triazol-4-yl)benzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
97%
With palladium diacetate; triethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 70℃; under 750.075 Torr; for 48h;Catalytic behavior;
General procedure: In a typical experiment Pd(OAc)2 (5.6mg, 0.025mmol), triphenylphosphine (13.2mg, 0.05mmol), iodoalkene (1-4) or iodoarene (5-19) (1mmol) were dissolved in DMF (10mL) under argon in a three-necked flask equipped with a reflux condenser and a balloon on the top. Aminotriazole nucleophile (a, b or c) (1.2mmol) and triethylamine (0.5mL) were added. The atmosphere was changed to carbon monoxide. (Caution: High pressure carbon monoxide should only be used with adequate ventilation (hood) using CO sensors as well.) The reaction was conducted for the given reaction time upon stirring at 70C. The mixture was then concentrated and evaporated to dryness. Toluene (15mL) was added to the residue, the precipitate (product) was filtered, washed with water on the filter and dried. The off-white powder-like material was dissolved in methanol, the palladium-black was filtered off and methanol was evaporated.
With copper(l) iodide; potassium carbonate In 1-methyl-pyrrolidin-2-one at 100℃; for 10h;
1-5 Synthesis of 2-(4-tert-butylphenyl)thiobenzoic acid (Intermediate E)
12 g of thiosalicylic acid, 24 g of potassium carbonate, 25 g of 4-tert-butyl iodobenzene, 380 mg of copper iodide and 74 g of N-methylpyrrolidone was stirred at 100 ° C. for 10 hours. The reaction was terminated by adding 400 g of 5% by mass hydrochloric acid at room temperature. After that, 400 g of ethyl acetate was added and the mixture was washed with water and separated. Then, the mixture was concentrated under reduced pressure, hexane was added to the obtained residue and recrystallized. The obtained crystals were separated by filtration, and dried by heating under reduced pressure to obtain Intermediate E as a target compound (yield 18 g, yield 81%)
81%
With copper(l) iodide; potassium carbonate In 1-methyl-pyrrolidin-2-one at 100℃; for 10h;
1-5 Synthesis Example 1-5: Synthesis of 2-(4-tert-butylphenyl)thiobenzoic acid
A mixture of 12 g of thiosalicylic acid, 24 g of potassium carbonate, 25 g of 4-tert-butyliodobenzene, 380 mg of copper iodide, and 74 g of N-methylpyrrolidone was stirred at 100° C. for 10 hours. The reaction solution was cooled to room temperature, to which 400 g of 5 wt % hydrochloric acid was added to quench the reaction. Ethyl acetate, 400 & was added to the solution, followed by water washing, separation, and vacuum concentration. Hexane was added to the concentrate for recrystallization. The resulting crystal was filtered and dried in vacuum at elevated temperature, obtaining the desired compound, Intermediate E (amount 18 g, yield 81%).
81%
With copper(l) iodide; potassium carbonate In 1-methyl-pyrrolidin-2-one at 100℃; for 10h;
1.1-5 Synthesis of 2-(4-tert-butylphenyl)thiobenzoic acid (Intermediate E)
A mixture of 12 g of thiosalicylic acid, 24 g of potassium carbonate, 25 g of 4-tert-butyliodobenzene, 380 mg of copper iodide, and 74 g of N-methylpyrrolidone was stirred at 100° C. for 10 hours. The reaction solution was cooled to room temperature, to which 400 g of 5 wt % hydrochloric acid was added to quench the reaction. Ethyl acetate, 400 g, was added to the solution, followed by water washing, separation, and vacuum concentration. Hexane was added to the concentrate for recrystallization. The resulting crystal was filtered and dried in vacuum at elevated temperature, obtaining the desired compound, Intermediate E (amount 18 g, yield 81%).
