* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Stage #1: With n-butyllithium; lithium 2-(dimethylamino)ethanolate In hexane at -20 - 0℃; for 1 h; Stage #2: at -20 - 0℃;
The 6,6'-dichloro-2,2'-bipyridine 52a was synthesized by reacting 2-chloropyridine with a mixture of BuLi/Me2N(CH2)2OLi as base for the regioselective lithiation at C-6 (Scheme 23). The 6-lithio-2-chloro-pyridine obtained appears to react with the starting chloropyridine so as to give the corresponding coupling product 52a with a yield of 47percent.
Reference:
[1] Organic Letters, 2000, vol. 2, # 6, p. 803 - 805
[2] Patent: US2010/298562, 2010, A1, . Location in patent: Page/Page column 34
[3] Organic Letters, 2000, vol. 2, # 6, p. 803 - 805
[4] Phosphorus and Sulfur and the Related Elements, 1987, vol. 34, p. 123 - 132
[5] Patent: CN107935919, 2018, A, . Location in patent: Paragraph 0049; 0051
2
[ 5140-72-7 ]
[ 53344-72-2 ]
Yield
Reaction Conditions
Operation in experiment
35%
at 100℃;
The 6,6'-dichloro-2,2'-bipyridine 52a can also be prepared via Stille heterocoupling between the 2-bromo-6-chloropyridine 55 and the 2-chloro-6-tributylstannylpyridine 56, with a yield of 35percent (Scheme 25).
With the aim of improving the preparation of 6,6'-dihalo-2,2'-bipyridines, a different synthesis strategy was envisioned. This synthesis is made up of three steps starting from the 2-chloro-6-methoxypyridine 57; homocoupling of the 2-chloro-6-methoxypyridine 57, followed by hydrolysis of the 6,6'-methoxy groups of the dimer 58, then halogenation of the bipyridinone 59 obtained (Scheme 26). The 2-chloro-6-methoxypyridine 57 is homocoupled in the presence of a stoichiometric amount of a solution (1:0.3:1) of zinc, NiBr2(PPh3)2 and nBu4NI, in DMF at 55° C., so as to give the 6,6'-methoxy-2,2'-bipyridine 58 with a yield of 94percent. The hydrolysis of the 6,6'-methoxy groups is carried out with a mixture of 33percent of hydrobromic acid in acetic acid, at 95° C. for 48 h, with a yield of 94percent. The bipyridinone 59 treated with an excess of phosphorus oxychloride or of phosphorus oxybromide at 95° C., gives, respectively, the 6,6'-dichloro-2,2'-bipyridine 52a and the 6,6'-dibromo-2,2'-bipyridine 52b with virtually quantitative yields.
With bis(bipyridine)nickel(II) bromide; sodium iodide In N,N-dimethyl-formamide at 20℃; for 3.3 h; Electrochemical reaction; Inert atmosphere
General procedure: To an undivided electrochemical cell, fitted by a zinc rod as the anode and surrounded by a nickel foam as the cathode, were added DMF (50 mL), 0.1 M NaI, and 1,2-dibromoethane (2.5 mmol, 215 μL). The mixture was electrolyzed under argon at a constant current intensity of 0.2 A at room temperature for 15-20 min. Then the current was stopped, and [Ni(bpy)]Br2 complex21 (1 mmol, 375 mg), 2,6-dichloropyridine (10 mmol, 1.48 g) or 2,6-dibromopyridine (10 mmol, 2.38 g) were sequentially added. The solution was electrolyzed at 0.1 A and room temperature until the starting material was totally consumed (3.3 h).
