Issue Date: January 1, 2007
New Frontiers For Ionic Liquids
Ten years ago, research on ionic liquids was a relatively unknown backwater of chemistry. Few chemists were familiar with these low-melting-point salts that have negligible vapor pressure, and barely a handful of books or review articles on chemistry mentioned them.
Since then, the field has grown almost exponentially. Between 1986 and 1996, fewer than 25 papers on ionic liquids were published each year. In 2005, almost 1,500 papers on the topic were published, and 2006 saw another bumper crop with over 1,000 papers published in the first six months.
Defined as salts with melting points below 100o C, ionic liquids typically consist of a heterocyclic nitrogen-containing organic cation and an inorganic anion. Salts that are liquid at room temperature are known as room-temperature ionic liquids.
Ionic liquids are now being developed and exploited for applications in numerous, and in some cases surprising, areas of science and technology. Nucleoside chemistry, biosensors, organic solvent nanofiltration, rocket propulsion, lubrication, and mineralogy are just a few examples.
"With a review on ionic liquids currently being published every two to three days, the activity in this field continues to grow unabated," says Kenneth R. Seddon, chemistry professor at Queen's University of Belfast and director of the Queen's University Ionic Liquids Laboratories (QUILL), in Northern Ireland. He adds that "the most exciting" developments have been the industrial applications based around the material properties of ionic liquids—for example, their use as media for gas storage and transport (C&EN, Aug. 1, 2005, page 33). In addition, their use as solvents in synthesis, homogeneous and heterogeneous catalysis, and biocatalysis continues to expand.
One of the attractions of these liquids is the potential to design and synthesize novel solvents with properties tailored for specific applications. An example is a new ionic liquid designed for nucleoside chemistry by a team led by Sanjay V. Malhotra, assistant chemistry professor at New Jersey Institute of Technology, Newark.
Nucleoside chemistry is mostly carried out in solvents such as dimethylformamide and dimethylsulfoxide because of the higher solubility of nucleosides in these solvents compared with other organic solvents. DMF and DMSO, though, are toxic. There are other problems as well. For example, benzoylation in these solvents is one of the most frequently used methods of protecting the sugar hydroxyl and base amine groups of nucleosides.
"Selective benzoylation of the hydroxyl groups over the amine groups is always an issue and even in the best cases, perbenzoylation occurs," Malhotra explains. "Lack of selectivity means that tedious chromatographic procedures are required to separate the desired compound for further reactions."
Following a systematic survey of the solubility of nucleosides in ionic liquids with different combinations of cations and anions, Malhotra's team came up with an ionic liquid, methoxyethyl-3-methylimidazolium trifluoroacetate, that is an efficient reaction medium for the selective benzoylation of hydroxyl groups in both ribo- and deoxyribonucleosides in good yields under ambient conditions. "We found that the nucleosides are more soluble in this ionic liquid than in DMF or DMSO," Malhotra says. "When we studied the protection of nucleosides in the ionic liquid, we obtained, to our delight, a single benzoylated product. There was no perbenzoylation."
The team also showed that the ionic liquid could be recycled several times without any significant drop in selectivity or yield of the benzoylated product. A paper describing the work has been accepted for publication in Tetrahedron Letters.
The exploration of conventional ionic liquids as novel solvents for a range of applications also continues apace. For instance, a team led by postdoc Gary A. Baker at Los Alamos National Laboratory has shown that the widely used water-miscible ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) and room-temperature [bmim] ionic liquids with other anions have potential as biosensor solvents for poorly water-soluble analytes such as pesticides, fungicides, fat-soluble metabolites, environmental pollutants, and illicit drugs (Chem. Commun. 2006, 2851).
The Los Alamos researchers carried out immunoanalyses that target a fluorescent hapten known as BODIPY FL. The dye, a spectral analog of fluorescein based on dipyrromethene boron difluoride, was dissolved in aqueous solutions containing a large volume fraction of a [bmim] ionic liquid. The team used polyclonal rabbit anti-BODIPY FL antibodies as the biorecognition elements. When the antibodies bind to the dye molecules, the green fluorescence is strongly quenched. The researchers showed that the antibodies bind with high affinity to the dye when they are dissolved in the water-ionic liquid mixtures, and also when they are immobilized on solid supports and immersed in pure [bmim] ionic liquids.
