Ionic Liquid Driven Nucleophilic Substitution of Squaric Acid to Squaramides

Abstract Solubility is a crucial encumbrance for the synthesis of squaramides through nucleophilic substitution of squaric acid. The reactions must be performed in an aqueous medium since squaric acid is insoluble in virtually all organic solvents. The scope of amine nucleophiles was consequently restricted to those amines soluble in water. Owing to remarkable solvating ability of ionic liquid, reactions of squaric acid with a variety of structurally diverse amine nucleophiles were achieved. Interestingly, a catalyst-free reaction in 1-butyl-3-methylimidazolium chloride or [bmim]Cl could produce squaramides up to 99% yield. With the same efficacies, [bmim]Cl could be reused for at least three cycles. The catalyst-free, ionic liquid mediated approach expanded the reactant scope and offered a simple, efficient, and environmentally friendly synthesis of squaramides.