With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; sodium formate; dicyclohexyl-carbodiimide; bis[2-(diphenylphosphino)phenyl] ether In tetrahydrofuran at 130℃; Inert atmosphere; Sealed tube;
4-(tert-butyl)-N-(5-(tert-butyl)-1,2,4-thiadiazol-2-yl)benzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
67%
With palladium diacetate; triethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 70℃;Inert atmosphere; Reflux;
General procedure: In a typical experiment Pd(OAc)2 (5.6mg, 0.025mmol), triphenylphosphine (13.1mg, 0.05mmol), iodobenzene (1) (or an other iodoaromatics, 2-18) (1.0mmol), and 2-amino-1,3,4-thiadiazol (a) (or its 5-substituted derivatives, b or c, or 2-amino-1,3-thiazole, d) (121.4mg, 1.2mmol) and triethylamine (0.5mL) were dissolved in DMF (10mL) under argon in a 100mL three-necked flask equipped with reflux condenser connected to a balloon filled with argon. The atmosphere was changed to carbon monoxide. The reaction was conducted for the given reaction time upon stirring at 70C and analyzed by TLC and GC-MS. The cooled reaction mixture was then concentrated and evaporated to dryness under reduced pressure. (0025) Method A. (2a, 14a, 1d-8d, 10d, 14d-16d): The residue was dissolved in chloroform (15mL) and washed three times with water (30mL). The organic phase was dried over Na2SO4, filtered and evaporated under reduced pressure to a solid material. Aforesaid compounds were subjected to column chromatography (Silicagel 60 (Merck), 0.063-0.200mm), EtOAc/CHCl3 eluent mixtures (the exact ratios are specified in Characterization for each compound; isolated yields are not optimized). (0026) Method B. (1a, 3a-13a, 15a-17a, 1b, 2b, 13b, 1c, 2c, 9d, 11d-13d, 17d): Toluene (15mL) was added to the residue, the insoluble material (product) was filtered, washed with water on the filter and dried. The off-white powder-like material was dissolved in methanol, the palladium-black was filtered off and methanol was evaporated.
9,9'-di-4-t-butylphenyl-9H,9'H-3,3'-bicarbazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
69%
With copper; potassium carbonate; In N,N-dimethyl-formamide; at 145℃;Inert atmosphere;
3,3'-Bicarbazole (1.0 g, 3 mmol), 1-t-butyl-4-iodobenzene (2.06 mL, 11.5 mmol), copper powder(1.1 g, 17 mmol), and K2CO3 (2.4 g, 17 mmol) were dissolved in 10 mL of anhydrous DMF undernitrogen. After heating the mixture at 145 C overnight, the reaction solution was filtered through aplug of celite. The filtered solution was poured into water and extracted with chloroform. The organicswere combined, washed with brine, and dried with sodium sulfate. After solvent removal, the productwas purified via column chromatography with 1:2 (v/v) chloroform-hexane as the eluent to yield 1.23 g(2.01 mmol, 69%) of BCz-tBuPh as a white solid. For OLED devices, the product was further purifiedtwice via vacuum sublimation. The sublimation yield was 74%. Mp 295 C. 1H-NMR (400 MHz,CDCl3): delta(ppm) 8.45 (d, J = 1.4 Hz, 2H), 8.24 (d, J = 7.7 Hz, 2H), 7.77 (dd, J = 8.5 Hz, J = 1.8 Hz, 2H),7.65-7.62 (m, 4H), 7.56-7.52 (m, 6H), 7.48-7.41 (m, 4H), 7.33-7.29 (m, 2H), 1.45 (s, 18H). 13C-NMR(100 MHz, CDCl3): delta (ppm) 150.4, 141.5, 140.1, 135.0, 134.3, 126.8, 126.5, 125.9, 125.8, 123.9, 123.5, 120.4,119.8, 118.9, 110.2, 110.0, 34.8, 31.5. Anal. calcd. for C44H40N2: C, 88.55; H, 6.76; N, 4.69; found: C,88.00; H, 6.84; N, 4.80%.
