(94d) Scaling Photochemistry: A Laser Focused Perspective on Reaction Engineering of Photochemical Transformations and Their Scale-up

Photochemical transformations differ significantly from thermochemical reactions leveraging discrete, high energy, excited states to access unique reactivity and selectivity. In contrast, thermochemical transformations operate in a ground state and must overcome an activation energy to transform into the product. The thermodynamic requirements of the system, described by a Boltzmann distribution, can require extreme temperatures, or a catalytic system needs to be incorporated to lower the energy of activation. However, these strategies can also enable unproductive pathways.

Once absorbed, photons will excite photosensitizers or photocatalysts to a desired excitation state that will then transfer the necessary energy to the substrate and transform it into the desired product at milder conditions via inherently selective pathways.

At AbbVie, we have made significant investments into our photochemistry platforms to enable rapid characterization, screening, optimization, and the scale-up of reactions from a 2-mL HPLC vial to a 17-L stirred tank reactor capable of operating a 2000 W (445 nm blue) laser. It is our intent to provide an overview of the optimal workflow to take proof of concept reactions to a highly powered laser platform.

This talk will focus on two parts: 1) the development and optimization workflows to make a β-aryl aldehyde, and 2) a discussion on the development and scale-up of a organocatalytic photoisomerization and dynamic crystallization that yielded >90% enantiomer resolution.

The benefits of photochemistry go beyond those listed here. The implementation of the photoisomerization conversion would have significant cost savings per 100 kg batch – if the process were to be commercialized. These impacts are only possible through the development of platform approach that is amenable to a variety of chemistries. We have accomplished this through the development of the 2000 W laser reactor and the tools to scale up to this platform.