Issue Date: September 29, 2008
Ionic Liquids Go To Market
IONIC LIQUIDS have been one of the more visible classes of chemicals during the past decade, and for good reason. The more chemists have explored the range of properties possible by mixing and matching cations and anions to make these low-melting-point salts—there are an estimated 1 billion possible combinations—the more impressed they have become with the potential for ionic liquids to lead to commercial successes in a variety of applications.
By definition, ionic liquids are salts that have a melting point below 100 °C; many of them exist as liquids at room temperature. The compounds typically consist of an organic cation, such as a nitrogen-containing heterocycle, coupled with an inorganic anion, although the cation or anion can be an organic or inorganic species.
The major difference between ionic liquids and conventional salts—such as table salt, NaCl—lies in the asymmetry of the cation-anion pair and the delocalized charges, which lower the melting point of the salts due to a "softening" of the crystal lattice. The result: N-Methylimidazolium chloride—with a voluminous organic cation—melts at only 75 °C, whereas NaCl melts at about 800 °C.
The initial fascination with the solvent, thermal, mechanical, and electrochemical properties of ionic liquids led to a lot of hype about how the salts might change the face of chemistry. Talk of the ability to design an ionic liquid with any set of properties one might want was plentiful.
But as reality has set in, the types of global-scale processes utilizing ionic liquids that were initially envisioned haven't appeared, at least not yet. Instead, a steady stream of small, niche applications has formed.
"Ionic liquids present a set of properties within a liquid that you didn't have before," notes Peter F. H. Schwab, an R&D manager in the Consumer Specialties business unit at Evonik Industries, in Essen, Germany. "Whenever a new technology like this emerges, there is always a little hype."
At first, people usually only see the positive aspects of such a material, Schwab says, and with ionic liquids the list of positive attributes is quite long. People came up with a lot of ideas for applications that seemed reasonable, he adds.
But at the end of the hype phase, people have to turn the ideas into reality. Replacing an existing technology that has been fine-tuned is difficult. "Chemists have realized that there is more to it than just replacing a liquid that you are currently using by pouring in an ionic liquid," Schwab observes.
A decade ago, when chemists' interest in ionic liquids began growing, the materials were considered primarily as environmentally safe alternatives to conventional organic solvents. To call ionic liquids "green" because they have essentially no vapor pressure and are readily recyclable seemed reasonable. That overgeneralization by some researchers turned out to be a bit foolhardy because some ionic liquids are made from decidedly ungreen starting materials and some ionic liquids are quite toxic.
But now that the focus of the chemical industry has shifted away from simply using ionic liquids as replacement solvents, the range of potential applications has broadened. The list of uses still includes solvent applications, but it has greatly expanded to include production of nanoparticles; electrolytes in sensors, solar cells, and lithium-ion and other types of batteries; multiphase catalysis; lubrication; performance additives for paints and coatings; chromatography columns; gas adsorption and storage; and pharmaceuticals and drug delivery systems—to name just a few.
"The success of ionic liquids will not necessarily be equated with large-scale chemistry," notes Robin D. Rogers, a chemistry professor and director of the Center for Green Manufacturing at the University of Alabama, Tuscaloosa. "It is more likely that small, niche—but valuable???applications will lead the way. I can confidently predict that ionic liquids will find commercial application in a wide variety of fields, including some that people haven't even thought of yet."
Rogers, one of the leading advocates for ionic liquids, is also codirector of Queen's University Ionic Liquids Laboratories, an industry-university consortium based in Belfast, Northern Ireland, that is dedicated to developing ionic liquid technologies for industrial applications. His research group has developed a variety of ionic liquids and applications that use them.
One example is dissolving and processing cellulose using 1-ethyl-3-methylimidazolium acetate and other ionic liquids, which is being commercially developed by BASF to make cellulose-polymer blends as unique types of plastics. Another example is using the ionic liquid lidocaine docusate as an analgesic with beneficial properties distinct from the traditional compound lidocaine hydrochloride, a topical anesthetic used in dentistry. A start-up company is being created by the university to further develop this pain medicine, Rogers says.
A parade of ionic liquid research has become standard fare at American Chemical Society national meetings. At the most recent meeting, held in Philadelphia last month, Rogers helped organize some of the approximately 200 lectures and poster presentations on the topic. He delivered a keynote lecture to the Division of Industrial & Engineering Chemistry that reviewed the growth of ionic liquid research and development during the past decade and the fledgling commercial applications.
