2-bromo-6-methyl-1-oxidopyridin-1-ium

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To cooled nitric acid (concentrated, 168 ml) was added sulfuric acid (concentrated, 300 ml) under cooling followed by 2-bromo-6-methyl-pyridine 1-oxide (35 g, 0.186 mol). The mixture was stirred at 70° C. for 4 hours, cooled to room temperature and poored slowly on crushed ice. A stream of nitrogen was bubbled through the mixture overnight. The mixture was basified to pH 8 under cooling with NaOH (10N, ca. 1 L), diluted with water (3 L) and extracted with DCM (5×). The combined organic phases were dried (sodium sulfate) and evaporated to dryness to yield 27.6 g of a yellow crystaline solid (0.118 mol, 57%). under cooling cooled to room temperature poored slowly on crushed ice A stream of nitrogen was bubbled through the mixture overnight under cooling with NaOH (10N, ca. 1 L) diluted with water (3 L) extracted with DCM (5×) The combined organic phases were dried (sodium sulfate) evaporated to dryness

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To cooled nitric acid (concentrated, 168 ml) was added sulfuric acid (concentrated, 300 ml) under cooling followed by 2-bromo-6-methyl-pyridine 1-oxide (35 g, 0.186 mol). The mixture was stirred at 70° C. for 4 hours, cooled to room temperature and poored slowly on crushed ice. A stream of nitrogen was bubbled through the mixture overnight. The mixture was basified to pH 8 under cooling with NaOH (10N, ca. 1 L), diluted with water (3 L) and extracted with DCM (5×). The combined organic phases were dried (sodium sulfate) and evaporated to dryness to yield 27.6 g of a yellow crystaline solid (0.118 mol, 57%). under cooling cooled to room temperature poored slowly on crushed ice A stream of nitrogen was bubbled through the mixture overnight under cooling with NaOH (10N, ca. 1 L) diluted with water (3 L) extracted with DCM (5×) The combined organic phases were dried (sodium sulfate) evaporated to dryness

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

Procedure: 2-Bromo-6-methylpyridine (36 g, 0.2 mol) was dissolved in acetic acid (700 ml), hydrogen peroxide (30%, 62 ml, 0.6 mol) was added and the mixture was stirred at 90° C. for 24 hours. After cooling to room temperature, the mixture was diluted with water (700 ml) and extracted with DCM (4×). The combined organic phases were washed with water, dried (sodium sulfate) and concentrated under reduced pressure to give 36 g of a red-brown liquid (0.19 mol, 94%) MS(APCI) m/z=188.0 [M+1]+. After cooling to room temperature extracted with DCM (4×) The combined organic phases were washed with water dried (sodium sulfate) concentrated under reduced pressure

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated nitric acid (4 mL) was added to cold concentrated sulfuric acid (7 mL). 2-Bromo-6-methyl-pyridine 1-oxide (820 mg, 4.36 mmol) was added to this and then heated at 70° C. for 4 h. The mixture was cooled and poured slowly into ice-cold water (100 mL) and basified to pH ˜8 with sodium bicarbonate solution. This was extracted with ethyl acetate (4×50 mL) then the combined organic layers were dried over anhydrous sodium sulfate and concentrated to give a residue which was purified by washing with pentane (50 mL) to afford 2-bromo-6-methyl-4-nitro-pyridine 1-oxide (0.41 g, 40%) as a free flowing yellow solid. The mixture was cooled This was extracted with ethyl acetate (4×50 mL) the combined organic layers were dried over anhydrous sodium sulfate concentrated to give a residue which was purified by washing with pentane (50 mL)

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

Procedure: Hydrogen peroxide (30%, 1.76 mL, 17.4 mmol) was added to a solution of 2-bromo-6-methyl-pyridine (1.0 g, 5.80 mmol) in acetic acid (20 mL), and heated for 24 h at 90° C. The reaction mixture was cooled to ambient temperature, and partitioned between dichloromethane and water. The aqueous phase was separated and extracted with dichloromethane. The combined organic phases were washed thoroughly with water and dried over anhydrous sodium sulfate. Concentration in vacuo afforded 2-bromo-6-methyl-pyridine 1-oxide (820 mg, 75%) as a brown liquid which was used in the next step without further purification. The reaction mixture was cooled to ambient temperature partitioned between dichloromethane and water The aqueous phase was separated extracted with dichloromethane The combined organic phases were washed thoroughly with water dried over anhydrous sodium sulfate Concentration in vacuo