With bis(bipyridine)nickel(II) bromide; sodium iodide In N,N-dimethyl-formamide at 20℃; Electrochemical reaction; Inert atmosphere
General procedure: The controlled current preparative electrolysis were carried out with a potentiostat/galvanostat equipment. Undivided cells with 20 mL compartment were used. Zn or Fe metallic rod with 8 mm diameter was used as the sacrificial anode. Ni foam (6 cm.x.3.5 cm) was used as the cathode. It could be re-used after washing with a 6 M HCl solution following by water and acetone, and dried. The same solution was used to clean the anode. A 5 mL DMF solution containing 7percent or 20percent of NiBr2*xH2O or [Ni(bpy)]Br221 and x mmol of the corresponding mixture of 2-bromomethylpyridines or 2,6-dihalopyridines (heterocouplings in Table 1, Table 2, Table 4 and Table 5), or (2.5 mmol) of 2,6-dihalopyridines (homocoupling in Table 3) was stirred or sonicated before the electrolysis, to ensure the solubilization of reagents. A pre-electrolysis was carried out with 15 mL of the electrolytic solution (DMF, 0.1 M NaI and 0.75 mmol of 1,2-dibromoethane), passing a charge of 146 C (I=150 mA). Then, the previous prepared solution of bromopicoline or bromopyridine and the catalyst in 5 mL DMF, was added to the electrolytic cell and the constant current electrolysis (I=100 mA) applied. It is important to ensure that the cell potential must not exceed 1.8 V in order to avoid the reduction of the substrate on the cathode surface. After the total consumption of the reagent (number of coulombs described in the tables), the reaction was stopped and the solvent removed under reduced pressure. The residue was dissolved in CH2Cl2 and washed with several portions of a 6 M NH4OH solution. After drying over Na2SO4, the organic layer was evaporated under reduced pressure.
40 %Chromat.
With bis(bipyridine)nickel(II) bromide; sodium iodide In N,N-dimethyl-formamide at 20℃; Electrochemical reaction; Inert atmosphere
General procedure: The controlled current preparative electrolysis were carried out with a potentiostat/galvanostat equipment. Undivided cells with 20 mL compartment were used. Zn or Fe metallic rod with 8 mm diameter was used as the sacrificial anode. Ni foam (6 cm.x.3.5 cm) was used as the cathode. It could be re-used after washing with a 6 M HCl solution following by water and acetone, and dried. The same solution was used to clean the anode. A 5 mL DMF solution containing 7percent or 20percent of NiBr2*xH2O or [Ni(bpy)]Br221 and x mmol of the corresponding mixture of 2-bromomethylpyridines or 2,6-dihalopyridines (heterocouplings in Table 1, Table 2, Table 4 and Table 5), or (2.5 mmol) of 2,6-dihalopyridines (homocoupling in Table 3) was stirred or sonicated before the electrolysis, to ensure the solubilization of reagents. A pre-electrolysis was carried out with 15 mL of the electrolytic solution (DMF, 0.1 M NaI and 0.75 mmol of 1,2-dibromoethane), passing a charge of 146 C (I=150 mA). Then, the previous prepared solution of bromopicoline or bromopyridine and the catalyst in 5 mL DMF, was added to the electrolytic cell and the constant current electrolysis (I=100 mA) applied. It is important to ensure that the cell potential must not exceed 1.8 V in order to avoid the reduction of the substrate on the cathode surface. After the total consumption of the reagent (number of coulombs described in the tables), the reaction was stopped and the solvent removed under reduced pressure. The residue was dissolved in CH2Cl2 and washed with several portions of a 6 M NH4OH solution. After drying over Na2SO4, the organic layer was evaporated under reduced pressure.
Reference:
[1] Phosphorus and Sulfur and the Related Elements, 1987, vol. 34, p. 123 - 132
10
[ 7275-43-6 ]
[ 53344-72-2 ]
Reference:
[1] Dalton Transactions, 2017, vol. 46, # 7, p. 2238 - 2248
[2] Journal of the Chinese Chemical Society, 2012, vol. 59, # 8, p. 934 - 939
[3] Research on Chemical Intermediates, 2017, vol. 43, # 6, p. 3539 - 3552
11
[ 13267-48-6 ]
[ 53344-72-2 ]
Reference:
[1] Journal of the Chemical Society, Perkin Transactions 1, 1980, p. 2527 - 2530
12
[ 39588-57-3 ]
[ 53344-72-2 ]
Reference:
[1] Bulletin of the Chemical Society of Japan, 1990, vol. 63, # 9, p. 2710 - 2712
13
[ 87512-28-5 ]
[ 7654-51-5 ]
[ 53344-72-2 ]
Reference:
[1] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 12, p. 3848 - 3850
14
[ 17228-64-7 ]
[ 53344-72-2 ]
Reference:
[1] Patent: US2010/298562, 2010, A1,
15
[ 21948-80-1 ]
[ 87512-28-5 ]
[ 119-91-5 ]
[ 53344-72-2 ]
Reference:
[1] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 12, p. 3848 - 3850
16
[ 2895-98-9 ]
[ 53344-72-2 ]
Reference:
[1] Bulletin of the Chemical Society of Japan, 1990, vol. 63, # 9, p. 2710 - 2712
17
[ 77145-64-3 ]
[ 53344-72-2 ]
Reference:
[1] Phosphorus and Sulfur and the Related Elements, 1987, vol. 34, p. 123 - 132
18
[ 39858-88-3 ]
[ 53344-72-2 ]
Reference:
[1] Patent: US2010/298562, 2010, A1,
19
[ 366-18-7 ]
[ 53344-72-2 ]
Reference:
[1] Journal of the Chemical Society, Perkin Transactions 1, 1980, p. 2527 - 2530
[2] Dalton Transactions, 2017, vol. 46, # 7, p. 2238 - 2248
[3] Research on Chemical Intermediates, 2017, vol. 43, # 6, p. 3539 - 3552
The 6,6'-dichloro-2,2'-bipyridine 52a was synthesized by reacting 2-chloropyridine with a mixture of BuLi/Me2N(CH2)2OLi as base for the regioselective lithiation at C-6 (Scheme 23). The 6-lithio-2-chloro-pyridine obtained appears to react with the starting chloropyridine so as to give the corresponding coupling product 52a with a yield of 47%.
