Iodine → 4-[3-(Methylsulfanyl)phenyl]-1-propylpiperidin-4-ol

Participants

Reaction Steps

3-Bromothioanisole (960 mg, 4.73 mmol) was dissolved in 10 mL of diethyl ether dried on Na. 1-Propyl-4-piperidone was dissolved in 8 mL of dry diethyl ether. Approximately 10% of the solution of 3-bromothioanisole in dry diethyl ether was added to magnesium (344 mg, 14.15 mmol) and a few iodine crystals in a dried 250 mL three-necked flask in a nitrogen atmosphere. When the brown mixture turned colourless, the remaining solution of 3-bromothioanisole in dry diethyl ether was added drop wise, while refluxing on a hot water bath in a nitrogen atmosphere. When all the solution was added, the reaction mixture was left to reflux for twenty minutes. Then, 10 mL of dry diethyl ether was added because of evaporation. It was left to reflux for 30 minutes. The reaction mixture turned yellow and then green. Gas forming was noticed even before refluxing. Then the reaction mixture was left to cool to room temperature. The solution of 1-propyl-4-piperidone in dry diethyl ether was added drop wise to the reaction mixture. The reaction mixture then consisted of a dark oil, white precipitation and some clear solution. The reaction mixture was worked up with saturated NH4Cl solution (30 mL). The organic layer was separated. The aqueous layer was extracted twice with diethyl ether. The organic layers were collected and washed with brine and dried on MgSO4 during the night. The solution was filtered and the solvent evaporated in vacuo on a rotavapor. No further purification. Yield: 460 mg (56%). IR (KBr): 3113, 2956, 2917, 2828, 2772, 2365, 1583, 1444, 1375, 1148, 1104, 1044, 780, 696 cm−1; 1H-NMR (CDCl3, 300 MHz): δ 7.280 (d), 7.159 (m), 2.820 (d), 2.484 (s), 2.433 (t), 2.195 (t), 1.761 (d), 1.588 (t), 0.924 (t) ppm; 13C-NMR (CDCl3, 300 MHz): δ 127.291, 123.521, 121.359, 119.865, 69.826, 59.311, 47.947, 36.864, 18.573, 14.310, 10.524 ppm; GCMS (EI): m/z 265 (M+), 236 (M−29), 218, 206, 118; GC (100-320° C., 15° C./min): 7.6 min.

Provenance & Evidence