4′-Methyl[2,2′-bipyridine]-4-carboxylic acid

A mixture of 1, 4-dioxane (250 mL), SeO2 (3.07 g, 27.7 mmol, 1.2 eq) and 4, 4'-dimethyl-2, 2'-bipyridine (3.07 g, 27.7 mmol, 1.2 eq) was stirred and refluxed for 24 h. When the reaction mixture turned pale yellow, Se was filtered off using afilter agent (Celite 545). The mixture was then cooled down and the solution was stored in a vacuum to remove solvent. The solid was subsequently recovered and dispersed in 95% ethanol (150 mL), followed by the addition of water (40 mL) containing AgNO3 (4.31 g, 25.4 mmol, 1.1 eq); 1.0 M NaOH (100 mL) was dropped for 20 min. The black mixture was stirred vigorously for 15 h at room temperature; the solvent was evaporated. Ag2O and Ag were filtered off and washed with 1.3 M NaOH aqueous solution. The solution was then extracted with dichloromethane to remove unreacted phenanthroline. The water layer was acidified with 1:1 (v/v) 4.0 N HCl/Acetic acid to a pH of 3.5 and allowed to cool to 0 C over 12 h. The white precipitate was collected by filtration. The solid was dried under vacuum and extracted with purified acetone for 3 d using a Soxhlet apparatus. The solvent was evaporated to obtain the product (2.52 g, 51 %) (Scheme 1).Synthesis of ligand; 40 g of 4, 4'-dimethyl-2, 2'-bipyridine was added to 1 liter of concentrated sulfuric acid having a concentration of 98 wt% little by little under stirring to be dissolved in the concentrated sulfuric acid. 55 g of potassium dichromate was added to the resulting solution little by little while the temperature of the solution was maintained at 65C or lower. The reaction mixture was left to be cooled to room temperature (23C) and poured into 12 liters of iced water under stirring. After 2 hours of stirring, the precipitate was collected by filtration and rinsed with water. The obtained solid was re-dissolved in ether and the resulting solution was let pass through a silica gel column to be purified, and the solvent was removed to obtain 3.8 g of a product. It was found that the product was 4-carboxy-4'-methyl-2, 2'-bipyridine by 1H-NMR analysis.Synthesis of ligand; 6.39 g of 4, 4'-dimethyl-2, 2'-bipyridine, 4.16 g of selenium dioxide and 375 ml (386.4 g) of 1, 4-dioxane were charged into a vessel, refluxed for 24 hours and thermally filtered. After the filtrate was concentrated, 225 ml of ethanol and an aqueous solution of silver nitrate (6.48 g/50 ml) were added to the concentrated filtrate, and further 100 ml of an aqueous solution of sodium hydroxide having a concentration of 1.5 mol/l was added to the resulting solution. This solution was stirred at room temperature for 15 hours. The solution was then filtered. The ethanol in the filtrate was removed under reduced pressure. The residual solution was washed with 150 ml of chloroform. When a mixed solution of acetic acid and 4N hydrochloric acid in a volume ratio of 1:1 was added to the solution after washing to adjust the pH of the solution to 3.5, a white solid precipitated out. This solid was left to stand at 10C for 24 hours, separated by filtration and dried. This solid was extracted with isopropyl alcohol, then the solvent was removed under reduced pressure to obtain 2.26 g of a product. It was found that the product was 4-carboxy-4'-methyl-2, 2'-bipyridine by 1H-NMR analysis. 1H-NMR (DMSO-d6, 298K, 270MHz, delta(ppm)) ; delta = 8.86 (d, 1H), 8.82 (s, 1H), 8.58 (d, 1H), 8.27 (s, 1H), 7.86 (s, 1H), 7.33 (d, 1H), 2.44 (s, 3H, Me)The combined basic filterate was extracted with DCM to remove unreacted aldehyde and adjusted to pH 3.5 with 1:1(v/v) 4N HCl/AcOH to afford white compound. After keeping overnight at -10 C. the compound was collected and dried to afford pure compound 2.9 g (77%). Mass Spect. (FAB) MW 215 [M+]; NMR assigned.