PHARMACEUTICALS for what is now widely called‘ chemistry in water’. 3- 5 They pioneered processes that use water and surfactants, aiming to mimic nature ' s principles in chemical reactions. The idea is that nature consistently conducts reactions in water, not in organic solvents.
In this context, micellar chemistry aligns with the principles of Green Chemistry. It enables chemical reactions to take place within nanomicelles dispersed in water. These nanomicelles are formed through the addition of surfactants, which are amphiphilic species possessing both a hydrophobic( water-repellent)‘ tail’ region and a hydrophilic( waterattracting)‘ head’ group.
When these amphiphiles are added to water, and above a certain concentration known as critical micelle concentration( CMC), they group together to create micelles( Figure 1). The‘ head’ regions face outward, interacting with the surrounding water, while the‘ singletail’ regions huddle together in the core of the micelle.
This technology enables reactions to take place under milder conditions, allowing the reduction or even
Figure 2 – Benefits of chemistry in water avoidance of rare and expensive metal catalysts, while minimising the use of organic solvents. The hydrophobic core serves as a unique reaction site with properties distinct from those of the bulk solution.
This enables the solubilisation of hydrophobic reactants, which are typically insoluble or sparingly soluble in water, thereby improving the interaction and accessibility of reactants to each other. Such enhancement can significantly influence reaction selectivity, promoting the production of desired products while minimising side reactions that may lead to impurities. As this works as a catalyst, many refer to these processes as‘ micellar catalysis’. It is important to note that our understanding of this catalytic process is still evolving and further insights into the underlying mechanism will likely improve its efficiency.
Potential benefits
Micellar chemistry offers environmental, cost, and quality benefits alike. By using water instead of toxic organic solvents, it reduces chemical waste and it also enables lower reliance on rare metals.
Dispersing reactants in water with surfactants like TPGS-750-M, it is effective in reactions like amide coupling( peptides), Suzuki-Miyaura, Heck and Sonogashira. 6 Recent advances allow‘ one-pot’, multistep reactions, cutting solvent use and simplifying purification7 and iron-based nanoparticles containing approximately 500 ppm palladium have demonstrated notable potential for achieving further reductions in catalyst loading
By solubilising water-insoluble reactants, micellar catalysis improves interaction and selectivity, yielding purer products with fewer side reactions. It also enhances facility by reducing flammable solvent storage and process safety, without requiring extra equipment( Figure 2).
Surfactants
Surfactants have an amphiphilic structure, which allows waterinsoluble materials to be dissolved and react in water. Various commercial surfactants are used in micellar chemistry( Figure 3).
Brij 30 performs well, but designer surfactants like TPGS-750-M and Savie offer broader advantages. TPGS-750-M, made from PEG-750 and Vitamin E linked by succinic acid, is widely effective across reactions. Savie improves biodegradability, forms uniform nano-sized micelles, has a lower CMC and is easier to handle because it is a powder. Coolade, a low-foaming surfactant, is ideal for gas-releasing reactions.
From lab to manufacturing
Hovione recently achieved a breakthrough by developing a synthetic step for an API using two parallel methods: one with traditional solvents, the other with micellar chemistry. The process replaces costly organic solvents with a 2 wt % surfactant solution in water, enhancing efficiency and sustainability.
Solvent use was cut by 75 %, mainly replaced by a water-based solution with a small amount of greener
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