(418d) Effects of Catalyst and Metals Pretreatment for the Continuous Hydrogenation of a Halogenated Aromatic Nitro Compound

Continuous processing for the synthesis of active pharmaceutical ingredients (APIs) continues to be a growing area of interest and investment. Continuous heterogeneous catalysis offers both safety and capital cost advantages over a traditional batch autoclave.

This investigation explored impurity control for the continuous hydrogenation of a halogenated aromatic nitro compound. The hydrogenation utilized a palladium catalyst for the reduction of an aromatic nitro compound to an aniline. In particular, the work involved development of a packed bed reactor for the continuous heterogeneous catalysis. Several challenges appeared in transitioning the chemistry from batch to continuous processing. These challenges were characterized using advanced monitoring techniques (flow-NMR, online HPLC, etc.) and investigated using a combination of batch and flow processing. As part of that effort, a catalyst pretreatment was investigated which had been demonstrated as effective in batch mode for suppressing an impurity. Parameters investigated included duration and temperature of pretreatment, as well as liquid flow profile. Also investigated was the effect of residual metals in the feed solution entering from a previous synthetic step. Feed pretreatment and its impact on reaction impurity profile and bed life were evaluated.