Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D₃

Abstract

The vitamin D 3 flow-chemical process is a good route for exercising circularity in chemistry; as the complex chemistry of this reaction limits the highest yield to only 25%, a recycling operation becomes mandatory. In this context, this research applies, for the first time, a circular economy assessment to a flow chemistry process, including reaction and separation. This is undertaken on the example of the photo-flow-chemical synthesis of vitamin D 3 , previously developed by our group. In the research reported here, we develop a separation process to recycle the unreacted starting material 7-dehydrocholesterol after the photo-flow irradiation. We use acetonitrile for separation, instead of methanol, in the industrial process. In just one run, 90% of vitamin is extracted using dry acetonitrile as a separation solvent at 30 °C. A cumulative extraction efficiency of >99% is achieved after a second extraction step. The acetonitrile separation process connects directly to the subsequent vitamin crystallization using the same solvent. This eliminates the need to evaporate methanol in the industrial process; rather, the product is obtained just by cooling down. The Material Circular Indicator has been used as a central metric, and we needed to redefine this circularity metrics proposed by the Ellen MacArthur Foundation's CE100 program to the world of flow chemistry. Rather than being able to take the parameter of lifetime and utility used in the original C100 definition, the frequency and dose of usage of medicinal products are taken here, both of which are connected to chemical productivity and waste generation. To explore the application of this adapted methodology to other pharmaceutical production processes, the results for the proposed vitamin D 3 flow-chemical process are compared with five processes for producing vitamins, painkillers, and an antibiotic. It is shown that the vitamin D 3 flow chemistry process with the new separation achieves a Material Circular Indicator of 0.94, a recycled fraction mass above 0.95, and an energy demand reduction by a factor of 2.

Quantitative Sustainability Assessment of Flow Chemistry–From Simple Metrics to Holistic Assessment

“…To do so requires adapting the procedure to each industrial activity and in the context of flow chemistry to chemistry in general and the pharmaceutical industry in particular. Therefore, with reference to the EMA methodology, 15 the MCI definition needs to be adapted to flow chemistry used for pharmaceutical production as described by Escriba-Gelonch et al 146 as follows.…”

“…While this methodology suits products like mobile phones and washing machines well, its application to a chemical product to be further converted by industry or a pharmaceutical product destined for human consumption is challenging. In this context, Escriba-Gelonch et al 146 adapted the MCI methodology to pharmaceutical syntheses procedures based on the process mass flows of chemicals, as follows: The lifetime and utility of a drug are redefined to reflect its status as a molecule, rather than an assembled product. Utility now refers to a normalized productivity, as the more pharmaceuticals are produced, the larger population that receives a health benefit.…”

Comparative Life Cycle Assessment of Different Production Processes for Waterborne Polyurethane Dispersions

“…Other advantages, such as precise residence time control, reproducibility, better product quality, safety, easy scalability, and small inventory are compelling reasons for the implementation of continuous flow reactors. Most importantly, continuous manufacturing also contributes toward greener and more sustainable processes. − …”

Economic Optimization of Local Australian Ammonia Production Using Plasma Technologies with Green/Turquoise Hydrogen

“…The circular process comprised the manufacture of ammonia from manure through the plasma technologies considered here. We have also introduced quantitative circularity assessments (circularity transition indicators) to chemical manufacturing. , Thus, we are now in the position to make complex assessments for those circular processes and can model real-world supply chains. While environmental assessments will be further assessed in future research, this article is about a complex cost assessment of a real-world chain of the new technologies, translating into a real-world transformation of supply chains and business models.…”