Continuous and Selective Hydrogenation of Heterocyclic Nitroaromatics in a Micropacked Bed Reactor

The hydrogenation of heterocyclic nitroaromatics is of great importance in the pharmaceutical industry for the synthesis of key intermediates. However, high selectivity is difficult to achieve in conventional batch reactors owing to severe back mixing and poor mass transfer performance, resulting in the high requirement for subsequent separation processes. In this work, a continuous flow system based on a micropacked bed reactor is developed for the selective hydrogenation of heterocyclic nitroaromatics and the reductions of 5-nitroisoquinoline to 5-aminoisoquinoline and 5-amino-1,2,3,4-tetrahydroisoquinoline are selected as the model reactions. With the optimal reaction conditions, maximal yields of 99.9% (5-aminoisoquinoline) and 99.3% (5-amino-1,2,3,4-tetrahydroisoquinoline) are obtained successfully. Moreover, this system exhibits remarkable performance for the selective hydrogenation of relevant heterocyclic nitroaromatics with all yields beyond the level of 97.5%. The continuous flow system enables efficient hydrogenation of heterocyclic nitroaromatics and remarkable selectivity of target products with shorter reaction time and safer operation compared with batch reactors.

Automated summary

A continuous flow system based on a micropacked bed reactor was developed for the selective hydrogenation of heterocyclic nitroaromatics, achieving high yields in model reactions and exceeding 97.5% in all relevant nitroaromatic reductions. Compared with batch reactors, the continuous flow system enables efficient hydrogenation of nitroaromatics with shorter reaction times and safer operation.