The demonstration that bioreceptor interactions can be maintained within room-temperature ionic liquid-based media is an important milestone, says Baker, who is now a researcher at Oak Ridge National Laboratory. "The antibodies remain active and target-selective in both dry and water-containing ionic liquids," he adds. "The work opens up a range of possibilities for bioaffinity-based separation and detection applications."
The use of ionic liquids can have both positive and negative impacts on chemical reactions. For example, it is well-established that some ionic liquids enhance the activity and stability of the palladium catalyst used in the Suzuki cross-coupling reaction between organoboron compounds and organic halides or related compounds. The reaction, which results in the formation of a carbon-carbon bond, is used in the pharmaceutical industry to prepare active ingredients. Ionic liquids, though, tend to have high viscosities compared with conventional molecular solvents. High viscosity slows heat and mass transfer in chemical processes and therefore lowers reaction rates.
Another issue is the recovery and reuse of ionic liquids. When products of a catalytic reaction in an ionic liquid are apolar, they can be extracted with an organic solvent that is immiscible with the ionic liquid. The ionic liquid and catalyst can then be separated and reused. Polar products, on the other hand, require polar extracting solvents. Such solvents may dissolve not only the products but also some of the ionic liquid.
The separation and purification of mixtures of ionic liquids, molecular solvents, reactants, products, and catalysts will be important for converting chemical reactions in ionic liquids into practical processes, says Andrew G. Livingston, a chemical engineering professor at Imperial College, London.
His group is using a technique known as organic-solvent nanofiltration to tackle these problems. The method relies on the use of STARMEM membranes supplied by the British company Membrane Extraction Technology and manufactured by Grace Davison Membranes, a division of Columbia, Md.-based W.R. Grace. These polyimide membranes enable small molecules to be separated from larger molecules.
In a recent paper, the group showed that Suzuki reactions can be carried out using single-phase mixtures of an ionic liquid and an organic solvent and that organic-solvent nanofiltration can be used to recover the products from the ionic liquid mixture and catalyst (Green Chem. 2006, 8, 373).
"We find that the technique is an easy and solvent-efficient way of recovering products from ionic liquids," Livingston says. "The ionic liquid gives all the beneficial effects, such as stabilizing the palladium catalyst against deactivation, when mixed with organic solvents. The solvent mixture is more easily processable, and the use of organic-solvent nanofiltration membranes makes product recovery easy."
In Belfast, a team led by Martyn J. Earle, assistant director of QUILL, has discovered room-temperature ionic liquids that are mutually immiscible. "We found that mixtures of some hydrophilic and hydrophobic ionic liquids form stable two-phase mixtures, particularly when the structures of the anions and cations are dissimilar," he says. "We also found that organic compounds, and other solutes such as iodine, greatly prefer one ionic liquid phase over the other."
The discovery of these biphasic ionic liquid systems could potentially be exploited for the separation of organic mixtures, countercurrent extraction, and applications such as battery technology where a permeable interface is required, according to Earle.
The biphasic systems typically consist of a hydrophobic phosphonium-based ionic liquid and a hydrophilic imidazolium ionic liquid (Chem. Commun. 2006, 2548). The two phases are not pure ionic liquids, however, because some imidazolium cations move from the lower phase into the upper phosphonium phase, and some of the phosphonium cations dissolve in the hydrophilic imidazolium layer.
design of a wide range of new energetic materials. One ion can be fine-tuned for its energy content, while the second ion can be independently fine-tuned to provide oxygen balance and the optimal physical properties or vice-versa."
In this same paper, Earle and coworkers report that some of these biphasic systems are also immiscible with water and alkanes. They prepared, for example, a stable tetraphasic mixture consisting of a top pentane layer, a phosphonium ionic liquid, water, and a bottom imidazolium ionic liquid layer.
"These multiphasic systems can be designed to suit an individual separation process to maximize its efficiency and yield," Earle says.
Earle also has synthesized a range of complex salts that emit light (fluorescence or phosphorescence). Some of these salts are liquid at room temperature, and all have melting points below 250
"We make the complexes by simply mixing a cation halide with a metal halide in the appropriate ratio," Earle notes. "We have also designed room-temperature ionic liquids that show many different colors depending on the metal in the anion. The colors can be fine-tuned by changing the structure of the cation. We can even make liquid-crystalline and magnetically active luminescent ionic compounds."
