Sulfuric Acid → 1-Azido-4-fluorobenzene

HRID 2365217Notes

Reaction equation

HRID 2365217 reaction equation
S(=O)(=O)(O)O.FC(F)(F)C(O)=O.[F:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=1.N([O-])=O.[Na+].[N-:25]=[N+:26]=[N-].[Na+]>O>[N:18]([C:17]1[CH:19]=[CH:20][C:14]([F:13])=[CH:15][CH:16]=1)=[N+:25]=[N-:26]

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 6422Trifluoroacetic acidHCID 97314-FluoroanilineHCID 33557Sodium AzideHCID 23668193Sodium Nitrite

Product 1

HCID 108879741-Azido-4-fluorobenzeneYield 96.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

Prepared in analogy to J. Org. Chem. (1989) 54:5938-5945. To a solution of sulfuric acid (40 mL) and trifluoroacetic acid (200 mL) was added 4-fluoroaniline (22.1 mL, 0.23 mol) dropwise. Then under ice-cooling a solution of sodium nitrite (20.6 g, 0.3 mol) in water (200 mL) was added over 30 min at 15-18° C. The solution was then stirred for 30 min while kept in the ice bath. A solution of sodium azide (25.42 g, 0.39 mol) in water (150 mL) was added dropwise over 30 min. Mixture was foaming and temperature went up to 10° C. while cooling with an ice bath. Reaction mixture was stirred without cooling for 1 h, then extracted with diethyl ether. The combined organic layers were washed with water two times. Then the combined organic layers were diluted with saturated aqueous sodium carbonate solution (500 mL) until the mixture became basic. The organic phase was separated and washed with brine, extracted again with diethyl ether. The organic layers were dried over sodium sulfate and evaporated at 40° C., minimum 50 mbar (already distillation of product), to afford the title product (30.42 g, 96%) as a brown liquid.

Workup

  1. customPrepared in analogy to J
  2. additionwas added over 30 min at 15-18° C
  3. customwent up to 10° C.
  4. temperaturewhile cooling with an ice bath
  5. customReaction mixture
  6. stirringwas stirred
  7. temperaturewithout cooling for 1 h
  8. extractionextracted with diethyl ether
  9. washThe combined organic layers were washed with water two times
  10. additionThen the combined organic layers were diluted with saturated aqueous sodium carbonate solution (500 mL) until the mixture
  11. customThe organic phase was separated
  12. washwashed with brine
  13. extractionextracted again with diethyl ether
  14. dry with materialThe organic layers were dried over sodium sulfate
  15. customevaporated at 40° C.
  16. distillationminimum 50 mbar (already distillation of product),

Sources & evidence

ORD record
ord-7bd23a7b78ee4ed99cfdf5a84f7bae67
Source dataset
uspto-grants-2014_04
Patent number
US08697696B2

Reaction notes

Loading…