One-pot synthesis of 5-norbornene-2,3-dicarboxylic anhydride with high exo/endo ratio in a microreactor under high temperature and appropriate pressure

Abstract

5-Norbornene-exo-2,3-dicarboxylic anhydride (exo-NDA), widely used in the synthesis of medicine and pesticide, was primarily obtained through the subsequent thermal isomerization of 5-norbornene-endo-2,3-dicarboxylic anhydride (endo-NDA) synthesized from cyclopentadiene (CPD) and maleic anhydride (MAH). Herein, density functional theory (DFT) was employed to elucidate the transition states and reaction pathways of different configurations. The endo-path exhibited a lower energy barrier, and the exo-isomer demonstrates greater structural stability. It was found that both high temperature and solvent polarity influenced the generation of NDA with different configurations. Due to considering solubility of MAH, an acetone/ethylbenzene mixed solvent was chosen for the reaction instead. According to the DFT calculations, we developed continuous-flow microreactor for high-efficiency one-pot synthesis of the isomers with exo/endo ratio of up to 1.19:1 as well as almost 100 % conversion and 98 % selectivity just in 2 min at 260 °C and 4 MPa, which CPD was generated in situ to participate in a series of Diels-Alder reactions instead of dicyclopentadiene as raw material existed at room temperature. Moreover, excessive or insufficient pressure in the reaction system should elevate byproduct formation, resulting in a decrease in reaction selectivity, as could prolonged residence time.