Phthalic Anhydride → N-(4-pyridinylamino)-1H-isoindole

Participants

Reaction Steps

Phthalic anhydride (5.1 g) and 4-hydrazinopyridine hydrochloride (5.0 g) were suspended in glacial acetic acid (300 ml), and the mixture was heated under reflux for 8 hrs. The reaction mixture was evaporated, and the residue was triturated with 2-propanol. The solid was collected and dried to give 8.0 g of N-(4-pyridinylamino)-1H-isoindole. 1M lithium aluminum hydride in tetrahydrofuran (72.5 ml) was added dropwise to a portion (4.0 g) of the above solid suspended in tetrahydrofuran (200 ml) at 0° C., under nitrogen. The reaction mixture was warmed to ambient temperature, stirred overnight, under nitrogen, and was added to ice water, with stirring. The mixture was extracted with 2-propanol/chloroform (1/4). The organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was chromatographed on silica gel, eluting with 5% methanol/chloroform. The appropriate fractions were collected and evaporated to yield 1.3 g (36%) of product free base. The free base was dissolved in methanol, and methanolic hydrogen chloride was added. The precipitate was collected to give 0.25 g (5.8%) of product, mp 253-255° C.

Provenance & Evidence