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If fewer chemical conversions are possible by working without protecting groups or by using enzymes, a drastic reduction of the footprint of a process can be achieved. Other Anastas principles, including waste prevention, design for energy efficiency, use of renewable feedstock and catalysis, remain very relevant.
After translating this initiative into key performance indicators( KPIs), Ajinomoto Sustainable Solutions developed the‘ ECOpass’, a calculation that combines process mass intensity( PMI) and other key aspects of our footprint. PMI represents the kilograms of raw material needed to make one kilogram of the final compound. This is combined with emission factors for materials, solvents, and building blocks.
We translate all the materials that are needed into kilograms of CO 2
. If you are generating a lot of waste, it’ s important to discern how best to handle it. For example are you burning aqueous phases or are you able to discard the active phase into your treatment plant? Do you have to burn your chemical solvent waste, or is it recyclable?
In two instances, our experts disagreed with Anastas’ theories: ' Less hazardous chemical syntheses ' and ' Safer chemistry for accident prevention '. Some hazardous chemical reagents are quite useful, including azides, cyanides and oxygen.
Azides and cyanides are chemicals that, when introduced in a molecule, serve as the simplest but most effective protecting groups for amines and amides. Oxygen has an explosion danger because we typically work in solvents. However, the use of oxygen as an oxidant in combination with a catalyst results in the greenest possible oxidation.
Shift your mindset around standard process development
Standard process development needs to drive sustainability forward. 75 % of the CO 2 footprint within a process, excluding building blocks, is generated by the work-up. In a classical process, you carry out reactions, add solvent, do extractions, change the solvent and conduct crystallisation, which generates a lot of waste.
Reducing solvent use or extractions slightly will not enact meaningful change. Therefore, the industry needs to revolutionise its approach to R & D. One option is striving for zero extractions and distillations, i. e. no work-up at all. In the past, this has been done effectively by telescoping stages in which a second chemical conversion is done directly without any intermediate work-up.
Another simple but underdeveloped methodology is doing slurry-to-slurry transformations, in which the final product crystallises at the end of reaction is to collect the product by filtration and recover the solvent. Overall, solvent usage must be readdressed.
Typically, chemists follow the literature precedent for solvent usage rather than trying aqueous chemistry. Instead, consider if the chemistry can be done in water. If that’ s too difficult, add a small amount of solvent. If that still doesn’ t address the issue, add an emulsifier or surfactant to perform micellar chemistry.
Starting a green process development revolution requires a lot of project preparation. The team must be trained, informed about new developments, and aware of green chemistry development principles. Let’ s consider a few examples.
Figure 3 gives an example out of the pharmaceutical business. 1 It shows six chemical stages conducted in aqueous medium and only the last stage, from API crude to pure, is still solvent. Work-ups can be simplified and reduced to specific stage workups if you have a good grasp on the critical impurities towards the API; you may be able to switch to less than three purifications throughout the synthetic scheme.
The pathway uses a few different tricks to drive sustainability. The first stage uses water while the second stage uses a tiny amount of THF in water. If one uses 15 % volume of THF instead of 5 volumes or 10 volumes, that’ s a major improvement.
Figure 3 also shows an amidecoupling stage using TCFH, a coupling reagent that can be used in water, which implies that even dehydration chemistry is possible in water. The only point that might be lacking
Figure 2- Green chemistry principles developed by Paul Anastas
1 waste |
2 atom economy |
3 less hazardous chemical syntheses |
4 designing safer chemicals |
5 safer solvents and auxiliaries |
6 design for eneregy efficiency |
7 use of renewable feedstocks |
8 reduce derivatives |
9 catalysis |
10 design for degradation |
11 real-time pollution prevention |
12 safer chemistry for accident pre- vention |
MAR / APR 2026 SPECCHEMONLINE. COM
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