Synthesis of 4-amino substituted 1,8-naphthalimide derivatives using palladium-mediated amination

• Pd-mediated amination of 4-bromo-1,8-naphthalimides is described.
• A readily available Pd/ligand combination is used, as opposed to a custom ligand.
• Mild reaction conditions are employed (≤80 °C) with a modest excess of amine.
• The methodology is particularly suited for large/bulky N-imide substituents.

Successful amination of 4-bromo-1,8-naphthalimides with ‘lengthy’ imide N-functionality has been achieved using a general palladium mediated approach (conventional thermal protocols were sub-optimal). Only readily available Pd/ligand combinations were considered and the resulting Buchwald–Hartwig procedure using Pd2(dba)3, Xantphos and Cs2CO3 is high yielding, relatively mild (40–80 °C, 24 h, yields 50–90%), requires only a modest excess of amine (3.0 equiv) and works equally well with other imide N-substituents. As such, the protocol complements existing methods but is superior for more complex substrates. Herein we compare this Pd mediated approach to the methods most commonly used and further demonstrate its utility by synthesising a number of new, highly fluorescent, 4-aminonaphthalimides.

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