Nitric Acid → 2-Fluoro-3-hydroxy-5-nitro-p-anisonitrile

HRID 1781853Notes

Reaction equation

HRID 1781853 reaction equation
C([O:4][C:5]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]([C:13]#[N:14])[C:6]=1[F:15])(=O)C.[N+:16]([O-])([OH:18])=[O:17]>>[F:15][C:6]1[C:5]([OH:4])=[C:10]([O:11][CH3:12])[C:9]([N+:16]([O-:18])=[O:17])=[CH:8][C:7]=1[C:13]#[N:14]

Participants

3

Reactant 2

HCID 944Nitric AcidHCID 539089783-Cyano-2-fluoro-6-methoxyphenyl acetate

Product 1

HCID 214591212-Fluoro-3-hydroxy-5-nitro-p-anisonitrile

Procedure

0.8 g of 3-cyano-2-fluoro-6-methoxyphenyl acetate are introduced in three portions at -15° into 5 ml of 96 percent nitric acid, whereupon the mixture is stirred at -10° for 1 hour. Thereupon, the reaction mixture is poured on to 50 g of ice. The mixture is extracted twice with 70 ml of ethyl acetate each time. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate and evaporated. The thus-obtained residue is dissolved in 50 ml of 1N sodium carbonate solution and 50 ml of methanol, whereupon the solution is stirred at 23° for 1 hour and the methanol is distilled off. The residal aqueous phase is adjusted to pH 2 at 0° with conc. hydrochloric acid and extracted twice with 100 ml of ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate and evaporated, and the residue is chromatographed on 45 g of silica gel with methylene chloride/methanol (97:3). After recrystallization from ether/hexane there is obtained 2-fluoro-3-hydroxy-5-nitro-p-anisonitrile of m.p. 112°-113°.

Workup

  1. extractionThe mixture is extracted twice with 70 ml of ethyl acetate each time
  2. washThe combined organic phases are washed with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. dissolutionThe thus-obtained residue is dissolved in 50 ml of 1N sodium carbonate solution
  6. stirring50 ml of methanol, whereupon the solution is stirred at 23° for 1 hour
  7. distillationthe methanol is distilled off
  8. customis adjusted to pH 2 at 0° with conc. hydrochloric acid
  9. extractionextracted twice with 100 ml of ethyl acetate
  10. washThe combined organic phases are washed with saturated sodium chloride solution
  11. dry with materialdried over sodium sulfate
  12. customevaporated
  13. customthe residue is chromatographed on 45 g of silica gel with methylene chloride/methanol (97:3)
  14. customAfter recrystallization from ether/hexane there

Sources & evidence

ORD record
ord-b8f987fdc9fe4f5a8808ad555f22f098
Source dataset
uspto-grants-1997_05
Patent number
US05633371

Reaction notes

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