With Ni(NO3)2-Ce(NO3)3-La(NO3)3-Mn(NO3)2-impregnated solid catalyst; In methanol; at 300℃; under 13351.3 Torr;
General procedure: The raw material of the reaction system is a pyridine derivative, at 115-130 , 20-30kpa reaction liquid discharged light component separated by distillation and a mixture of the crude 2,2'-bipyridine derivative, pyridine derivative apply.The crude 2,2'-bipyridyl atmospheric boiling point less than 300 deg.] C, and 2,2'-bipyridine derivative crude was purified by distillation, rectification column plate number of 28.1, a pressure of 2.4kPa, tower bottom temperature of 190 , column top temperature of 148 , a reflux ratio of 0.3: 1.An atmospheric boiling point above 300 deg.] C of the crude 2,2'-bipyridyl derivative using a solvent and recrystallized from methanol, and petroleum ether Purification: The crude product that is dissolved in an equal weight of a solvent, heated to 40 , to be dissolved was cooled to 5 crystallized solid was filtered, dried to give 2,2'-bipyridine derivative finished, the crystallization mother liquor applied.
tetrakis(triphenylphosphine) palladium(0); In toluene; at 100℃;
The 6,6'-dichloro-2,2'-bipyridine 52a can also be prepared via Stille heterocoupling between the 2-bromo-6-chloropyridine 55 and the 2-chloro-6-tributylstannylpyridine 56, with a yield of 35% (Scheme 25).
With the aim of improving the preparation of 6,6'-dihalo-2,2'-bipyridines, a different synthesis strategy was envisioned. This synthesis is made up of three steps starting from the 2-chloro-6-methoxypyridine 57; homocoupling of the 2-chloro-6-methoxypyridine 57, followed by hydrolysis of the 6,6'-methoxy groups of the dimer 58, then halogenation of the bipyridinone 59 obtained (Scheme 26). The 2-chloro-6-methoxypyridine 57 is homocoupled in the presence of a stoichiometric amount of a solution (1:0.3:1) of zinc, NiBr2(PPh3)2 and nBu4NI, in DMF at 55 C., so as to give the 6,6'-methoxy-2,2'-bipyridine 58 with a yield of 94%. The hydrolysis of the 6,6'-methoxy groups is carried out with a mixture of 33% of hydrobromic acid in acetic acid, at 95 C. for 48 h, with a yield of 94%. The bipyridinone 59 treated with an excess of phosphorus oxychloride or of phosphorus oxybromide at 95 C., gives, respectively, the 6,6'-dichloro-2,2'-bipyridine 52a and the 6,6'-dibromo-2,2'-bipyridine 52b with virtually quantitative yields.
