Sulfuric Acid → 2-Chloro-6-fluoro-4-iodobenzonitrile

HRID 1409309Notes

Reaction equation

HRID 1409309 reaction equation
N[C:2]1[CH:9]=[C:8]([F:10])[C:5]([C:6]#[N:7])=[C:4]([Cl:11])[CH:3]=1.S(=O)(=O)(O)O.N([O-])=O.[Na+].[I-:21].[K+]>C(#N)C.O>[Cl:11][C:4]1[CH:3]=[C:2]([I:21])[CH:9]=[C:8]([F:10])[C:5]=1[C:6]#[N:7]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 4875Potassium IodideHCID 23668193Sodium NitriteHCID 596358834-Amino-2-chloro-6-fluorobenzonitrile

Product 1

HCID 671681832-Chloro-6-fluoro-4-iodobenzonitrileYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

4-Amino-2-chloro-6-fluorobenzonitrile (293 mmol, 50 g) was dissolved in ACN (1550 ml) and water (460 ml). Sulphuric acid (879 mmol, 46.9 ml) was added carefully. The reaction mixture was cooled to 0° C. Sodium nitrite (322 mmol, 22.25 g) dissolved in water (150 ml) was slowly added keeping the reaction temperature below 10° C. Thereafter potassium iodide (586 mmol, 97 g) dissolved in 150 ml of water was added slowly while keeping the reaction temperature below 10° C. The reaction mixture was allowed to warm up to RT and stirred overnight at RT. The phases were separated and the organic phase was evaporated. Ethyl acetate was added into the evaporation residue and washed three times with 10% aqueous NaHSO3. The organic phase was evaporated and the residue was dissolved in DCM. 5 g of active carbon was added and stirred for 2 h. The mixture was filtered through a layer of Celite and washed with DCM. The DCM-phase was evaporated and heptanes were added into the residue. The mixture was heated to 60° C. and stirred for 2 h. The oil and heptanes layers were separated by decantation. The heptanes phase was evaporated and 39.6 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): δ 8.06-8.10 (m, 1H), 8.10-8.11 (m, 1H).

Workup

  1. additionwas slowly added
  2. customthe reaction temperature below 10° C
  3. additionwas added slowly
  4. customthe reaction temperature below 10° C
  5. temperatureto warm up to RT
  6. customThe phases were separated
  7. customthe organic phase was evaporated
  8. additionEthyl acetate was added into the evaporation residue
  9. washwashed three times with 10% aqueous NaHSO3
  10. customThe organic phase was evaporated
  11. dissolutionthe residue was dissolved in DCM
  12. addition5 g of active carbon was added
  13. stirringstirred for 2 h
  14. filtrationThe mixture was filtered through a layer of Celite
  15. washwashed with DCM
  16. customThe DCM-phase was evaporated
  17. additionheptanes were added into the residue
  18. temperatureThe mixture was heated to 60° C.
  19. stirringstirred for 2 h
  20. customThe oil and heptanes layers were separated by decantation
  21. customThe heptanes phase was evaporated

Sources & evidence

ORD record
ord-7cead925ed6748238dd705fe4bddd24d
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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