OPTIMIZATION Christian Noti, a Ph.D. student at ETH, sets up the MIT microreactor system to study an organic reaction.
	COURTESY OF PETER H. SEEBERGER

The team, led by professor of chemical engineering Klavs F. Jensen at Massachusetts Institute of Technology and professor of organic chemistry Peter H. Seeberger at the Swiss Federal Institute of Technology (ETH), Zurich, showed that the continuous-flow silicon microfluidic microreactor can be used to optimize the yield and selectivity of a variety of reactions using milligram amounts of starting materials.

"We have demonstrated the ability to scan the reaction space--yield, selectivity, and rates--as functions of reaction variables, such as composition, flow rates, and temperature, for complex organic transformations that are moisture sensitive," Jensen says.

The MIT-ETH team showed, for example, that the device, developed at MIT, can be used to systematically study and determine the optimal reaction conditions for glycosylation reactions [Chem. Commun., 2005, 578].

"The selectivities and yields of glycosylation reactions are notoriously hard to predict," Seeberger says. "Our system allows numerous glycosylations to be performed in a short time and with little material. Microreactors have not been used before for the screening and optimization of such complex reactions."

One of the glycosylations studied by the researchers was the synthesis of the disaccharide formed by the mannosylation of diisopropylidene galactose with mannosyl trichloroacetimidate. They carried out 44 reactions at varying temperatures using just over 2 mg of the mannosyl compound for each reaction. The reactor residence times ranged from around 25 to 215 seconds.

"It would have been possible to carry out only two or three of these experiments in the same time using conventional laboratory techniques, and more material would have been required," Jensen says. "The ability to rapidly explore reaction conditions not only offers opportunities for optimizing yield and selectivity, but also provides sufficient data to investigate reaction paths and chemical kinetics."

Jensen, Seeberger, and coworkers have demonstrated advantages of using their microreactor for direct fluorinations, phosgene synthesis and phosgenation reactions, diazotizations, hydrogenations, oxidations, and other organic reactions. They also have shown that the device is amenable to integrated reaction monitoring using mass spectrometry, gas chromatography, Fourier transform infrared spectroscopy, and other common types of spectroscopy.

"Microreactors will become the round-bottom flasks of the 21st century," Seeberger says. "We are now applying these reactors to a host of other chemical reactions."