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated nitric acid (4 mL) was added to cold concentrated sulfuric acid (7 mL). 2-Bromo-6-methyl-pyridine 1-oxide (820 mg, 4.36 mmol) was added to this and then heated at 70° C. for 4 h. The mixture was cooled and poured slowly into ice-cold water (100 mL) and basified to pH ˜8 with sodium bicarbonate solution. This was extracted with ethyl acetate (4×50 mL) then the combined organic layers were dried over anhydrous sodium sulfate and concentrated to give a residue which was purified by washing with pentane (50 mL) to afford 2-bromo-6-methyl-4-nitro-pyridine 1-oxide (0.41 g, 40%) as a free flowing yellow solid. The mixture was cooled This was extracted with ethyl acetate (4×50 mL) the combined organic layers were dried over anhydrous sodium sulfate concentrated to give a residue which was purified by washing with pentane (50 mL)

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

Procedure: Hydrogen peroxide (30%, 1.76 mL, 17.4 mmol) was added to a solution of 2-bromo-6-methyl-pyridine (1.0 g, 5.80 mmol) in acetic acid (20 mL), and heated for 24 h at 90° C. The reaction mixture was cooled to ambient temperature, and partitioned between dichloromethane and water. The aqueous phase was separated and extracted with dichloromethane. The combined organic phases were washed thoroughly with water and dried over anhydrous sodium sulfate. Concentration in vacuo afforded 2-bromo-6-methyl-pyridine 1-oxide (820 mg, 75%) as a brown liquid which was used in the next step without further purification. The reaction mixture was cooled to ambient temperature partitioned between dichloromethane and water The aqueous phase was separated extracted with dichloromethane The combined organic phases were washed thoroughly with water dried over anhydrous sodium sulfate Concentration in vacuo

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To cooled nitric acid (concentrated, 168 ml) was added sulfuric acid (concentrated, 300 ml) under cooling followed by 2-bromo-6-methyl-pyridine 1-oxide (35 g, 0.186 mol). The mixture was stirred at 70° C. for 4 hours, cooled to room temperature and poured slowly on crushed ice. A stream of nitrogen was bubbled through the mixture overnight. The mixture was basified to pH 8 under cooling with NaOH (10N, ca. 1 L), diluted with water (3 L) and extracted with DCM (5×). The combined organic phases were dried (sodium sulfate) and evaporated to dryness to yield 27.6 g of a yellow crystalline solid (0.118 mol, 57%). under cooling cooled to room temperature poured slowly on crushed ice A stream of nitrogen was bubbled through the mixture overnight under cooling with NaOH (10N, ca. 1 L) diluted with water (3 L) extracted with DCM (5×) The combined organic phases were dried (sodium sulfate) evaporated to dryness

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

Procedure: 2-Bromo-6-methylpyridine (36 g, 0.2 mol) was dissolved in acetic acid (700 ml), hydrogen peroxide (30%, 62 ml, 0.6 mol) was added and the mixture was stirred at 90° C. for 24 hours. After cooling to room temperature, the mixture was diluted with water (700 ml) and extracted with DCM (4×). The combined organic phases were washed with water, dried (sodium sulfate) and concentrated under reduced pressure to give 36 g of a red-brown liquid (0.19 mol, 94%) MS (APCI) m/z=188.0 [M+1]+. After cooling to room temperature extracted with DCM (4×) The combined organic phases were washed with water dried (sodium sulfate) concentrated under reduced pressure

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To cooled nitric acid (concentrated, 168 ml) was added sulfuric acid (concentrated, 300 ml) under cooling followed by 2-bromo-6-methyl-pyridine 1-oxide (35 g, 0.186 mol). The mixture was stirred at 70° C. for 4 hours, cooled to room temperature and poored slowly on crushed ice. A stream of nitrogen was bubbled through the mixture overnight. The mixture was basified to pH 8 under cooling with NaOH (10N, ca. 1 L), diluted with water (3 L) and extracted with DCM (5×). The combined organic phases were dried (sodium sulfate) and evaporated to dryness to yield 27.6 g of a yellow crystaline solid (0.118 mol, 57%). under cooling cooled to room temperature poored slowly on crushed ice A stream of nitrogen was bubbled through the mixture overnight under cooling with NaOH (10N, ca. 1 L) diluted with water (3 L) extracted with DCM (5×) The combined organic phases were dried (sodium sulfate) evaporated to dryness