2-bromo-1-oxidopyridin-1-ium;hydrochloride

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

Procedure: In 14 ml of N,N-dimethylformamide was suspended 0.38 g of sodium hydride (60% in oil) followed by addition of 1.00 g of 3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazine. Then, 1.01 g of 2-bromopyridine N-oxide hydrochloride was added with ice-cooling and the mixture was stirred at 70° C. for 16 hours. The reaction mixture was poured in ice-water and extracted with ethyl acetate. The organic layer was washed with aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography and elution was carried out with chloroform-acetone (3:1) to give 0.34 g of 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide as oil. Then, a solution of hydrochloric acid in ethanol (prepared from 1 ml of concentrated hydrochloric acid and 5 ml of ethanol) was added thereto and the solvent was distilled off. The resulting residue wad recrystallized from acetone to give 182 mg of 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide hydrochloride. cooling extracted with ethyl acetate The organic layer was washed with aqueous sodium chloride solution dried over anhydrous magnesium sulfate the solvent was distilled off The residue was subjected to silica gel column chromatography and elution

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

Procedure: In 10 ml of N,N-dimethylformamide was dissolved 2.66 g of 3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazine followed by addition of 1.02 g of sodium hydride (60% in oil) and the mixture was stirred at room temperature for 30 minutes. Then, 2.77 g of 2-bromopyridine N-oxide hydrochloride was added with ice-cooling and, after the evolution of heat had subsided, the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured in water and extracted with ethyl acetate. The organic layer was separated and dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was chromatographed on a silica gel column using chloroform as the eluent to give crude 2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide. cooling after the evolution of heat the mixture was stirred at room temperature for 2 hours extracted with ethyl acetate The organic layer was separated dried over anhydrous magnesium sulfate filtered The filtrate was concentrated under reduced pressure the residue was chromatographed on a silica gel column

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

Procedure: In 14 ml of N,N-dimethylformamide was suspended 0.38 g of sodium hydride (60% in oil) followed by addition of 1.00 g of 3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazine. Then, 1.01 g of 2-bromopyridine N-oxide hydrochloride was added with ice-cooling and the mixture was stirred at 70° C. for 16 hours. The reaction mixture was poured in ice-water and extracted with ethyl acetate. The organic layer was washed with aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography and elution was carried out with chloroform-acetone (3:1) to give 0.34 g of 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide as oil. Then, a solution of hydrochloric acid in ethanol (prepared from 1 ml of concentrated hydrochloric acid and 5 ml of ethanol) was added thereto and the solvent was distilled off. The resulting residue wad recrystallized from acetone to give 182 mg of 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide hydrochloride. cooling extracted with ethyl acetate The organic layer was washed with aqueous sodium chloride solution dried over anhydrous magnesium sulfate the solvent was distilled off The residue was subjected to silica gel column chromatography and elution

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

Procedure: In 10 ml of N,N-dimethylformamide was dissolved 2.66 g of 3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazine followed by addition of 1.02 g of sodium hydride (60% in oil) and the mixture was stirred at room temperature for 30 minutes. Then, 2.77 g of 2-bromopyridine N-oxide hydrochloride was added with ice-cooling and, after the evolution of heat had subsided, the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured in water and extracted with ethyl acetate. The organic layer was separated and dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was chromatographed on a silica gel column using chloroform as the eluent to give crude 2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide. cooling after the evolution of heat the mixture was stirred at room temperature for 2 hours extracted with ethyl acetate The organic layer was separated dried over anhydrous magnesium sulfate filtered The filtrate was concentrated under reduced pressure the residue was chromatographed on a silica gel column

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

Procedure: In 14 ml of N,N-dimethylformamide was suspended 0.38 g of sodium hydride (60% in oil) followed by addition of 1.00 g of 3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazine. Then, 1.01 g of 2-bromopyridine N-oxide hydrochloride was added with ice-cooling and the mixture was stirred at 70° C. for 16 hours. The reaction mixture was poured in ice-water and extracted with ethyl acetate. The organic layer was washed with aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was subjected to silica gel column chromatography and elution was carried out with chloroform-acetone (3:1) to give 0.34 g of 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide as oil. Then, a solution of hydrochloric acid in ethanol (prepared from 1 ml of concentrated hydrochloric acid and 5 ml of ethanol) was added thereto and the solvent was distilled off. The resulting residue wad recrystallized from acetone to give 182 mg of 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide hydrochloride. cooling extracted with ethyl acetate The organic layer was washed with aqueous sodium chloride solution dried over anhydrous magnesium sulfate the solvent was distilled off The residue was subjected to silica gel column chromatography and elution

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

Procedure: In 10 ml of N,N-dimethylformamide was dissolved 2.66 g of 3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazine followed by addition of 1.02 g of sodium hydride (60% in oil) and the mixture was stirred at room temperature for 30 minutes. Then, 2.77 g of 2-bromopyridine N-oxide hydrochloride was added with ice-cooling and, after the evolution of heat had subsided, the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured in water and extracted with ethyl acetate. The organic layer was separated and dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was chromatographed on a silica gel column using chloroform as the eluent to give crude 2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide. cooling after the evolution of heat the mixture was stirred at room temperature for 2 hours extracted with ethyl acetate The organic layer was separated dried over anhydrous magnesium sulfate filtered The filtrate was concentrated under reduced pressure the residue was chromatographed on a silica gel column

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 0.76 g portion of imidazole was added to 7 ml of N,N-dimethylformamide and mixed with 0.2 g of 90% lithium hydride under ice-cooling and then the mixture was stirred for 40 minutes. Next, 2.17 g of 2-bromopyridine N-oxide hydrochloride was gradually added thereto, the mixture was stirred at room temperature for about 1 hour and further heated at 80° C. for about 1 hour, and then the solvent was evaporated and the thus obtained mixture was subjected to a silica gel column chromatography and eluted with chloroform-methanol-28% aqueous ammonia (10:0.9:0.1, v/v/v) to obtain 1.21 g of the title compound as light yellow crystals. cooling the mixture was stirred at room temperature for about 1 hour the solvent was evaporated eluted with chloroform-methanol-28% aqueous ammonia (10:0.9:0.1, v/v/v)

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

Procedure: To a suspension of 0.38 g sodium hydride (60% in paraffin composition) in 14 ml dimethylformamide, was added 1.00 g 3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazine, and 1.01 g 2-bromopyridine N-oxide hydrochloride was further added under ice-cooling, and the mixture was stirred for 16 hours at 70° C. The reaction mixture was poured to ice water, the resulting mixture was extracted with ethyl acetate, and the extract was washed with an aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent was distilled off from the dried solution under reduced pressure, the residue was subjected to column chromatography on silica gel, and elution was conducted by the use of a 3:1 mixture of chloroform and acetone, thus giving 0.34 g of 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide. Ethanolic solution of hydrogen chloride (a mixture of 1 ml concentrated hydrochloric acid and 5 ml ethanol) was then added to the product obtained above, the solvent was distilled off from the mixture, and the residue was recrystallized from acetone, thus giving 182 mg of 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide hydrochloride. was further added under ice- cooling the resulting mixture was extracted with ethyl acetate the extract was washed with an aqueous solution of sodium chloride dried over anhydrous magnesium sulfate The solvent was distilled off from the dried solution under reduced pressure the residue was subjected to column chromatography on silica gel, and elution was conducted by the use of a 3:1 mixture of chloroform and acetone