Purpose Novel process windows allow the development of faster, flexible, and greener processes. Therefore, novel process windows were applied to develop a greener process for the synthesis of vitamin D 3. In this study the environmental impacts of several batch pathways to obtain vitamin D 3 are benchmarked against the continuous microflow process, where novel process windows such as high temperature and pressure were applied. To evaluate the environmental impact of these processes, life cycle assessments were conducted. Methods A new process concept was developed to optimize and simplify the synthesis of crystalline vitamin D 3. This process was conducted in microflow by combining UV photoirradiation and high-p,T (photo-high-p,T) processing. Microreactors allow a high photon flux and enable the harsh conditions, respectively. The process was coupled with an integrated continuous crystallization, and its feasibility has been proven and reported before. The potential environmental impacts were assessed from a cradleto-gate perspective. Both processes, continuous and batch, were modeled in Aspen Plus using foreground data from the experimental continuous setup, and background data from different patents. The assessment was performed in the software Umberto NXL LCA using the ReCiPe Midpoint 2008 method. Results and discussion The continuous process has a significantly lower environmental impact than the batch processes. This lower impact is largely due to the fact that fewer amounts of material, particularly solvents, are used. Moreover, the continuous process is faster and has fewer steps, i.e., process-simplified. Among the industrial processes, the synthesis conducted in isopropanol has the lowest environmental impact, although, even in this case, the impact is between 20 and 30 times higherdepending on the conditions-compared with the continuous process. When the batch process is conducted in benzene, the worst environmental impact is obtained. Finally, recycle of the solvent for the best batch case was assessed. This improved the batch process to make it comparable with the continuous process. Conclusions The continuous production of vitamin D 3 leads to an interesting alternative to the industrial process. Continuous manufacturing of vitamin D 3 is faster, requires fewer steps, and uses less solvents compared with the industrial synthesis. However, although the environmental impact of this continuous process is already lower than that of the batch processes, the continuous process can still benefit from further optimization, particularly the introduction of a recycle loops for the solvents methyl tert-butyl ether and acetonitrile.

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In this study, the environmental impacts of three ibuprofen production routes, namely, the BHC, the Bogdan, and the newly developed enzymatic synthetic routes (modified Bogdan process), are assessed and compared by the application of life cycle assessment (LCA). Based on the data obtained through literature and laboratory-based experiments, a pilot-scale production with a capacity of 500 g/day of ibuprofen was simulated to generate inventory data for the LCA study, using Aspen Plus V11. The wellestablished BHC process was chosen as the benchmark to quantify the operational and environmental benefits of the innovative enzymatic Bogdan flow synthetic process. The comparison highlights the benefit of adopting the modified Bogdan synthesis route via an enzymatic catalyst. Results show that a general reduction of environmental impact is achievable across the whole set of impact categories of the analysis, and the magnitude of such reduction depends on the efficiency of recycling in the production system. Considering a 50% efficiency of recycling, the modified Bogdan system achieves lower environmental impacts in some impact categories like Acidification, Ecotoxicity of freshwater, Human toxicity, Particulate matter, and Resource depletion (mineral, fossils, renewables) while having higher impacts on the rest of the impact categories. Yet, the new process proposed here scores better environmental performances in all of the impact categories when the enzyme recycling is close to 100%, which is promising for future technology development.

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