4-Bromo-2,2''-bipyridine

A 5 L round-bottom flask was substituted with nitrogen gas, and 107 g of Formula 1-c (0.43 mol) was added thereto, and dissolved by addition of 2.7 L of chloroform. At 0° C., 180.3 g of tribromophosphine (1.92 mol) was slowly dropwise added thereto, followed by stirring at 60° C. for 2 hours. The resultant product was cooled to room temperature, added to 2 L of water, added with a sodium hydroxide aqueous solution until pH reached 11, and extracted with methylene chloride. Then, an organic layer was separated. After removal of moisture, and removal of a solvent by vacuum distillation, the precipitated solid was washed with ethanol, and filtered so as to provide 100 g of Formula 1-d brown solid (yield 99percent).Under a nitrogen atmosphere, asolution of 4-bromo-2, 2’-bipyridineN-oxide (786 mg, 3.13 mmol) in drychloroform (10 mL) was cooled to0 °C and PBr3 (1.0 mL, 10 mmol) wasadded. After refluxing for 5 h, the solution was poured into ice water, basified with 6 Naqueous NaOH solution and extracted with CHCl3. The organic layer was dried overanhydrous Na2SO4 and concentrated to give white solid 8 (728 mg, 3.09 mmol, 98.7percent).1H NMR (CDCl3): = 8.69 (d, J = 5.0 Hz, 1H), 8.63 (d, J = 1.8 Hz, 1H), 8.49 (d, J =5.1 Hz, 1H), 8.39 (d, J = 8.0 Hz, 1H), 7.83 (dt, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 7.48 (dd, J1= 5.1 Hz, J2 = 1.8 Hz, 1H), 7.34 (ddd, J1 = 7.5 Hz, J2 = 4.8 Hz, J3 = 1.6 Hz, 1H). IR(KBr): = 1565, 1545, 1452, 1386, 1280, 1066, 994, 833, 787, 687 cm-1. Mp:51.5-53 °C. ESI-MS: m/z = 256.9, 258.9 [8+Na]+ (calcd. for C10H7N2Br+Na = 256.9, 258.9).The stirred suspension of C (27.0 g; 0.108 mol) in 500 ml ofchloroform was cooled to 0°C and 50 ml of phosphorus tribromide was added (0.526 mol)was added dropwise. The mixture obtained was refluxed for 2 h, poured onto ice andneutralized with 20percent NaOH. The organic phase was separated and the water layer wasextracted with dichloromethane (3 x 100 ml). The combined organic extracts were washedwith cold water (100 ml), dried with Na2SO4 and evaporated. The crude product wascrystallized from ethanol, to give 20.9 g of white powder crystals (mp 53-55 °C; yield 83percent).Compound 3 (1.7 g, 8.1 mmol) was dissolved in 20.0 cm3glacial acetic acid. To this solution 3.0 cm3 acetylbromide (40.5 mmol) were added. The solution immediatelyturned yellow. The microwave vessel was sealedand heated to 130 C in a way that during a period of10 min 130 C had to be reached using a maximumpower of 1000 W. The reaction temperature then wasmaintained for 2 h after which the vessel was allowed tocool down to room temperature. After cooling, thesolution was poured onto ice and basified to pH 10–11with sodium hydroxide solution (6 N). The aqueous phasewas extracted three times with CH2Cl2 (40 cm3 each).The solvent was evaporated under reduced pressure. Theobtained light brown oil solidified at room temperatureovernight. The crude product was further purified bydistillation under reduced pressure to obtain a white solid.Yield: 75percent (1.6 g, 6.8 mmol); m.p.: 53–55 C; MS (EI):m/z (percent) = 234.3 (85) [M?], 235.9 (83) [M?], 155.1 (100)[M?–Br].Under a nitrogen atmosphere, acetylbromide (2.0 mL, 27 mmol) wasadded to a solution of4-nitro-2, 2’-bipyridine N-oxide (1.00g, 4.60 mmol) in glacial acetic acidand the mixture was refluxed for 4 h. After cooling to room temperature, the mixturewas poured into ice water and basified with 16 N aqueous NaOH solution and extractedwith CHCl3. The organic layer was dried over anhydrous Na2SO4 and concentrated toafford the mixture of 4-bromo-2, 2’-bipyridine N-oxide and 8. The mixture was purified bysilica gel column choromatography with ethyl acetate/hexane/triethylamine (v/v/v, 40/13/1) to obtain 4-bromo-2, 2’-bipyridine N-oxide (927 mg, 3.69 mmol, 80.3percent) and 8(158 mg, 0.673 mmol, 14.6percent) as a white solid. 1H NMR (CDCl3): = 8.95 (d, J = 8.0 Hz, 1H), 8.74 (d, J = 4.9 Hz, 1H), 8.41 (d, J =8.0Hz, 1H), 8.15 (d, J = 6.9 Hz, 1H), 7.85 (dt, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 7.40-7.35 (m, 2H). IR (KBr): = 3065, 1584, 1567, 1463, 1437, 1396, 1254, 1235, 824, 737, 649 cm-1.Mp: 107-108 °C.ESI-MS: m/z = 272.9, 274.9 [M+Na]+ (calcd. for C10H7N2OBr+Na = 272.9, 274.9).

Molecular Weight:235.08
XLogP3:2.4
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:233.97926
Monoisotopic Mass:233.97926
Topological Polar Surface Area:25.8
Heavy Atom Count:13
Complexity:163
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes