Sulfuric Acid → 1-(2-methoxy-5-nitrophenyl)piperazine

HRID 1710596Notes

Reaction equation

HRID 1710596 reaction equation
S(=O)(=O)(O)O.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.[N+:20]([O-])([O-:22])=[O:21].[K+].[OH-].[Na+]>C(OCC)C.O>[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N+:20]([O-:22])=[O:21])=[CH:10][C:9]=1[N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 1118Sulfuric Acid2×HCID 13461-(2-Methoxyphenyl)piperazineHCID 14798Sodium HydroxideHCID 24434Potassium Nitrate2×

Product 1

HCID 37831381-(2-methoxy-5-nitrophenyl)piperazineYield 57.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

63 mL of 5 M sulphuric acid were dropwise added to 60 g of commercially available 1-(2-methoxyphenyl)-piperazine (312 mmol) within 30 minutes at 0° C., followed by the addition of 306 mL of concentr ated sulphuric acid. The mixture was stirred for 90 minutes. Then 25.2 g of potassium nitrate (249.65 mmol) were added in portions within 1 h. After stirring for 3 h, another 3.16 g of potassium nitrate (31.2 mmol) were added. When the reaction was complete, the mixture was poured onto 1 kg of ice water and the pH was adjusted to pH 12 with aqueous sodium hydroxide. 300 mL of water were added, the aqueous phase was extracted three times with 300 mL of ethyl acetate each. The organic phases were combined, dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure to yield 48.7 g of crude product. This material was dissolved in a small amount of diethyl ether. Crystallization started upon scratching the glass surface. The residue was filtered, washed with cold diethyl ether, and dried to yield 34.2 g of the title compound.

Workup

  1. additionfollowed by the addition of 306 mL of concentr
  2. stirringAfter stirring for 3 h
  3. extractionthe aqueous phase was extracted three times with 300 mL of ethyl acetate each
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was evaporated under reduced pressure
  7. customto yield 48.7 g of crude product
  8. customCrystallization
  9. filtrationThe residue was filtered
  10. washwashed with cold diethyl ether
  11. customdried

Sources & evidence

ORD record
ord-c045986d83434bf79e5062a1f977ea9e
Source dataset
uspto-grants-2010_09
Patent number
US07790727B2

Reaction notes

Loading…