Sodium Iodide → 6-Iodopyridine-3-carboxylic acid

HRID 324197Notes

Reaction equation

HRID 324197 reaction equation
[I-:1].[Na+].I.Cl[C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][N:6]=1>CC(C)=O>[I:1][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][N:6]=1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 24841Hydrogen iodideHCID 792226-Chloronicotinic acid

Product 1

HCID 8190626-Iodopyridine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Sodium iodide (20.59 g, 137.40 mmol) was cooled to −78° C. under argon and then hydriodic acid (97.13 g, 759.34 mmol) was added. The cooling bath was removed and the suspension was stirred for 5 minutes. To this mixture was added 6-chloronicotinic acid (22.09 g, 140.20 mmol) and the resulting mixture was slowly warmed to ambient temperature with stirring. The mixture was heated to reflux at 125° C. for 24 hours, cooled to ambient temperature and poured into acetone (500 ml) at 0° C. The yellow solid was collected by filtration and washed with 200 ml of 1N aqueous NaHSO3 solution. Recrystallization from methanol (crystals were washed with ethyl ether) afforded the title compound as white crystals: mp 177-179° C. [lit. mp 187-192, Newkome et al. “Reductive Dehalogenation of Electron-Poor Heterocycles: Nicotinic Acid Derivatives” J Org. Chem. 51: 953-954 (1986). 1H NMR (DMSO-d6): δ 8.81 (1H, dd, J=0.8, 2.4 Hz), 8.01 (1H, dd, J=0.8, 8.2 Hz), 7.91 (1H, dd, J=2.4, 8.2 Hz).

Workup

  1. customThe cooling bath was removed
  2. stirringwith stirring
  3. temperatureThe mixture was heated
  4. temperatureto reflux at 125° C. for 24 hours
  5. temperaturecooled to ambient temperature
  6. filtrationThe yellow solid was collected by filtration
  7. washwashed with 200 ml of 1N aqueous NaHSO3 solution
  8. customRecrystallization from methanol (crystals were washed with ethyl ether)

Sources & evidence

ORD record
ord-750d8cda35384b5eb28fbe8b54165e12
Source dataset
uspto-grants-2001_04
Patent number
US06218128B1

Reaction notes

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