With tris-(dibenzylideneacetone)dipalladium(0); acetic anhydride; magnesium; triphenylphosphine; zinc(II) chloride In tetrahydrofuran at 55℃; for 12h; Inert atmosphere; Sealed tube;
With ruthenium(III) trichloride hydrate; 1,4-bis(2'-diphenylphosphino-3'-methylimidazolium)butane triflate; triethylamine In 1-methyl-pyrrolidin-2-one at 120℃; for 16h; Autoclave;
36 %Chromat.
With palladium diacetate; potassium carbonate at 100℃; for 3h;
2.2. Carbonylation reactions
General procedure: In a typical experiment, the catalyst precursor (Pd(OAc)2, if otherwise not stated: 0.280mg, 0.00125mmol), 0.5mmol of iodoaromatic compounds, 0.625mmol (1.5 equiv.) of O-nucleophile were dissolved in 2.5mL of solvent followed by addition of 1.25mmol (2.5 equiv.) of base. The reaction mixture was placed in a glass inlet tube into a 25mL Parr Hastelloy-C high-pressure reactor equipped with manometer, safety relief, thermometer and a magnetic stirrer. The reactor was flushed with 10bar of CO three times and placed into a pre-heated oil bath at the given temperature. The final pressure was adjusted at the elevated temperature. The reaction mixture was then stirred for 4h. The pressure was monitored and maintained throughout the reaction. After cooling and venting of the autoclave after a given reaction time, the solution was removed and immediately analyzed by GC-FID and/or GC-MS.
The method for synthesizing the aphid butyl fluoride ester intermediate p-tert-butyl phenylacetonitrile comprises the following steps: 1) Under argon conditions,Isopropyl cyanoacetate,Mix potassium tert-butoxide and tert-butanol,Warming up to 105 C,The control pressure is 5 atmospheres.Within 40 minutes1 mol of t-butyl iodobenzene and DMSO solution were added in 3 batches,Then control the reaction temperature to 120 C,The reaction pressure is 7 atmospheres.The reaction is over 3h,Then add deionized water,Control the reaction temperature to 150C, the reaction pressure is 9 atmospheres,Continue the reaction for 6h; The ratio of 4-tert-butyl iodobenzene to isopropyl cyanoacetate is 1:1.45, the ratio of isopropyl cyanoacetate to organic base is 1:1.62, and the ratio of isopropyl cyanoacetate to DMSO is 1 g: 12 ml, the ratio of 4-tert-butyl iodobenzene to DMSO is 1 g: 6 ml, and the ratio of potassium t-butoxide to deionized water is 1:13.2) The system removes the solvent by a rotary evaporator.Then transfer the residue to the water,Add benzene and stir,Layered,The organic phase was collected and dried over anhydrous sodium sulfate.Then, the filtrate was collected by filtration, and the filtrate was distilled under reduced pressure to collect a fraction of 78 to 79 C (0.1 torr).The product was obtained in a molar yield of 97.2% and an HPLC purity of 98.3%.
4-(4-(tert-butyl)phenyl)-4-(4-methoxyphenyl)but-3-en-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64%
With 4,5-Diazafluoren-9-one; oxygen; cesium acetate; palladium diacetate; In dimethyl sulfoxide; at 100℃; for 16h;Sealed tube;
General procedure: A tube (30 mL) equipped with a magnetic stirring bar was charged with 1 (1.5 mmol), 2 (5.25 mmol), Pd(OAc)2 (10 mol%), L1 (10 mol%), and CsOAc (6.0 mmol) in DMSO (1.5 mL), then the tube was sealed, purged with O2, and the mixture was stirred at 100 C for 16 h. At the end of the reaction, the mixture was partitioned between EtOAc (30mL) and H2O (30 mL). The organic layer was separated, and the aqueous layer was extracted further with EtOAc (3 × 30 mL). The combined organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Then, the crude mixture was purified by column chromatography (silica gel; n-hexane/EtOAc) to afford the desired product.
