Selective hydrogenation of functionalized nitro aromatics

Currently, we are developing processes for sustainable drug manufacturing as part of the CHEM21 project, which was launched in 2012. This project is funded by the EU (FP7/2007-2013). In close cooperation with the Bayer Pharma AG as partner, halogenated nitro aromatics are converted to anilines selectively. Aromatic nitro compounds are readily available and can be functionalized easily. After selective reduction, aniline as well as halogen substituents can be used in a wide range of functionalization reactions. However, selective reduction of the nitro group requires utilizing stoichiometric amounts of reducing agents in many cases. To make this transformation more efficient and sustainable, we have developed a continuous catalytic process. After identifying suitable catalysts in batch, the selective hydrogenation was optimised in a flow reactor. The Modular Microreaction System of Ehrfeld Mikrotechnik BTS was used combining flexible mixers, reactors, heat exchangers, sensors and actuators. Based on the experiences with 1-iodo-4-nitrobenzene as a model substrate, we have investigated transformations, which are important for the synthesis of the actual APIs (active pharmaceutical ingredient) vismodegib and clofazimine. Successful transfer to a continuous process in a micro reactor was realized for both substrates, albeit only stoichiometric reductions had been described previously. Using cobalt based catalyst systems in a cartridge reactor, both of these anilines could be obtained with more than 88% isolated yield (>98% purity).