Intoxicating Chemistry

In a fit of whimsy, a research group at Northern Arizona University has taken a crack at using commercial brands of distilled alcohols as solvents to carry out common organic syntheses. Besides providing a bit of fun and helping draw the chemical interest of students, the research has the practical aspect of using ethanol as a green solvent to replace halogenated and other types of petroleum-derived solvents that are toxic and environmentally problematic.

Nathan B. Fisher, a graduate student in Stephanie K. Hurst’s group, presented the preliminary work on Aug. 28, during a Division of Inorganic Chemistry session at the American Chemical Society national meeting in Denver.

“For some time we have been creating new types of palladium sandwich complexes,” Hurst explained. “Our group was celebrating the end of the semester last year, just before Christmas, when I pointed out the great pity that we couldn’t run our reactions in beer. Nate countered by pointing out that he thought something like vodka would be better.

“We both knew of the importance of moving to greener solvents,” Hurst continues, “because we want to reduce the amount of chlorinated solvents we use in the lab, in particular dichloromethane. It turns out that 40% ethanol—the same percentage of ethanol in most brand names of rum, scotch, tequila, and vodka—is an optimal concentration for our catalysts to run Suzuki coupling reactions.”

The chemistry features tripalladium(0) sandwich complexes, which allow the Northern Arizona team to use a palladium catalyst that does not need to be reduced from an initial Pd(II) species, Fisher said. They first tried the reactions in water, which worked poorly. But then they tried various ethanol-water mixtures, which provided higher yields; 100% ethanol works best, with 96% yield. But Fisher pointed out that with 40% ethanol the yield only drops to 86%. With liquors, he noted, gin works best, but all types provided better than 90% yields.

The team hasn’t yet carried out analytical tests on the liquors to determine what else besides ethanol and water might be present to help the reactions. “Something is in there helping to push the reactions,” Fisher said. “And it seems the cheaper, lower quality liquors provide better results than the better liquors or pure ethanol.”

“I often joke with my students that I now have to pay for our solvents out of my own pocket, because the university and NSF take a dim view of using grant money to buy alcohol,” Hurst said.

“But there is the benefit of being able to drink the leftovers,” Fisher mused.

The alcoholic chemistry study isn’t the first time chemists have tried using commercial liquors as solvents. For example, Thomas E. Goodwin of Hendrix College in Conway, Ark., once reported a palladium-catalyzed cross-coupling of an alkyne and iodonitrobenzene in 95% ethanol. His group also successfully ran the reaction in vodka (C&EN, April 15, 1996, page 34).

“I like the Hurst group’s work and their idea for systematically trying different types of liquors, and I would like to see their full results,” Goodwin told C&EN. “There of course could be some practical problems with scaling these reactions up using the commercial brand alcohols, but one could just take cheap, untaxed ethanol as they did and mix it with water in the desired ­proportions.”

Goodwin leads the Toad Suck Institute for Green Organic Chemistry at Hendrix, an initiative in which he and his colleagues focus on creating greener versions of standard organic lab course experiments (C&EN, May 28, 2007, page 38). Goodwin noted he has developed an experiment in which vodka or rubbing alcohol (70% isopropyl alcohol) is used as the solvent for sodium borohydride reduction of a ketone. “We often use rubbing alcohol for recrystallizations as well,” he said.

Goodwin notes the alcoholic work is complementary to recent developments in green “on water” reactions popularized by K. Barry Sharpless of Scripps Research Institute in which insoluble reactants are merely stirred in water at ambient temperature, as opposed to using traditional petrochemical-based solvents. “It’s amazing how often that works,” Goodwin said.

Both Hurst and Goodwin laud the use of the distilled spirits as a good teaching tool to engage students. “It also is serving as an excellent recruitment tool,” Hurst added.