6,6'-Dichloro-2,2'-bipyridine

The 6, 6'-dichloro-2, 2'-bipyridine 52a was synthesized by reacting 2-chloropyridine with a mixture of BuLi/MeThe 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, NiBrGeneral 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)]BrGeneral 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 NiBrGeneral 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 NiBrThe 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).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%.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.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.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.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.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.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.

Molecular Weight:225.07
XLogP3:3.4
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:223.9908036
Monoisotopic Mass:223.9908036
Topological Polar Surface Area:25.8
Heavy Atom Count:14
Complexity:169
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes