Methanol → 2-(7-amino-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazin-4-yl)pyridine N-oxide

HRID 37126Notes

Reaction equation

HRID 37126 reaction equation
[CH3:1][C:2]1([CH3:22])[CH2:7][N:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N+:9]=2[O-:14])[C:5]2[CH:15]=[CH:16][C:17]([N+:19]([O-])=O)=[CH:18][C:4]=2[O:3]1.[Cl-].[NH4+].CO>[Zn].O>[NH2:19][C:17]1[CH:16]=[CH:15][C:5]2[N:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][N+:9]=3[O-:14])[CH2:7][C:2]([CH3:22])([CH3:1])[O:3][C:4]=2[CH:18]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 105661912-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide

Product 1

HCID 158572082-(7-amino-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazin-4-yl)pyridine N-oxideYield 101%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

To a mixture of 8.05 g of 2-(3,4-dihydro-2,2-dimethyl-7-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide, 28.50 g of ammonium chloride, 140 ml of methanol and 140 ml of water was added 34.94 g of zinc dust with ice-cooling, and the mixture was stirred at 5° C. for 14 hours. The insolubles were filtered off, and the filtrate was concentrated and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off to give 7.32 g of crude 2-(7-amino-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazin-4-yl)pyridine N-oxide. (2) In 30 ml of methylene chloride was dissolved 6.72 g of 2-(7-amino-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazin-4-yl)pyridine N-oxide obtained in (1) above followed by addition of 2.6 ml of acetic anhydride with ice-cooling, and the mixture was stirred at room temperature for 4 hours. To the reaction mixture was added 20 ml of methanol to decompose excess acetic anhydride, and the solvent was distilled off to give 8-40 g of crude 2-(7-acetamido-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazin-4-yl)pyridine N-oxide. (3) In 35 ml of acetic acid was dissolved 8.76 g of 2-(7-acetamido-3,4-dihydro-2,2-dimethyl-2H-1,4-benzoxazin-4-yl)pyridine N-oxide obtained in (2) above followed by dropwise addition of a solution of nitric acid in acetic acid (prepared from 1.49 ml of fuming nitric acid and 16 ml of acetic acid) with ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The organic layer was washed with water 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 (1:1) to obtain crystals. Recrystallization from 40 ml of ethanol gave 5.10 g of 2-(7-acetamido-3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide.

Workup

  1. temperaturecooling
  2. filtrationThe insolubles were filtered off
  3. concentrationthe filtrate was concentrated
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off

Sources & evidence

ORD record
ord-9902c145868540189244dca1b9c103ee
Source dataset
uspto-grants-1995_05
Patent number
US05420126

Reaction notes

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