Iodine → 5-Iodo-6-methylpyridin-2-amine

HRID 2276040Notes

Reaction equation

HRID 2276040 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[I:9](O)(=O)(=O)=O.S(=O)(=O)(O)O.II>C(O)(=O)C.O>[I:9][C:3]1[CH:4]=[CH:5][C:6]([NH2:8])=[N:7][C:2]=1[CH3:1]

Participants

7

Reactant 4

HCID 807IodineHCID 1118Sulfuric AcidHCID 157652-Amino-6-methylpyridineHCID 65185Metaperiodic acid

Product 1

HCID 9596135-Iodo-6-methylpyridin-2-amineYield 384.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 6-methyl-pyridin-2-ylamine (30 g, 278 mmol, 1 eq) in acetic acid (167 mL) was added periodic acid (12.7 g, 55.6 mmol, 0.2 eq) followed by addition of sulphuric acid (4.8 mL, 90.8 mmol, 0.34 eq), water (33 mL) and iodine (28.7 g, 111 mmol, 0.4 eq) at room temperature. Resulting reaction mixture was heated at 80° C. for 6 hours. After complete consumption of starting material, reaction mixture was cooled and poured into sodium thiosulfate solution (200 mL), reddish oil was settled down at the bottom. Reaction mixture was decanted from reddish oil, and filtrate was basified with 50% sodium hydroxide solution (100 mL), yellow colored solid was formed. Resulting solid was extracted with diethyl ether (2×200 mL) and dried over sodium sulfate. Organic layer was concentrated under reduced pressure to afford brown semi solid (60 g, crude). Crude was purified by column chromatography using silica gel (100-200 mesh). Desired compound was eluted at 15% EtOAc in hexane to get title compound as faint brown solid (50 g, 77%). 1H NMR (400 MHz, CDCl3) δ: 2.52 (s, 3H), 4.43 (bs, 2H), 6.09 (d, J=8.4 Hz, 1H), 7.65 (d, J=8.44 Hz, 1H). LC-MS (m/z): 235.3 (M+H).

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material, reaction mixture
  4. temperaturewas cooled
  5. additionpoured into sodium thiosulfate solution (200 mL), reddish oil
  6. customReaction mixture
  7. customwas decanted from reddish oil, and filtrate
  8. customyellow colored solid was formed
  9. customResulting solid
  10. extractionwas extracted with diethyl ether (2×200 mL)
  11. dry with materialdried over sodium sulfate
  12. concentrationOrganic layer was concentrated under reduced pressure
  13. customto afford brown semi solid (60 g, crude)
  14. customCrude was purified by column chromatography
  15. washDesired compound was eluted at 15% EtOAc in hexane

Sources & evidence

ORD record
ord-78a424c23f3a428e8b83417bac61e054
Source dataset
uspto-grants-2015_09
Patent number
US09131697B2

Reaction notes

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