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The solvent dichloromethane, or DCM, is commonly used to strip paint and cut grease. It's also what generations of chemistry students have used to dissolve pain reliever tablets in a lab exercise designed to teach them how to isolate compounds in a mixture.

But when the U.S. Environmental Protection Agency banned most uses of DCM last year, Dartmouth and potentially thousands of other schools that teach introductory organic chemistry were left scrambling. To continue using DCM, schools would need to closely monitor its use, effectively preventing them from using the solvent in student laboratories with large numbers of beginner chemists.

The solution devised by visiting scholar Steve Wright '81 and senior lecturer Cathy Welder has now drawn national attention: Their article detailing safer solvent substitutions was recently ranked among the most read in the Journal of Chemical Education.

"Everybody recognized right away that finding a substitute was the only real choice," says Wright, a teaching assistant for Introductory Organic Chemistry.

Wright returned to Dartmouth last summer after retiring from a long career as a chemist at Pfizer. He had offered to volunteer as a TA for introductory organic chemistry while setting up a lab with his long ago adviser, professor emeritus Gordon Gribble.

Wright was the obvious person to assign the DCM substitution task. At Pfizer, he had helped to scale promising drug compounds by eliminating or finding safer alternatives to toxic or hazardous ingredients. Working with the team behind the anti-COVID drug Paxlovid, he cut the number of atoms involved in the drug's action mechanism from 11 to two.

He also had a longstanding interest in chemistry education, publishing experiments easy enough to be done at home with common household ingredients like table salt and vitamin C. A decade ago, he established a green chemistry prize for senior chemistry majors at Dartmouth.

"I came of age in the 1970s, when energy was scarce, and everything cost more than it used to," he says. "I became adept at finding ways to cope and compensate. Ultimately, green chemistry comes down to getting more done with less. Less input, less energy, less waste, less cost, and less trouble."

'First penguin in the water'

Wright began using DCM in chemistry labs as a high school student, and continued to do so as a chemistry major and TA at Dartmouth. The properties that allow DCM to peel paint off walls also make it an effective solvent to dissolve compounds and monitor reactions. DCM is immiscible, meaning it doesn't dissolve in water, and it evaporates easily, simplifying the process of separating and extracting compounds. Unlike many other solvents, it won't catch on fire, making it an attractive choice in teaching labs.

DCM, however, is a known carcinogen that the EPA has been trying to phase out for years. Though safer alternatives have been around for a while, chemists have been reluctant to switch. "It's not trivial to change out solvents for reactions," says Welder. "You change one thing, and you often have to change something else."

"No one wants to take a chance with their work, their materials, their time," says Wright. "No one wants to be the first penguin in the water."

Last fall, Wright took the plunge at the request of Welder, whom he had assisted in the lab over the summer. He quickly zeroed in on ethyl acetate and MTBE as replacement candidates for the course's pain reliever and wintergreen oil labs. Over four days, he and Welder tested them in the student lab, on student equipment. They recently shared their in the Journal of Chemical Education.

Dartmouth's organic chemistry students are asked in their first semester to use a mix of DCM and lye to isolate and identify the active ingredients in over-the-counter pain relief tablets—both aspirin and an analgesic called phenacetin. The following term, they convert aspirin to wintergreen oil, monitoring the reaction by thin layer chromatography and isolating the wintergreen oil they synthesized by extraction with DCM.

As the aspirin turns to methyl salicylate, the molecule that gives wintergreen gum its woodsy scent, students are meant to take note of the intermediate compound, salicylic acid, which is found in birch and willow trees and has been used throughout the ages to relieve pain. Ingested directly, salicylic acid causes stomach aches; aspirin was invented to ease its delivery.

"In both labs, the choice of aspirin is primarily to engage students with a molecule they are already familiar with and have seen on store shelves," says Wright.

Their experiments confirmed that ethyl acetate worked well as a stand-in for DCM in the pain reliever lab. They also discovered that swapping a weaker base like baking soda for lye slowed down some unwanted side reactions enough to make the aspirin extraction step easier and more successful for students.

Their experiments confirmed that a close relative to ethyl acetate, MTBE, a compound added to gasoline to increase its oxygen content and improve mileage, worked best as a DCM replacement in the wintergreen lab.

The new solvents were introduced into the teaching lab this year, and the biggest adjustment for students was the time it takes to finish the lab. Ethyl acetate and MTBE take longer to evaporate because of their higher boiling points. "It takes students a little longer," says Welder. "They just have to wait their turn to evaporate the solvent on a rotary evaporator."

Alternative solvents and beyond

Elsewhere at Dartmouth, researchers are trying to minimize DCM use while following the EPA's new ventilation guidelines.

"What happens in student labs doesn't necessarily translate into research labs," says Dartmouth Professor of Chemistry Ivan Aprahamian. "Nonetheless, every chemistry department in the country will have to change the way they run their undergraduate organic labs, and this article will guide them through the process."

With the DCM paper behind him, Wright has turned to the project he's working on with Gribble—to try and synthesize anti-cancer compounds found in some types of sea sponge. Wright says he'll also continue to document DCM substitutions in other use cases.

"Lots of people talk about it, but no one has made the effort to show how to do it," he says. "Without the 'showing how,' people will continue to use dichloromethane."