2,6-Dibromopyridine oxide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:62.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,6-dibromopyridine 1-oxide (34.0 g, 0.13 mol) in sulfuric acid (120 mL) was cooled to 0-5° C. followed by addition of nitric acid (60 mL). The reaction mixture was stirred at the same temperature for 10-15 min then heated to 60-65° C. for 20 h. The reaction was then cooled to rt, poured into ice-cold water and neutralized with aqueous ammonia solution. The resulting solution was stirred for 10 min at 0-5° C. then filtered and dried to obtain the desired product as a pale yellow solid (32 g, 83%). The reaction was then cooled to rt The resulting solution was stirred for 10 min at 0-5° C. then filtered dried

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice-cold solution of 2,6-dibromopyridine (50 g, 0.21 mol) in trifluoroacetic acid (250 mL) was added 30% H2O2 solution (70 mL) drop wise over 1 h. The reaction mixture was washed, heated to 100° C. for 16 h then cooled to rt, poured into 1.50 L of water and the precipitate filtered. The solid thus obtained (10 g) was the starting material (2,6-dibromopyridine). The filtrate was extracted with dichloromethane (3×1 L) and the combined organic layer was washed with 0.50 M K2CO3 solution (3×500 mL). The organic layer was then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was treated with hexane then filtered to obtain the desired product as an off white solid (38.50 g, 72% and 90% yield based on the recovery of the starting material). The reaction mixture was washed then cooled to rt poured into 1.50 L of water the precipitate filtered The solid thus obtained (10 g) The filtrate was extracted with dichloromethane (3×1 L) the combined organic layer was washed with 0.50 M K2CO3 solution (3×500 mL) The organic layer was then dried over anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was treated with hexane then filtered

Conditions: temp:79.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,6-dibromo pyridine 1-oxide (10 g, 39.5 mmol) was added to 65 mL of concentrated sulfuric acid at room temperature without cooling. Concentrated sulfuric acid (15 ml) and nitric acid (13.3 ml) were mixed and placed in a pressure equalising dropping funnel. The reaction mixture was heated to 79° C. then the nitrating mixture was added in portions over 25 minutes. When the addition was complete the mixture was stirred at 83-85° C. for 3.5 hours. The mixture was cooled to room temperature and slowly poured onto ˜250 g crushed ice. A very pale yellow solid formed which was filtered off and washed with water (100 ml), dried in vacuum oven at 50° C. overnight to give 10.9 g of the title compound. without cooling the nitrating mixture was added in portions over 25 minutes When the addition The mixture was cooled to room temperature slowly poured onto ˜250 g crushed ice A very pale yellow solid formed which was filtered off washed with water (100 ml) dried in vacuum oven at 50° C. overnight

Conditions: temp:79.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,6-dibromo pyridine 1-oxide (10 g, 39.5 mmol) was added to 65 mL of concentrated sulfuric acid at room temperature without cooling. Concentrated sulfuric acid (15 ml) and nitric acid (13.3 ml) were mixed and placed in a pressure equalising dropping funnel. The reaction mixture was heated to 79° C. then the nitrating mixture was added in portions over 25 minutes. When the addition was complete the mixture was stirred at 83-85° C. for 3.5 hours. The mixture was cooled to room temperature and slowly poured onto ˜250 g crushed ice. A very pale yellow solid formed which was filtered off and washed with water (100 ml), dried in vacuum oven at 50° C. overnight to give 10.9 g of the title compound. without cooling the nitrating mixture was added in portions over 25 minutes When the addition The mixture was cooled to room temperature slowly poured onto ˜250 g crushed ice A very pale yellow solid formed which was filtered off washed with water (100 ml) dried in vacuum oven at 50° C. overnight

