Micellar Catalysis: A Toolkit for Discovery and Process Development

Sustainability is no longer a choice for industry and research. Environmental concerns are affecting all industries including chemistry, and as science has done throughout time, it needs to adapt to address the needs of the world. Organic solvents which are used ubiquitously in chemical processes are unsustainable and not environmentally friendly due to the manner in which they are disposed of. Water has been deemed “nature’s solvent” and a “universal solvent” that is a greener alternative to organic solvents. The main difficulty in using water as a solvent in synthesis is that many organic molecules are not soluble in water which can lead to poor reaction outcomes. Micellar catalysis offers an opportunity to aid in facilitating otherwise impossible or slow chemistry in water. Additionally, the hydrophobic effect can accelerate organic reactions that take place in the micelle core and ionic surfactants can provide stabilising charge effects which are beneficial in some organic reactions. With surfactants possessing such unique qualities resulting in them being used in many applications, there are a vast amount of chemicals that have been classified as surfactants. Therefore, when applying surfactants to organic synthesis how does one choose which surfactant will give optimal results when there are so many to choose from? We herein report a successful generation and application of the first surfactant principal component map to be used for surfactant selection in micellar catalysis. Various physicochemical studies of the surfactants were performed, including dynamic light scattering, cryogenic scanning electron microscopy and optical microscope imaging analysis to determine important properties to be used for the surfactant map. These studies revealed that whilst micellar properties may be relevant it’s likely that the system is similar to an emulsion, therefore, emulsion descriptors were additionally included in the dataset. The surfactant map has been successfully used in surfactant optimisation for two N-alkylation reactions, identifying favourable chemical space. It was unsuccessfully applied to a Sonogashira coupling and an amide bond forming reaction, however these results may be used in future studies and map optimisation. Challenges were encountered when attempting to monitor micellar reactions which would not be present with organic solvents. These included issues of sampling non-homogenous reactions and solubility issues when using an internal standard in the presence of surfactants. I conclude that these micellar systems are not as effortless to investigate and apply to synthetic chemistry as documented in the literature. The surfactant principal component map has shown to be successful for two synthetic reactions; however, in science there is always room for improvement and the results obtained in this project can be used to further develop the surfactant map so it can be streamlined for in industry and research. This will further widen the field of micellar catalysis and not restrict research in this area to designer surfactants which are so commonly used.