Removal of the Phthalyl (Phthaloyl) Group by Hydrazinolysis [1]

Abstract

Phthalyl-glycyl-glycine (2.62 g, 10 mmol) is added to a 1 M solution of hydrazine hydrate [2] in absolute ethanol (10 ml). The mixture is diluted with ethanol (30 ml) and heated under reflux for one hour [3]. The alcohol is removed in vacuo, the residue treated with 2 N HCl (25 ml) at 50 °C for 10 minutes [4] and kept at room temperature for 30 min. The insoluble phthalyl-hydrazine is removed by filtration and the filtrate evaporated to dryness in vacuo. The dipeptide hydrochloride is recrystallized from boiling ethanol to afford the purified salt (monohydrate, 1.73 g) which is then dissolved in water (20 ml) and treated with the anion exchange resin [5] Amberlite-IR4B until a drop of the solution gives no positive reaction for chloride ion with AgNO₃-HNO₃. The resin is filtered off, washed with water and the filtrate concentrated to about 20 ml. The solution is heated on a stream bath, diluted with absolute ethanol until crystallization starts and allowed to cool to room temperature. The crystals, colorless plates, are collected, washed with 95% ethanol and dried. The pure dipeptide thus obtained (1.07 g, 81%) decomposes, without melting, at 215–222 °C.