Acetonitrile → 1-Propylpyrrolidine-2,4-dione

HRID 1110362Notes

Reaction equation

HRID 1110362 reaction equation
C([CH:6]1[C:10](=[O:11])[CH2:9][N:8]([CH2:12][CH2:13][CH3:14])[C:7]1=[O:15])(OCC)=O.C(#N)C.O=C1CC(=O)CN1>C(OCC)(=O)C>[CH2:12]([N:8]1[CH2:9][C:10](=[O:11])[CH2:6][C:7]1=[O:15])[CH2:13][CH3:14]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 5514912,4-PyrrolidinedioneHCID 14074904HCID 14074904, compound

Product 1

HCID 135603831-Propylpyrrolidine-2,4-dione

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Freshly prepared 1-propyl-2,4-dioxopyrrolidine was prepared by heating together 3-carboethoxy-1-propyl-2,4-dioxopyrrolidine (1.16 g) (U.S. Pat. No. 4,511,568, Example 52d describes the preparation of the methoxy compound; the ethoxy compound may be prepared in a similar manner), and acetonitrile (100 ml). After heating for 1.5 hours the volatiles were removed under aspirator vacuum and the residue consisting of crude 2,4-dioxopyrrolidine was taken up in toluene (4 ml). This solution was added dropwise to a refluxing mixture of 2-amino-3-methylbenzonitrile from Example 1(0.48 g) and p-toluenesulfonic acid (36 mg) in toluene (10 ml). The refluxing mixture was surmounted with a Dean-Stark trap to collect water evolved in the reaction as the azeotrope with toluene. Following the addition of 2,4-dioxopyrrolidine (about 60 minutes), the mixture was heated for an additional 2 hours, then excess toluene was removed by distillation. After cooling to ambient temperature, the residue was partitioned between ethyl acetate and saturated aqueous NaHCO3. After separation of the layers, the ethyl acetate layer was washed once with brine, dried (MgSO4) and concentrated to leave an orange gum. Chromatographing the material over silica gel using ethyl acetate as the eluent afforded the desired product (0.70 g, 75%) as a white solid; tlc, Rf =0.21, silica gel, ethyl acetate.

Workup

  1. temperatureAfter heating for 1.5 hours the volatiles
  2. customwere removed under aspirator vacuum
  3. additionThis solution was added dropwise to a refluxing mixture of 2-amino-3-methylbenzonitrile from Example 1(0.48 g) and p-toluenesulfonic acid (36 mg) in toluene (10 ml)
  4. customto collect water
  5. customevolved in the reaction as the azeotrope with toluene
  6. temperaturethe mixture was heated for an additional 2 hours
  7. customexcess toluene was removed by distillation
  8. customthe residue was partitioned between ethyl acetate and saturated aqueous NaHCO3
  9. customAfter separation of the layers
  10. washthe ethyl acetate layer was washed once with brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customto leave an orange gum

Sources & evidence

ORD record
ord-1c941d77b39140c8ba2da55c93b0a678
Source dataset
uspto-grants-1990_12
Patent number
US04975435

Reaction notes

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