Different stages of a chemical reaction with the samarium diiodide reagent. The flask on the left contains a yellow, inactive form of the compound—over time, the compound becomes active and turns purple, as seen on the right. This color change occurs because the oxidation state of the Samarium reagent changes from 3+ to 2+ , or from Sm(III) to Sm(II), which means it gains an electron. Credit: Caltech/Chungkeun Shin
Caltech chemists have devised a new method to scale up samarium diiodide for use in industrial settings. First discovered in 1879, samarium is a highly useful reagent for molecule synthesis commonly used in the pharmaceutical industry.
Despite its extensive use, scaling up the reagent has proved difficult. "The reagent is air sensitive, so you often have to prepare the solution fresh, right before the reaction," said Caltech graduate student Chungkeun Shin, "And we often have to use large amounts of it, even in small reactions, so it's not practical for running industrial-scale reactions."
The solution developed by the team, published in Science, allows the samarium diiodide to recycle itself for continued use throughout a single reaction. This recycling process greatly reduces the amount of solvents required and eliminates the need for fresh preparation of the reagent.
"Samarium diiodide has been used in academia for the synthesis of natural products like taxol, an anticancer agent, but the reagent is not practical for creating products like this on industrial scales," says Sarah Reisman, Professor and Chair of Caltech's Division of Chemistry. "The breakthrough is that now we can translate some of these interesting reactions into process development or discovery."
Previous attempts at similar methodologies have been limited by the samarium-oxygen bond often formed by the reagent - rendering it inactive. "It's been very difficult to recycle samarium back to its active state until now," said Caltech graduate student Emily Boyd. "The reagent often ends up with a very strong samarium-oxygen bond that is hard to break and makes it difficult to recycle the reagent."
To break this bond the researchers utilized a mild acid which is a significant improvement for industrial use over the harsh chemicals used previously. The method presented by the team offers a scalable and versatile approach for increasing samarium reagent production at an industrial scale.