With copper(I) oxide; potassium phosphate In 1-methyl-pyrrolidin-2-one at 160℃; for 12h; Inert atmosphere; Schlenk technique;
N-Aryl Indoles 3; General Procedure
General procedure: A mixture of Cu2O (0.02 mmol), K3PO4 (0.4 mmol), indole-2-carboxylic acid (1) (0.2 mmol), and aryl halide (2) (0.2 mmol) in NMP (2.0 mL) was stirred at room temperature under a N2 atmosphere. The mixture was then heated to 160 °C and stirred at this temperature for 12 h. After completion of the reaction, the mixture was cooled to room temperature and diluted with EtOAc. The mixture was washed with H2O and aq NaCl, dried over MgSO4 and filtered. After evaporation of the solvent, the residue was purified by preparative thin-layer chromatography on silica gel with PE/EtOAc (50:1) as eluent to give the product 3.
(3-methoxy-9,10,10-trioxo-9,10-dihydro-10λ6-thioxanthen-2-yl)(4-t-butylphenyl)iodonium nonafluorobutanesulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
6.4 g
4 g of 1-t-butyl-4-iodobenzene is added to 16 g of sulfuric acid, and then 10 g of potassium persulfate is added little by little at 10 C. or lower, and the mixture is stirred for 30 minutes. After stirring, 3.7 g of 3-methoxythioxanthen-9-one is added, and the mixture is further stirred at 25 C. for 3 hours. After stirring, 30 g of pure water is added at 10 C. or lower, then 40 g of methylene chloride and 5.7 g of potassium nonafluorobutanesulfonate are added, and the mixture is stirred at 25 C. for about 2 hours. The reaction solution is separated, washed with 30 g of pure water three times, and then methylene chloride is distilled off to obtain a crude product. The crude product was purified by silica gel column chromatography (methylene chloride / methanol = 90/10 (volume ratio)) to give (3-methoxy-9,10,10-trioxo-9,10-dihydro-10lambda6-thioxanthen- 6.4 g of 2-yl) (4-t-butylphenyl) iodonium nonafluorobutanesulfonate are obtained. 3-methoxythioxanthen-9-one can be synthesized according to Synthesis Examples 1 to 3.
With (1,2-dimethoxyethane)dichloronickel(II); (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; caesium carbonate; 4,4'-di-tert-butyl-2,2'-bipyridine In N,N-dimethyl acetamide at 25 - 30℃; for 24h; Sealed tube; Irradiation;
With palladium diacetate; triethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 70℃; under 750.075 Torr; for 24h;
General procedure: In a typical experiment Pd(OAc)2 (5.6 mg, 0.025 mmol), triphenylphosphine (13.1 mg, 0.05 mmol), iodobenzene (a) (110 mL, 1.0 mmol) (or an other iodoaromatics, b-i) (1.0 mmol), nucleophile 1 (159.8 mg, 1.2 mmol) (or an other nucleophile, 2e3) (1.2 mmol) and triethylamine (0.5 mL) were dissolved in DMF (10 mL) under argon in a 100 mL three-necked flask equipped with a gas inlet, reflux condenser with a balloon (filled with argon, connected via gas inlet) at the top. The argon atmosphere was changed to carbon monoxide by applying low vacuum/carbon monoxide flushing (three times) through the gas inlet (with tap) equipped to the flask. (The application of a carbon monoxide atmosphere is sufficient, no bubbling of CO is necessary.) The reaction was conducted for the given reaction time upon stirring at 70 C and analysed by GC-MS (internal standard: dodecane). The cooled reaction mixture was then concentrated and evaporated to dryness under reduced pressure. Method A. (1d, 1f, 1h, 2a, 2d, 2e, 2h): The residue was dissolved in chloroform (15 mL) and washed three times with water (30 mL). The organic phase was dried over Na2SO4, filtered and evaporated under reduced pressure to a solid material. Aforesaid compounds were subjected to column chromatography (Silicagel 60 (Merck), 0.063e0.200 mm), EtOAc/CHCl3 eluent mixtures (the exact ratios are specified in Characterization for each compound; isolated yields are not optimized. Method B. (1a-1c, 1e, 1g, 1i, 2b, 2c, 2f, 2g, 2i): Toluene (15 mL) was added to the residue, the insoluble material (product) was filtered, washed with water on the filter and dried. The powder-like material was dissolved in methanol, the palladium-black was filtered off and methanol was evaporated.
