Research & Projects
Expanding the Use of Cyrene as a Solvent for Sustainable Organic Synthesis
Cyrene is a new, biodegradable solvent produced from cellulose with a superior health and safety profile compared to other polar aprotic solvents. The extent that cyrene could replace other solvents such as dimethylformamide (DMF) and N-methyl-2-pyrrolidone (NMP) in many synthesis reactions remains unknown. Both DMF and NMP are derived from fossil fuels, can be rapidly absorbed through the skin, and are shown to be reproductive hazards in studies done on mice. DMF is also a potent liver toxin and is coming under increasing regulatory pressure by the European Union. Cyrene does have some key disadvantages for synthesis reactions, being known to decompose in the presence of strong acids and bases as well as strong oxidizing and reducing agents.
Over the course of this research, cyrene was used as a solvent in 14 organic chemistry reactions: radical bromination, reductive amination, Fischer esterification, reduction, oxidation, electrophilic aromatic substitution, nucleophilic aromatic substitution, Diels-Alder cycloaddition, sulfonation, aldol condensation, Knoevenagel condensation, olefin metathesis, Hantzsch dihydropyridine synthesis, and Hantzsch pyrrole synthesis. Reactions were carried out in a microwave at a 1 mmol scale in both cyrene and a control solvent to confirm that both the intended product was formed and that the cyrene did not decompose. The most successful reactions were scaled up to 10 mmol and carried out conventionally in a round bottom flask. The products were isolated and characterized by GCMS and NMR spectroscopy. The six reactions with good conversion to product and low degradation of cyrene were: the Diels-Alder cycloaddition, Koevenagel condensation, olefin metathesis, nucleophilic aromatic substitution, Hantzsch dihydropyridine synthesis, and Hantzsch pyrrole synthesis. The reactions with equal or greater yields compared to control solvents were the Diels-Alder cycloaddition and olefin metathesis.