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

Participants

Reaction Steps

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).

Provenance & Evidence