Cyrene™ as a bio-alternative dipolar aprotic solvent: a waste minimizing and molar efficient protocol for the synthesis of amides from acid chlorides and primary amines in the bio-available solvent Cyrene™ is disclosed. This protocol removed the use of toxic solvents, such as dimethylformamide and dichloromethane. A simple aqueous work-up procedure for the removal of the high boiling solvent Cyrene™ resulted in up to a 55-fold increase in molar efficiency (Mol E.%) versus standard operating procedures. In order to rapidly compare the molar efficiency of this process against other methodologies an Excel based Mol. E% calculator was developed that automates many of the calculations. An investigation into the hydration of Cyrene™ found that it readily hydrates to form a geminal diol in the presence of water and that this process is exothermic.
Bousfield, T., Pearce, K., Nyamini, S., Angelis-Dimakis, A., & Camp, J. (2019). Synthesis of amides from acid chlorides and amines in the bio-based solvent Cyrene™. Green Chemistry, 21(13), 3675-3681. https://doi.org/10.1039/c9gc01180c