Acetic Acid → 2-(6-CHLORO-3-NITROPYRIDIN-2-YL)ACETONITRILE

HRID 2394333Notes

Reaction equation

HRID 2394333 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][N:9]=1.ClC1C=CC(O[CH2:23][C:24]#[N:25])=CC=1.C(O)(=O)C.Cl>O1CCCC1>[Cl:7][C:8]1[N:9]=[C:10]([CH2:23][C:24]#[N:25])[C:11]([N+:14]([O-:16])=[O:15])=[CH:12][CH:13]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 783082-Chloro-5-nitropyridineHCID 3064442-(4-Chlorophenoxy)acetonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 107980012-(6-CHLORO-3-NITROPYRIDIN-2-YL)ACETONITRILEYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of potassium t-butoxide (24.69 g, 220 mmol, 2.2 eq) in anhydrous tetrahydrofuran (150 ml) at -50° C. under nitrogen, a solution of 2-chloro-5-nitropyridine (15.85 g, 100 mmol) and (4-chlorophenoxy)acetonitrile (E. Grochowski et al., Bull. Acad. Pol. Sci. Ser. Sci. Chim., 11, 443 (1963)) (18.44 g, 110 mmol, 1.1 eq) in anhydrous tetrahydrofuran (150 ml) was added dropwise at such a rate that the reaction temperature was maintained at -40° to -50° C. with cooling in a dry ice/acetone bath. The resultant purple colored reaction mixture was then stirred at -78° C. under nitrogen for 1 hour, at which time glacial acetic acid (20 ml, 0.35 mol, 3.5 eq) was added to the reaction, and the mixture was allowed to warm to room temperature. A solution of 5% HCl (100 ml) was added to the reaction mixture and this aqueous mixture was extracted with ethyl ether (100 ml) and then with methylene chloride (2×100 ml). The extracts were combined, dried over magnesium sulfate, and passed through a silica gel filter (approximately 150 g) followed by methylene chloride (1200 ml). This filtrate was evaporated under reduced pressure, and the residual oil was chromatographed using silica gel (approximately 300 g) and eluted with 25% hexanes in methylene chloride to afford an oil (Rf =0.52 in methylene chloride) which was triturated in cold anhydrous ether to afford 6-chloro-3-nitro-2-pyridyl acetonitrile (1.37 g, 7%) as a white crystalline solid: mp, 121.5°-123.5° C. Further elution yielded another oil (Rf =0.48 in methylene chloride) which was triturated with cold anhydrous ethyl ether to afford (2-chloro-5-nitro-4-pyridyl)acetonitrile (1.87 g, 9%) as a white crystalline solid, m.p. 87°-89° C. IR (KBr) 3080, 2240, 1600, 1545, 1520, 1450, 1390, 1340, 1135 cm-1.

Workup

  1. temperaturewas maintained at -40° to -50° C.
  2. temperaturewith cooling in a dry ice/acetone bath
  3. additionwas added to the reaction
  4. extractionthis aqueous mixture was extracted with ethyl ether (100 ml)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfilter (approximately 150 g)
  7. customThis filtrate was evaporated under reduced pressure
  8. customthe residual oil was chromatographed
  9. washeluted with 25% hexanes in methylene chloride
  10. customto afford an oil (Rf =0.52 in methylene chloride) which
  11. customwas triturated in cold anhydrous ether

Sources & evidence

ORD record
ord-cfa2055ab0aa405e9def7ae47ea4df91
Source dataset
uspto-grants-1998_09
Patent number
US05811432

Reaction notes

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