The unique tunable properties of ionic liquids, unavailable from molecular compounds or crystalline salts, are bringing the liquids under even more intense scrutiny, according to Robin D. Rogers, chemistry professor and director of the Center for Green Manufacturing at the University of Alabama, Tuscaloosa. As a result of their composition, ionic liquids offer a unique architectural platform with which to deliver different chemical and physical functionality segregated into different ion components in the same compound, he tells C&EN. "The properties of both cation and anion components can be independently modified, enabling tunability in the design of new functional materials, while retaining the core desirable features of the ionic liquid state of matter."
Several groups have been attempting to exploit the dual tunable nature of ionic liquids to develop new materials with a high energy density that might be used as liquid monopropellants for rockets. Many liquid propellants combine a fuel, such as kerosene, and an oxidizer, such as liquid oxygen. These are known as bipropellants. The rocket is propelled by the gases that are rapidly released when the fuel is oxidized. Propellants that combine a fuel and oxidizer in a single compound are called monopropellants. Ammonium perchlorate and ammonium nitrate are two examples. The ammonium is the fuel that is oxidized by perchlorate or nitrate, respectively. But such compounds are solids.
The problem with a solid rocket propellant is that it is hard to turn off once it has been ignited, observes adjunct chemistry professor Karl O. Christe of the University of Southern California, Los Angeles. It is therefore allowed to burn until all the propellant has been consumed.
Liquid propellants can be switched on and off. Liquid bipropellants, however, have the drawback that they require two tanks to store the fuel and oxidant separately, two pumps, flow controllers, and other equipment, which means heavier hardware and more complexity.
Liquid monopropellants are simpler to use and can be fired for the short periods needed to stabilize and adjust the movement of rockets and spaceships. "The performance of liquid monopropellants is usually considerably lower than that of liquid bipropellants and solid monopropellants," Christe explains. "They are therefore not used for main propulsion."
The state-of-the art liquid monopropellant is hydrazine, which decomposes in a series of highly exothermic reactions to form hydrogen, nitrogen, and ammonia. Hydrazine, however, has a high vapor pressure and is carcinogenic.
Earlier this year, Christe and coworkers described an "oxygen-balanced" energetic ionic liquid that offers improved performance as a liquid monopropellant (Angew. Chem. Int. Ed. 2006, 45, 4981). It consists of the oxidizing tetranitratoaluminate anion and the energetic 1-ethyl-4,5-dimethyltetrazolium cation. "The monopropellant uses a complex anion as a high-oxygen carrier and allows for complete combustion of the large organic cation," Christe says. The compound avoids the vapor toxicity of hydrazine, has better energy density, and performs as well as liquid bipropellants, he adds.
"Safety issues and environmental concerns have produced an outstanding need for new, safe, high-performance propellants and explosives," Rogers says. "Ionic liquids allow compartmentalized
A team that includes Rogers, University of Florida chemistry professor Alan R. Katritzky, and QUILL researcher John D. Holbrey has been searching for ionic liquids that incorporate energetic azolate anions. The team recently described 28 novel tetraalkylammonium and [bmim] salts prepared by combining four cations with seven heterocyclic tetrazolate, triazolate, and imidazolate anions (Chem. Eur. J. 2006, 12, 4630).
"The modular way in which the azolates can be combined with cationic partners provides a systematic, easy route to the controlled preparation of synthetic targets with specific energetic performance requirements," Rogers says.
Ideally, energetic ionic compounds, whether solid or liquid, should have densities in excess of 2.0 g cm-3 and be rich in nitrogen, according to Jean'ne M. Shreeve, chemistry professor at the University of Idaho, Moscow.
"High density means more bang per unit volume," she says. "The generation of molecular nitrogen as an end product of propulsion or explosion is highly desirable to avoid environmental pollution and health risks as well as to reduce detectible plume signatures."
Shreeve points out that the perfect high-energy-density material should also have low viscosity, low melting point, low shock and friction sensitivities, low carbon content, low vapor pressure, low cost, and high thermal and hydrolytic stabilities; it should also be nontoxic. "The design chemist must be a juggler fit for a king's court to meld effectively all of these requirements," she adds.