With bis(bipyridine)nickel(II) bromide; sodium iodide; In N,N-dimethyl-formamide; at 20℃;Electrochemical reaction; Inert atmosphere;
General procedure: The controlled current preparative electrolysis were carried out with a potentiostat/galvanostat equipment. Undivided cells with 20 mL compartment were used. Zn or Fe metallic rod with 8 mm diameter was used as the sacrificial anode. Ni foam (6 cm×3.5 cm) was used as the cathode. It could be re-used after washing with a 6 M HCl solution following by water and acetone, and dried. The same solution was used to clean the anode. A 5 mL DMF solution containing 7% or 20% of NiBr2·xH2O or [Ni(bpy)]Br221 and x mmol of the corresponding mixture of 2-bromomethylpyridines or 2,6-dihalopyridines (heterocouplings in Table 1, Table 2, Table 4 and Table 5), or (2.5 mmol) of 2,6-dihalopyridines (homocoupling in Table 3) was stirred or sonicated before the electrolysis, to ensure the solubilization of reagents. A pre-electrolysis was carried out with 15 mL of the electrolytic solution (DMF, 0.1 M NaI and 0.75 mmol of 1,2-dibromoethane), passing a charge of 146 C (I=150 mA). Then, the previous prepared solution of bromopicoline or bromopyridine and the catalyst in 5 mL DMF, was added to the electrolytic cell and the constant current electrolysis (I=100 mA) applied. It is important to ensure that the cell potential must not exceed 1.8 V in order to avoid the reduction of the substrate on the cathode surface. After the total consumption of the reagent (number of coulombs described in the tables), the reaction was stopped and the solvent removed under reduced pressure. The residue was dissolved in CH2Cl2 and washed with several portions of a 6 M NH4OH solution. After drying over Na2SO4, the organic layer was evaporated under reduced pressure.
16%Chromat.; 40%Chromat.
With bis(bipyridine)nickel(II) bromide; sodium iodide; In N,N-dimethyl-formamide; at 20℃;Electrochemical reaction; Inert atmosphere;
General procedure: The controlled current preparative electrolysis were carried out with a potentiostat/galvanostat equipment. Undivided cells with 20 mL compartment were used. Zn or Fe metallic rod with 8 mm diameter was used as the sacrificial anode. Ni foam (6 cm×3.5 cm) was used as the cathode. It could be re-used after washing with a 6 M HCl solution following by water and acetone, and dried. The same solution was used to clean the anode. A 5 mL DMF solution containing 7% or 20% of NiBr2·xH2O or [Ni(bpy)]Br221 and x mmol of the corresponding mixture of 2-bromomethylpyridines or 2,6-dihalopyridines (heterocouplings in Table 1, Table 2, Table 4 and Table 5), or (2.5 mmol) of 2,6-dihalopyridines (homocoupling in Table 3) was stirred or sonicated before the electrolysis, to ensure the solubilization of reagents. A pre-electrolysis was carried out with 15 mL of the electrolytic solution (DMF, 0.1 M NaI and 0.75 mmol of 1,2-dibromoethane), passing a charge of 146 C (I=150 mA). Then, the previous prepared solution of bromopicoline or bromopyridine and the catalyst in 5 mL DMF, was added to the electrolytic cell and the constant current electrolysis (I=100 mA) applied. It is important to ensure that the cell potential must not exceed 1.8 V in order to avoid the reduction of the substrate on the cathode surface. After the total consumption of the reagent (number of coulombs described in the tables), the reaction was stopped and the solvent removed under reduced pressure. The residue was dissolved in CH2Cl2 and washed with several portions of a 6 M NH4OH solution. After drying over Na2SO4, the organic layer was evaporated under reduced pressure.
With bis(bipyridine)nickel(II) bromide; sodium iodide; In N,N-dimethyl-formamide; at 20℃; for 3.3h;Electrochemical reaction; Inert atmosphere;
General procedure: To an undivided electrochemical cell, fitted by a zinc rod as the anode and surrounded by a nickel foam as the cathode, were added DMF (50 mL), 0.1 M NaI, and 1,2-dibromoethane (2.5 mmol, 215 muL). The mixture was electrolyzed under argon at a constant current intensity of 0.2 A at room temperature for 15-20 min. Then the current was stopped, and [Ni(bpy)]Br2 complex21 (1 mmol, 375 mg), 2,6-dichloropyridine (10 mmol, 1.48 g) or 2,6-dibromopyridine (10 mmol, 2.38 g) were sequentially added. The solution was electrolyzed at 0.1 A and room temperature until the starting material was totally consumed (3.3 h).
