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

HRID 1762263Notes

Reaction equation

HRID 1762263 reaction equation
[FH:1].N[C:3]1[C:4]([Cl:10])=[N:5][CH:6]=[C:7]([Cl:9])[CH:8]=1.N([N+]([O-])=O)=O>CS(C)=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 61526Nitrogen trioxideHCID 27999993-Amino-2,5-dichloropyridine

Product 1

HCID 109648772,5-Dichloro-3-fluoropyridineYield 92.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A 500 ml polytetrafluoroethylene reactor equipped with stirrer, thermometer and reflux condenser is charged with 120 g of hydrogen fluoride. A solution of 40.7 g (0.25 mol) of 3-amino-2,5-dichloropyridine in 60 ml of dimethyl sulfoxide is added dropwise at a temperature in the range from 0° C. to +10° C. Over 11/2 hours, 24.7 g (0.325 mol) of dinitrogen trioxide are introduced into this solution at a temperature in the range from +°50 C. to 60° C. The resultant nitrogen is removed from the reactor through the reflux condenser. Gas evolution ceases after a total of 3 hours at 50° C. to 60° 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 phases are dried over sodium sulfate. The solution is separated by distillation, affording 38.2 g (92.1% of theory) of 2,5-dichloro-3-fluoropyridine.

Workup

  1. customA 500 ml polytetrafluoroethylene reactor equipped with stirrer
  2. temperaturethermometer and reflux condenser
  3. customto 60° C
  4. customThe resultant nitrogen is removed from the reactor through the reflux condenser
  5. customafter a total of 3 hours
  6. customat 50° C. to 60° C
  7. addition150 ml of methylene chloride are added to the reaction mixture which
  8. additionis then poured into ice water
  9. customThe organic phase is separated
  10. extractionthe aqueous phase is extracted several times with methylene chloride
  11. dry with materialThe combined organic phases are dried over sodium sulfate
  12. customThe solution is separated by distillation

Sources & evidence

ORD record
ord-ca0bd438a6d34904829ad1ba4a3881cf
Source dataset
uspto-grants-1989_05
Patent number
US04831148

Reaction notes

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