N-substituted pyrrole carboxylic acid derivatives from 3,4-dihydroxyketons.

ABSTRACT

Since the chemical industry is largely dependent on petrol-based feedstocks, new sources are required for a sustainable industry. Conversion of biomass to high-value compounds provides an environmentally friendly and sustainable approach, which might be a potential solution to reduce petrol-based starting materials. This also applies for N-heterocycles, which are a common structural motif in natural products, pharmaceuticals and functional polymers. The synthesis of pyrroles is a well-studied and established process. Nevertheless, most routes described are not in line with the principles of green and sustainable chemistry and employ harsh reaction conditions and harmful solvents. In this study, 3,4-dihydroxyketons are used as excellent platform chemicals for the production of N-substituted pyrrole-2-carboxylic- and pyrrole-2,5-dicarboxylic acids, as they can be prepared from glucose through the intermediate d-glucarate and converted into pyrrolic acid derivatives under mild conditions in water. The scope of this so far unknown reaction was examined using a variety of primary amines and aqueous ammonium chloride leading to pyrrolic acid derivatives with N-substituents like alkane-, alkene-, phenyl- and alcohol-groups with yields up to 20 %. The combination of both, enzymatic conversion and chemical reaction opens up new possibilities for further process development. Therefore, a continuous chemo-enzymatic system was set up by first employing an immobilized enzyme to catalyze the conversion of d-glucarate to the 3,4-dihydroxyketone, which is further converted to the pyrrolic acid derivatives by a chemical step in continuous flow.