With 1-methyl-pyrrolidin-2-one; iron(III)-acetylacetonate; In tetrahydrofuran; diethyl ether; at 20℃; for 3h;
To the suspension of 6,6'-dichloro-(2,2')bipyridinyl (10 g, 44.4 mmol; J. Chem. Soc. Perkin I 1980, 2527; Org. Lett. 2000, 803) and iron(III) acetylacetonate (1.57 g, 4.44 mmol) in tetrahydrofuran (200 mL) and l-methyl-2- pyrrolidinone (25 mL) was added dropwise methyl magnesium bromide (34.1 mL, 102 mmol; 3.0 M in diethyl ether) within 2.5 h and stirring was continued for another 30 min. at room temperature. After addition of ethyl acetate and water the suspension was filtered over Hyflo. The organic layer was separated, washed with brine, dried over sodium sulfate and evaporated in vacuo. The remainder was purified on silica gel, using dichloromethane/ethanol 98:2 as eluent to deliver 6-chloro-6'-methyl-(2,2')bipyridinyl as a white powder, m.p. 135-136C.
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 7h;Schlenk technique; Inert atmosphere;
General procedure: Oven-dried Schlenk flask was evacuated and backfilled with argon three times. In the stream of argon heteroaryl dichloride (1 eq), K2CO3 (3 eq) were placed thereto. Secondary phosphine oxide (2.4 eq) was dissolved in DMF (15 ml/mmol) and the solution was added to the flask. The solution was bubbled with argon for 10 min and Pd(OAc)2 (0.02 eq) and dppf (0.04 eq) were added to the flask simultaneously. The resulting mixture was heated at 80oC for 7 h and then poured into fourfold excess of brine. The mixture was extracted with CH2Cl2 three times (40 ml/mmol each). Combined organic extracts were washed with brine to remove traces of DMF, dried over anhydrous Na2SO4 and then evaporated to dryness. The residue was purified by column chromatography on silica gel 40-60 using CH2Cl2-MeOH mixture as eluent.
[2,2'-bipyridine]-6,6'-diylbis(tert-butyl(phenyl)phosphine oxide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 7h;Schlenk technique; Inert atmosphere;
General procedure: Oven-dried Schlenk flask was evacuated and backfilled with argon three times. In the stream of argon heteroaryl dichloride (1 eq), K2CO3 (3 eq) were placed thereto. Secondary phosphine oxide (2.4 eq) was dissolved in DMF (15 ml/mmol) and the solution was added to the flask. The solution was bubbled with argon for 10 min and Pd(OAc)2 (0.02 eq) and dppf (0.04 eq) were added to the flask simultaneously. The resulting mixture was heated at 80oC for 7 h and then poured into fourfold excess of brine. The mixture was extracted with CH2Cl2 three times (40 ml/mmol each). Combined organic extracts were washed with brine to remove traces of DMF, dried over anhydrous Na2SO4 and then evaporated to dryness. The residue was purified by column chromatography on silica gel 40-60 using CH2Cl2-MeOH mixture as eluent.
6,6’-bis(1,2-dicarba-closo-dodecaboran-1-yl)-2,2’-bipyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73%
General procedure: To an oven-dried reaction vessel equipped with a stir bar and septum, carborane (oCB, mCB, 1E, or 2A =CB, 0.50-1.50 mmol, 1.0-2.0 eq.), solvent (~2 mL), and KHMDS (0.23-4.50 mmol, 1.0-6.0 eq.) were added. After stirring at room temperature for 30-60 minutes, the aryl halide (0.46-1.50 mmol, 1.0-2.0 eq.)was added to the K2[CB] solution. The vessel was sealed, and the reaction was stirred for 14 hours at 25-80C. Reaction progress was monitored via GC-MS, and upon completion the reaction was quenched by the addition of sat. Et3N·HCl or sat. NaHCO3. The resulting biphasic mixture was transferred to aseparatory funnel, and the organic and aqueous layers were separated. The aqueous phase was extracted with ethyl acetate (3 x 10 mL), and the organic phases were combined, dried over MgSO4, and filtered.The solvent was removed under reduced pressure to yield the crude product, which was then purified using silica gel flash column chromatography to yield the desired product. Specific reaction conditions are listed in Table S4.
