Acetic Acid → 2-(4-(Methylthio)benzyl)isoindoline-1,3-dione

Reaction equation

[CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH2:8])=[CH:5][CH:4]=1.[C:11]1(=O)[O:16][C:14](=[O:15])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.C(O)(=O)C>>[CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][N:8]2[C:14](=[O:15])[C:13]3[C:12](=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:11]2=[O:16])=[CH:5][CH:4]=1

Participants

Reactant 3

HCID 176Acetic Acid

HCID 6811Phthalic Anhydride

HCID 27600804-(Methylthio)benzylamine

Product 1

HCID 79600652-(4-(Methylthio)benzyl)isoindoline-1,3-dione

Procedure

A mixture of 4-(methylthio)benzylamine (2.00 mL, 2.20 g, 14.38 mmol) and phthalic anhydride (2.39 g, 15.79 mmol) in acetic acid (40 mL, 42 g, 700 mmol) is heated at reflux for 3 h. The mixture is concentrated under reduced pressure, and the residue is partitioned between water and dichloromethane. The phases are separated, and the aqueous phase is extracted twice with dichloromethane. The combined organic layers are concentrated under reduced pressure and the residue is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 9:1 to 7:3). Yield: 3.60 g (88% of theory); ESI mass spectrum: [M+H]+=284; r.t. HPLC: 0.75 min (X001_004).