Thionyl Chloride → 5-Chloro-N-(1,3-dioxo-1,3-dihydro-2-benzofuran-4-yl)-2-thiophenecarboxamide

HRID 1455671Notes

Reaction equation

HRID 1455671 reaction equation
[Cl:1][C:2]1[S:3][C:4]([C:7]([OH:9])=O)=[CH:5][CH:6]=1.S(Cl)(Cl)=O.[NH2:14][C:15]1[CH:25]=[CH:24][CH:23]=[C:17]2[C:18]([O:20][C:21](=[O:22])[C:16]=12)=[O:19]>N1C=CC=CC=1>[Cl:1][C:2]1[S:3][C:4]([C:7]([NH:14][C:15]2[C:16]3[C:21](=[O:22])[O:20][C:18](=[O:19])[C:17]=3[CH:23]=[CH:24][CH:25]=2)=[O:9])=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 950485-Chloro-2-thiophenecarboxylic acidHCID 3455514-Aminoisobenzofuran-1,3-dione

Product 1

HCID 113926535-Chloro-N-(1,3-dioxo-1,3-dihydro-2-benzofuran-4-yl)-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

To prepare the required acid chloride, 27.77 g of 2-chloro-5-thiophenecarboxylic acid (0.171 mol) are suspended in 50 ml of thionyl chloride (0.685 mol) and stirred at 90° C. for 90 min (after 15 min, a clear solution is formed). The resulting solution is concentrated under reduced pressure, twice subjected to azeotropic distillation with toluene, dissolved in 60 ml of toluene and, over a period of 40 min and at 20° C., added dropwise to a solution of 17.98 g (110.2 mmol) of 3-aminophthalic anhydride in 200 ml of pyridine. The mixture is stirred at RT overnight, the pyridine is evaporated under reduced pressure and the residue is twice stirred with toluene and re-evaporated. 1 l of ethyl acetate and 0.5 l of KH2PO4 buffer (pH=4-5) are added and the mixture is then shaken vigorously and filtered off with suction, and the solids are washed with ethyl acetate, pressed thoroughly dry and dried under reduced pressure over P2O5. The mother liquor is extracted three times with ethyl acetate and evaporated and the residue is stirred with ethyl acetate and filtered off with suction. This gives a total of 19.77 g (58.3% of theory) of the target compound of m.p. 195° C.

Workup

  1. customa clear solution is formed)
  2. concentrationThe resulting solution is concentrated under reduced pressure
  3. distillationtwice subjected to azeotropic distillation with toluene
  4. dissolutiondissolved in 60 ml of toluene and, over a period of 40 min and at 20° C.
  5. stirringThe mixture is stirred at RT overnight
  6. customthe pyridine is evaporated under reduced pressure
  7. stirringthe residue is twice stirred with toluene
  8. customre-evaporated
  9. addition1 l of ethyl acetate and 0.5 l of KH2PO4 buffer (pH=4-5) are added
  10. stirringthe mixture is then shaken vigorously
  11. filtrationfiltered off with suction
  12. washthe solids are washed with ethyl acetate
  13. custompressed thoroughly dry
  14. dry with materialdried under reduced pressure over P2O5
  15. extractionThe mother liquor is extracted three times with ethyl acetate
  16. customevaporated
  17. stirringthe residue is stirred with ethyl acetate
  18. filtrationfiltered off with suction
  19. customThis gives a total of 19.77 g (58.3% of theory) of the target compound of m.p. 195° C.

Sources & evidence

ORD record
ord-18b080f175c64c47b02f35e96ea66727
Source dataset
uspto-grants-2009_01
Patent number
US07482472B2

Reaction notes

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