When it comes to commercial processes, BASF has the largest ionic liquid patent portfolio and access to the broadest range of potential applications, Rogers notes. The company landed the first publicly announced ionic liquid commercial application in 2003 with its BASIL process—biphasic acid scavenging utilizing ionic liquids. The process uses N-methylimidazole to replace triethylamine as an acid scavenger in the synthesis of alkoxyphenylphosphines, which serve as precursors to make photoinitiators used in ultraviolet-light-curable coatings and other applications.
WHEN CHEMISTS use triethylamine, the waste by-product triethylammonium chloride forms an insoluble paste that is difficult to handle. The imidazole reacts with the acid to form the ionic liquid N-methylimidazolium chloride, which partitions the reaction mixture into two phases so that the product can be isolated. The process permits use of a smaller reactor, significantly increases the yield, speeds up the reaction, and allows the imidazole to be recycled. BASF now uses the process for additional reactions and is licensing the technology.
Most major petrochemical companies have invested in ionic liquid technology as well, Rogers notes, but most of them have yet to announce commercial applications. One exception is PetroChina, which has a process called ionikylation that employs an aluminum chloride-based ionic liquid in place of sulfuric acid or hydrofluoric acid catalysts. The company uses ionikylation in a 65,000-ton-per-year plant for the alkylation of isobutene, a key refinery process to make gasoline. This is by far the largest commercial process utilizing an ionic liquid to date, Rogers notes.
A number of other companies, including Eli Lilly & Co., Air Products & Chemicals, Linde, Wacker Chemie, Arkema, and Scionix, have pilot-scale ionic liquid technologies under development. But as Rogers points out, many companies provide technological know-how related to ionic liquids to develop larger markets for their products—they don't just make and sell ionic liquids.
At Evonik, for example, chemists are using ionic liquids as solvents in an in-house process to functionalize polysiloxanes. Siloxanes modified with polyether, alkyl, and aryl groups are among Evonik's best-selling products, notes Schwab, who also spoke at the Philadelphia meeting. Polyethersiloxanes are used as stabilizers and cell openers in polyurethane foams and as antifoams, emulsifiers, wetting agents, and dispersants. However, the expensive homogeneous platinum or rhodium catalyst needed to facilitate the hydrosilylation reactions is not recycled during the standard process.
Evonik chemists devised a solution in which they use an ionic liquid to immobilize and then recover the catalyst, Schwab explains. Once the hydrosilylation reaction is complete, the functionalized siloxane can be phase-separated, and the ionic liquid and catalyst can be recycled a number of times without the need for further purification.
Other key applications that are commercialized or nearing commercialization by Evonik include using ionic liquids as paint additives, lubricants, and refrigeration fluids. In these areas, "ionic liquids could have a significant impact over the next few years," Schwab says. "In the long term, ionic liquids might very well revolutionize some fields because they offer a completely new tool set." To harvest the full potential of the materials, "more awareness and patience" are needed, he adds.
BASF, Evonik, and Merck KGaA, which are all based in Germany, along with U.S.-based Cytec Industries, are part of a small group of global players in the ionic liquids arena that are looking at a variety of commercial opportunities. Nippon Chemical Industrial and other companies in Japan are also active in ionic liquids, with a focus on batteries and electrochemical applications.
IN ADDITION to these larger companies, there are a handful of start-up ionic liquid firms trying to spread their wings, with most of them based in Europe. One of these companies is Ionic Liquids Technologies (IoLiTec), based in Denzlingen, Germany. It was founded in 2003 by Thomas J. S. Schubert as one of the first companies to actively pursue ionic liquids on an exclusive basis. In Philadelphia Schubert gave several talks that analyzed the field of ionic liquids and described some of the commercial applications IoLiTec is developing or has already commercialized.
More than 1,500 ionic liquids have been described in the chemical literature, and some 500 ionic liquids are produced commercially, Schubert notes. IoLiTec currently has a portfolio of 200 ionic liquids that it can produce, although they only now are beginning to find themselves in commercial applications. For example, one of IoLiTec's ionic liquids is being used in a humidity sensor for food testing and other applications. Schubert has built the company's business plan on the idea that it will have 10 to 15 ionic liquids that it produces for commercial applications at up to a ton scale within the next decade.
