Chemistry in Water is a green technology that allows classical organic reactions often used in the synthesis of active pharmaceutical ingredients and intermediates to be carried out in water. Based on pioneering micellar technology, developed by Professor Bruce Lipshutz of the University of California, Santa Barbara, Evonik offers this highly sustainable technology for the industrial scale production of pharma intermediates and APIs.
Also known as ‘micellar chemistry’, Chemistry in Water uses surfactant-forming microscopic spheres (micelles) in water which function as nanoreactors. These enable organic reactions, which are generally run in organic solvents, to be performed in water.
The technology is based on Vitamin-E derived designer surfactants such as TPGS-750-M, that self-assemble into micellular-shaped nano-reactors. TPSG-750-M is fully removable below the Limit of Quantification (LOQ).
Improving sustainability by reducing the use of organic solvents and boosting reaction performance
Chemistry in Water reduces the need for organic solvents in organic reactions, resulting in waste reduction during chemical production. Other benefits of Chemistry in Water include improved reaction performance, higher yields and increased selectivity. Chemistry in Water can also reduce catalyst loading. The mild reaction conditions enabled by Chemistry in Water help reduce the energy consumption and waste production for many reaction processes.
Which reactions work with Chemistry in Water?
Chemistry in Water has been tested and applied in a broad range of reaction types, including:
- Suzuki Miyaura couplings
- Stille couplings
- Heck couplings
- SNAr reactions
- Aryl aminations
- Amide bond reactions
- Heterogeneous catalysis
- Peptide couplings
- Biocatalytic transformations
Example: Buchwald-Hartwig Coupling in water
In this reaction the dioxane used in classical reaction conditions is replaced by water and tBuOH as co-solvent. These conditions reduce the catalyst loading from 5 mol% to 1 mol%. The reaction temperature is reduced from 100 °C to 50 °C.
Example: Amide Coupling with in situ formed mixed anhydride in water
Here, the 2-MeTHF typically used under classical conditions is substituted by water. Chemistry in water improves the regioselectivity so there is no formation of the pivaloyl-byproduct known under classical conditions. The reaction sequence is short and there is no need for freebasing.
A sustainable solution in our broad portfolio of advanced technologies
Evonik serves as a fully integrated development and manufacturing partner with capabilities to manufacture customized APIs/HPAPIs. To address specific customer needs, Evonik has established a broad portfolio of advanced technologies which can be combined to support multi-step API synthesis. Chemistry in Water now joins our other technologies including continuous processing, fermentation, PEGs and mPEGs, transition metal catalysis, biocatalysis as well as organometallic and cryogenic chemistry.
To find out more or discuss your project with us, please get in touch.