[2,2'-bipyridine]-6,6'-diylbis(di-tert-butylphosphine oxide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
50%
With 1,1'-bis(diisopropylphosphino)ferrocene; potassium tert-butylate; palladium diacetate; In toluene; at 110℃; for 7h;Schlenk technique; Inert atmosphere;
General procedure: An oven-dried Schlenk flask was evacuated and back-filled with argon three times. (Hetero)aryl (di)halide (1 equiv), base (1.5 equiv per halogen) and a solution of SPO (1.2 equiv per halogen) in anhydrous solvent (5 mL/mmol per halogen) were added to the flask. The solution was bubbled with argon for 10 min and Pd(OAc)2 (1 mol% per halogen) and ferrocene-based bidentate phosphine ligand (2 mol% per halogen) were added to the flask simultaneously [2.5 mol% Pd(OAc)2 per halogen and 5 mol% dppf per halogen for compounds 2j, 2l, 2r, 2t, 2w]. The resulting mixture was heated at the indicated temperature for the given time. Workup procedures are described below for two different conditions. Final purification of crude products was achieved by column chromatography on silica gel (40-60 mum) using CH2Cl2-MeOH as eluent. Reaction scale and yields are shown in Table 1 (2a-w), Scheme 1 (3a-h) and Scheme 2 (4a-g). Notice that all compounds with two phosphine oxide groups are beige-to-brown solids or slowly solidifying viscous brown oils. Conditions I: ligand: dppf, solvent: DMF, base: Cs2CO3 (2d-n, 2q, 2r, 2t-w, 4a-g) or K2CO3 (3a-h), temperature: 120 C, time: 7 h (20 h for 2j, 2l, 2r, 2w). Workup: after cooling, the reaction mixture was poured into a fourfold excess of brine. The mixture was extracted three times with CH2Cl2 (40 mL/mmol each). The combined organic layers were washed with brine to remove traces of DMF, dried over Na2SO4 and then evaporated to dryness. Conditions II: ligand: dippf, solvent: toluene, base: t-BuOK, temperature: 110 C, time: 7 h. Workup: after cooling, the reaction mixture was evaporated to dryness. Then, the mixture was diluted with CH2Cl2 (40 mL/mmol) and washed with water and brine (40 mL/mmol). The organic layer was dried over Na2SO4 and the CH2Cl2 was removed under reduced pressure.
[2,2'-bipyridine]-6,6'-diylbis(dicyclohexylphosphine oxide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
With 1,1'-bis(diisopropylphosphino)ferrocene; potassium tert-butylate; palladium diacetate; In toluene; at 110℃; for 7h;Schlenk technique; Inert atmosphere;
General procedure: An oven-dried Schlenk flask was evacuated and back-filled with argon three times. (Hetero)aryl (di)halide (1 equiv), base (1.5 equiv per halogen) and a solution of SPO (1.2 equiv per halogen) in anhydrous solvent (5 mL/mmol per halogen) were added to the flask. The solution was bubbled with argon for 10 min and Pd(OAc)2 (1 mol% per halogen) and ferrocene-based bidentate phosphine ligand (2 mol% per halogen) were added to the flask simultaneously [2.5 mol% Pd(OAc)2 per halogen and 5 mol% dppf per halogen for compounds 2j, 2l, 2r, 2t, 2w]. The resulting mixture was heated at the indicated temperature for the given time. Workup procedures are described below for two different conditions. Final purification of crude products was achieved by column chromatography on silica gel (40-60 mum) using CH2Cl2-MeOH as eluent. Reaction scale and yields are shown in Table 1 (2a-w), Scheme 1 (3a-h) and Scheme 2 (4a-g). Notice that all compounds with two phosphine oxide groups are beige-to-brown solids or slowly solidifying viscous brown oils. Conditions I: ligand: dppf, solvent: DMF, base: Cs2CO3 (2d-n, 2q, 2r, 2t-w, 4a-g) or K2CO3 (3a-h), temperature: 120 C, time: 7 h (20 h for 2j, 2l, 2r, 2w). Workup: after cooling, the reaction mixture was poured into a fourfold excess of brine. The mixture was extracted three times with CH2Cl2 (40 mL/mmol each). The combined organic layers were washed with brine to remove traces of DMF, dried over Na2SO4 and then evaporated to dryness. Conditions II: ligand: dippf, solvent: toluene, base: t-BuOK, temperature: 110 C, time: 7 h. Workup: after cooling, the reaction mixture was evaporated to dryness. Then, the mixture was diluted with CH2Cl2 (40 mL/mmol) and washed with water and brine (40 mL/mmol). The organic layer was dried over Na2SO4 and the CH2Cl2 was removed under reduced pressure.
