Urea → 4-Fluoro-1H-isoindole-1,3(2H)-dione

HRID 2118827Notes

Reaction equation

HRID 2118827 reaction equation
Cl[C:2]1[CH:12]=[CH:11][CH:10]=[C:4]2[C:5](OC(=O)[C:3]=12)=[O:6].S(Cl)(Cl)=O.S1(CCCC1)(=O)=O.[F-:24].[K+].N[C:27]([NH2:29])=[O:28]>CC(C)=O.O>[F:24][C:2]1[CH:12]=[CH:11][CH:10]=[C:4]2[C:5]([NH:29][C:27](=[O:28])[C:3]=12)=[O:6]

Participants

8

Reactant 5

HCID 1176UreaHCID 24386Thionyl Chloride2×HCID 31347SulfolaneHCID 670143-Chlorophthalic anhydrideHCID 522689Potassium Fluoride

Product 1

HCID 220646324-Fluoro-1H-isoindole-1,3(2H)-dioneYield 84.5%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

500 parts (2.739 moles) of 3-chlorophthalic anhydride and 49.9 parts of thionyl chloride are added to 820 parts of sulfolane, while stirring. The mixture is stirred for 30 minutes at 100° C., after which the evolution of gas is complete. Excess thionyl chloride is stripped off under reduced pressure from a water pump, after which 175 parts of potassium fluoride are added and stirring is continued for 6 hours at 210° C. The mixture is cooled to 60° C., and 82 parts (1.37 moles) of urea are then added. The mixture is stirred for 1 hour 30 minutes at 130° C., when evolution of gas is complete, after which stirring is continued for a further 15 minutes at 170° C. The mixture is then cooled to room temperature, 300 parts of acetone are added, while stirring, and the predominantly inorganic precipitate is filtered off under suction. The filtrate is freed from acetone in a rotary evaporator, and the residue is then distilled over a 10 cm packed column at a bath temperature of 140°-170° C. under 0.4 mbar. The distillation residue is stirred with water, and the product is filtered off under suction, washed with methyl tert.-butyl ether and dried, 382 parts (84.5% of theory) of 3-fluorophthalimide of melting point 176°-179° C. being obtained. By treating the inorganic residue with 300 parts of acetone, separating off the extract and evaporating it down under reduced pressure, a further 29 parts (6.8% of theory) of 3-fluorophthalimide of melting point 166°-178° C. are isolated.

Workup

  1. stirringThe mixture is stirred for 30 minutes at 100° C.
  2. stirringstirring
  3. stirringThe mixture is stirred for 1 hour 30 minutes at 130° C.
  4. stirringafter which stirring
  5. waitis continued for a further 15 minutes at 170° C
  6. temperatureThe mixture is then cooled to room temperature
  7. stirringwhile stirring
  8. filtrationthe predominantly inorganic precipitate is filtered off under suction
  9. customThe filtrate is freed from acetone in a rotary evaporator
  10. distillationthe residue is then distilled over a 10 cm
  11. customtemperature of 140°-170° C.
  12. stirringThe distillation residue is stirred with water
  13. filtrationthe product is filtered off under suction
  14. washwashed with methyl tert.-butyl ether
  15. customdried

Sources & evidence

ORD record
ord-03988274c63c4a98b1b67769de9b0145
Source dataset
uspto-grants-1987_07
Patent number
US04680412

Reaction notes

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