Clean, Green Chemistry
Nicholas Leadbeater has a reputation. People call him a “microwave chemist,” because he–you guessed it– is a chemist who uses microwaves in his laboratory. But even though these humble machines have enabled him to develop chemical techniques that are faster, cleaner, and “greener” than many similar methods before them, the associate professor of chemistry doesn’t give them too much credit. “There’s nothing magical to microwaves,” he says. “We use microwaves to facilitate what we do, and that’s chemistry– chemistry with a purpose and a use.” Using two of the chemical reactions that earned the Nobel Prize in chemistry earlier this month, Leadbeater has over the past decade discovered techniques for making natural products, pharmaceuticals, polymers, and other advanced materials with a fraction of the waste, in a fraction of the time, and at a fraction of the cost. The techniques he has developed allow scientists to quickly and easily create products, such as potential new medicines, to be tested for use in the marketplace. “Our work builds on what these famous Nobel Prize winners [Richard Heck, Ei-ichi Negishi, and Akira Suzuki] did: we’re developing new ways to build new molecules,” says Leadbeater.
A Clean Water Act
Conventional chemistry often uses a combination of high temperature, a high level of pressure, a catalyst, and a liquid chemical solvent to make a chemical reaction happen. But the appeal of microwaves was that they allowed chemists like Leadbeater to reach higher temperatures and pressures more safely and easily than conventional heating methods. This led to his first discovery. Chemical reactions generally need to occur in some sort of fluid, and the standard approach is to use organic chemicals as solvents. Using water and his microwave, Leadbeater shortened the famous Suzuki reaction—the procedure named for Akira Suzuki that won him a share of this year’s Nobel Prize—from several hours down to just five minutes. Not only did this procedure save chemists immense amounts of time, but it also greatly reduced the waste byproducts created when using organic solvents. Now, instead of having to incinerate their waste, Leadbeater found that much of it was clean enough to reuse. Leadbeater then turned his attention to the other part of the equation: chemical catalysts. The element palladium was traditionally thought to be the best catalyst for these Suzuki reactions, but wasn’t as readily available as other more common metals. When Leadbeater found that the reactions worked just as well using copper or lead, he says, “alarm bells started going off in my head.” Leadbeater then set about describing the minimum amount of palladium needed to run a Suzuki reaction. He found that the metal was necessary in only trace amounts: 50 parts per billion, or the equivalent of 50 drops of ink in a tanker truck full of water.
Creating amounts of newly-discovered products large enough to be tested for commercial use meant that chemists would now need to scale up their research. Reactions that produced a milligram would need instead to produce a kilogram of product. “Getting to this level of scaling was a big leap because of engineering and safety issues,” says Leadbeater. Microwaves not only afford greater heating and pressure, but need to be constructed with a cavity that protects the reaction from the outside world, and vice versa. However, with the right microwave equipment, Leadbeater and his recently graduated students William Devine, Chad Kormos, and Jason Schmink showed that it is possible to easily scale up these reactions. Leadbeater says these discoveries are also an invaluable tool in the classroom. Microwaves have made it possible to complete a reaction in the laboratory that once took hours in mere minutes, a feat that allows students much more flexibility and time to actually experiment in the lab. Leadbeater’s microwave chemistry techniques have been included in one of the major organic chemistry lab manuals in the country (Clean, Fast Organic Chemistry: Microwave-assisted Laboratory Experiments, 2006). Although not all chemistry teaching labs have access to microwaves, a growing number are investing in them, he says.
Going with the Flow
Despite using microwaves extensively in his lab, Leadbeater is now turning his attention to another new technique that could be the next wave of chemistry innovation. Called flow chemistry, this new idea uses a metal or plastic tube coiled tens or hundreds of times around a central heating apparatus. Reaction mixtures are flushed through these coils, which heats the liquid evenly and effectively. Using this approach allows much greater control over the time a reaction is exposed to heat, which Leadbeater says can eliminate unwanted byproducts. Leadbeater and many of his colleagues think that flow chemistry is the field’s next big thing. “Seeing what we can do with flow chemistry is a hot topic at the moment,” he says. “We’re starting to feel excitement now about flow. It’s the same kind of excitement we were feeling with microwaves 10 years ago.” Although microwaves have contributed greatly to Leadbeater’s success over the last decade, he firmly believes that technology is simply a tool to do more interesting chemistry, and he’ll never be wed to just one technique. “We want to be the early adopters when new equipment becomes available,” he adds. “You’ve got to recognize an opportunity and just jump.”