Iodine → 2-Chloro-5-iodo-1,3-dimethoxybenzene
Reaction equation
[Cl:1][C:2]1[C:8]([O:9][CH3:10])=[CH:7][C:5](N)=[CH:4][C:3]=1[O:11][CH3:12].S(=O)(=O)(O)O.N([O-])=O.[Na+].[I-:22].[Na+].II.S([O-])([O-])(=O)=S.[Na+].[Na+]>O>[Cl:1][C:2]1[C:8]([O:9][CH3:10])=[CH:7][C:5]([I:22])=[CH:4][C:3]=1[O:11][CH3:12]Participants
Conditions
- Temperature
- 0 °C
Procedure
4-Chloro-3,5-dimethoxyaniline (2) (6.61 g, 35.2 mmol) was added to a mixture of sulfuric acid (9.39 mL, 176 mmol) and H2O (100 mL) at 00° C. Sodium nitrite (3.16 g, 45.8 mmol) was added and the reaction mixture was stirred at 0° C. for 30 min. The mixture was added to a pre-warmed mixture of sodium iodide (21.1 g, 141 mmol), iodine (4.47 g, 17.6 mmol), sulphuric acid (8 mL) and H2O (100 mL) at 80° C. and the resulting mixture was heated at reflux for 30 min. The mixture was allowed to cool to RT and then 40% sodium thiosulfate solution (200 mL) was added. The product was extracted with EtOAc (300 mL), the solvent was removed in vacuo and the residue was purified by silica gel chromatography (120 g, 0-50% EtOAc in isohexanes) to afford 2-chloro-5-iodo-1,3-dimethoxybenzene (3) (7.16 g, 67% yield).
Workup
- temperaturethe resulting mixture was heated
- temperatureat reflux for 30 min
- temperatureto cool to RT
- extractionThe product was extracted with EtOAc (300 mL)
- customthe solvent was removed in vacuo
- customthe residue was purified by silica gel chromatography (120 g, 0-50% EtOAc in isohexanes)
Sources & evidence
- ORD record
- ord-a7e27046576a44458eb50d74d470fc8c
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09447028B2
Reaction notes
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