DESs: New ionic fluids


You will surely have heard of ILs or ionic liquids, which were discovered more than a century ago, but have you hear of the new variety of ionic fluids called Deep Eutectic Solvents or DES?
I had certainly not come across DES until this recent joint publication by Spanish and Scottish research groups. (http://onlinelibrary.wiley.com/doi/10.1002/anie. 201400889/abstract)
A Deep Eutectic Solvent is a type of ionic solvent with special properties. It is composed of two or three cheap and safe components that together form an eutectic mixture, with a melting point much lower than either of the individual components. They were first described in 2003 when Abbot and co-workers reported on a low melting mixture of a 1:2 mole ratio of choline chloride (2-hydroxyethyl-trimethylammonium chloride [ChCl]) and urea. Since then many different mixtures have been described. In most cases a DES is obtained by mixing a quaternary ammonium salt with metal salts or a hydrogen bond donor (HBD) that has the ability to form a complex with the halide anion of the quaternary ammonium salt (Scheme 1). Thus the components of such solvents are low in cost, biodegradable and low in toxicity and synthesis of DESs is 100% atom economic, easy to handle and no purification is required and it is easily recycled. Moreover, in comparison to common organic solvents they are less volatile and not flammable making them ideal green alternative media.
carol 1

Since their preparation, DES have found applications in a variety of synthetic procedures such as brominations, polymerizations, dehydrations, cycloadditions, hydrogenations, condensations, NaBH4-reductions and in Heck and Stille coupling reactions. However it is this latter publication that firstly reports the successful coexistence of Grignard or organolithium reagents and green solvents within the same solution using Deep Eutectic Solvents.

We are all familiar with Grignard reactions and you don’t need to be a chemist to have heard of them. As a synthetic chemist you will have definitely carried out one of these reaction, if not more, and you will know that addition of Grignard reagents (or organolithiums) to carbonyl groups requires the use of aprotic dry solvents under inert atmosphere and at temperatures ranging from 0˚C to –78˚C and therefore the use of glycerol (Gly) or even water would definitely not be your choice of solvent. Hevia and co-cowerkers, however, report chemoselective addition of Grignard reagents (Table 1) and organolithiums (Table 2) to ketones using the eutectic mixtures 1ChCl/2Gly, 1qChCl/2EG and 1ChCl/2H2O at room temperature and in air

carol2

carol3

It is of interest to point out that the addition reaction of the Grignard reagents or organolithium is orders of magnitude faster than their protonation by water, ethylene glycol (EG) or glycerol (Gly) present in the DES and that the reactions are completed immediately (2-3s) suggesting a kinetic activation of the alkylating reagents. The authors speculate that the ammonium salt ChCl present in the DESs employed may have a further role than as a component of the DES mixture. Although not isolated in their work, they believe that an anionic magnesiate (from the Grignard reagents) and a dianionic halolithiate (from the organolithium) species are formed that have and enhanced nucleophilic power which favor the addition reaction in DES over the competing protonation process.
Although choline chloride is not a chemical we currently stock in the lab I am tempted to order it and have it ready for my next Grignard reaction so that I can test this simple methodology, which avoids use of Schlenk techniques and low temperatures. Are you not tempted to try it too?

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2 thoughts on “DESs: New ionic fluids

  1. Does anyone know if these types of DES mixtures have been studied (or used) as potential formulation solvents for in vivo studies?

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