Imidazole → N,N-Dimethyl-1H-imidazole-1-sulfonamide

Participants

Reaction Steps

Imidazole (1) (20.0 g, 0.29 mol), triethylamine (41.0 mL, 0.29 mol) and N,N-dimethylsulfamoyl chloride (31.6 mL, 0.29 mol) were added to 320 mL of benzene. The reaction was stirred for 48 h at room temperature (rt) and then filtered. The filtrate was collected and concentrated under reduced pressure. Vacuum distillation of the crude product (˜0.5 mmHg, 115°-118° C.) afforded 38.7 g (76%) of a clear and colorless oil. Upon cooling the product solidifies to give white crystals (2). 1-(Dimethylsulfamoyl) imidazole (2) (18.8 g, 0.11 mol) was added to 430 mL of tetrahydrofuran (THF). The solution was cooled to −78° C. A solution of n-butyl lithium (n-BuLi) in hexane (1.6M, 70.9 mL, 0.11 mol) was added dropwise to the reaction flask. Upon completion, the reaction was stirred for 1 h at −78° C. t-Butyldimethylsilylchloride (17.8 g, 0.12 mol) in 50 mL of THF was added via cannula to the reaction. After the addition was completed the reaction mixture was warmed slowly to rt and then stirred for 24 h. The reaction was diluted with water and the organic layer separated. The organic phase was washed with brine and then dried over sodium sulfate. The mixture was filtered and the filtrate concentrated under reduced pressure. Column chromatography (20% ethyl acetate/hexane as eluant) afforded a light yellow solid. Recrystallization from pentane gave 30 g (94%) of white crystals (3). 1-Dimethylsulfamoyl-2-t-butyldimethylsilyl imidazole (3) (5.0 g, 17.3 mmol) was added to 100 mL of THF. The solution was cooled to −20° C. A solution of secondary butyl lithium (s-BuLi) in hexane (1.3M, 14.6 mL, 19 mmol) was added dropwise to the reaction flask. Upon completion the reaction was stirred for 1 h at −20° C. 8 mL of dimethylformamide (DMF) was added to the reaction and then stirred at rt for 3.5 h. The reaction was diluted with water and the organic layer separated. The organic phase was washed with brine and then dried over sodium sulfate. The mixture was filtered and the filtrate concentrated under reduced pressure. Column chromatography (20% ethyl acetate/hexane) afforded a light yellow oil. Upon cooling the product solidifies to give yellow crystals of 1-dimethylsulfamoyl-2-t-butyldimethylsilyl -5-imidazolecarboxaldehyde (4).

Provenance & Evidence