P-Toluic Acid → 3-(Chlorosulfonyl)-4-methylbenzoic acid
Reaction equation
[Cl:1][S:2]([OH:5])(=O)=[O:3].[CH3:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=1>>[CH3:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][C:8]=1[S:2]([Cl:1])(=[O:5])=[O:3]Participants
Conditions
- Temperature
- 130 °C
Procedure
A round bottom flask was charged with chlorosulfonic acid (170 mL, 2.57 mol) at 0° C. and 4-methyl benzoic acid (50 g, 0.37 mol) was added portion wise. The reaction mixture was heated at 130° C. for 5 h. The reaction mixture was then poured over ice and stirred for 10 minutes. The solids formed were filtered, washed with cold water and dried to afford 4-methyl-3-(chlorosulfonyl)benzoic acid as a white powder. This compound (80 g, 0.34 mol) was then charged into a round bottom flask containing sodium sulfite (200 g, 2.05 mol) and water (80 mL) portion wise. Aqueous sodium hydroxide (6 N) was then added dropwise till the pH of the reaction mixture reaches 10 and the reaction was stirred overnight. The reaction was then made acidic (pH 2) by addition of 2N HCl. The solids formed were filtered and dried to get 4-methyl-3-sulfinobenzoic acid as a white solid. This compound (55 g, 0.275 mol) was charged into a round bottom flask containing potassium carbonate (75.8 g, 0.55 mol) and N,N-dimethylformamide (450 mL). Methyl iodide (68.1 mL, 1.10 mol) was added slowly and the reaction was stirred for 4 hours. The reaction mixture was then diluted with water and extracted with EtOAc. The solvents were removed under reduced pressure to get the title compound as a white solid.
Workup
- additionThe reaction mixture was then poured over ice
- customThe solids formed
- filtrationwere filtered
- washwashed with cold water
- customdried
Sources & evidence
- ORD record
- ord-50ebc92e2a92427c8aefc1e3c8bf86a9
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08946439B2
Reaction notes
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