Iodine → Bis[2-(benzyloxycarbonylamino)-2-methylpropyl]-disulfide

Participants

Reaction Steps

To a solution of 45.4 g (179 mmol) of benzyl 1,1-dimethyl-2-(methylthio)ethylcarbamate in aqueous methanol (obtained by adding 5.22 g (290 mmol) of water to 150 ml of methanol) was added 33.46 g (188 mmol) of N-bromosuccinimide in small portions with stirring. The reaction was carried out at room temperature for 2 hours, after which the reaction solution was made weakly basic with saturated aqueous sodium hydrogencarbonate solution and then the methanol was distilled off. Water was added to the residue, followed by three runs of extraction with ethyl acetate. The extract solution was washed three times with water and then once with saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was distilled off and the thus obtained crude benzyl 1,1-dimethyl-2-(methylsulfinyl)ethylcarbamate was dissolved in acetic anhydride (150 ml), and the reaction was carried out with refluxing for 4 hours. The excess acetic anhydride and acetic acid were distilled off under reduced pressure to obtain a residue containing crude [2-(benzyloxycarbonylamino)-2-methylpropyl]thiomethyl acetate. This residue was dissolved in methanol (300 ml), followed by adding thereto 19.54 g (77 mmol) of iodine, and the reaction was carried out with refluxing for 5 hours. After the reaction mixture was cooled to room temperature, an aqueous sodium hydrogensulfite solution was added thereto to reduce the excess iodine. The reaction solution was made weakly basic with saturated aqueous sodium hydrogencarbonate solution, after which the methanol was distilled off. Water was added to the residue, followed by three runs of extraction with ethyl acetate. The extract solution was washed with saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was distilled off and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain 10.0 g (yield 23%) of bis[2-(benzyloxycarbonylamino)-2-methylpropyl]-disulfide.

Provenance & Evidence