Sulfuric Acid → 5-Chloro-6-iodo-1H-isoindole-1,3(2H)-dione

HRID 1930799Notes

Reaction equation

HRID 1930799 reaction equation
N[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[C:7](=[O:12])[NH:6][C:5]2=[O:13].S(=O)(=O)(O)O.N([O-])=O.[Na+].[I-:23].[K+]>O.O1CCCC1.C(OCC)(=O)C>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4](=[CH:3][C:2]=1[I:23])[C:5](=[O:13])[NH:6][C:7]2=[O:12]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 4875Potassium IodideHCID 28008205-AMINO-6-CHLOROISOINDOLINE-1,3-DIONEHCID 23668193Sodium Nitrite

Product 1

HCID 577536055-Chloro-6-iodo-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolvent4×HCID 21939870Tetrahydrofuran ethyl acetateSolvent

Conditions

Temperature
5 °C

Procedure

To a stirred suspension of 96.1 mmol 5-amino-6-chloroisoindoline-1,3-dione (commercial, CAS: 5566-48-3) in 170 ml water was added dropwise at 10° C. a solution of 11 ml concentrated sulfuric acid in 50 ml water. After cooling the mixture to 5° C., a solution of 120 mmol sodium nitrite in 40 ml water was added dropwise and stirring continued at 0° C. for 90 min. A solution of 327 mmol potassium iodide in 80 ml water was then added dropwise over 40 min while maintaining the reaction temperature between 0 and 5° C. The reaction mixture was then warmed to room temperature and subsequently heated at 35° C. for 45 min and then 60° C. for 30 min before being recooled to room temperature and diluted with tetrahydrofuran/ethyl acetate (1/2). The phases were separated and the organic phase washed sequentially with aqueous sodium thiosulphite and brine and then dried over sodium sulfate and concentrated in vacuo. The residue was resuspended in 300 ml dichloromethane, stirred for 10 min at room temperature, and the resulting crystals collected by filtration to yield the title compound as a light brown solid. MS (m/e): 308.9 ({37Cl}M+, 35%), 306.9 ({35Cl}M+, 100%).

Workup

  1. temperaturewhile maintaining the reaction temperature between 0 and 5° C
  2. temperatureThe reaction mixture was then warmed to room temperature
  3. temperaturesubsequently heated at 35° C. for 45 min
  4. wait60° C. for 30 min before being recooled to room temperature
  5. customThe phases were separated
  6. washthe organic phase washed sequentially with aqueous sodium thiosulphite and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. stirringstirred for 10 min at room temperature
  10. filtrationthe resulting crystals collected by filtration

Sources & evidence

ORD record
ord-893e70d5b7934850b103fd1936d93458
Source dataset
uspto-grants-2012_05
Patent number
US08188139B2

Reaction notes

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