A Three-Step Route to Functionalized Pyrrole-2,5-Dicarboxylic Acids from Galactaric Acid

Galactaric acid (GalA), one of the key biomass-derived organic acids, serves as a promising starting material for the synthesis of several platform chemicals, including muconic acid, 2,5-furandicarboxylic acid (FDCA), and pyrones, which can replace conventional petroleum-based chemicals. Recently, GalA has also been investigated as a precursor for nitrogen-containing heterocycles, such as pyrrole-2,5-dicarboxylic acids (PDCAs), which find applications in macromolecular chemistry, metal-organic framework (MOF) synthesis, and polymer production. To date, only two procedures have been reported for the synthesis of N-substituted PDCAs (R-PDCA), in which either the final products were not isolated, or the overall process required up to six reaction steps. This work focuses on the development of a simple and scalable route to functionalized PDCA compounds starting from GalA. The optimized synthetic procedure enabled the high-yield production of a library of PDCA derivatives through a three-step process involving a 2-pyrone salt as a key intermediate. All the products were isolated without the need for any chromatographic purification and fully characterized. Metrics were used to evaluate the greenness of the presented process and to compare it with the two previously reported procedures, demonstrating the viability of this synthesis for obtaining N-substituted PDCA compounds.