Thiophene-3-carboxylic acid → 5-Chlorothiophene-3-carboxylic acid

HRID 732019Notes

Reaction equation

HRID 732019 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=[O:7])=[CH:2]1.[Cl:9]N1C(=O)CCC1=O>C(O)(=O)C>[Cl:9][C:5]1[S:1][CH:2]=[C:3]([C:6]([OH:8])=[O:7])[CH:4]=1

Participants

4

Reactant 2

HCID 6918Thiophene-3-carboxylic acidHCID 31398Chlorosuccinimide

Product 1

HCID 8190495-Chlorothiophene-3-carboxylic acidYield 67.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Thiophene-3-carboxylic acid (17.51 g, 136.6 mmol) and 1-chloro-pyrrolidine-2,5-dione (23.7 g) was refluxed in acetic acid (200 ml) for 4 h under argon before pouring onto water (700 ml). Repeated extraction with several small portions of DCM, followed by back extraction from the combined organics with several small portions of 2 M aqueous sodium hydroxide, gave a combined alkaline aqueous solution that was washed with DCM before acidified with conc. HCl to precipitate the crude material. This precipitate was recrystallized from water to yield 14.98 g of the title compound as a grey solid contaminated with approximately 20 mol % of a dichlorinated byproduct as judged from MS and 1H-NMR. 1H NMR (DMSO-d6) d (ppm): 8.15 (d, 1H), 7.37 (d, 1H).

Workup

  1. additionbefore pouring onto water (700 ml)
  2. extractionextraction with several small portions of DCM
  3. extractionfollowed by back extraction from the combined organics with several small portions of 2 M aqueous sodium hydroxide
  4. customgave a combined alkaline aqueous solution that
  5. washwas washed with DCM
  6. customto precipitate the crude material
  7. customThis precipitate was recrystallized from water

Sources & evidence

ORD record
ord-1a295756486244348e01433628db0292
Source dataset
uspto-grants-2009_09
Patent number
US07585881B2

Reaction notes

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