Simple and efficient synthesis

A new ruthenium-based catalyst helps clean up a fundamental chemical reaction

Originally published online: December 2007

The synthesis of chemical compounds known as amides is fundamentally important in biological and chemical systems because these groups appear frequently and form the links that hold together the building blocks of peptides. However, existing methods for amide synthesis generally use toxic and costly coupling reagents and produce hazardous by-products.

Now, a team at Israel’s Weizmann Institute of Science, led by David Milstein, has used a rationally designed ruthenium complex to couple two starting compounds together, an amine and an alcohol, to produce an amide with only hydrogen gas as by-product. The researchers showed this versatile catalyst could be used with a range of amines and alcohols with good-to-excellent yields.

Moreover, the reaction was shown to have quite specific reactivity. When the reactant contained two primary amine groups (where the nitrogen atom is attached to one carbon atom), a product with two amides was formed; and when the reactant contained one primary and one secondary amine (where the nitrogen atom is attached to two carbon atoms), a product with a single amide resulted by reaction with only the primary amine.

Milstein hopes that this catalyst and method can be developed and then used as a general method in synthetic chemistry laboratories.

Reference
Gunanathan C., Ben-David Y. & Milstein D. Direct Synthesis of Amides from Alcohols and Amines with Liberation of H₂. Science 2007, 317, 790–792