[(Cp*)Ir(mu-Cl)Cl]2 (39.8 mg, 0.05 mmol) was dissolved in methanol(20 mL) followed by addition of the 4-methyl-4?-carboxy-2, 2?-bipyridine ligand (21.4 mg, 0.10 mmol). The mixture was stirred at313 K overnight. The final yellow solution was filtered, concentratedand NH4PF6 (163 mg, 1.0 mmol) was added to the solution. This solutionwas kept at 277 K overnight. The yellow precipitate was collectedby filtration and dried under vacuum. Yield 66 mg, 91%; 1H NMR(400 MHz, d4-MeOD, 298 K): delta 9.11 (d, 1H, J = 5.8 Hz), 9.00 (s, 1H), 8.81 (d, 1H, J=5.8 Hz), 8.61 (s, 1H), 8.26 (d, 1H, J=5.8 Hz), 7.71 (d, 1H, J = 6.1 Hz), 2.70 (s, 3H), 1.72 (s, 15H); 13C NMR (125 MHz, d4-MeOD, 298 K): 165.79, 158.15, 155.99, 155.08, 154.10, 152.47, 143.72, 131.21, 129.19, 126.65, 124.58, 91.28, 21.39, 8.67; high resolutionESI-MS m/z calcd for [(M-PF6-H)+Na]+ 599.1040, found599.1038.4, 4'-Dimethyl-2, 2'-bipyridine (1.5 g, 8 mmol) and selenium dioxide (887.68 mg, 8 mmol) were refluxed in 100 ml of 1, 4-dioxane for 24 hours, after cooling to room temperature, the black solid was filtered off and solvent was removed by evaporation to give a white solid. This solid was dissolved by stirring with 100 ml of ethyl acetate, the insoluble material was filtered off, and the filtrate was washed three times with 20 ml of a 1.0 M sodium carbonate solution. The organic phase was extracted three times with 50 ml of 0.3 M sodium metabisulfite solution, the aqueous phase was combined, the pH was adjusted to 10 with sodium carbonate solution, and extracted four times with 20 ml of chloroform, the organic phase was combined, which was dried over anhydrous sodium sulfate and solvent was removed by evaporation to give a crude product. The crude product was purified by column chromatography eluting with petroleum ether / ethyl acetate (1: 4) to give aldehyde-substituted bipyridine 398 mg was obtained in a yield of 25%. The aldehyde-substituted bipyridine was dissolved in 20 ml of ethanol, stirred with 4 ml of a silver nitrate aqueous solution, then 10 ml of a 1.0 M aqueous sodium hydroxide solution was slowly added and reacted at room temperature for 15 hours. The solvent was removed by evaporation and the solid was washed twice with 4 ml of 1.3 M sodium hydroxide and 4 ml of water, the combined filtrate was extracted three times with 10 ml of chloroform, aqueous phase pH was 3.5 with 4 M hydrochloric acid, the resulting white solid was filtered and dried in vacuo to give carboxy-substituted bipyridine 258 mg, yield 60%. The resulting carboxyl substituted bipyridine (1.3 mmol) was all dissolved in 20 ml DMF, then aminothiazole compound (300 mg, 1.3 mmol), 1-hydroxy-7-azobenzotriazole (1.3 mmol, 177 mg), 4-dimethylaminopyridine (1.3 mmol, 146 mg), 1-ethyl-carbonyldiimide hydrochloride (1.3 mmol, 87 mg) were added thereto, and stirred at room temperature for 6 hours. The obtained solid was filtered, washed four times with 25 ml of water and dried in vacuo to give the Aminothiazole functional group-substituted polypyridine ligand (L1) 457 mg, yield 82%. All the obtained L1 (1.06 mmol) and the compound cis-[Ru(bpy)2Cl2].2H2O (442 mg, 0.85 mmol) were refluxed under 20 ml of ethylene glycol and argon gas protection for 8 hours. After cooling to room temperature, 10 ml of a saturated aqueous solution of ammonium hexafluorophosphate was added, the obtained orange precipitate was filtered, washed once with 15 ml of water, washed three times with 30 ml of anhydrous diethyl ether and dried in vacuo to give crude product. The crude product is subjected to neutral alumina column chromatography, and the only orange component is eluted with acetonitrile to obtain the target polypyridyl ruthenium complex Ru1, amount 616 mg, yield 64%