Amide bond formation in aqueous solution: direct coupling of metal carboxylate salts with ammonium salts at room temperature

Herein, we report a green, expeditious, and practically simple protocol for direct coupling of carboxylate salts and ammonium salts under ACN/H2O conditions at room temperature without the addition of tertiary amine bases. The water-soluble coupling reagent EDC center dot HCl is a key component in the reaction. The reaction runs smoothly with unsubstituted/substituted ammonium salts and provides a clean product without column chromatography. Our reaction tolerates both carboxylate (which are unstable in other forms) and amine salts (which are unstable/volatile when present in free form). We believe that the reported method could be used as an alternative and suitable method at the laboratory and industrial scales.

Automated summary

The study presents a green, rapid, and simple method for direct coupling of carboxylate salts and ammonium salts at room temperature without the addition of tertiary amine bases, utilizing a water-soluble coupling reagent EDC·HCl. The reaction tolerates both carboxylate and amine salts, providing a clean product without column chromatography, and can be used as an alternative method in laboratory and industrial scales.