p-Toluenesulfonic acid → 1-(Dimethoxymethyl)-4-(methylsulfanyl)benzene

Participants

Reaction Steps

A solution of 4-methylsulfanylbenzaldehyde 1 (10 g, 66 mmol), (MeO)3CH (8.6 mL, 79 mmol) and p-TsOH (0.25 g, 1.3 mmol) in MeOH (130 mL) was stirred for 18 h. The remaining pTsOH was decomposed by addition of NaOMe. After 5 min, the mixture was evaporated in vacuo, and passed through a pad of SiO2 (95:5 hexane/Et2O) to afford 1-(1,1-dimethoxy-methyl)-4-methylsulfanyl-benzene 2. The residue after evaporation was dissolved into CH2Cl2 (360 mL) and treated with MCPBA (41 g, 240 mmol). After 18 h, the mixture was filtered and the filtrate evaporated. The residue was partitioned between EtOAc and 1 M NaOH. The organic layer was washed with 1 M NaOH (2×), washed with brine, dried (MgSO4), filtered and evaporated to afford 1-(1,1-dimethoxy-methyl)-4-methanesulfonylbenzene 3. The residue was dissolved into THF (130 mL) and treated with 2% H2SO4 (3.4 mL). After 2 h, the solvent was evaporated, and the residue was partitioned between EtOAc and NaHCO3. The organic layer was dried (MgSO4), filtered and evaporated to afford 12 g (98% for three steps) of 4-methylsulfonylbenzaldehyde 4 as a white solid; 1H NMR δ 3.11 (s, 3H), 8.09 (d, 2H, J=8.6), 8.14 (d, 2H, J=8.6), 10.15 (s, 1H).

Provenance & Evidence