Nitrite → 2-Chloropyridine-3,5-dicarbonitrile

HRID 842706

Reaction equation

HRID 842706 reaction equation
N([O-])=O.[Na+].S(=O)(=O)(O)O.[ClH:10].[NH+]1C=CC=CC=1.N[C:18]1[C:23]([C:24]#[N:25])=[CH:22][C:21]([C:26]#[N:27])=[CH:20][N:19]=1.N([O-])=O.NC1C=CC=CN=1>C(O)(=O)C>[Cl:10][C:18]1[C:23]([C:24]#[N:25])=[CH:22][C:21]([C:26]#[N:27])=[CH:20][N:19]=1

Participants

8

Reactant 6

HCID 946NitriteHCID 1118Sulfuric AcidHCID 104392-AminopyridineHCID 2959122-Aminopyridine-3,5-dicarbonitrileHCID 21584435Pyridinium hydrochlorideHCID 23668193Sodium Nitrite

Product 1

HCID 109865792-Chloropyridine-3,5-dicarbonitrile

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent3×

Conditions

Temperature
0 °C

Procedure

Acetic acid (37 mL) was added over 10 min to sodium nitrite (13.4 g, 0.194 mol) with stirring. Concentrated sulfuric acid (12.3 mL) was added over 5 min to the resulting thick slurry which was then cooled to 0° C. In a separate flask, pyridinium hydrochloride (14.4 g, 0.125 mol) was added to a stirred mixture of 2-amino-3,5-dicyanopyridine (4.0 g, 27.75 mmol) in acetic acid (55 mL) and the resulting mixture was cooled to 0° C. to give a thick slurry. The nitrite slurry was added to the aminopyridine slurry over 5 min with stirring at 0° C. Acetic acid (50 mL) was added and the thick slurry was warmed to rt. After 1 h at rt the mixture was warmed to 50° C. and after a further 1 h, it was poured into an ice/water mixture (500 mL). The aqueous mixture was extracted with methylene chloride (4 times) and the combined extracts were dried (Na2SO4) and evaporated to a yellow solid. The crude product was purified by chromatography on silica (chloroform/methanol gradient, 1-3% methanol) to give the title compound as a solid:

Workup

  1. temperaturethe resulting mixture was cooled to 0° C.
  2. customto give a thick slurry
  3. stirringwith stirring at 0° C
  4. temperaturethe thick slurry was warmed to rt
  5. temperatureAfter 1 h at rt the mixture was warmed to 50° C. and after a further 1 h
  6. extractionThe aqueous mixture was extracted with methylene chloride (4 times)
  7. dry with materialthe combined extracts were dried (Na2SO4)
  8. customevaporated to a yellow solid
  9. customThe crude product was purified by chromatography on silica (chloroform/methanol gradient, 1-3% methanol)

Sources & evidence

ORD record
ord-776e8a69ae014a50b6323e1008fa6882
Source dataset
uspto-grants-2002_04
Patent number
US06376499B1

Linked notes

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