"We want to have a broad portfolio," Schubert says. "That strategy allows us to be flexible and lets the market lead us to the best ionic liquids for our customer's needs."
One of IoLiTec's biggest projects has been developing a continuous-flow microreactor to produce ionic liquids, rather than using traditional batch processes. Because most applications will be small, usually only a couple of tons of ionic liquid per application per year, a microreactor that can quickly be configured to produce different types of ionic liquids on a kilogram-per-day scale could be an advantage. IoLiTec currently has one microreactor that it developed through a project funded by the German government. Microreactors offer the flexibility to quickly scale up production by adding a second shift or by adding additional microreactors.
Intellectual property for specific ionic liquid applications is difficult to obtain for small companies, Schubert says. Rather than taking a standard approach, "we want to define ourselves by being innovators in producing high-quality ionic liquids," he explains. "Continuous-flow systems are probably the right way to do that."
In addition to the humidity sensor, IoLiTec is approaching commercial release of other sensors, including an explosives detector. "We have developed these sensor chips with special electrolytes resulting in high sensitivity and very low response times combined with long-term stability," Schubert says. In the chips, adsorption of the analyte on an ionic liquid film stimulates a concentration-dependent change in the resistance or capacitance of the ionic liquid that can be detected.
IoLiTec also is making dyes and ionic liquid electrolytes for dye-sensitized solar cells (DSSCs), which are alternatives to semiconductor-based solar cells, Schubert relates. In DSSCs, light passes through a transparent coated glass electrode and interacts with the sensitizer dye. Electrons gleaned from the dye are transported by the ionic liquid electrolyte to a second coated glass electrode. The cells typically are sealed, so the extremely low vapor pressure of ionic liquids is a key property; pressure does not build up inside. Commercial applications of DSSCs entering the market include power sources to recharge portable electronics and smart windows in buildings, Schubert says.
ALTHOUGH ionic liquids have been around for some time now, relatively little work has been done to develop commercial applications for the pharmaceutical and biomedical fields. But that situation is changing.
At the ACS meeting in Philadelphia, ionic liquids enthusiast Sanjay V. Malhotra, who is a lab director at the National Cancer Institute (NCI), in Frederick, Md., organized a symposium on ionic liquids for biomedical applications. Among the topics covered were the use of ionic liquids as components of nanoparticle and other types of drug delivery systems; as solvents for protein folding and unfolding; and as replacement solvents to help improve the synthesis of nucleoside-based antiviral drugs, including some drugs that are already on the market and are used to treat HIV.
"Many people, particularly those in industry, have shied away from ionic liquids because some of them are toxic," Malhotra says, when discussing his research. "We decided to see if we could take advantage of this tunable [negative] chemical property of ionic liquids and turn it into an advantage." For example, nontoxic ionic liquids can be used for drug delivery systems, he says, whereas toxic ionic liquids can be harnessed and used in the same way chemotherapeutics are used to treat cancer.
To test the anticancer potential of ionic liquids, Malhotra and coworkers at NCI initially screened about 70 selected compounds covering eight different classes of ionic liquids by administering them to mice and rats. Most of the ionic liquids were toxic, he says, but those that were not were tested for their potential use in drug formulations.
The most toxic ionic liquids from the study were tested in vitro against NCI's 60 cancer cell lines, which cover nine different types of cancers. In the end, two of the ionic liquids have moved to advanced studies to evaluate them against the growth of tumor cells. Malhotra and colleagues are having similar success in identifying ionic liquids for anti-HIV therapies.
"Our studies illustrate for the first time the possibilities of tailoring clinically useful ionic liquids, based on their integrated in vitro and in vivo screening, for drug formulations and anticancer potential," Malhotra says.
The advances achieved so far at NCI get Malhotra excited about the prospects for continued success. Although NCI is not in the business of commercializing drugs, the agency is a critical part of the drug development process. Once additional efficacy studies are completed, NCI could hand off the potential drugs to a pharmaceutical company to pursue human clinical trials and take the drugs to market.
"Many chemists are interested to see that there is this emerging area in ionic liquids," Malhotra says. "It gives those of us in the field a lot of new territory to explore."
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