Teaching an Old Compound New Tricks: Reversible Transamidation in Maleamic Acids

Area of Science:

• Organic Chemistry
• Chemical Biology
• Materials Science

Background:

• Dynamic combinatorial chemistry (DCC) utilizes reversible covalent bonds for creating responsive compound libraries.
• Amide bonds are typically stable and require harsh conditions or catalysts for exchange, limiting their use in DCC.
• Discovering new dynamic covalent bonds is crucial for advancing DCC applications.

Purpose of the Study:

• To explore reversible amide formation and transamidation in maleamic acids.
• To investigate the stimuli-responsiveness of maleamic acid equilibria.
• To establish maleamic acids as a new tool for DCC.

Main Methods:

• Investigated maleamic acids in organic solvents at room temperature.
• Utilized Brønsted acid and base stimuli to control amide-anhydride equilibria.
• Demonstrated uncatalyzed transamidation and controlled library distributions.

Main Results:

• Maleamic acids exist in equilibrium with their precursors, responsive to acid-base stimuli.
• Reversible transamidation occurs without catalysts at room temperature.
• Tunable control over kinetic and thermodynamic regimes was achieved by varying conditions.

Conclusions:

• Maleamic acids provide a novel platform for reversible amide chemistry under mild conditions.
• This work introduces maleamic acids as a valuable addition to the dynamic combinatorial chemistry toolbox.
• The findings facilitate the development of new responsive materials and chemical biology tools.