Advancing Arsenazo III Synthesis by Batch-to-Flow Translation and Additive Reactor Manufacturing

Continuous flow synthesis is inherently safer for handling strongly exothermic reactions like diazotizations and often guarantees a higher and more consistent product quality compared to traditional batch synthesis. However, developing a flow setup is often costly and time-consuming. Additive manufacturing (3D printing) addresses this challenge by reducing the production time and cost of flow reactors. To the best of our knowledge, this work presents the first continuous flow synthesis of Arsenazo III. This azo dye forms highly stable complexes with metal ions, which facilitates the photometric detection of metal ions, especially rare-earth metals. Guided by results from the initial batch experiments, we designed a continuous reactor setup that efficiently accommodates the sequential diazotization and azo coupling steps required for Arsenazo III synthesis. The process combines a tube-in-tube reactor with a static mixer for fast diazotization and a continuous stirred tank reactor (CSTR) for controlled azo coupling. The use of 3D printing enabled the customization of the involved reactors according to the required reaction conditions and the implementation of process control instruments to regulate these conditions (temperature and pH). Hydrodynamic evaluation through residence time distribution and micromixing analyses confirmed the suitable performance of the CSTR. Together, these elements enabled the robust continuous production of Arsenazo III, achieving a space-time yield of 49.6 kg h–1 m–3.