Chlorosuccinimide → 1-(Thiophen-3-yl)-1,3-dihydro-2H-indol-2-one

HRID 1196917Notes

Reaction equation

HRID 1196917 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([N:6]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=[CH:7]2)=[CH:2]1.ClN1C(=[O:21])CCC1=O>C(Cl)Cl>[S:1]1[CH:5]=[CH:4][C:3]([N:6]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:8][C:7]2=[O:21])=[CH:2]1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 14819382HCID 14819382, compound

Product 1

HCID 148193781-(Thiophen-3-yl)-1,3-dihydro-2H-indol-2-oneYield 72.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(3-thienyl)indole (9.14 g, 0.0459 M) in 350 ml of dry methylene chloride under a nitrogen atmosphere was added 6.44 g (0.0482 M) of N-chlorosuccinimide (NCS) at room temperature. The reaction was stirred at room temperature for 2 hours, then concentrated in vacuo. The resulting foamy residue was immediately dissolved in 190 ml of glacial acetic acid. The resulting mixture was heated to 70° C. followed by the addition of 49.5 ml of 85% H3PO4 and heating of the reaction mixture to reflux for one hour. The mixture was then cooled to room temperature, poured onto ice water, basified to pH ~11-12 with Na2CO3 and extracted with ethyl acetate (3×500 ml). The combined ethyl acetate extracts were washed with water, brine, dried (MgSO4), filtered and concentrated in vacuo leaving dark brown-black oil. Purification of the crude product on a silica gel column (elution with CH2Cl2, followed by elution with 90% CH2Cl2 --10% CH3OH) gave a total of 7.2 grams (72.8%) of brown crystalline solid; m.p. 62°-67° C. MS: M+= 215. IR(KBr) 5.9 μ(s) c=O. NMR(CDCl3)delta: 3.6 (s, 2H), 6.7-7.4 (m, 7H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resulting foamy residue was immediately dissolved in 190 ml of glacial acetic acid
  3. temperatureThe resulting mixture was heated to 70° C.
  4. additionfollowed by the addition of 49.5 ml of 85% H3PO4
  5. temperatureheating of the reaction mixture
  6. temperatureto reflux for one hour
  7. temperatureThe mixture was then cooled to room temperature
  8. additionpoured onto ice water
  9. extractionextracted with ethyl acetate (3×500 ml)
  10. washThe combined ethyl acetate extracts were washed with water, brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customleaving dark brown-black oil
  15. customPurification of the crude product
  16. washon a silica gel column (elution with CH2Cl2, followed by elution with 90% CH2Cl2 --10% CH3OH)

Sources & evidence

ORD record
ord-85614fe2744840308bd9fe5daf3b4f56
Source dataset
uspto-grants-1992_05
Patent number
US05116854

Reaction notes

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