Academic Award | Chemical & Engineering News
Volume 92 Issue 42 | p. 32
Issue Date: October 20, 2014 | Web Date: October 16, 2014

Academic Award

Department: Science & Technology | Collection: Green Chemistry, Sustainability
News Channels: Environmental SCENE, Organic SCENE
Keywords: oxidation, TEMPO, waste reduction, flow chemistry

Shannon S. Stahl, University of Wisconsin, Madison, for developing aerobic oxidation reactions for pharmaceutical synthesis using an inexpensive copper catalyst and O2

As oxidizing reagents go, molecular oxygen is as green as they get. But two issues have stood in O2’s way, according to chemistry professor Shannon S. Stahl of the University of Wisconsin, Madison. “The combination of O2 with organic solvents is widely viewed as an insurmountable safety challenge,” Stahl says. “And there aren’t any aerobic oxidation reactions good enough to bother dealing with the safety issue.”

Stahl and his research group recently knocked down both barriers, an accomplishment that many in the pharmaceutical industry will welcome. O2 is rarely considered as an oxidant because of the risk of fire or explosion. That leaves chemists the option of using traditional oxidants such as permanganate and hypochlorite, which are often hazardous, generate excessive waste, or are costly. In many cases, alternative synthetic routes are chosen that avoid oxidation altogether, even if they are less efficient.

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GREEN OXIDATIONS
Stahl’s team developed a catalyst system that enables safe O2 oxidations of various alcohols to aldehydes (shown).
Graphic shows a catalyst system that enables safe O2 oxidations of alcohols to aldehydes, example structures of which are shown.
 
GREEN OXIDATIONS
Stahl’s team developed a catalyst system that enables safe O2 oxidations of various alcohols to aldehydes (shown).

Jessica M. Hoover, Janelle E. Steves, and their coworkers in Stahl’s group worked around those shortcomings by discovering a catalytic system made up of a copper(I) bipyridine complex and the nitroxyl radical TEMPO. This catalyst works well to mediate selective oxidation of primary alcohols to aldehydes, oxidative coupling of alcohols with ammonia to make nitriles, and other reactions. The reactions proceed at room temperature in acetonitrile solvent with O2 from the air as the oxidant. The procedure avoids costly precious-metal catalysts and undesirable halogenated solvents. And water is the only waste product.

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David Mannel (kneeling) works on a continuous-flow O2 oxidation reactor as Root (left) and Stahl (right) look on.
Credit: Courtesy of Shannon Stahl
Photo of David Mannel (kneeling) working on a continuous-flow O2 oxidation reactor as Root (left) and Stahl (right) look on.
 
David Mannel (kneeling) works on a continuous-flow O2 oxidation reactor as Root (left) and Stahl (right) look on.
Credit: Courtesy of Shannon Stahl

To explore strategies for implementing the aerobic oxidations, Stahl has collaborated with Wisconsin chemical engineering professor Thatcher W. Root. Stahl has also established a unique noncompetitive research collaboration with Eli Lilly & Co., Merck & Co., and Pfizer. One of the most promising approaches emerging from these efforts involves a continuous-flow reactor for safely scaling up O2 oxidations that are complete in as little as three minutes.

“This work is spectacular,” says Cornell University chemistry professor Geoffrey W. Coates, a 2012 award winner. “This is a real tour de force that combines mechanistic studies with organic synthesis and very elegantly applies it to an important area of chemistry.”

Sustainability and economics are key when it comes to developing green reactions, Coates adds. Stahl’s approach includes everything process chemists look for––improving safety, saving time, reeling in cost, and preventing waste. “The interaction with leading pharmaceutical companies is a validation that this chemistry is on its way to the top.”

 
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