May 28, 2015

NSF grant to support new paradigm for ether creation

Patrick Dussault, professor of chemistry, leads an organic chemistry lecture. Dussault has earned a three-year National Science Foundation grant to examine new methods of synthesizing ethers.
Craig Chandler | University Communications

Craig Chandler | University Communications
Patrick Dussault, professor of chemistry, leads an organic chemistry lecture. Dussault has earned a three-year National Science Foundation grant to examine new methods of synthesizing ethers.

University of Nebraska-Lincoln chemist Patrick Dussault has earned a three-year National Science Foundation grant to explore new methods for synthesizing the class of chemical compounds known as ethers.

The compounds, which feature an oxygen atom singly bonded to two carbon atoms, have been widely used as surgical anesthetics and fuel additives. They also serve as structural components of pharmaceutical drugs, polymers and other synthetic materials.

Dussault aims to update the ether cookbook by expanding the slim chapter on organic peroxides, a family of molecules that appears to reverse how the standard ingredients interact to produce the compounds.

Conventional ether synthesis has relied on reactions between nucleophilic oxygen atoms – those inclined to share their electrons – and electrophilic carbon atoms that readily accept them.

The flipped approach entails so-called “carbanions” – carbon molecules featuring a surplus of electrons – donating pairs of those electrons to electrophilic oxygen atoms found in the organic peroxides.

“We want to completely reverse the normal polarity order in which people make ethers,” said Dussault, a Charles Bessey Professor of chemistry. “What we’re trying to do is … add a valuable new synthetic tool by showing that you can take advantage of this.

“It’s always nice to have a different tool, because different tools work for different purposes. There are classes of molecules where the traditional way doesn’t work very well. Interestingly, our way often seems to work remarkably well for those.”

The new synthesis approach seeks to capitalize on the unusual nature of peroxides, which feature two oxygen atoms whose mutual bond makes them uncharacteristically unstable and hungry for the electrons offered by carbon atoms.

“We’re trying to tame the reactivity of peroxides and apply it to a fairly important kind of bond formation in chemistry,” Dussault said. “Bond formation, to chemists – and to people who make drugs and fertilizers and whatever else – is kind of akin to structural elements for engineers. If you want to build a certain (structure), you have to be able to form certain bonds.”

Though chemists have known about the flipped polarity of the peroxide-carbanion reaction for some time, they have generally considered it an impractical curiosity, Dussault said. He and colleague Keith Kuwata, a theoretical chemist from Macalester College, are aiming to gain a better grasp of peroxide reactivity and the mechanisms that control ether bond formation.

Preliminary results support their hope that the peroxide-to-ether conversion can be developed into a reliable and high-yielding reaction, he said.

The researchers are also looking to hone their control over reactions of non-symmetric peroxide molecules, which feature different atomic groups on either end. Historically, chemists have successfully introduced carbanions on only the less crowded end of such molecules. However, Dussault and Kuwata have found that peroxides bearing certain groups will react as expected no matter how crowded one end happens to get.

“That’s pretty valuable, because the construction of a molecule may require you to know that you can selectively deliver one or the other oxygen (atom) of a peroxide,” Dussault said. “We think we can achieve that type of complete control.

“But we don’t completely understand this. We’re collaborating because we’re not quite sure why it’s all working the way it is.”

The overall grant is about $400,000 over three years. Dussault will also use the NSF funding to create a website for researchers interested in working with or learning more about peroxides, some of which can be dangerously unstable.

This reputation for instability has led fellow researchers to regularly contact Dussault about best practices for safely handling peroxides, he said. It’s inspired him to develop a digital warehouse of guidelines, tips and answers to common questions.

“What we’re trying to do is simply … start grouping the safety literature that we think is relevant,” said Dussault, who has worked with peroxides for more than 20 years. “We’re trying to put down a middle ground and say, ‘Here’s what we do in our group. Here are the things that we would be comfortable doing and the things we would not be comfortable with.’ We’re going to be putting up information and updating it very regularly.”