Greener Methods: Catalytic Amide Bond Formation

Introduction

Amide bonds are one of the most frequently utilized disconnections in organic synthesis. Methods to form this vital functionality are commonly superstoichiometric, leading to considerable waste in the process. These facts have led the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR) to identify the catalytic formation of amide bonds as a key initiative for Green Chemistry.¹

We are proud to offer a number of products used in catalytic amidation technology.²

Representative Transformations

In 2007, Milstein and coworkers reported the ruthenium-catalyzed dehydrogenative coupling of amines and alcohols to give amide products.³

Madsen and coworkers later reported an alternate catalyst system for this dehydrogenative coupling with broader scope.⁴

More recently, Hall and coworkers have demonstrated boronic acid catalyzed amidations using carboxylic acids as substrates.⁵

References

1. Constable DJC, Dunn PJ, Hayler JD, Humphrey GR, Leazer, Jr. JL, Linderman RJ, Lorenz K, Manley J, Pearlman BA, Wells A, et al. Key green chemistry research areas?a perspective from pharmaceutical manufacturers. Green Chem.. 9(5):411-420. https://doi.org/10.1039/b703488c

2. Pattabiraman VR, Bode JW. 2011. Rethinking amide bond synthesis. Nature. 480(7378):471-479. https://doi.org/10.1038/nature10702

3. Gunanathan C, Ben-David Y, Milstein D. 2007. Direct Synthesis of Amides from Alcohols and Amines with Liberation of H2. Science. 317(5839):790-792. https://doi.org/10.1126/science.1145295

4. Nordstrøm LU, Vogt H, Madsen R. 2008. Amide Synthesis from Alcohols and Amines by the Extrusion of Dihydrogen. J. Am. Chem. Soc.. 130(52):17672-17673. https://doi.org/10.1021/ja808129p

5. Al-Zoubi R, Marion O, Hall D. 2008. Direct and Waste-Free Amidations and Cycloadditions by Organocatalytic Activation of Carboxylic Acids at Room Temperature. Angew. Chem. Int. Ed.. 47(15):2876-2879. https://doi.org/10.1002/anie.200705468