Tetrahydrofuran → 5-phenylsulfanyl-1H-imidazole

Participants

Reaction Conditions

Reaction Steps

1-(N,N-dimethylsulfamoyl)imidazole (1.5 g, 8.6 mmol) was taken up in 28 mL of THF. The solution was cooled to −78° C. and n-BuLi (5.4 mL, 8.6 mmol) added dropwise via syringe. After stirring at −78° C. for 1 h TBSCl (1.3 g, 8.56 mmol) in 10 mL of THF was added. The bath was removed and the reaction allowed to warm-up to rt. The reaction mixture was stirred overnight. The reaction mixture was cooled to −20° C. and n-BuLi (5.4 mL, 8.6 mmol) added. After 45 min phenyldisulfide (1.9 g, 8.6 mmol) in 8 mL of THF was added. The reaction mixture was stirred at rt for 48 h. The reaction mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was collected and washed with water and then brine. The solution was dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (2.5% EtOAc/hexane) afforded 2.8 g (7.0 mmol) of 2-(t-butyldimethylsilyl)-5-phenylsulfanylimidazole-1-sulfonic acid dimethylamide (1) as a yellow color oil. The compound (1) (2.8 g, 7.0 mmol) was dissolved in THF and the solution cooled to 0° C. TBAF (7.0 mL, 7.0 mmol) was added dropwise to the solution. The reaction mixture was stirred overnight at rt. The next day the reaction was quenched with water and extracted with ethyl acetate. The organic layer was washed with water followed by brine. The solution was dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (50% EtOAc/hexane) afforded 474 mg of 5-phenylsulfanylimidazole-1-sulfonic acid dimethylamide (2) and 290 mg of 5-phenylsulfanyl-1H-imidazole (3) (H). The 478 mg of (2) was added to 2N HCl and the solution heated at reflux for 2 h. The reaction mixture was made basic with 2N NaOH and extracted with ethyl acetate. The organic layer was washed with water followed by brine. The solution was dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (EtOAc) afforded (3) as a white crystalline solid. A combined total of 360 mg (2.0 mmol) of (3) is recovered.

Provenance & Evidence