With palladium diacetate; triethylamine; triphenylphosphine In N,N-dimethyl-formamide at 70℃; for 24h; chemoselective reaction;
4.2. Aminocarbonylation of iodoaromatics using 2- aminobenzimidazole (1) (or 2-aminobenzoxazole (2)) under atmospheric carbon monoxide pressure
General procedure: In a typical experiment Pd(OAc)2 (5.6 mg, 0.025 mmol), triphenylphosphine (13.1 mg, 0.05 mmol), iodobenzene (a) (110 mL, 1.0 mmol) (or an other iodoaromatics, b-i) (1.0 mmol), nucleophile 1 (159.8 mg, 1.2 mmol) (or an other nucleophile, 2e3) (1.2 mmol) and triethylamine (0.5 mL) were dissolved in DMF (10 mL) under argon in a 100 mL three-necked flask equipped with a gas inlet, reflux condenser with a balloon (filled with argon, connected via gas inlet) at the top. The argon atmosphere was changed to carbon monoxide by applying low vacuum/carbon monoxide flushing (three times) through the gas inlet (with tap) equipped to the flask. (The application of a carbon monoxide atmosphere is sufficient, no bubbling of CO is necessary.) The reaction was conducted for the given reaction time upon stirring at 70 C and analysed by GC-MS (internal standard: dodecane). The cooled reaction mixture was then concentrated and evaporated to dryness under reduced pressure. Method A. (1d, 1f, 1h, 2a, 2d, 2e, 2h): The residue was dissolved in chloroform (15 mL) and washed three times with water (30 mL). The organic phase was dried over Na2SO4, filtered and evaporated under reduced pressure to a solid material. Aforesaid compounds were subjected to column chromatography (Silicagel 60 (Merck), 0.063e0.200 mm), EtOAc/CHCl3 eluent mixtures (the exact ratios are specified in Characterization for each compound; isolated yields are not optimized. Method B. (1a-1c, 1e, 1g, 1i, 2b, 2c, 2f, 2g, 2i): Toluene (15 mL) was added to the residue, the insoluble material (product) was filtered, washed with water on the filter and dried. The powder-like material was dissolved in methanol, the palladium-black was filtered off and methanol was evaporated.
With bis-triphenylphosphine-palladium(II) chloride; 2,2'-azobis(isobutyronitrile); oxygen; triethylamine In N,N-dimethyl-formamide at 110℃; for 4h; Schlenk technique; Sealed tube;
1.2. General Procedure for PdCl2(PPh3)2 catalyzed hydroformylation of alkynes
General procedure: Standard reaction condition: PdCl2(PPh3)2(0.021g, 0.03mmol), glyoxylic acidmonohydrate (0.552g, 6.0mmol) and AIBN (0.082g, 0.05mmol) were transferred intoa 50ml Schlenk tube that was filled with oxygen. DMF (2.0 mL) and aryl halide (1.0mmol) were added to the reaction tube. After Et3N (0.606g, 6.0 mmol) were added,the tube was sealed, and the mixture was stirred at 110 °C for 4-8 h. Upon completionof the reaction, the mixture was poured into saturated aqueous NaCl solution (25ml)and extracted with CH2Cl2 (4x15ml), The combined organic layers were washedwith brine (4x20ml), dried over MgSO4, filtered, and concentrated. The residue waspurified by flash chromatography on silica gel to obtain the desired product by usinglight petroleum ether/ethyl acetate as the eluent.
