Water → (2,6-Difluorophenyl)thiourea

Participants

Reaction Steps

Benzoyl chloride (5.44 g, 38 mmol) was added dropwise to a solution of ammonium thiocyanate (2.55 g, 42.6 mmol) in acetone. Solution was refluxed for 10 minutes at which time a solution of 2,6-difluoro-aniline (5.0 g, 38.8 mmol) in acetone was added dropwise and the solution refluxed for approximately 5 minutes. The solution was then poured into 500 mL of water and a resulting solid precipitated out. The separated crystalline solid was collected by filtration and then heated in a NaOH solution (3 g in 50 mL H2O). The solution was acidified with conc. HCl, then made slightly basic using conc. NH4OH. Crystalline solid was seen and collected to obtain (2,6-difluoro-phenyl)-thiourea. A mixture of the thiourea (5.7 g, 30.3 mmol), AcONa (2.43 g) and ClCH2CO2H (2.86 g) in AcOH (20 mL) was heated to reflux at 130 C.° for four hours. The mixture was poured onto water and the formed solid was isolated by filtration. It was washed with water to give the desired thiazolidinone (a compound of formula IV in which R is 2,6-difluorophenyl) (6.75 g, 29.6 mmol). A mixture of the thiazolidinone (200 mg, 0.8 mmol), 6-formyl quinoline (137 mg, 0.8 mmol) and AcONa (211 mg, 2.4 mmol) in AcOH (10 mL) was heated to reflux at 130 C.° for 2 days. Water was added to the solution and generated a solid that was collected by filtration and washed with water, followed by desiccation in vacuo to afford the title compound as a yellow solid. ES (±) MS m/e=368.0 (M+H). HPLC (rt)−4.53 m

Provenance & Evidence