[2,2'-bipyridine]-6,6'-diylbis(bis(3,5-dimethylphenyl)phosphine oxide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
91%
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 7h;Schlenk technique; Inert atmosphere;
General procedure: An oven-dried Schlenk flask was evacuated and back-filled with argon three times. (Hetero)aryl (di)halide (1 equiv), base (1.5 equiv per halogen) and a solution of SPO (1.2 equiv per halogen) in anhydrous solvent (5 mL/mmol per halogen) were added to the flask. The solution was bubbled with argon for 10 min and Pd(OAc)2 (1 mol% per halogen) and ferrocene-based bidentate phosphine ligand (2 mol% per halogen) were added to the flask simultaneously [2.5 mol% Pd(OAc)2 per halogen and 5 mol% dppf per halogen for compounds 2j, 2l, 2r, 2t, 2w]. The resulting mixture was heated at the indicated temperature for the given time. Workup procedures are described below for two different conditions. Final purification of crude products was achieved by column chromatography on silica gel (40-60 mum) using CH2Cl2-MeOH as eluent. Reaction scale and yields are shown in Table 1 (2a-w), Scheme 1 (3a-h) and Scheme 2 (4a-g). Notice that all compounds with two phosphine oxide groups are beige-to-brown solids or slowly solidifying viscous brown oils. Conditions I: ligand: dppf, solvent: DMF, base: Cs2CO3 (2d-n, 2q, 2r, 2t-w, 4a-g) or K2CO3 (3a-h), temperature: 120 C, time: 7 h (20 h for 2j, 2l, 2r, 2w). Workup: after cooling, the reaction mixture was poured into a fourfold excess of brine. The mixture was extracted three times with CH2Cl2 (40 mL/mmol each). The combined organic layers were washed with brine to remove traces of DMF, dried over Na2SO4 and then evaporated to dryness. Conditions II: ligand: dippf, solvent: toluene, base: t-BuOK, temperature: 110 C, time: 7 h. Workup: after cooling, the reaction mixture was evaporated to dryness. Then, the mixture was diluted with CH2Cl2 (40 mL/mmol) and washed with water and brine (40 mL/mmol). The organic layer was dried over Na2SO4 and the CH2Cl2 was removed under reduced pressure.
[2,2'-bipyridine]-6,6'-diylbis(dioctylphosphine oxide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 20h;Schlenk technique; Inert atmosphere;
General procedure: An oven-dried Schlenk flask was evacuated and back-filled with argon three times. (Hetero)aryl (di)halide (1 equiv), base (1.5 equiv per halogen) and a solution of SPO (1.2 equiv per halogen) in anhydrous solvent (5 mL/mmol per halogen) were added to the flask. The solution was bubbled with argon for 10 min and Pd(OAc)2 (1 mol% per halogen) and ferrocene-based bidentate phosphine ligand (2 mol% per halogen) were added to the flask simultaneously [2.5 mol% Pd(OAc)2 per halogen and 5 mol% dppf per halogen for compounds 2j, 2l, 2r, 2t, 2w]. The resulting mixture was heated at the indicated temperature for the given time. Workup procedures are described below for two different conditions. Final purification of crude products was achieved by column chromatography on silica gel (40-60 mum) using CH2Cl2-MeOH as eluent. Reaction scale and yields are shown in Table 1 (2a-w), Scheme 1 (3a-h) and Scheme 2 (4a-g). Notice that all compounds with two phosphine oxide groups are beige-to-brown solids or slowly solidifying viscous brown oils. Conditions I: ligand: dppf, solvent: DMF, base: Cs2CO3 (2d-n, 2q, 2r, 2t-w, 4a-g) or K2CO3 (3a-h), temperature: 120 C, time: 7 h (20 h for 2j, 2l, 2r, 2w). Workup: after cooling, the reaction mixture was poured into a fourfold excess of brine. The mixture was extracted three times with CH2Cl2 (40 mL/mmol each). The combined organic layers were washed with brine to remove traces of DMF, dried over Na2SO4 and then evaporated to dryness. Conditions II: ligand: dippf, solvent: toluene, base: t-BuOK, temperature: 110 C, time: 7 h. Workup: after cooling, the reaction mixture was evaporated to dryness. Then, the mixture was diluted with CH2Cl2 (40 mL/mmol) and washed with water and brine (40 mL/mmol). The organic layer was dried over Na2SO4 and the CH2Cl2 was removed under reduced pressure.