With bis-triphenylphosphine-palladium(II) chloride; 1,1,3,3-Tetramethyldisiloxane; tetrabutylammomium bromide In 1,4-dioxane at 120℃; for 18h; Inert atmosphere;
5 Specific Example 5:
Specific embodiment five: 130.1 mg (0.5 mmol) 4-tert-butyl iodobenzene, 550.3 mg (5 mmol) dimethyl sulfite, 35.1 mg (0.05 mmol) bistriphenylphosphonium dichloride palladium(II) , 100.7 mg (0.75 mmol) 1,1,3,3-tetramethyldisiloxane, 161.3 mg (0.5 mmol) tetrabutylammonium bromide were added to the reaction tube,heated at120oC for 18 hours, after the reaction was over Cooling, filtering, rotary evaporation of the filtrate to remove the solvent, the residue was subjected to silica gel column chromatography, petroleum ether elution, TLC detection, combined with the effluent containing the product, the solvent was distilled off by a rotary evaporator, and it was vacuum dried to obtain 75.8 mg of a white solid Tert-butyl methyl sulfone, the yield is 72%.
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 60℃; for 3h;
84.84-1 Example 84 (84-1) 9- (4-tert-Butylphenyl) -8-nonanoic acid (Example compound 84-1)
Reference Example Compound 8 (150 mg), 1-tert-butyl-4-iodobenzene (0.207 mL), copper (I) iodide (28 mg), dichloropalladium triphenylphosphine (41 mg), N, N-diisopropylethylamine ( A mixture of 0.67 mL) and tetrahydrofuran (3.9 mL) was stirred at 60 ° C. for 3 hours. 1N Hydrochloric acid was added to the reaction mixture, the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 75: 25-55: 45) to give the title compound (140 mg) as a brown solid.
N-(4-tert-butylphenyl)-1,3-diphenyl-1H-pyrazol-5-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With potassium hydroxide; bis(dibenzylideneacetone)-palladium(0); XPhos In toluene; <i>tert</i>-butyl alcohol at 90℃; for 24h; Inert atmosphere; Schlenk technique;
Synthesis of 1,3-disubstituted N-aryl-1H-pyrazol-5-amines 1a-v (General method)
General procedure: 1,3-Disubstituted1H-pyrazol-5-amine (1 mmol) was dissolved in degassedPhMe-t-BuOH, 5:1 mixture (5 ml) (t-BuOH-H2O, 1:1 forcompounds 1i,m,q,t) in Schlenck tube under Ar atmosphere.Aryl halide (1.1 mmol) was added to the reaction mixturefollowed by the addition of XPhos (5 mol %), Pd2(dba)3(1 mol %), and KOH (1 mmol). The reaction mixture washeated at 90°C for 24 h, cooled to room temperature, thensolids were filtrated off and the filtrate was evaporated. Theresidue was purified by column chromatography on silicagel (Al2O3 for compound 1v), eluent PhMe (for compounds1a-d,f-i,k,m,n,r,s,u,v), CH2Cl2 (for compound 1e), or gradientmixture of PhMe-EtOAc (for compounds 1j,l,o-q,t).Products 1a,b,f,g,k,o,r,u were additionally recrystallizedfrom petroleum ether - EtOAc mixture.
Stage #1: Ethyl bromodifluoroacetate; 1-tert-butyl-4-iodobenzene With copper In dimethyl sulfoxide at 60℃; for 12h; Inert atmosphere;
Stage #2: With methanol; water; potassium carbonate at 20℃; for 2h; Inert atmosphere;
With (1,2-dimethoxyethane)dichloronickel(II); [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; 2,6-bis(pyrazole)pyridine; zinc In 1,4-dioxane; N,N-dimethyl acetamide at 80℃; for 2.5h; Irradiation; regioselective reaction;
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