The Idaho team has synthesized and characterized a variety of salt-based energetic materials including new quaternary salts of pentafluorosulfanyl-substituted imidazolium, triazolium, and pyridinium salts that contain highly oxidizing anions, such as dinitramide (Eur. J. Inorg. Chem. 2006, 3221). The new salts generally exhibit good physical properties, including moderately high density and good thermal and hydrolytic stabilities, according to the authors. Most also have a melting point below 100
Shreeve and colleagues also are developing ionic liquids as high-temperature lubricants that could be used in aircraft engines. Current aircraft lubricants can be used only up to 150 oC, and engines in advanced military aircraft will need lubricants that function reliably to around 300
The paper describes a series of new dicationic ionic liquids that decompose between 350 and 460
Meanwhile, researchers at QUILL and the American Museum of Natural History, in New York City, are exploiting ionic liquids as optical immersion fluids for examining inclusions in gems and minerals. Inclusions provide mineralogists with important clues about the physical and chemical environment in which the gems and minerals grew.
Inclusions are "impurities" such as gases, liquids, or other minerals that become trapped in gems and minerals when they crystallize deep inside Earth, explains QUILL Assistant Director Maggel Deetlefs. The inclusions in a gem are most often examined under an optical microscope. The gem is immersed in a fluid with a matching refractive index to eliminate interference from light reflected from the gem's surface.
Refractive indices often uniquely identify a gem or mineral, but they tend to be high. Diamond, for example, has a refractive index of 2.42, whereas many liquids, such as water or ethanol, have refractive indices in the range 1.30 to 1.40. High-refractive-index immersion fluids currently in use often contain arsenic, observes Michael Shara, a curator at the American Museum of Natural History. These compounds are not only poisonous, but they are also solid at room temperature and unstable.
Deetlefs and colleagues are aiming to develop benign ionic liquids with refractive indices greater than 1.50 that can replace the high-refractive-index liquids traditionally used in mineralogy. "As a bonus, we are also collecting valuable refractive index data for pure ionic liquids," she says. "Like melting points, the refractive indices can serve as compound identifiers."
Last year, Deetlefs, Seddon, and Shara described the synthesis of a range of ionic liquids, many of which are novel, with refractive indices greater than 1.40 (New. J. Chem. 2006, 30, 317). The ionic liquids are based on the 1-alkyl-3-methylimidazolium cation. The team also showed that the refractive indices of a series of ionic liquids involving the same anion increase as the alkyl chain length in the cation decreases.
The highest refractive index achieved in the study was 2.08 for an ionic liquid with a 1-ethyl-methylimidazolium cation and an I9
By mixing the high-refractive-index ionic liquids in simple ratios, it is possible to generate hundreds, if not thousands, of novel immersion refractive-index-matching media. These can be used for examining inclusions and also for determining the refractive indices of a wide variety of gems and minerals. The use of ionic liquids not only makes refractive index measurements "more precise" but also substantially reduces health risks to experimentalists, Deetlefs and coworkers note.
The surging interest in ionic liquids has led to many applications where the purity of the liquids is a key issue. "The physical and chemical properties of ionic liquids are often strongly dependent on impurities like halides or residual water," observes Thomas J. S. Schubert, chief executive officer of Ionic Liquids Technologies (IoLiTec), a company he cofounded four years ago in Denzlingen, Germany.
"For example, 1% NaCl in an ionic liquid can increase the viscosity by 30%," he says. "The determination of impurities is therefore important where there is a demand for high-purity materials with defined, reproducible quality." He adds that impurities can also be used as additives to tune the properties of ionic liquids.
According to Schubert, the method of choice for quantifying impurities in ionic liquids is ion exchange chromatography. With this method, it is possible to detect a variety of inorganic and organic ions, including Na
Schubert observes that more than 1,500 ionic liquids have been described in the literature, and some 500 ionic liquids are produced commercially on a lab scale for R&D purposes by IoLiTec and other companies. The numbers, he suggests, are likely to rise to tens of thousands as research interest and applications expand.
Seddon estimates that, in theory at least, a million or so simple ionic liquids are feasible. "Years ago, I predicted that ionic liquids would change the face of organic chemistry," he says. "It is clear now that they have the potential to revolutionize all activities where liquids can be used."
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