Dimethylformamide → 1H-Pyrrole-2,4-dicarbonitrile

HRID 1094858Notes

Reaction equation

HRID 1094858 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.ClS([N:10]=[C:11]=O)(=O)=O.[CH3:13][N:14](C=O)C.[OH-].[Na+]>C(#N)C.CCOC(C)=O>[NH:1]1[CH:5]=[C:4]([C:13]#[N:14])[CH:3]=[C:2]1[C:11]#[N:10]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8027PyrroleHCID 14798Sodium HydroxideHCID 70918Chlorosulfonyl isocyanate

Product 1

HCID 5759051H-Pyrrole-2,4-dicarbonitrileYield 73.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ACN (15 mL) was added pyrrole (1.03 mL, 14.9 mmol) which was cooled in an ice/salt bath. Chlorosulfonyl isocyanate (2.73 mL, 31.3 mmol) was diluted in ACN (5 mL) and then added to the reaction dropwise over the following 30 min. The ice/salt bath was removed and the solution was allowed to warm to rt over the next 1.5 h. The solution was then cooled in an ice/salt bath and DMF (5.00 mL, 65.0 mmol) was slowly added via an addition funnel. The solution was allowed to slowly warm to rt over 17 h. The solution was cooled in an ice/salt bath and aq 1N NaOH (50 mL) was added followed by EtOAc (50 mL). The solution was transferred to a separatory funnel, and the organic layer was isolated and the aqueous layer was back extracted with EtOAc (2×). The collected organic was washed with aq saturated NaHCO3 followed by H2O (100 mL). The aqueous layers were back extracted with EtOAc (2×50 mL). The combined organic layers were collected, dried (MgSO4), concentrated onto silica gel, and purified by column chromatography (9:1 v/v CH2Cl2-EtOAc) to afford 1.28 g of the above compound as a white solid (10.9 mmol, yield 73%). 1H-NMR (DMSO-d6) δ 13.29 (br s, 1H), 8.00 (s, 1H), 7.49 (s, 1H); LCMS RT=1.65 min.

Workup

  1. temperaturewas cooled in an ice/salt bath
  2. additionadded to the reaction dropwise over the following 30 min
  3. customThe ice/salt bath was removed
  4. temperatureThe solution was then cooled in an ice/salt bath
  5. temperatureto slowly warm to rt over 17 h
  6. temperatureThe solution was cooled in an ice/salt bath
  7. customThe solution was transferred to a separatory funnel
  8. customthe organic layer was isolated
  9. extractionthe aqueous layer was back extracted with EtOAc (2×)
  10. washThe collected organic was washed with aq saturated NaHCO3
  11. extractionThe aqueous layers were back extracted with EtOAc (2×50 mL)
  12. customThe combined organic layers were collected
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated onto silica gel
  15. custompurified by column chromatography (9:1 v/v CH2Cl2-EtOAc)

Sources & evidence

ORD record
ord-5a7a53549caa4765a6521b6449a31776
Source dataset
uspto-grants-2012_03
Patent number
US08133995B2

Reaction notes

Loading…