3,4,5,6-Tetrahydrophthalic anhydride → 2,3,5,6,7,8-Hexahydrophthalazine-1,4-dione

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Reaction Conditions

Reaction Steps

A mixture of 3,4,5,6-tetrahydrophthalic anhydride (3.5 g, 23 mmol), hydrazine hydrate (2.0 mL), sodium acetate (15.4 g, 188 mmol) in 100 mL of acetic acid is heated at 100° C. overnight. Upon cooling, a white solid is formed and collected by filtration. The solid is washed with water and dried to give 2,3,5,6,7,8-hexahydro-phthalazine-1,4-dione. The solid is taken up in 15 mL of POCl3. The resultant mixture is heated at reflux overnight. After cooled, the excess POCl3 is removed under reduced pressure. Crushed ice is added to the residue followed by careful addition of solid Na2CO3 to pH 9. The product is extracted with EtOAc twice. The combined extract is washed with brine, dried and concentrated. The residue is purified by flash silica gel column (Hexanes/EtOAc 4:1) to give 1,4-dichloro-5,6,7,8-tetrahydro-phthalazine as a white solid. 1H NMR: (CDCl3) 2.74 (m, 4H), 1.87 (m, 4H).

Provenance & Evidence