Hydrofluoric Acid → 2,5-Dichloro-3-fluoropyridine

HRID 1762260Notes

Reaction equation

HRID 1762260 reaction equation
[FH:1].N[C:3]1[C:4]([Cl:10])=[N:5][CH:6]=[C:7]([Cl:9])[CH:8]=1.N([O-])=O.[Na+]>S1(CCCC1)(=O)=O>[Cl:10][C:4]1[C:3]([F:1])=[CH:8][C:7]([Cl:9])=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 14917Hydrofluoric AcidHCID 27999993-Amino-2,5-dichloropyridineHCID 23668193Sodium Nitrite

Product 1

HCID 109648772,5-Dichloro-3-fluoropyridineYield 82.7%

Reagents, catalysts & solvents 1

HCID 31347SulfolaneSolvent

Procedure

A 500 ml polytetrafluoroethylene reactor equipped with stirrer, thermometer and reflux condenser is charged with 60 g of hydrogen fluoride. A solution of 40.7 g (0.25 mol) of 3-amino-2,5-dichloropyridine in 100 ml of sulfolane is added dropwise at a temperature in the range from 0° C. to +10° C. Then 20.7 g (0.3 mol) of sodium nitrite are introduced into this solution at +50° C. The resultant nitrogen is removed from the reactor through the reflux condenser. Gas evolution ceases after 2 hours at +50° C. 150 ml of methylene chloride are added to the reaction mixture which is then poured into ice water. The two-phase mixture is neutralised with concentrated ammonia solution. The organic phase is separated and the aqueous phase is extracted several times with methylene chloride. The combined organic phase are dried over sodium sulfate and concentrated by evaporation. The solution of the sulfolane product is separated by distillation, affording 34.3 g (82.6% of theory) of 2,5-dichloro-3-fluoropyridine.

Workup

  1. customA 500 ml polytetrafluoroethylene reactor equipped with stirrer
  2. temperaturethermometer and reflux condenser
  3. customThe resultant nitrogen is removed from the reactor through the reflux condenser
  4. addition150 ml of methylene chloride are added to the reaction mixture which
  5. additionis then poured into ice water
  6. customThe organic phase is separated
  7. extractionthe aqueous phase is extracted several times with methylene chloride
  8. dry with materialThe combined organic phase are dried over sodium sulfate
  9. concentrationconcentrated by evaporation
  10. customThe solution of the sulfolane product is separated by distillation

Sources & evidence

ORD record
ord-0debdcc8130548e88a749c949bde0532
Source dataset
uspto-grants-1989_05
Patent number
US04831148

Reaction notes

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