Practical Outcome of Azaphthalimide Reduction with Zn/AcOH at Various Temperatures

Reduction of 4-aza- and 5-azaphthalimides with Zn dust in acetic acid resulted in two distinctoutcomes: i) in the 4-aza series, the reduction process stopped at the stage of 3-hydroxy-4-azaisoindolin-1-ones (isolated in 69-90% yield), presumably, stabilized by an intramolecular hydrogen bond; more forcing condition (110°C, 2 days) are required to obtain 4-azaisoindolin-1-ones; ii) in the 5-aza series, even at low temperatures (~10°C), overreduction could not be avoided; practical yields of 4-azaisoindolin-1-ones (59-85%) were achieved using elevated temperatures (50°C). The method described offers a practical alternative to hitherto reported sodium borohydride reduction of 4-azaphthalimides, which suffers from poor selectivity andisolated yields. Reductive manipulation of 5-azaphthalimides was studied for the first time.