Scaling Helicene Synthesis via Photochemical Oxidation─A Comparison between Batch and Flow Reactors

Helicenes are a class of helically chiral, aromatic molecules that are often functionalized and are of interest for a variety of applications due to their axial chirality. However, their syntheses are typically conducted under high dilution conditions to prevent undesirable side reactions and require large volumes of solvent, which makes scaling up a challenge. This study discusses the challenges of scaling helicene syntheses and offers facile strategies to address some of these challenges. The increased interest for using helicenes to address materials, sensing, and electronic applications necessitates that strategies for scaling them effectively with high purity need to be developed. It is well-known that flow chemistry facilitates more reproducible, scalable, safe, and efficient options for chemical synthesis, making it a valuable tool in both academic and industrial settings, as it allows for precise control over reaction conditions such as stoichiometry, mixing, temperature, and reaction time, leading to greater yields and better selectivity for a variety of reaction classes. Using quantitative 1H-NMR and isolated yields of the desired product and notable side products, we evaluated three reactor systems: 1L-batch, 5L-batch, and flow reactors towards the synthesis of a [5]-helicene tetraester (5HLTE). After initial optimization, the optimal conditions were used to demonstrate the scalability and provided throughput of ∼5 g/day in a 5 mL reactor flow system, scaling linearly with reactor volume. Discrete control of purity is vital for these applications in that impurities may provide incorrect structure–property conclusions when applied to organic electronics and polymer mechanical properties.