Ionic Liquid Technologies
Ionic Liquids (ILs) are defined as salts that melt below 100 °C and whose melts are composed of discrete ions. There is an extremely wide range of possible anion and cation combinations taken from a pool of organic and inorganic ions. Consequently, ionic liquids are often considered as tunable “designer solvents”, meaning that all properties can be tuned by varying the structure of the component ions to obtain desired characteristics, e.g. polarity, density, viscosity, hydrophobicity, hydrogen-bonding capability, thermal stability or toxicity. The interest in their applications has led to the development of an extensive range of IL ions, and to the exploration of applications, including the use as electrolytes, lubricants, biphasic chemical processes, or biomass processing.
1. Biomass processing - Advanced fluid strategies for active ingredient isolation
Natural products obtained from plant matter continue to provide a diverse and unique source of bioactive compounds for drug manufacturing: A significant part of drugs approved for marketing in the last 25 years owe their existence to a natural product. To date, the extraction of active ingredients from biomass is mainly performed using solvent extraction processes; however this is always associated with the dangers of handling large volumes of volatile and combustible solvents, human risk and safety issues and poor environmental performance. Consequently, there is a constant need forcing the pharmaceutical industry to search for more benign strategies while equally taking safety, economic and environmental criteria into account.
Towards the greener drug production: Developing novel ionic liquid-based processes
In this project, we develop novel, ionic liquid-based strategies for the reactive dissolution of biomass, e.g. star anise seeds using different functionalized ILs as solvent and reaction media towards the isolation of important pharmaceutical intermediates. This procedure provided a single-step, higher yielding and environmentally benign strategy towards the synthesis of the anti-influenza drug Tamiflu™ and was recently awarded the INITS award 2012.
Exploring ionic liquid – biomass interactions
In a joint project with the department of Computational Biological Chemistry we have a more detailed look into IL-active ingredient interactions and performed MD simulations on valuable pharmaceutical ingredients, e.g. shikimic acid dissolved in different ILs. This allows calculating hydrogen bonding between ionic liquid and active ingredient and correlate the experimental isolation yield with the calculated interactions. This has importance for the future development of the project, as we are now able to predict the best IL for specific active ingredient isolation.
Ressmann et al. Green Chem. 2012, 14, 940; Ressmann et al. Green Chem. 2011, 3, 1442; Bica et al. Green Chem. 2011, 13, 1997.
2. Chiral Ionic Liquids
Considering a 300 billion dollar market in 2009 for the US the large field of pharmaceuticals is of constant interest for research and development. After some serious incidents in the past, it is nowadays well known that chirality plays an important role in drug specificity. Indeed, nine of the top ten drug sales in 2009 were chiral compounds and six are sold on the market as single enantiomers. Chiral ionic liquids (CILs) have been recognized for years as an alternative strategy to carry out chiral transformation, especially in areas such as chiral solvents or (organo-)catalysts. It is our particular interest to develop novel chiral ionic liquids, to evaluate the chiral recognition potential, and to explore novel applications in asymmetric catalysis and for the separation of racemic compounds.
Additionally, ionic liquid-supported chiral ligands and catalysts provide novel recycling strategies in asymmetric synthesis. The ability of ionic liquids to form stable 3-layer systems can be efficiently used to recover expensive chiral ligands or (organo-)catalysts after one catalytic cycle. This allows combining the known and positive effects in asymmetric synthesis of chiral ligands with profitable properties of ionic liquids, for example recycling of the catalyst or adaptable solubility.
Vasiloiu et al. Catalysis Today 2013, 200, 80; Bica et al. Eur. J. Org. Chem. 2008, 20, 3453; Bica et al. Synthesis 2007, 9, 1333.
3. Catalysis in Water – Ionic Liquid Micellar Solutions and Microemulsions
The growing interest in alternative solvents, e.g. ionic liquids, water or supercritical fluids is mostly caused by the possibility to avoid handling of large volumes of volatile organic solvents that are always associated with human risk, safety issues and poor environmental performance.
In terms of modern synthetic chemistry, water has been much under-investigated as a solvent for chemical transformations basically because of poor solubility of organic molecules. The effective concentration within the micelle can be quite high, and hence, reaction rates might be increased relative to those normally observed in organic media. Considering the known enhancements of ionic liquids in chemical reactivity or catalytic performance, we investigate IL-water micellar solutions and micro emulsions as particularly promising reaction media for synthesis and transition metal catalysis.
Bica et al. Chem. Commun. 2012, 48, 5013.
Dr. Katharina Bica