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,6-dibromo pyridine (79 g, 334 mmol) was dissolved in 800 ml of dry dichloromethane and cooled under nitrogen to 5° C. then urea hydrogen peroxide (104 g, 1.1 mol) was added in one portion. When the mixture had cooled again to 3° C., a solution of trifluoro acetic acid anhydride (140 mL, 1 mol) in 100 ml DCM was added via dropping funnel over 45 min, whilst keeping the temperature between 5-7° C. The mixture was allowed to warm to room temperature and stirred for 20 hours. The mixture was cooled in an ice bath to 10° C. and 10% aq. Na2SO3 (˜50 g/500 ml) was added dropwise over 60 minutes until test with starch iodide paper was negative. The resulting mixture was filtered to remove a quantity of fluffy solid and the layers were separated. The aqueous layer was extracted with dichloromethane (2×200 ml) and the combined extracts were dried over MgSO4 and concentrated under reduced pressure to give a light brown solid. Recrystallisation of crude product using 600ml of boiling acetone gave 48.47 g of the title compound. When the mixture had cooled again to 3° C. over 45 min between 5-7° C to warm to room temperature The mixture was cooled in an ice bath to 10° C. The resulting mixture was filtered to remove a quantity of fluffy solid the layers were separated The aqueous layer was extracted with dichloromethane (2×200 ml) the combined extracts were dried over MgSO4 concentrated under reduced pressure to give a light brown solid Recrystallisation of crude product

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,6-dibromopyridine-N-oxide (6.28 g) was dissolved in concentrated sulphuric acid (20 ml) with stirring. A mixture of concentrated sulphuric acid (20 ml) and concentrated nitric acid (10 ml) was then continuously added dropwise. The solution was then heated at 90° C. for 3 hours with stirring, poured onto ice and then basified with sodium hydroxide. The solution was then continuously extracted with ether, and recrystallised from ethanol to give pale yellow leaflets of 4-nitro-2,6-dibromopyridine-N-oxide (1.2 g, 16%), m.p. 222° C.-224° C. was then continuously added dropwise with stirring poured onto ice The solution was then continuously extracted with ether recrystallised from ethanol

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 20 g (78 mmol) of 2,6-dibromopyridine 1-oxide is warmed to 40° C. in 70 ml of H2SO4. Nitrating acid (70 ml of H2SO4 and 34 ml of fuming HNO3) is added to the solution at this temperature. The reaction mixture is heated at 90° C. for 3 h. After cooling, the reaction mixture is poured into 800 ml of ice-water. The solid which has precipitated out is filtered off and washed with water. After drying, the 2,6-dibromo-4-nitropyridine 1-oxide (17.9 g) is suspended in 200 ml of chloroform, 6 ml of phosphorus tribromide (64 mmol) are added at room temperature, and the mixture is stirred for 1 h and then heated under reflux for 2 days. After cooling, the solution is poured into 500 ml of ice-water, and the mixture is neutralised using solid NaHCO3. The aqueous phase is separated off and extracted a number of times with CHCl3, and the combined organic phases are washed with a sodium thiosulfate solution and then with water, dried and evaporated. The residue is recrystallised from EtOH. Yield: 41.7 g (148 mmol), 70% of theory. After cooling The solid which has precipitated out is filtered off washed with water After drying heated under reflux for 2 days After cooling The aqueous phase is separated off extracted a number of times with CHCl3 the combined organic phases are washed with a sodium thiosulfate solution with water, dried evaporated The residue is recrystallised from EtOH

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 20 g (78 mmol) of 2,6-dibromopyridine 1-oxide is warmed to 40° C. in 70 ml of H2SO4. Nitrating acid (70 ml of H2SO4 and 34 ml of fuming HNO3) is added to the solution at this temperature. The reaction mixture is heated at 90° C. for 3 h. After cooling, the reaction mixture is poured into 800 ml of ice-water. The solid which has precipitated out is filtered off and washed with water. After drying, the 2,6-dibromo-4-nitropyridine 1-oxide (17.9 g) is suspended in 200 ml of chloroform, 6 ml of phosphorus tribromide (64 mmol) are added at room temperature, and the mixture is stirred for 1 h and then heated under reflux for 2 days. After cooling, the solution is poured into 500 ml of ice-water, and the mixture is neutralised using solid NaHCO3. The aqueous phase is separated off and extracted a number of times with CHCl3, and the combined organic phases are washed with a sodium thiosulfate solution and then with water, dried and evaporated. The residue is recrystallised from EtOH. Yield: 41.7 g (148 mmol), 70% of theory. After cooling The solid which has precipitated out is filtered off washed with water After drying heated under reflux for 2 days After cooling The aqueous phase is separated off extracted a number of times with CHCl3 the combined organic phases are washed with a sodium thiosulfate solution with water, dried evaporated The residue is recrystallised from EtOH

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: