Biocatalytic Synthesis of Diethyl Succinate in Hydrophobic Trioctylphosphine Oxide (TOPO)-Based Reactive DES

Diethyl succinate (DEtS) synthesis by lipase-catalyzed direct esterification was successfully carried out in succinic acid (SA):trioctylphosphine oxide (TOPO) mixtures acting as reactive deep eutectic solvents (rDES). By this strategy, the succinic acid concentration in this non-aqueous eutectic mixture reaches up to 1.92 M at room temperature, enabling a suitable reaction system for the biocatalytic double esterification of SA with ethanol (EtOH) to yield DEtS. The best results were obtained when using an SA:TOPO equimolar ratio and a stepwise addition of EtOHinto the reaction system, leading to 92% SA conversion and 60% selectivity for the DEtS product synthesis after 20 h at 60 °C. For the subsequent pure product separation, the direct addition of dimethyl sulfoxide into the reaction system provokes TOPO crystallization, which is easily removed by filter centrifugation at room temperature. This novel approach, TOPO-based rDES, has been demonstrated as a green and low-waste strategy for biocatalytic diester synthesis under mild conditions, validated by green metrics.