DoE-Based Optimization of a Photocatalytic C-Alkylation Reaction in a 3D-Printed Photoreactor

Photocatalysis provides a sustainable approach to chemical synthesis by enabling energy-efficient transformations under mild conditions. In this study, we present a comprehensive method that combines the development of photocatalytic reactions with process optimization, using a standardized 3D-printed photoreactor platform. We utilized the organophotocatalyst 4CzIPN to systematically optimize the visible-light-mediated carbon-carbon bond formation between the CH-acidic methyl cyanoacetate and 1,1-diphenylethylene. This optimization was performed through a 2⁴ full factorial design of experiments (DoE) resulting in a 48% improvement in yield (up to 91%). To address the persistent challenge of reproducibility in photochemical research, we employed a custom-designed, 3D-printed, open-access photoreactor. This design allows for standardized conditions and enhanced process optimization. We conducted a systematic investigation of various reaction parameters, including the conditions and the substrate scope. To assess the sustainability of the process, we introduced a modified energy economy factor specifically tailored for photoreactions, which illustrates a significant increase in energy efficiency. Finally, we demonstrate the possible implementation of the optimized reaction in continuous flow synthesis, underscoring the practical applicability of this methodology for advancing the design of scalable and sustainable photochemical manufacturing.