Phosphorus oxychloride → 2-chloro-5-phenylnicotinonitrile

HRID 233615Notes

Reaction equation

HRID 233615 reaction equation
P(Cl)(Cl)(Cl)=O.[C:6]([C:8]1[C:9](=O)[NH:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:13]=1)#[N:7].P(Cl)(Cl)(Cl)(Cl)[Cl:22]>>[Cl:22][C:9]1[C:8]([C:6]#[N:7])=[CH:13][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][N:10]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 2970612-oxo-5-phenyl-1H-pyridine-3-carbonitrile

Product 1

HCID 27640432-chloro-5-phenylnicotinonitrileYield 91.6%

Conditions

Temperature
140 °C

Procedure

Under a nitrogen atmosphere, 68.4 grams (0.45 mole) of phosphorus oxychloride is warmed to a gentle reflux, and 38.9 grams (0.18 mole) of 3-cyano-5-phenylpyridin-2-one is added. Upon completion of addition, 93.6 grams (0.45 mole) of phosphorous pentachloride is added in small portions to maintain the gentle reflux. Upon completion of addition, the reaction mixture is then warmed slowly to about 140° C. where it is stirred for one hour. The reaction mixture is cooled, and excess phosphorus oxychloride is removed under reduced pressure. The concentrate is then poured into 400 grams of ice, where it is stirred until the ice melts. The mixture is then extracted with three 200 mL portions of methylene chloride and 100 mL of diethyl ether. The combined extracts are washed with 150 mL of water and 150 mL of an aqueous solution saturated with sodium chloride. The organic layer is dried with sodium sulfate and filtered. The filtrate is concentrated under reduced pressure at 30° C. to a residue. The residue is distilled under vacuum, yielding 35.4 grams of 2-chloro-3-cyano-5-phenylpyridine, bp 175°-179° C./4 mm Hg., as a crystalline material. The crystalline 2-chloro-3-cyano-5-phenylpyridine is recrystallized from hexane/methylene chloride, mp 149°-150° C.

Workup

  1. additionis added
  2. additionis added in small portions
  3. temperatureto maintain the gentle reflux
  4. additionUpon completion of addition
  5. temperatureThe reaction mixture is cooled
  6. customexcess phosphorus oxychloride is removed under reduced pressure
  7. additionThe concentrate is then poured into 400 grams of ice, where it
  8. stirringis stirred until the ice
  9. extractionThe mixture is then extracted with three 200 mL portions of methylene chloride and 100 mL of diethyl ether
  10. washThe combined extracts are washed with 150 mL of water and 150 mL of an aqueous solution saturated with sodium chloride
  11. dry with materialThe organic layer is dried with sodium sulfate
  12. filtrationfiltered
  13. concentrationThe filtrate is concentrated under reduced pressure at 30° C. to a residue
  14. distillationThe residue is distilled under vacuum

Sources & evidence

ORD record
ord-a20b78105f9440fd83f4bfc67487b2d4
Source dataset
uspto-grants-1997_01
Patent number
US05593998

Reaction notes

Loading…