Iodine → 1,3-Difluoro-2-iodobenzene

HRID 2182777Notes

Reaction equation

HRID 2182777 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[CH:3]=1.C([Li])CCC.[I:14]I.[O-]S([O-])(=S)=O.[Na+].[Na+]>C1COCC1.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[I:14]

Participants

7

Reactant 4

HCID 807IodineHCID 97411,3-DifluorobenzeneHCID 24477Sodium ThiosulfateHCID 178418339Butyllithium

Product 1

HCID 27827381,3-Difluoro-2-iodobenzeneYield 88.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

(Roe, A. M., Burton, R. A.; Willey, G. L., Baines, M. W., Rasmussen, A. C. J. Med. Chem. 1968, 11, 814-819. Tamborski, C.; Soloski, E. J. Org. Chem. 1966, 31, 746-749. Grunewald, G. L.; Arrington, H. S.; Bartlett, W. J.; Reitz, T. J., Sall, D. J. J. Med. Chem. 1986, 29, 1972-1982.) 1,3-Difluorobenzene (57.05 g, 0.5 M) in THF (75 mL) was added to a −78° C. stirred solution of n-butyllithium (n-BuLi) (200 mL, 2.5 M/hexanes, 0.5 M) and THF (500 mL) under N2. By controlling the addition rate the internal temperature was maintained below −70° C. The total addition time was ˜½ hour. The resulting slurry was stirred an additional ½ hour, then the dispersion was treated with a solution of Iodine (126.9 g, 0.5 M) in THF (300 mL) at a rate that maintained an internal temperature below −70° C. After complete addition the mixture was allowed to warm to room temperature, and was treated with H2O (100 mL) and 10% aqueous Na2S2O3 solution (100 mL) and stirred. The layers were separated and the aqueous layer extracted with hexanes (2×250 mL). The combined organic layer was washed with 10% aqueous Na2S2O3 solution (100 mL), H2O (100 mL), saturated aqueous NaCl solution (100 mL), dried (Na2SO4) filtered and concentrated to give a yellow oil (106.5 g). Distillation at ˜1-5 mm at −80° C. provided a light yellow oil (89.5 g, 75%). 1H NMR (400 MHz, CDCl3) δ 7.30 (m, 1H), 6.87 (m, 2H). GCMS m/e 240 (M+).

Workup

  1. temperaturewas maintained below −70° C
  2. additionThe total addition time
  3. temperaturethat maintained an internal temperature below −70° C
  4. additionAfter complete addition the mixture
  5. stirringstirred
  6. customThe layers were separated
  7. extractionthe aqueous layer extracted with hexanes (2×250 mL)
  8. washThe combined organic layer was washed with 10% aqueous Na2S2O3 solution (100 mL), H2O (100 mL), saturated aqueous NaCl solution (100 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-4d1a23207d6244d9b7dd4a5545309970
Source dataset
uspto-grants-2005_05
Patent number
US06897310B2

Reaction notes

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